Cholawat Pacharinsak, DVM, PhD Assistant Professor and Director of Anesthesia, Pain Management, and Surgery, at Stanford University’s Department of Comparative Medicine; he is a Diplomate of the American College of Veterinary Anesthesia and Analgesia (DACVAA). He received his DVM from Chulalongkorn University, Thailand and trained in an Anesthesiology/Pain Management residency program and received his Master's degree at Washington State University. He completed his PhD in Comparative and Molecular Biosciences from the University of Minnesota. Prior to arriving at Stanford, Dr. Pacharinsak was a faculty member in Anesthesiology and Pain Management at Michigan State University and Purdue University; and served as a Clinical Specialist at UCLA’s David Geffen School of Medicine. His research focuses on understanding the neurobiology of cancer pain, chemotherapeutic-induced peripheral neuropathy, acute surgical pain models, and methods to improve clinical pain management e.g. sustained release analgesics supporting refinement. Research methodology includes electrophysiologic and behavioral techniques.

Academic Appointments

Administrative Appointments

  • Assistant Professor, Stanford University (2011 - Present)

Honors & Awards

  • Board Certification, Diplomate American College of Veterinary Anesthesia and Analgesia (Dipl. ACVAA) (2010)

Professional Education

  • Ph.D., University of Minnesota, Neurobiology of Pain
  • Residency, Washington State University, Anesthesiology and Pain Management
  • M.S., Washington State University, Pain Management
  • D.V.M., Chulalongkorn University, Veterinary Medicine

All Publications

  • 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


    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


    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

  • 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
  • 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


    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


    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
  • 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


    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


    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


    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


    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. n., Seymour, T. L., Felt, S. A., Pacharinsak, C. n. 2017; 56 (1): 63–68


    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

  • 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


    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


    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


    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


    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


    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


    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
  • 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


    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


    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


    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


    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


    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


    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


    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
  • 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


    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