Cholawat Pacharinsak, DVM, PhD

All Publications

• Tiletamine/Zolazepam and Ketamine with Dexmedetomidine (TKD) Cocktail Is as Effective as Tiletamine/Zolazepam and Ketamine with Xylazine (TKX) in Providing Pig General Anesthesia. Animals : an open access journal from MDPI Akaraphutiporn, E., Durongphongtorn, S., Jampachaisri, K., Sharp, P., Pacharinsak, C., Wangdee, C. 2024; 14 (19)

  Abstract

  This study aimed to evaluate dexmedetomidine as an alternative to xylazine in pigs. We compared TKD (0.05 mL/kg) to TKX (0.05 mL/kg) in 20 male pigs undergoing unilateral cryptorchid castration (short-term, 45-min) or bilateral cryptorchid castration (long-term, 90-min). We hypothesized that TKD would be comparable to TKX for both short-term and long-term anesthesia. Monitored parameters were classified into duration and physiological categories, including induction and recovery times, reflexes, heart rate (HR), respiratory rate (RR), arterial blood pressure, oxygen saturation (%SpO2), end-tidal carbon dioxide (ETCO2), and body temperature (TEMP). Isoflurane levels were also recorded, if used. Results showed no significant differences in duration parameters between TKD and TKX for either short-term or long-term anesthesia (induction: 1 min; recovery: 18-35 min). Physiological parameters were mostly similar between groups, although TKD caused slightly higher blood pressure during short-term anesthesia. Isoflurane levels (0.1-0.6%) were comparable between groups. Overall, the results suggest that TKD provides anesthesia comparable to TKX in pigs undergoing unilateral or bilateral cryptorchid surgery requiring short-term and long-term anesthesia.

  View details for DOI 10.3390/ani14192881

  View details for PubMedID 39409830

• General Anesthesia Induced by a Combination of Medetomidine/Vatinoxan with Ketamine and Buprenorphine-ER in C57BL/6J Mice (Mus musculus). Journal of the American Association for Laboratory Animal Science : JAALAS Tien, K., Franco, B., Alamaw, E. D., Jampachairsi, K., Casey, K., Huss, M., Pacharinsak, C. 2024

  Abstract

  Medetomidine/vatinoxan (Zenalpha®) is a novel anesthetic combination used as a sedative and analgesic in dogs. Vatinoxan minimizes adverse cardiopulmonary effects associated with medetomidine administration while preserving sedation and analgesia. In this study, we evaluated the clinical safety and efficacy of 3 dosage combinations of Zenalpha with ketamine and buprenorphine extended release (ER) as compared with xylazine with ketamine and buprenorphine-ER for anesthesia of C57BL/6J mice. We hypothesized that anesthesia with 0.5 mg/kg of Zenalpha would more reliably provide a surgical anesthetic plane, lower mortality, and fewer adverse physiologic effects as compared with anesthesia with 8 mg/kg of xylazine. Ten-week-old male and female C57BL/6J mice were randomly administered 1 of 4 anesthetic cocktails subcutaneously: ketamine (80 mg/kg) and buprenorphine-ER (0.5 mg/kg) with 1) xylazine (8 mg/kg; XKB); 2) Zenalpha (0.25 mg/kg; ZKB/0.25); 3) Zenalpha (0.5 mg/kg; ZKB/0.5); or 4) Zenalpha (1.0 mg/kg; ZKB/1.0). Following drug administration, we assessed the anesthesia induction time by measuring the time to loss of righting reflex and loss of paw withdrawal reflex (PWR). Upon reaching a loss of righting reflex, physiologic parameters including heart rate, respiratory rate, oxygen saturation, indirect mean arterial blood pressure, body temperature, jaw tone, and skin color were monitored every 5 min. Thirty minutes after anesthetic drug administration (TA), atipamezole (1 mg/kg SC) was administered. Recovery time was determined through time until return of PWR, righting reflex, and ambulation. Mice were monitored for 3 d postanesthesia. Results included: 1) ZKB anesthesia caused loss of PWR in a dose-dependent manner; 2) physiologic parameters were similar between XKB and ZKB mice by TA in 100% O₂; 3) ZKB groups took longer to recover and had a 20% to 30% mortality rate in the mid-to-high dosage groups. We conclude that anesthesia with 0.5 mg/kg of Zenalpha more reliably produced a surgical anesthetic plane but also led to decreased mean arterial pressure and increased mortality as compared with anesthesia with 8 mg/kg of xylazine. We recommend using Zenalpha (0.25 to 1.0 mg/kg) with 80 mg/kg ketamine and 0.5 mg/kg buprenorphine-ER to provide general anesthesia in C57BL/6 mice, along with supplemental 100% oxygen and atipamezole.

  View details for DOI 10.30802/AALAS-JAALAS-23-000120

  View details for PubMedID 39237287

• Mouse Anesthesia and Analgesia. Current protocols Schwartz, K., Pacharinsak, C. 2024; 4 (4): e1006

  Abstract

  Providing anesthesia and analgesia for mouse subjects is a common and critical practice in the laboratory setting. This practice is necessary for performing invasive procedures, achieving prolonged immobility for sensitive imaging modalities (magnetic resonance imaging, for instance), and providing intra- and post-procedural pain relief. In addition to facilitating the procedures performed by the investigator, the provision of anesthesia and analgesia is crucial for the preservation of animal welfare and for humane treatment of animals used in research. Furthermore, anesthesia and analgesia are important components of animal use protocols reviewed by Institutional Animal Care and Use Committees, requiring careful consideration and planning for the particular animal model. In this article, we provide technical guidance for the investigator, covering the provision of anesthesia by two routes (injectable and inhalant), guidelines for monitoring anesthesia, current techniques for recognition of pain, considerations for administering preventative analgesia, and considerations for post-operative care. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Injectable anesthesia Basic Protocol 2: Inhalant anesthesia Basic Protocol 3: Assessing pain.

  View details for DOI 10.1002/cpz1.1006

  View details for PubMedID 38646951

• Carprofen Attenuates Postoperative Mechanical and Thermal Hypersensitivity after Plantar Incision in Immunodeficient NSG Mice. Comparative medicine Alamaw, E. D., Casey, K. M., Tien, K., Franco, B. D., Gorman, G., Cotton, R. M., Nagamine, C., Jampachaisri, K., Sharp, P., Pacharinsak, C., Huss, M. K. 2024

  Abstract

  Immunodeficient NSG mice are reported to be less responsive to buprenorphine analgesia. Here, we used NSG mice to compare the efficacy of the commonly used dose of carprofen (5 mg/kg) with 5 and 10 times that dose (25 and 50 mg/kg) for attenuating postoperative mechanical and thermal hypersensitivity following an incisional pain model. Male and female NSG mice (n = 45) were randomly assigned to one of 4 groups and received daily subcutaneous injections for 3 d: saline (5 mL/kg), 5 mg/kg carprofen (Carp5), 25 mg/kg carprofen (Carp25), and 50 mg/kg carprofen (Carp50). Mechanical and thermal hypersensitivity were assessed 24 h before and at 4, 24, and 48 h after surgery. Plasma carprofen concentrations were measured in a separate group of mice (n = 56) on days 0 (at 2, 4, 12, and 23 h), 1, and 2 after the first, second, and third doses, respectively. Toxicity was assessed through daily fecal occult blood testing (n = 27) as well as gross and histopathologic evaluation (n = 15). Our results indicated that the saline group showed both mechanical and thermal hypersensitivity throughout the study. Carp5 did not attenuate mechanical or thermal hypersensitivity at any time point. Carp25 attenuated mechanical and thermal (except for the 4-h time point) hypersensitivity. Carp50 attenuated only thermal hypersensitivity at 24 h. Fecal occult blood was detected in 1 of 8 Carp25-treated mice at 48 and 72 h. Histopathologic abnormalities (gastric ulceration, ulcerative enteritis, and renal lesions) were observed in some Carp50-treated mice. Plasma carprofen concentrations were dose and time dependent. Our results indicate that Carp25 attenuated postoperative mechanical and thermal hypersensitivity more effectively than Carp5 or Carp50 in NSG mice with incisional pain. Therefore, we recommend providing carprofen at 25 mg/kg SID for incisional pain procedures using immunodeficient NSG mouse.

  View details for DOI 10.30802/AALAS-CM-23-000058

  View details for PubMedID 38553034

• Comparing Three Formulations of Buprenorphine in an Incisional Pain Model in Mice. Journal of the American Association for Laboratory Animal Science : JAALAS Lopez-Echeverria, G., Alamaw, E., Gorman, G., Jampachaisri, K., Huss, M. K., Pacharinsak, C. 2023

  Abstract

  This study compared the therapeutic effects in mice of 3 different formulations of buprenorphine. These formulations were standard buprenorphine hydrochloride (Bup-HCL) and 2 different extended-release buprenorphine formulations (Bup-ER and Ethiqa-XR [Bup-XR]). Drugs were evaluated based on their ability to attenuate thermal hypersensitivity in a mouse plantar incisional pain model. We hypothesized that Bup-HCL would attenuate postoperative thermal hypersensitivity at 20 min after administration, and that Bup-ER and Bup-XR would attenuate thermal hypersensitivity at 40 min after administration. Male C57BL6/J mice were randomly assigned to 1 of 4 treatment groups: 1) saline, 5 mL/kg SC, once; 2) Bup-HCL, 0.1 mg/kg SC, once; 3) Bup-ER, 1 mg/kg, SC, once; and 4) Bup-XR, 3.25 mg/kg, SC, once. Thermal hypersensitivity was assessed on the day before surgery and again on the day of surgery at 20, 40, 60, 90, and 120 min after drug administration. Thermal hypersensitivity after surgery was not different among the Bup-HCL, Bup-ER and Bup-XR groups at any timepoint. In addition, all buprenorphine treatment groups showed significantly less thermal hypersensitivity after surgery than did the saline group. Subjective observations suggested that mice that received Bup-ER or Bup-XR became hyperactive after drug administration (83 and 75% of mice tested, respectively). Our results indicate that Bup-HCL, Bup-ER, or Bup-XR attenuate thermal hypersensitivity related to foot incision by 20 min after administration.

  View details for DOI 10.30802/AALAS-JAALAS-23-000011

  View details for PubMedID 38030144

• Effects of atipamezole on selected physiologic parameters in cynomolgus macaques (Macaca fascicularis). Journal of medical primatology Schwartz, K., Zhang, M., Franco, B., Jampachaisri, K., Cotton, R. M., Huss, M. K., Fisher, K. M., Darian-Smith, C., Sharp, P., Pablo, L., Pacharinsak, C. 2023

  Abstract

  Atipamezole, an α-2 adrenergic receptor antagonist, reverses the α-2 agonist anesthetic effects. There is a dearth of information on the physiological effects of these drugs in cynomolgus macaques (Macaca fascicularis). We assessed atipamezole's physiologic effects. We hypothesized atipamezole administration would alter anesthetic parameters.Five cynomolgus macaques were sedated with ketamine/dexmedetomidine intramuscularly, followed 45 min later with atipamezole (0.5 mg/kg). Anesthetic parameters (heart rate, blood pressure [systolic (SAP), diastolic (DAP), and mean (MAP) blood pressure], body temperature, respiratory rate, and %SpO2) were monitored prior to and every 10 min (through 60 min) post atipamezole injection.While heart rate was significantly increased for 60 min; SAP, DAP, MAP, and temperature were significantly decreased at 10 min.This study indicates subcutaneous atipamezole results in increased heart rate and transient blood pressure decrease. These findings are clinically important to ensure anesthetist awareness to properly support and treat patients as needed.

  View details for DOI 10.1111/jmp.12682

  View details for PubMedID 37908039

• Assessment of a Combination of Tiletamine/ Zolazepam, Ketamine, and Dexmedetomidine for Anesthesia of Swine (Sus domesticus). Journal of the American Association for Laboratory Animal Science : JAALAS Bunnag, N., Akaraphutiporn, E., Durongphongtorn, S., Soontornvipart, K., Sharp, P., Pacharinsak, C., Wangdee, C. 2023

  Abstract

  This study investigated an injectable swine anesthetic induction using tiletamine/zolazepam and ketamine in combinationwith either dexmedetomidine (TKD) or xylazine (TKX). We hypothesized that TKD would accelerate anesthesia onset andprolong recovery compared TKX in swine undergoing a noninvasive radiographic procedure. A randomized crossover experimentwas performed on 6 healthy, intact, male miniature swine. Swine were randomly assigned to one of 2 groups: 1) 5 mg/kg tiletamine/zolazepam, 2.5 mg/kg ketamine, and 0.0125 mg/kg dexmedetomidine (TKD) or 2) 5 mg/kg tiletamine/zolazepam,2.5 mg/kg ketamine, and 2.5 mg/kg xylazine (TKX). Either TKD or TKX was administered intramuscularly at 0.05 mL/kg toprovide anesthesia for a 45-min radiographic procedure. Atipamezole was administered at 45 min after TKD or TKX administration.During anesthesia, swine were monitored for anesthetic-duration parameters (time to sternal recumbency [onsetof anesthesia], lateral recumbency, loss of palpebral reflex, return of the palpebral reflex, and return to sternal recumbency[onset of recovery]) and physiologic parameters (heart rate, %SpO2, noninvasive blood pressure, and body temperature).Anesthetic-duration and physiologic parameters did not differ between groups at any time point. The results indicate TKDand TKX provide comparable general anesthesia in swine undergoing a radiographic examination.

  View details for DOI 10.30802/AALAS-JAALAS-22-000083

  View details for PubMedID 37704401

• Focused ultrasound-induced inhibition of peripheral nerve fibers in an animal model of acute pain. Regional anesthesia and pain medicine Anderson, T. A., Pacharinsak, C., Vilches-Moure, J., Kantarci, H., Zuchero, J. B., Butts-Pauly, K., Yeomans, D. 2023

  Abstract

  Moderate-to-severe acute pain is prevalent in many healthcare settings and associated with adverse outcomes. Peripheral nerve blockade using traditional needle-based and local anesthetic-based techniques improves pain outcomes for some patient populations but has shortcomings limiting use. These limitations include its invasiveness, potential for local anesthetic systemic toxicity, risk of infection with an indwelling catheter, and relatively short duration of blockade compared with the period of pain after major injuries. Focused ultrasound is capable of inhibiting the peripheral nervous system and has potential as a pain management tool. However, investigations of its effect on peripheral nerve nociceptive fibers in animal models of acute pain are lacking. In an in vivo acute pain model, we investigated focused ultrasound's effects on behavior and peripheral nerve structure.Focused ultrasound was applied directly to the sciatic nerve of rats just prior to a hindpaw incision; three control groups (focused ultrasound sham only, hindpaw incision only, focused ultrasound sham+hindpaw incision) were also included. For all four groups (intervention and controls), behavioral testing (thermal and mechanical hyperalgesia, hindpaw extension and flexion) took place for 4 weeks. Structural changes to peripheral nerves of non-focused ultrasound controls and after focused ultrasound application were assessed on days 0 and 14 using light microscopy and transmission electron microscopy.Compared with controls, after focused ultrasound application, animals had (1) increased mechanical nociceptive thresholds for 2 weeks; (2) sustained increase in thermal nociceptive thresholds for ≥4 weeks; (3) a decrease in hindpaw motor response for 0.5 weeks; and (4) a decrease in hindpaw plantar sensation for 2 weeks. At 14 days after focused ultrasound application, alterations to myelin sheaths and nerve fiber ultrastructure were observed both by light and electron microscopy.Focused ultrasound, using a distinct parameter set, reversibly inhibits A-delta peripheral nerve nociceptive, motor, and non-nociceptive sensory fiber-mediated behaviors, has a prolonged effect on C nociceptive fiber-mediated behavior, and alters nerve structure. Focused ultrasound may have potential as a peripheral nerve blockade technique for acute pain management. However, further investigation is required to determine C fiber inhibition duration and the significance of nerve structural changes.

  View details for DOI 10.1136/rapm-2022-104060

  View details for PubMedID 36822815

• Bupivacaine as a euthanasia agent for African Clawed Frogs (Xenopus laevis). PloS one Navarro, K., Jampachaisri, K., Chu, D., Pacharinsak, C. 2022; 17 (12): e0279331

  Abstract

  Immersion in tricaine methanesulfonate (i.e. TMS) has been used for euthanasia of Xenopus laevis (African Clawed frogs). However, the time for preparation and potential human health hazards may pose as a barrier for large group culls. Here, we aimed to investigate whether immersion in bupivacaine is an effective means to euthanize this species. In experiment one, frogs (n = 10/group) were randomly assigned to 1-h immersion in 1 of 3 treatment groups: 1) TMS-5 (MS-222, 5g/L); 2) TMS-10 (MS-222, 10 g/L); or 3) Bupi-1.5 (0.5% Bupivacaine, 1.5 g/L). Frogs were then removed from solutions, rinsed with system water, and placed into a recovery cage. Heart rate was evaluated audibly via doppler ultrasound flow over 1 min at immediate removal (T1h), at 2 (T2h), and 3 (T3h) h in the recovery cage. In experiment two, frogs (n = 7/group) underwent 5-h & 19-h immersion in either TMS-5 or Bupi-1.5, with heart rate assessment at 5 and 19 hrs. Righting reflex and withdrawal reflex of the hindlimb were tested during the experiments. Experiment one-after the 1-h immersion, Bupi-1.5 treated animals had decreased heart rates compared to TMS-5 and TMS-10 treated animals by T2h. Neither TMS-5, TMS-10, nor Bupi-1.5 ceased heart rate after the 1-h immersion. Experiment two-after the 5-h immersion, Bupi-1.5 and TMS-5 treated animals were comparable in heart rates. 43% of TMS-5 animals and 14% of the Bupi-1.5 animals had completely ceased heart rates at T5h. At 19 h all remaining animals exhibited rigor mortis and had ceased heart rate. We recommend 19-h of immersion using either TMS-5 or Bupi-1.5 for cessation of heart rate in African Clawed frogs. These data are strong support for the use of secondary physical methods for euthanasia in African Clawed frogs when euthanasia by immersion is performed.

  View details for DOI 10.1371/journal.pone.0279331

  View details for PubMedID 36542627

• Efficacy of Supplemental Diet Gels for Preventing Postoperative Weight Loss in Mice (Mus musculus). Journal of the American Association for Laboratory Animal Science : JAALAS Gates, K. V., Alamaw, E., Jampachaisri, K., Huss, M. K., Pacharinsak, C. 2022

  Abstract

  This study investigated whether the use of commercially available diet gels prevented the postoperative weight loss associated with major survival surgery in mice. C57BL/6 mice were divided into 3 groups (n = 9 per group) that received moistened chow pellets alone or with one of 2 commercially available diet gels. Mice began receiving the test diets 3 d before surgery (baseline) and were weighed daily for 7 d after surgery. On day 0, mice underwent ventral midline laparotomy, during which the intestines were manipulated for 2 min and a segment of jejunum was briefly clamped. Compared with the baseline value for the same group, body weights for the mice that received moistened chow only were significantly lower on all postoperative days (days 1 through 7). In contrast, body weights of mice that received both moistened chow and diet gel differed from baseline only on days 2 and 3 for one product and were never different from baseline for the other product. This study indicates that the combination of diet gel and moistened chow prevented or mitigated postoperative weight loss after a laparotomy procedure in mice.

  View details for DOI 10.30802/AALAS-JAALAS22-000030

  View details for PubMedID 36410729

• A Review of Long-acting Parenteral Analgesics for Mice and Rats. Journal of the American Association for Laboratory Animal Science : JAALAS Huss, M. K., Pacharinsak, C. 2022

  Abstract

  Appropriate analgesia is a crucial part of rodent postoperative and postprocedural pain. Providing appropriate analgesia is an ethical obligation, a regulatory requirement, and an essential element of obtaining quality scientific results and conducting reproducible data. Meeting these requirements is facilitated by practical, efficient and safe delivery methods for providing analgesia. Over the last decade, long-acting analgesics have gained widespread use in research animal medicine to avoid or treat postoperative or postprocedural pain while minimizing handling-related time and stress. Long-acting formulations of analgesics suitable for rodents are available for opioids, NSAIDs, and local anesthetics. The goal of this review is to summarize the currently available long-acting formulations of analgesics for rodents and to provide recommendations to veterinarians and researchers regarding their use.

  View details for DOI 10.30802/AALAS-JAALAS-22-000061

  View details for PubMedID 36379476

• Dexmedetomidine Effectively Sedates Asian Elephants (Elephas maximus). Animals : an open access journal from MDPI Buranapim, N., Kulnanan, P., Chingpathomkul, K., Angkawanish, T., Chansitthiwet, S., Langkaphin, W., Sombutputorn, P., Monchaivanakit, N., Kasemjai, K., Namwongprom, K., Boonprasert, K., Bansiddhi, P., Thitaram, N., Sharp, P., Pacharinsak, C., Thitaram, C. 2022; 12 (20)

  Abstract

  This study investigated the sedative effects of dexmedetomidine in Asian elephants. We hypothesized that 2 g/kg dexmedetomidine would provide sufficient standing sedation. A crossover design study was performed in three Asian elephants. Each elephant was assigned to 1 of 3 treatment groups-1 (D1), 1.5 (D1.5) or 2 (D2) g/kg dexmedetomidine (intramuscular injection, IM) with a two-week 'washout period' between doses. Elephants were monitored for 120 min. At 120 min (Ta), atipamezole was administered IM. Sedation and responsiveness scores were evaluated. Physiological parameters (pulse rate, respiratory rate, and %SpO2) and clinical observations were monitored during the study and for 3 days post drug administration. D2 provided the longest sedation (approximately 70 min), compared to D1 and D1.5. After Ta, each elephant's sedative stage lessened within 10-15 min without complications. No significant abnormal clinical observations were noted throughout and during the 3-days post study period. These data suggest that a single 2 g/kg IM dexmedetomidine injection provides sufficient standing sedation for approximately 70 min in Asian elephants.

  View details for DOI 10.3390/ani12202787

  View details for PubMedID 36290172

• Efficacy of 3 Buprenorphine Formulations for the Attenuation of Hypersensitivity after Plantar Incision in Immunodeficient NSG Mice. Journal of the American Association for Laboratory Animal Science : JAALAS Arthur, J. D., Alamaw, E. D., Jampachairsri, K., Sharp, P., Nagamine, C. M., Huss, M. K., Pacharinsak, C. 2022

  Abstract

  Buprenorphine is perhaps the most prescribed analgesic for management of postoperative pain in mice. Although various buprenorphine formulations are effective in commonly used immunocompetent mouse strains, a knowledge gap exists regarding its efficacy in immunodeficient mice. Here we used a plantar incision to evaluate the efficacy of 3 buprenorphine formulations for attenuating postoperative mechanical and thermal hypersensitivity in the immunodeficient NSG mouse strain. We also characterized the pharmacokinetics of these formulations over a 72-h period. We hypothesized that all 3 buprenorphine formulations evaluated-the standard preparation and 2 extended-release products (Bup-HCl, Bup-ER, and Bup-XR, respectively)-would attenuate postoperative mechanical and thermal hypersensitivity resulting from a plantar incision in NSG mice. Male and female NSG mice (n = 48) were allocated to 4 treatment groups: saline (0.9% NaCl, 5 mL/kg SC once); Bup-HCl (0.1 mg/kg SC, BID for 2 d); Bup-ER (1.0 mg/kg SC once); and Bup-XR (3.25 mg/kg SC once). Mechanical and thermal hypersensitivity assessments were conducted 24 h before surgery and at 4, 8, 24, 48, and 72 h afterward. All groups of mice showed mechanical and thermal hypersensitivity within the first 24 h after surgery. Behavioral pain indicators (guarding, toe-touching [intermittent partial weight bearing], licking the incision, vocalizations) were observed in some mice from each group at every postoperative time point. Plasma buprenorphine was measured in a separate group of mice and concentrations surpassed the suggested therapeutic level (1.0 ng/mL) for less than 4 h for Bup-HCl, for at least 24 h for Bup-ER, and for 72 h for Bup-XR. Our results indicate that at the dosages studied, these buprenorphine formulations do not adequately attenuate postoperative mechanical and thermal hypersensitivity in the plantar incisional model in NSG mice. These findings support the need for strain-specific analgesic protocols for mice used in research.

  View details for DOI 10.30802/AALAS-JAALAS-22-000058

  View details for PubMedID 36068076

• Use of Ketamine or Xylazine to Provide Balanced Anesthesia with Isoflurane in C57BL/6J Mice. Journal of the American Association for Laboratory Animal Science : JAALAS David, E. M., Pacharinsak, C., Jampachaisri, K., Hagan, L., Marx, J. O. 2022

  Abstract

  Balanced anesthesia—the use of a combination of drugs to achieve a desired anesthetic plane—offers many benefits, including smoother induction and recovery and fewer adverse effects than occur with individual drugs. Although premedication prior to inhalant anesthesia is routine in other species, mice are commonly induced with gas anesthesia alone. The hypothesis of this study was that premedication with ketamine or xylazine would safely reduce the stress of isoflurane induction and lower the minimum alveolar concentration (MAC) of isoflurane. Young adult male and female C57BL/6J mice were premedicated with ketamine (100 mg/kg), xylazine (4 mg/kg), or isotonic crystalloid (0.1 mL) and were used in 4 experiments. First, isoflurane induction was video recorded under all test conditions, and the videos were scored according to a behavioral ethogram to identify signs of distress. Mice in the ketamine group experienced tremors and ataxia before and during induction. Therefore, ketamine was given after induction with isoflurane in subsequent experiments. Second, the MAC value for each anesthetic protocol was determined by using quantal and bracketing analysis. Third, mice were anesthetized according to the 3 protocols, and vital parameters were monitored for 60 min. Finally, anesthetized mice were challenged with hypoxia and hypovolemia, and vital parameters were monitored. Premedication with xylazine significantly reduced the stress scores for isoflurane induction (control, 7.3 ± 1.5; ketamine, 6.0 ± 3.0; xylazine, 3.1 ± 1.0). Ketamine and xylazine both reduced the MAC of isoflurane (control, 1.89%; ketamine, 0.96%; xylazine, 1.20%). All mice survived 60 min of anesthesia and the hypoxia-hypovolemia challenge. Premedication with xylazine reduced the stress of induction and lowered the necessary dose of isoflurane in C57BL/6J mice to maintain a surgical plane of anesthesia. We recommend administering xylazine before isoflurane induction and anesthesia of healthy mice that are undergoing procedures in which 100% oxygen is provided and anticipated blood loss is less than 10% to 15% of the total blood volume.

  View details for DOI 10.30802/AALAS-JAALAS-21-000125

  View details for PubMedID 35940848

• Anesthetic effects of dexmeditomidine-tiletamine/zolazepam combination in cats undergoing ovariohysterectomy THAI JOURNAL OF VETERINARY MEDICINE Jiwlawat, N., Pacharinsak, C., Durongphongtorn, S. 2022; 52 (2): 267-274

  View details for DOI 10.14456/tjvm.2022.30

  View details for Web of Science ID 000849792600005

• Extended-release Buprenorphine, an FDAindexed Analgesic, Attenuates Mechanical Hypersensitivity in Rats (Rattus norvegicus). Journal of the American Association for Laboratory Animal Science : JAALAS Alamaw, E. D., Franco, B. D., Jampachaisri, K., Huss, M. K., Pacharinsak, C. 1800; 61 (1): 81-88

  Abstract

  A new extended-release buprenorphine (XR), an FDA-indexed analgesic, has recently become available to the laboratory animal community. However, the effectiveness and dosing of XR has not been extensively evaluated for rats. We investigated XR's effectiveness in attenuating postoperative hypersensitivity in a rat incisional pain model. We hypothesized that high dose of XR would attenuate mechanical and thermal hypersensitivity more effectively than the low dose of XR in this model. We performed 2 experiments. In experiment 1, male adult Sprague-Dawley rats (n = 31) were randomly assigned to 1 of the 4 treatment groups: 1) saline (saline, 0.9% NaCl, 5 mL/kg, SC, once); 2) sustained-release buprenorphine (Bup-SR; 1.2 mg/kg, SC, once), 3) low-dose extended-release buprenorphine (XR-Lo; 0.65 mg/kg, SC, once), and 4) high-dose extended-release buprenorphine (XR-Hi; 1.3 mg/kg, SC, once). After drug administration, a 1 cm skin incision was made on the plantar hind paw under anesthesia. Mechanical and thermal hypersensitivity were evaluated 1 d before surgery (D-1), 4 h after surgery (D0), and for 3 d after surgery (D1, D2, and D3). In experiment 2, plasma buprenorphine concentration (n = 39) was measured at D0, D1, D2, and D3. Clinical observations were recorded daily, and a gross necropsy was performed on D3. Mechanical and thermal hypersensitivity were measured for 3 d (D0-D3) in the saline group. Bup-SR, XR-Lo, and XR-Hi effectively attenuated mechanical hypersensitivity for D0-D3. Plasma buprenorphine concentrations remained above 1 ng/mL on D0 and D1 in all treatment groups. No abnormal clinical signs were noted, but injection site reactions were evident in the Bup-SR (71%), XR-Lo (75%), and XR-Hi (87%) groups. This study indicates that XR-Hi did not attenuate hypersensitivity more effectively than did XR-Lo in this model. XR 0.65 mg/kg is recommended to attenuate postoperative mechanical hypersensitivity for up to 72 h in rats in an incisional pain model.

  View details for DOI 10.30802/AALAS-JAALAS-21-000081

  View details for PubMedID 34903316

• Effectiveness of two extended-release buprenorphine formulations during postoperative period in neonatal rats. PloS one Zhang, M., Alamaw, E., Jampachaisri, K., Huss, M., Pacharinsak, C. 2022; 17 (10): e0276327

  Abstract

  Information on the effectiveness of a new long-lasting buprenorphine formulation, extended-release buprenorphine, in the neonatal rat is very limited. This study compares whether a high dose of extended-release buprenorphine (XR-Hi) attenuates thermal hypersensitivity for a longer period than a low dose of extended-release buprenorphine (XR-Lo) in a neonatal rat incisional pain model. Two experiments were performed. Experiment one: Male and female postnatal day-5 rat pups (n = 38) were randomly assigned to 1 of 4 treatment groups and received a subcutaneous administration of one of the following: 1) 0.9%NaCl (Saline), 0.1 mL; 2) sustained release buprenorphine (Bup-SR), 1 mg/kg; 3) XR-Lo, 0.65 mg/kg; and 4) XR-Hi, 1.3 mg/kg. Pups were anesthetized with sevoflurane in 100% O2 and a 5 mm long skin incision was made over the left lateral thigh and underlying muscle dissected. The skin was closed with surgical tissue glue. Thermal hypersensitivity testing (using a laser diode) and clinical observations were conducted 1 hour (h) prior to surgery and subsequently after 1, 4, 8, 24, 48, 72 h of treatment. Experiment two: The plasma buprenorphine concentration level was evaluated at 1, 4, 8, 24, 48, 72 h on five-day-old rat pups. Plasma buprenorphine concentration for all treatment groups remained above the clinically effective concentration of 1 ng/mL for at least 4 h in the Bup-SR group, 8 h in XR-Lo and 24 h in XR-Hi group with no abnormal clinical observations. This study demonstrates that XR-Hi did not attenuate postoperative thermal hypersensitivity for a longer period than XR-Lo in 5-day-old rats; XR-Hi attenuated postoperative thermal hypersensitivity for up to 4 h while Bup-SR and XR-Lo for at least 8 h in this model.

  View details for DOI 10.1371/journal.pone.0276327

  View details for PubMedID 36251720

• Mouse Anesthesia: The Art and Science. ILAR journal Navarro, K. L., Huss, M., Smith, J. C., Sharp, P., Marx, J. O., Pacharinsak, C. 2021

  Abstract

  There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks, months, or beyond. It is critical to perform anesthesia according to the approved research protocol using appropriately handled and administered pharmaceutical-grade compounds whenever possible. Sufficient documentation of the anesthetic event and procedure should also be performed to meet the legal, ethical, and research reproducibility obligations. However, this regulatory and documentation process may lead to the use of a few possibly oversimplified anesthetic protocols used for mouse procedures and anesthesia. Although a frequently used anesthetic protocol may work perfectly for each mouse anesthetized, sometimes unexpected complications will arise, and quick adjustments to the anesthetic depth and support provided will be required. As an old saying goes, anesthesia is 99% boredom and 1% sheer terror. The purpose of this review article is to discuss the science of mouse anesthesia together with the art of applying these anesthetic techniques to provide readers with the knowledge needed for successful anesthetic procedures. The authors include experiences in mouse inhalant and injectable anesthesia, peri-anesthetic monitoring, specific procedures, and treating common complications. This article utilizes key points for easy access of important messages and authors' recommendation based on the authors' clinical experiences.

  View details for DOI 10.1093/ilar/ilab016

  View details for PubMedID 34180990

• Lipid bound extended release buprenorphine (high and low doses) and sustained release buprenorphine effectively attenuate post-operative hypersensitivity in an incisional pain model in mice (Mus musculus). Animal models and experimental medicine Navarro, K., Jampachaisri, K., Huss, M., Pacharinsak, C. 2021; 4 (2): 129-137

  Abstract

  Background: Extended-release buprenorphine (XR) is indicated for pain management in rodents, but little is known about its use in mice. This study aimed to investigate whether high dose XR effectively attenuates post-operative hypersensitivity better than low dose XR in a mouse model of incisional pain.Methods: Mice (n=44) were randomly assigned to 1 of 4 treatment groups: (a) saline (1ml/kg SC, once); (b) sustained release buprenorphine (Bup-SR, 1mg/kg SC, once); (c) low dose extended-release buprenorphine (XR-lo, 3.25mg/kg SC, once); (d) high dose extended-release buprenorphine (XR-hi, 6.5mg/kg SC, once). On days -1, 0 (4hours), 1, 2, and 3, mechanical and thermal hypersensitivities were evaluated, and plasma buprenorphine concentrations were measured.Results: Mechanical (days 0-2) and thermal (days 0-1) hypersensitivities were observed in the saline group. Bup-SR, XR-lo, and XR-hi attenuated mechanical hypersensitivity on days 0, 1, and 2. None of the treatment groups, except XR-Lo on day 0, attenuated thermal hypersensitivity on days 0 or 1. Plasma buprenorphine concentration peaked at 4hours (day 0) in all treatment groups and remained greater than 1ng/mL on days 0-2. No abnormal clinical observations or gross pathologic findings were seen in any groups.Conclusion: The results indicate XR-hi did not effectively attenuate post-operative hypersensitivity better than XR-lo. Thus both 3.25 and 6.5mg/kg XR are recommended for attenuating post-operative hypersensitivity for at least up to 48hours in mice.

  View details for DOI 10.1002/ame2.12157

  View details for PubMedID 34179720

• Tiletamine/zolazepam and dexmedetomidine with tramadol provide effective general anesthesia in rats. Animal models and experimental medicine Limprasutr, V., Sharp, P., Jampachaisri, K., Pacharinsak, C., Durongphongtorn, S. 2021; 4 (1): 40–46

  Abstract

  Background: Tiletamine/zolazepam is a dissociative anesthetic combination commonly used in small animals but information is limited in rats. The alpha-2 agonist, dexmedetomidine, has gained popularity in laboratory animal anesthesia. Tramadol is a weak opioid mu agonist. The aim of this study was to assess whether the tiletamine/zolazepam/dexmedetomidine (ZD) combination effectively provides a surgical anesthesia plane comparable to tiletamine/zolazepam/dexmedetomidine with tramadol (ZDT) in a minor procedure in rats.Methods: Rats were induced with ZD or ZDT. After the loss of paw withdrawal, a small incision was made on the rats' left thighs as a surgical stimulus. Rats were maintained under a surgical anesthesia plane by assessing the loss of the paw withdrawal reflex for 45minutes, then atipamezole was administered. Monitored anesthesia parameters included: (a) physiological parameters - pulse rate (PR), respiratory rate (RR), tissue oxygen saturation (%SpO2), and body temperature; (b) duration parameters - induction time, onset and duration of surgical anesthesia plane, onset of recovery, and recovery time.Results: PR was significantly lower at 10minutes in ZD and 5minutes in ZDT groups. No difference was observed for RR, %SpO2, and body temperature. Likewise, there were no differences for duration parameters: induction time was less than 3minutes; onset and duration of surgical anesthesia plane were approximately 5 and 45minutes, respectively; onset of recovery (time to move) was 51minutes; and recovery time was 52minutes, respectively.Conclusion: These data suggest the ZD combination provides a surgical anesthesia plane comparable to ZDT in a rat incisional pain model.

  View details for DOI 10.1002/ame2.12143

  View details for PubMedID 33738435

• Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus). PloS one Blaney, A. n., Jampachaisri, K. n., Huss, M. K., Pacharinsak, C. n. 2021; 16 (2): e0246213

  Abstract

  Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in a neonatal rat model of incisional pain. Male and female postnatal day 3 Sprague Dawley rat pups (n = 34) were randomly assigned to one of four treatment groups: 1) saline (control), 0.1 mL, once subcutaneously (SC); 2) buprenorphine HCl (Bup HCl), 0.05 mg/kg, once SC; 3) low dose Bup SR (low-SR), 0.5 mg/kg, once SC; 4) high dose Bup SR (high-SR), 1 mg/kg, once SC. Pups were anesthetized with sevoflurane and a 0.5-cm long skin incision was made over the left lateral thigh. The underlying muscle was dissected and closed using surgical glue. Thermal hypersensitivity testing was performed at 24 h prior to surgery and subsequently at 1, 4, 8, 24, and 48 h post-surgery using an infrared diode laser. Thermal hypersensitivity was attenuated at 1 h post-surgery in the Bup HCl group, while it was attenuated through the entire postoperative period in both low-SR and high-SR groups. This data suggests that a single dose of low-SR (0.5 mg/kg) or high-SR (1 mg/kg) effectively attenuates thermal hypersensitivity for at least 8 h in neonatal rat pups.

  View details for DOI 10.1371/journal.pone.0246213

  View details for PubMedID 33534864

• Differential effects of four intramuscular sedatives on cardiorespiratory stability in juvenile guinea pigs (Cavia porcellus). PloS one Sixtus, R. P., Pacharinsak, C., Gray, C. L., Berry, M. J., Dyson, R. M. 2021; 16 (11): e0259559

  Abstract

  Non-invasive physiological monitoring can induce stress in laboratory animals. Sedation reduces the level of restraint required, thereby improving the validity of physiological signals measured. However, sedatives may alter physiological equilibrium introducing unintended bias and/or, masking the experimental outcomes of interest. We aimed to investigate the cardiorespiratory effects of four short-acting sedatives in juvenile guinea pigs.12 healthy, 38 (26-46) day-old Dunkin Hartley guinea pigs were included in this blinded, randomised, crossover design study. Animals were sedated by intramuscular injection using pre-established minimum effective doses of either alfaxalone (5 mg/kg), diazepam (5 mg/kg), ketamine (30 mg/kg), or midazolam (2 mg/kg) administered in random order with a minimum washout period of 48 hours between agents. Sedative depth, a composite score comprised of five assessment criteria, was observed every 5-min from dosing until arousal. Physiological monitoring of cardiorespiratory status included measures of heart rate, blood pressure, respiratory rate, and peripheral microvascular perfusion.Ketamine and alfaxalone were most effective in inducing stable sedation suitable for physiological monitoring, and diazepam less-so. Midazolam was unsuitable due to excessive hypersensitivity. All sedatives significantly increased heart rate above non-sedated control rates (P<0.0001), without altering blood pressure or microvascular perfusion. Alfaxalone and ketamine reduced respiratory rate relative to their control condition (P<0.0001, P = 0.05, respectively), but within normative ranges.Ketamine and alfaxalone are the most effective sedatives for inducing short duration, stable sedation with minimal cardiorespiratory depression in guinea pigs, while diazepam is less-so. However, alfaxalone is the most appropriate sedative for longitudinal studies requiring multiple physiological timepoints.

  View details for DOI 10.1371/journal.pone.0259559

  View details for PubMedID 34780534

• Buprenorphine, but not lidocaine, effectively attenuates post-operative thermal hypersensitivity in an incisional model in neonatal rats (Rattus norvegicus) SCANDINAVIAN JOURNAL OF LABORATORY ANIMAL SCIENCE Katz, E. M., Huss, M. K., Jampachaisri, K., Pacharinsak, C. 2021; 47 (1): 1–11

  View details for Web of Science ID 000627574200001

• The Stability and Efficacy of Tricaine Methanesulfonate (MS222) Solution After Long-Term Storage JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Katz, E. M., Chu, D. K., Casey, K. M., Jampachaisri, K., Felt, S. A., Pacharinsak, C. 2020; 59 (4): 393–400

  Abstract

  Tricaine methanesulfonate (MS222) is widely used for the anesthesia and euthanasia of laboratory zebrafish. Fresh solutions have been recommended for each use; however, researchers often mix and store concentrated stock solutions for convenience and to reduce occupational exposure and environmental waste. While this is common practice, published guidelines are often inconsistent. Thus, the objective of this study was to evaluate the stability and anesthetic efficacy of MS222 after long-term storage and to develop specific storage parameters. Stock solutions (100 mg/mL MS222) were mixed and stored in amber jars at 4 °C and -20 °C for 2- and 6-mo. Stability of the solutions was analyzed using liquid chromatography-ion trapmass spectrometry and compared with fresh MS222. Fifty adult (30 male, 20 female) wildtype AB zebrafish (Danio rerio) wererandomly anesthetized with 150 mg/L of one of the following MS222 solutions to evaluate anesthetic efficacy: 1) freshly prepared(0m); 2) 2 mo at 4 °C (2m4); 3) 2 mo at -20 °C (2m-20); 4) 6 mo at 4 °C (6m4); 5) 6 mo at -20 °C (6m-20). Time to cessation of swimming, loss of equilibrium, lack of response to von Frey (VF) stimulation, return of equilibrium, and resumption of swimming were compared between groups. Two fish from each group were euthanized at 24-h and 2-wk after anesthesia, and histopathology was performed. All solutions were determined to be stable under all storage conditions. No clinically significant differences were observed between the fresh and stored stock groups during anesthetic testing. No evidence ofanesthetic-related histologic changes were noted in the gills, skin, kidneys, muscle, and central nervous system. Hepatic megalocytosis and a reduction in hepatic vacuolation were seen to varying degrees across all groups, but did not follow a treatment-related trend. Therefore, 100 mg/mL solutions of MS222 can be stored in amber jars at 4 °C or -20 °C for 6 mo and still used to effectively anesthetize zebrafish.

  View details for DOI 10.30802/AALAS-JAALAS-19-000067

  View details for Web of Science ID 000569144100009

  View details for PubMedID 32532365

  View details for PubMedCentralID PMC7338872

• Effects of Standard and Sustained-release Buprenorphine on the Minimum Alveolar Concentration of Isoflurane in C57BL/6 Mice. Journal of the American Association for Laboratory Animal Science : JAALAS LaTourette, P. C., David, E. M., Pacharinsak, C., Jampachaisri, K., Smith, J. C., Marx, J. O. 2020; 59 (3): 298–304

  Abstract

  Both standard and sustained-release injectable formulations of buprenorphine (Bup and BupSR, respectively) are used as preemptive analgesics, potentially affecting gas anesthetic requirements. This study tested the effects of Bup and BupSR on isoflurane requirements and confirmed that buprenorphine could reduce isoflurane requirements during a laparotomy in mice. We hypothesized that both Bup and BupSR would significantly decrease the required minimum alveolar concentration (MAC) of isoflurane. C57BL/6 mice received either isotonic crystalloid fluid (control), Bup (0.1 mg/kg), or BupSR (1.2 mg/kg) subcutaneously 10 min prior to the induction of anesthesia. Each anesthetized mouse was tested at 2 isoflurane concentrations. A 300-g noxious stimulus was applied at each isoflurane concentration, alternating between hindfeet. In addition, a subset of mice underwent terminal laparotomy or 60 min of anesthesia after injection with Bup, BupSR, or saline to ensure an appropriate surgical plane of anesthesia. Mice were maintained at the lowest isoflurane concentration that resulted in 100% of mice at a surgical plane from the aforementioned MAC experiments (control, 2.0%; Bup and BupSR, 1.7%). Analysis showed that both Bup and BupSR significantly decreased isoflurane requirements by 25.5% and 14.4%, respectively. The isoflurane MAC for the control injection was 1.80% ± 0.09%; whereas Bup and BupSR decreased MAC to 1.34% ± 0.08% and 1.54% ± 0.09%, respectively. Sex was not a significantly different between the injection groups during MAC determination. All of the mice that underwent surgery achieved a surgical plane of anesthesia on the prescribed regimen and recovered normally after discontinuation of isoflurane. Lastly, heart and respiratory rates did not differ between mice that underwent surgery and those that were anesthetized only. Bup and BupSR are MAC-sparing in male and female C57BL/6 mice and can be used for effective multimodal anesthesia.

  View details for DOI 10.30802/AALAS-JAALAS-19-000106

  View details for PubMedID 32268932

• High dose propofol effectively euthanizes zebrafish (Danio rerio) THAI JOURNAL OF VETERINARY MEDICINE Chu, D. K., Jampachaisri, K., Pacharinsak, C. 2020; 50 (1): 13–16

  View details for Web of Science ID 000545122600002

• Use of Flavored Tablets of Gabapentin and Carprofen to Attenuate Postoperative Hypersensitivity in an Incisional Pain Model in Rats (Rattus norvegicus). Journal of the American Association for Laboratory Animal Science : JAALAS Zude, B. P., Jampachaisri, K., Pacharinsak, C. 2020; 59 (2): 163–69

  Abstract

  Providing postoperative analgesia to rats by oral administration, compared with injections, reduces stress from frequent handling and is technically easier for investigators. The purpose of this study was to investigate whether bacon-flavored tablets containing gabapentin, carprofen or a combination of both drugs effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Forty-eight Sprague-Dawley rats were randomly assigned to 1 of 5 treatment groups: placebo tablet; a single, subcutaneous injection of buprenorphine sustained release at 1.2 mg/kg; gabapentin 90 mg/tablet; carprofen 5 mg/tablet; gabapentin 90 mg and carprofen 5 mg/tablet (gabapentin/carprofen). Tablets were given to rats on days -3, -2, -1, 0 (surgery), 1, and 2. Rats were anesthetized using isoflurane. A 1 cm skin incision was made aseptically on the plantar surface of the left hindpaw and closed by using suture. Mechanical (von Frey monofilament) and thermal (Hargreaves method) hypersensitivity were tested daily, and analyzed on days -1, 1, 2, and 3. The amount of tablet consumed was recorded daily; postoperatively rats consumed 101 to 133 mg/kg of gabapentin, 5.5 to 5.8 mg/kg of carprofen, and 86-137/1.9-3 mg/kg of gabapentin/carprofen, respectively. Both the gabapentin and carprofen groups displayed attenuated mechanical hypersensitivity on all 3 postsurgical days and decreased thermal hypersensitivity on Day 3. The gabapentin/ carprofen group showed attenuated mechanical hypersensitivity on Day 2 and 3, but no significant reduction of thermal hypersensitivity. These data suggest that both gabapentin and carprofen, given orally by flavored tablet, effectively attenuate postoperative mechanical hypersensitivity for 3 d after surgery in a rat model of incisional pain.

  View details for DOI 10.30802/AALAS-JAALAS-19-000093

  View details for PubMedID 32075700

• Continuous Rate Infusion of Alfaxalone during Ketamine-Xylazine Anesthesia in Rats. Journal of the American Association for Laboratory Animal Science : JAALAS Heng, K. n., Marx, J. O., Jampachairsi, K. n., Huss, M. K., Pacharinsak, C. n. 2020; 59 (2): 170–75

  Abstract

  Alfaxalone is an injectable anesthetic agent that is used in veterinary medicine for general anesthesia. We evaluated the safety and efficacy of alfaxalone delivered through continuous rate infusion by comparing ketamine-xylazine-alfaxalone (KXA) anesthesia with ketamine-xylazine (KX) anesthesia in Sprague-Dawley rats. Anesthesia was induced in male and female rats by using subcutaneous KX. After induction, rats in the KXA group received alfaxalone (10 mg/kg/h IV) for 35 min, whereas rats in the KX group did not receive alfaxalone. At the end of the trial, alfaxalone was discontinued, and xylazine was reversed in all rats by using atipamezole. Throughout anesthesia, we assessed forepaw withdrawal reflex (FPWR), hindpaw withdrawal reflex (HPWR), response to surgical stimulation, heart rate, respiratory rate, SpO₂, body temperature, and time to standing. KXA produced a reliable surgical plane of anesthesia, as evidenced by the loss of both FPWR and HPWR and lack of response to surgical stimulation in all 16 rats, whereas only 6 of the 16 rats in the KX group lost HPWR. No rat in the KXA group regained a paw withdrawal reflex during alfaxalone administration, whereas 3 of the 12 rats (25%) in the KX group that reached a surgical plane of anesthesia exited that plane within the 35-min timeframe. Neither heart rate, respiratory rate, SpO₂, body temperature, nor time to standing differed between KXA and KX groups; and there were no sex-associated differences in anesthesia response. These results indicate that alfaxalone (10 mg/kg/h IV) delivered through continuous rate infusion, in combination with ketamine and xylazine, provides a safe, prolonged, and reliable surgical plane of anesthesia in rats.

  View details for DOI 10.30802/AALAS-JAALAS-19-000122

  View details for PubMedID 32059754

• Doppler and oscillometric mean blood pressure best represent direct blood pressure measurements in anesthetized rhesus macaques (Macaca mulatta). Journal of medical primatology Kang, S. C., Jampachaisri, K., Pacharinsak, C. 2019

  Abstract

  BACKGROUND: Indirect blood pressure measurements are often used to guide clinical decisions, but few studies have verified their agreement with direct arterial blood pressure in nonhuman primates. Here, the accuracy and precision of Doppler (DOP) and oscillometric (OS) [systolic (OSsys), mean (OSmean), and diastolic (OSdias)] blood pressure readings were assessed in rhesus macaques.METHODS: DOP and OS were utilized to measure blood pressure values in nine anesthetized rhesus macaques, which were compared to direct measurements via a saphenous arterial catheter. All measurements were taken simultaneously every 5min for 60-240min.RESULTS: DOP and OSsys underestimated direct systolic arterial pressure with a bias ± precision of 10.21±6.37mmHg and 11.67±11.55mmHg, respectively. OSmean correlated well with direct mean arterial pressure with a bias ± precision of 7.25±7.35mmHg.CONCLUSIONS: DOP provided the better representation of systolic blood pressure, and OSmean provided a useful representation of mean arterial pressure in anesthetized rhesus macaques.

  View details for PubMedID 30644561

• Influence of Pain and Analgesia on Orthopedic and Wound-healing Models in Rats and Mice. Comparative medicine Huss, M. K., Felt, S. A., Pacharinsak, C. n. 2019

  Abstract

  The surgical stress response and resulting physiologic changes can lead to postoperative complications and negatively impact animal welfare. Although appropriate pain management is crucial to reduce the pain and stress response to surgery,analgesic choice can significantly affect bone and wound healing. This review aims to summarize data from rat and mouse studies and to provide recommendations for integrating analgesia into orthopedic and wound healing models in these species. Data from other species, such as humans, rabbits and other rodents, is included, where available. From these data, we conclude that for orthopedic surgical models, opioids, local anesthetics and dissociative agents have minimal impact onfracture healing; cyclooxygenase 2 (COX2) selective nonsteroidal antiinflammatory drugs (NSAID) may be used in the shortterm;and steroids should be avoided. For wound healing models, short-term systemic or topical opioids have negligible impact on wound healing; NSAID or local anesthetics may be used short-term; and systemic steroids should be avoided. Alternative analgesics such as tramadol, gabapentin, ketamine, and acetaminophen warrant consideration and further evaluation for both orthopedic and wound healing models. In all cases, researchers and veterinarians should work together todetermine the appropriate analgesic plan to minimize pain, as well as to minimize unwanted effects on the orthopedic and wound healing models themselves.

  View details for DOI 10.30802/AALAS-CM-19-000013

  View details for PubMedID 31561753

• Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats (Rattus norvegicus). Journal of the American Association for Laboratory Animal Science : JAALAS Kang, S. C., Jampachaisri, K., Seymour, T. L., Felt, S. A., Pacharinsak, C. 2017; 56 (1): 63-68

  Abstract

  The local anesthetic bupivacaine is valuable for perioperative analgesia, but its use in the postoperative period is limited by its short duration of action. Here, we evaluated the application of a slow-release liposomal formulation of bupivacaine for postoperative analgesia. The aim was to assess whether liposomal bupivacaine effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats (n = 36) were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC every 12 h for 2 d; buprenorphine HCl, 0.05 mg/kg SC every 12 h for 2 d (Bup HCl); 0.5% bupivacaine, 2 mg/kg SC local infiltration once (Bupi); liposomal bupivacaine, 1 mg/kg SC local infiltration once (Exp1); and liposomal bupivacaine, 6 mg/kg SC local infiltration once (Exp6). Mechanical and thermal hypersensitivity were evaluated daily on days -1, 0, 1, 2, 3, and 4. The saline group exhibited both hypersensitivities through all 4 evaluated postoperative days. Bup HCl attenuated mechanical hypersensitivity for 2 d and thermal hypersensitivity for 1 d. Bupi attenuated only thermal hypersensitivity for 4 d. Rats in the Exp1 group showed attenuation of both mechanical and thermal hypersensitivity for 4 d, and those in the Exp6 group had attenuation of mechanical hypersensitivity on day 0 and thermal hypersensitivity for 4 d. These data suggest that a single local infiltration of liposomal bupivacaine at a dose of 1 mg/kg SC effectively attenuates postoperative mechanical and thermal hypersensitivity for 4 d in a rat model of incisional pain.

  View details for PubMedID 28905717

  View details for PubMedCentralID PMC5250497

• Handbook of Laboratory Animal Anesthesia and Pain Management: Rodents edited by Pacharinsak, C., Smith, J. C. CRC Press Taylor & Francis Group. 2017
• Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus) JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Seymour, T. L., Adams, S. C., Felt, S. A., Jampachaisri, K., Yeomans, D. C., Pacharinsak, C. 2016; 55 (3): 300-305

  Abstract

  Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

  View details for Web of Science ID 000375510400008

  View details for PubMedID 27177563

• The Physiologic Effects of Isoflurane, Sevoflurane, and Hypothermia Used for Anesthesia in Neonatal Rats (Rattus norvegicus). Journal of the American Association for Laboratory Animal Science Huss, M. K., Chum, H. H., Chang, A. G., Jampachairsi, K., Pacharinsak, C. 2016; 55 (1): 83-88

  Abstract

  Information regarding effective anesthetic regimens for neonatal rat pups is limited. Here we investigated whether isoflurane or sevoflurane anesthesia maintains physiologic parameters more consistently than does hypothermia anesthesia in neonatal rat pups. Rat pups (age, 4 d) were randomly assigned to receive isoflurane, sevoflurane, or hypothermia. Physiologic parameters monitored at 1, 5, 10, and 15 min included heart rate (HR), respiratory rate (RR), and oxygen saturation (%SpO2). Other parameters evaluated were loss and return of righting reflex, paw withdrawal reflex, and maternal acceptance. Corticosterone and glucose were sampled at 20 min and 24 h after anesthesia induction. Once a surgical plane of anesthesia was achieved, a skin incision was made on the right lateral thigh. After the procedure, all pups were accepted and cared for by their dam. Isoflurane- and sevoflurane-treated pups maintained higher HR, RR, %SpO2, and glucose levels than did hypothermia-treated pups. For both the isoflurane and sevoflurane groups, HR and RR were significantly lower at 10 and 15 min after anesthesia than at 1 min. Compared with hypothermia, isoflurane and sevoflurane anesthesia provided shorter times to loss of and return of the righting reflex. Although corticosterone did not differ among the groups, glucose levels were higher at 20 min after anesthesia induction than at 24 h in all anesthetic groups. We conclude that both isoflurane and sevoflurane anesthesia maintain physiologic parameters (HR, RR, %SpO2) more consistently than does hypothermia anesthesia in 4-d-old rat pups.

  View details for PubMedID 26817984

• Mouse anesthesia and analgesia. Current protocols in mouse biology Adams, S., Pacharinsak, C. 2015; 5 (1): 51-63

  Abstract

  Providing anesthesia and analgesia for mouse subjects is a common and critical practice in the laboratory setting. These practices are necessary for performing invasive procedures, achieving prolonged immobility for sensitive imaging modalities (magnetic resonance imaging for instance), and providing intra- and post-procedural pain relief. In addition to facilitating the procedures performed by the investigator, the provision of anesthesia and analgesia is crucial for the preservation of animal welfare and for humane treatment of animals used in research. Furthermore, anesthesia and analgesia are important components of animal use protocols reviewed by Institutional Animal Care and Use Committees, requiring careful consideration and planning for the particular animal model. In this article, we provide technical outlines for the investigator covering the provision of anesthesia by two routes (injectable and inhalant), guidelines for monitoring anesthesia, current techniques for recognition of pain, and considerations for administering preventative analgesia. © 2015 by John Wiley & Sons, Inc.

  View details for DOI 10.1002/9780470942390.mo140179

  View details for PubMedID 25727200

• Antinociceptive Effects of Sustained-Release Buprenorphine in a Model of Incisional Pain in Rats (Rattus norvegicus). Journal of the American Association for Laboratory Animal Science Chum, H. H., Jampachairsri, K., McKeon, G. P., Yeomans, D. C., Pacharinsak, C., Felt, S. A. 2014; 53 (2): 193-197

  Abstract

  Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats.

  View details for PubMedID 24602547

• Mechanisms of Cancer Pain Pain Management in Veterinary Practice Pacharinsak, C., Beitz, A. J. edited by Egger, C. M., Love, L., Doherty, T. 2013
• Pain Management Pocket Handbook of Nonhuman Primate Clinical Medicine Pacharinsak, C., Sharp, P. edited by Courtney, A. CRC Press Taylor & Francis Group. 2013: 35-54
• Anesthesia in Nonhuman Primates Pocket Handbook of Nonhuman Primate Clinical Medicine Pacharinsak, C., Sharp, P. edited by Courtney, A. CRC Press Taylor & Francis Group. 2013; 1ST: 1-34

  View details for DOI 10.1201/b12934

• Endotracheal intubation in swine LAB ANIMAL Chum, H., Pacharinsak, C. 2012; 41 (11): 309-311

  Abstract

  Swine are commonly used as research models for cardiovascular surgery and disease, gastrointestinal disease, organ transplantation and intra-renal surgery. These surgical models require anesthesia and, consequently, endotracheal intubation in order to protect the airway; prevent aspiration of saliva, blood and foreign materials; and maintain positive pressure ventilation of the animal. Successful intubation is vital to the stable maintenance of swine under inhalational anesthesia. Here we discuss key features of swine anatomy that make intubation challenging, equipment necessary for successful intubation and techniques for endotracheal intubation in swine.

  View details for Web of Science ID 000310653800016

  View details for PubMedID 23079913

• Microfluidic Single-Cell Analysis Shows That Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation CIRCULATION RESEARCH Gu, M., Nguyen, P. K., Lee, A. S., Xu, D., Hu, S., Plews, J. R., Han, L., Huber, B. C., Lee, W. H., Gong, Y., de Almeida, P. E., Lyons, J., Ikeno, F., Pacharinsak, C., Connolly, A. J., Gambhir, S. S., Robbins, R. C., Longaker, M. T., Wu, J. C. 2012; 111 (7): 882-893

  Abstract

  Induced pluripotent stem cells (iPSCs) hold great promise for the development of patient-specific therapies for cardiovascular disease. However, clinical translation will require preclinical optimization and validation of large-animal iPSC models.To successfully derive endothelial cells from porcine iPSCs and demonstrate their potential utility for the treatment of myocardial ischemia.Porcine adipose stromal cells were reprogrammed to generate porcine iPSCs (piPSCs). Immunohistochemistry, quantitative PCR, microarray hybridization, and angiogenic assays confirmed that piPSC-derived endothelial cells (piPSC-ECs) shared similar morphological and functional properties as endothelial cells isolated from the autologous pig aorta. To demonstrate their therapeutic potential, piPSC-ECs were transplanted into mice with myocardial infarction. Compared with control, animals transplanted with piPSC-ECs showed significant functional improvement measured by echocardiography (fractional shortening at week 4: 27.2±1.3% versus 22.3±1.1%; P<0.001) and MRI (ejection fraction at week 4: 45.8±1.3% versus 42.3±0.9%; P<0.05). Quantitative protein assays and microfluidic single-cell PCR profiling showed that piPSC-ECs released proangiogenic and antiapoptotic factors in the ischemic microenvironment, which promoted neovascularization and cardiomyocyte survival, respectively. Release of paracrine factors varied significantly among subpopulations of transplanted cells, suggesting that transplantation of specific cell populations may result in greater functional recovery.In summary, this is the first study to successfully differentiate piPSCs-ECs from piPSCs and demonstrate that transplantation of piPSC-ECs improved cardiac function after myocardial infarction via paracrine activation. Further development of these large animal iPSC models will yield significant insights into their therapeutic potential and accelerate the clinical translation of autologous iPSC-based therapy.

  View details for DOI 10.1161/CIRCRESAHA.112.269001

  View details for PubMedID 22821929

• Analgesic Effects of Sustained Release Buprenorphine in an Incisional Model of Hyperalgesia in Rats (Rattus norvegicus) Chum, H., McKeon, G., Yeomans, D. C., Jampachaisri, K., Pacharinsak, C., Felt, S. AMER ASSOC LABORATORY ANIMAL SCIENCE. 2012: 692–92

  View details for Web of Science ID 000313303300260

• Differential modulation of neurons in the rostral ventromedial medulla by neurokinin-1 receptors JOURNAL OF NEUROPHYSIOLOGY Brink, T. S., Pacharinsak, C., Khasabov, S. G., Beitz, A. J., Simone, D. A. 2012; 107 (4): 1210-1221

  Abstract

  The rostral ventromedial medulla (RVM) is part of descending circuitry that modulates nociceptive processing at the level of the spinal cord. RVM output can facilitate pain transmission under certain conditions such as inflammation, and thereby contribute to hyperalgesia. Evidence suggests that substance P and activation of neurokinin-1 (NK-1) receptors in the RVM are involved in descending facilitation of nociception. We showed previously that injection of NK-1 receptor antagonists into the RVM attenuated mechanical and heat hyperalgesia produced by intraplantar injection of capsaicin. Furthermore, intraplantar injection of capsaicin excited ON cells in the RVM and inhibited ongoing activity of OFF cells. In the present studies, we therefore examined changes in responses of RVM neurons to mechanical and heat stimuli after intraplantar injection of capsaicin and determined the role of NK-1 receptors by injecting a NK-1 receptor antagonist into the RVM prior to capsaicin. After capsaicin injection, excitatory responses of ON cells and inhibitory responses of OFF cells evoked by mechanical and heat stimuli applied to the injected, but not contralateral, paw were increased. Injection of the NK-1 antagonist L-733,060 did not alter evoked responses of ON or OFF cells but attenuated the capsaicin-evoked enhanced responses of ON cells to mechanical and heat stimuli with less of an effect on the enhanced inhibitory responses of OFF cells. These data support the notion that descending facilitation from RVM contributes to hyperalgesia and that NK-1 receptors, presumably located on ON cells, play an important role in initiating descending facilitation of nociceptive transmission.

  View details for DOI 10.1152/jn.00678.2011

  View details for Web of Science ID 000301518000014

  View details for PubMedID 22031765

• Preclinical Derivation and Imaging of Autologously Transplanted Canine Induced Pluripotent Stem Cells JOURNAL OF BIOLOGICAL CHEMISTRY Lee, A. S., Xu, D., Plews, J. R., Nguyen, P. K., Nag, D., Lyons, J. K., Han, L., Hu, S., Lan, F., Liu, J., Huang, M., Narsinh, K. H., Long, C. T., de Almeida, P. E., Levi, B., Kooreman, N., Bangs, C., Pacharinsak, C., Ikeno, F., Yeung, A. C., Gambhir, S. S., Robbins, R. C., Longaker, M. T., Wu, J. C. 2011; 286 (37): 32697-32704

  Abstract

  Derivation of patient-specific induced pluripotent stem cells (iPSCs) opens a new avenue for future applications of regenerative medicine. However, before iPSCs can be used in a clinical setting, it is critical to validate their in vivo fate following autologous transplantation. Thus far, preclinical studies have been limited to small animals and have yet to be conducted in large animals that are physiologically more similar to humans. In this study, we report the first autologous transplantation of iPSCs in a large animal model through the generation of canine iPSCs (ciPSCs) from the canine adipose stromal cells and canine fibroblasts of adult mongrel dogs. We confirmed pluripotency of ciPSCs using the following techniques: (i) immunostaining and quantitative PCR for the presence of pluripotent and germ layer-specific markers in differentiated ciPSCs; (ii) microarray analysis that demonstrates similar gene expression profiles between ciPSCs and canine embryonic stem cells; (iii) teratoma formation assays; and (iv) karyotyping for genomic stability. Fate of ciPSCs autologously transplanted to the canine heart was tracked in vivo using clinical positron emission tomography, computed tomography, and magnetic resonance imaging. To demonstrate clinical potential of ciPSCs to treat models of injury, we generated endothelial cells (ciPSC-ECs) and used these cells to treat immunodeficient murine models of myocardial infarction and hindlimb ischemia.

  View details for DOI 10.1074/jbc.M111.235739

  View details for Web of Science ID 000294726800078

  View details for PubMedID 21719696

  View details for PubMedCentralID PMC3173214

• Comparison of rectal and tympanic core body temperature measurement in adult Guyanese squirrel monkeys (Saimiri sciureus sciureus) JOURNAL OF MEDICAL PRIMATOLOGY Long, C. T., Pacharinsak, C., Jampachaisri, K., McKeon, G. P., Howard, A. M., Albertelli, M. A., Felt, S. A. 2011; 40 (2): 135-141

  Abstract

  Measuring core body temperature in a manner that is safe for animals and veterinary personnel is an important part of a physical examination. For nonhuman primates, this can involve increased restraint, additional stress, as well as the use of anesthetics and their deleterious effects on body temperature measurements. The purpose of this study was to compare two non-invasive methods of infrared tympanic thermometry to standard rectal thermometry in adult squirrel monkeys.Tympanic temperatures were collected from 37 squirrel monkeys and compared to rectal temperatures using a human and veterinary infrared tympanic thermometer.Compared with rectal temperature measurements, the human tympanic thermometer readings were not significantly different, while the veterinary tympanic thermometer measurements were significantly higher (P<0.05). There were no differences between sexes.The tympanic thermometer designed for use in humans can be used in adult squirrel monkeys as an alternative to rectal thermometry for assessing core body temperature.

  View details for DOI 10.1111/j.1600-0684.2010.00449.x

  View details for Web of Science ID 000287965500009

  View details for PubMedID 20946145

• Analgesic Effects of Tramadol, Tramadol-Gabapentin, and Buprenorphine in an Incisional Model of Pain in Rats (Rattus norvegicus) JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE McKeon, G. P., Pacharinsak, C., Long, C. T., Howard, A. M., Jampachaisri, K., Yeomans, D. C., Felt, S. A. 2011; 50 (2): 192-197

  Abstract

  Postoperative pain management in laboratory animals relies heavily on a limited number of drug classes, such as opioids and nonsteroidal antiinflammatory drugs. Here we evaluated the effects of saline, tramadol, tramadol with gabapentin, and buprenorphine (n = 6 per group) in a rat model of incisional pain by examining thermal hyperalgesia and weight-bearing daily for 6 d after surgery. All drugs were administered preemptively and continued for 2 consecutive days after surgery. Rats treated with saline or with tramadol only showed thermal hyperalgesia on days 1 through 4 and 1 through 3 after surgery, respectively. In contrast, buprenorphine-treated rats showed no thermal hyperalgesia on days 1 and 2 after surgery, and rats given tramadol with gabapentin showed reduced thermal hyperalgesia on days 2 and 4. For tests of weight-bearing, rats treated with saline or with tramadol only showed significantly less ipsilateral weight-bearing on day 1 after surgery, whereas rats given either buprenorphine or tramadol with gabapentin showed no significant change in ipsilateral weight-bearing after surgery. These data suggest that tramadol alone provides insufficient analgesia in this model of incisional pain; buprenorphine and, to a lesser extent, tramadol with gabapentin provide relief of thermal hyperalgesia and normalize weight-bearing.

  View details for Web of Science ID 000288643600006

  View details for PubMedID 21439212

• Cannabinoid Modulation of Cutaneous A delta Nociceptors During Inflammation JOURNAL OF NEUROPHYSIOLOGY Potenzieri, C., Brink, T. S., Pacharinsak, C., Simone, D. A. 2008; 100 (5): 2794-2806

  Abstract

  Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB(1) and CB(2)). However, it is currently unknown if cannabinoids alter the response properties of nociceptors. In the present study, correlative behavioral and in vivo electrophysiological studies were conducted to determine if peripheral administration of the cannabinoid receptor agonists arachidonyl-2'-chloroethylamide (ACEA) or (R)-(+)-methanandamide (methAEA) could attenuate mechanical allodynia and hyperalgesia, and decrease mechanically evoked responses of Adelta nociceptors. Twenty-four hours after intraplantar injection of complete Freund's adjuvant (CFA), rats exhibited allodynia (decrease in paw withdrawal threshold) and hyperalgesia (increase in paw withdrawal frequency), which were attenuated by both ACEA and methAEA. The antinociceptive effects of these cannabinoids were blocked by co-administration with the CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) but not with the CB(2) receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-y l](4-methoxyphenyl)methanone (AM630). ACEA and methAEA did not produce antinociception under control, non-inflamed conditions 24 h after intraplantar injection of saline. In parallel studies, recordings were made from cutaneous Adelta nociceptors from inflamed or control, non-inflamed skin. Both ACEA and methAEA decreased responses evoked by mechanical stimulation of Adelta nociceptors from inflamed skin but not from non-inflamed skin, and this decrease was blocked by administration of the CB(1) receptor antagonist AM251. These results suggest that attenuation of mechanically evoked responses of Adelta nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB(1) receptors during inflammation.

  View details for DOI 10.1152/jn.90809.2008

  View details for Web of Science ID 000260795600030

  View details for PubMedID 18784270

• NK-1 receptors in the rostral ventromedial medulla contribute to hyperalgesia produced by intraplantar injection of capsaicin PAIN Pacharinsak, C., Khasabov, S. G., Beitz, A. J., Simone, D. A. 2008; 139 (1): 34-46

  Abstract

  The rostral ventromedial medulla (RVM) is an area of the brainstem involved in the descending modulation of nociception at the level of the spinal cord. Although the RVM is involved in the inhibition or facilitation of nociception, the underlying mechanisms are not understood. Here we examined the role of the neuropeptide substance P and neurokinin-1 (NK-1) receptors located in the RVM on withdrawal responses evoked by mechanical and heat stimuli applied to the rat hindpaw under normal conditions and during hyperalgesia produced by capsaicin. The mechanical withdrawal threshold was obtained using von Frey monofilaments applied to the plantar surface of the hindpaw. Sensitivity to heat was determined by measuring the latency to withdrawal from radiant heat applied to the plantar surface. Mechanical and heat hyperalgesia were defined as a decrease in withdrawal response threshold or latency, respectively. Rats were prepared with a chronic cannula and either vehicle or the NK-1 receptor antagonists, L-733,060 or RP-67580, was injected into the RVM. Paw withdrawal responses were obtained before and after RVM injection, and then at 5, 30, and 60 min after an intraplantar injection of capsaicin (10 microg). Injection of the NK-1 antagonists at doses of 0.5 pmol or higher did not alter withdrawal responses to mechanical or heat stimuli under normal conditions but reduced the duration of nocifensive behavior and the mechanical and heat hyperalgesia produced by capsaicin. These findings suggest that the activation of NK-1 receptors in the RVM contributes to the hyperalgesia produced by capsaicin.

  View details for DOI 10.1016/j.pain.2008.02.032

  View details for Web of Science ID 000260159200005

  View details for PubMedID 18407414

• Animal models of cancer pain COMPARATIVE MEDICINE Pacharinsak, C., Beitz, A. 2008; 58 (3): 220-233

  Abstract

  Modern cancer therapies have significantly increased patient survival rates in both human and veterinary medicine. Since cancer patients live longer they now face new challenges resulting from severe, chronic tumor-induced pain. Unrelieved cancer pain significantly decreases the quality of life of such patients; thus the goal of pain management is to not only to alleviate pain, but also to maintain the patient's physiological and psychological well-being. The major impediment for developing new treatments for cancer pain has been our limited knowledge of the basic mechanisms that drive cancer pain and the lack of adequate animal cancer pain models to study the molecular, biochemical and neurobiological pathways that generate and maintain cancer pain. However this situation has recently changed with the recent development of several novel animal models of cancer pain. This review will focus on describing these animal models, many of them in rodents, and reviewing some of the recent information gained from the use of these models to investigate the basic mechanims that underlie the development and maintenance of cancer pain. Animal models of cancer pain can be divided into the following five categories: bone cancer pain models, non-bone cancer pain models, cancer invasion pain models, cancer chemotherapeutic-induced peripheral neuropathy models, and spontaneous occurring cancer pain models. These models will be important not only for enhancing our knowledge of how cancer pain is generated, but more importantly for the development of novel therapeutic regimes to treat cancer pain in both domestic animals and humans.

  View details for Web of Science ID 000256870700001

  View details for PubMedID 18589864

• Effective Pain Management in Small Animals 15th Congress of the Federation-of-Asian-Veterinary-Association/FAV-OIE Joint Symposium on Emerging Diseases Pacharinsak, C. THAI VETERINARY MED ASSOC ROYAL PATRONAGE. 2008: S85–S85

  View details for Web of Science ID 000263555600020

• Postoperative analgesia in dogs receiving epidural morphine plus medetomidine JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS Pacharinsak, C., Greene, S. A., Keegan, R. D., Kalivas, P. W. 2003; 26 (1): 71-77

  Abstract

  This investigation was carried out to compare the postoperative analgesia and plasma morphine concentrations in dogs given epidural morphine or epidural morphine combined with medetomidine prior to surgery. Twelve dogs (seven males and five females) with ruptured cranial cruciate ligaments presented to the Washington State University Veterinary Teaching Hospital. Six dogs received an epidural injection of morphine (0.1 mg/kg) and six dogs received epidural morphine (0.1 mg/kg) combined with medetomidine (0.005 mg/kg). Numeric rating scale (NRS) pain scores and cumulative pain scores (CPS) were assigned to 10-min segments of video. Video segments, heart rates and respiratory rates were recorded prior to premedication and at 4, 8, 12, 18 and 24 h after epidural injection. Blood was sampled from the cephalic vein at each of these times and during anesthesia at 0.5, 1, 2 and 3 h after epidural injection. Data were analyzed using either Friedman's test or one-way anova for repeated measures. In the morphine group, significant increases compared with premedication values were detected at 4, 8 and 12 h after epidural injection for NRS and at 4 and 12 h after epidural injection for CPS. In the morphine plus medetomidine group, NRS was significantly higher at 4 and 8 h whereas there were no differences from baseline values for CPS. Plasma morphine concentrations were not significantly different between treatment groups, but were significantly increased compared with preinjection values at 0.5, 1, 12, 18, and 24 h in the morphine plus medetomidine group. Epidurally administered morphine combined with medetomidine was associated with only minor benefits based on subjective pain scoring when compared with morphine alone in these dogs undergoing repair of a ruptured cranial cruciate ligament.

  View details for Web of Science ID 000181056100005

  View details for PubMedID 12603778