Dr. Carroll joined Stanford's Pain Medicine Faculty in 2004. He is board-certified in four different specialties: Headache Medicine by the United Council for Neurologic Subspecialties; Addiction Medicine by the American Board of Addiction Medicine; Pain Medicine by the American Board of Anesthesiology; and Anesthesiology by the American Board of Anesthesiology. His primary focus is on chronic daily headaches, chronic migraine, occipital neuralgia, and New Daily Persistent Headaches (NDPH) especially as related to related to spinal cerebrospinal fluid (CSF) leaks, and nerve injuries. He has collaborated With Stanford's Neuroradiology and Neurology Headache divisions to create the Stanford CSF leak program, and Stanford's Peripheral Nerve Injury Pain Program. He has spoken at numerous national meetings on CSF leaks, management of the pain from nerve injuries, and factors influencing opioid cessation. He has conducted visiting professorships at Johns Hopkins University, Vanderbilt University, Cedar-Sinai Medical Center, University of California at Davis Medical Center, and others.
Dr. Carroll graduated summa cum laude and Phi Beta Kappa from Columbia University, and then graduated with an M.D. from Columbia University. He was a Research Fellow at the Experimental Immunology Branch at the National Cancer Institute at the National Institutes of Health in Bethesda Maryland. He completed his internship in Internal Medicine, residency in Anesthesiology, fellowship in Pain Medicine, and was elected Chief Resident of Anesthesiology from 2001-2002 at Stanford University Medical Center.
Dr. Carroll completed Stanford's two-year Clinical Research training program earning a M.S. degree in clinical epidemiology from Stanford in 2006. He has published over 30 original articles including research funded by the Foundation for Anesthesia Education and Research (FAER); the National Institute for Drug Abuse (NIDA); and the Stanford Institute for Neuro-Innovation & Translational Neurosciences (SINTN).
In addition to his clinical and research responsibilities, Dr. Carroll helps select and train Stanford's Anesthesia residents, and runs the Morbidity and Mortality conference for Stanford's Pain Management division.
- Cerebrospinal fluid (CSF) Leaks
- New Daily Persistent Headache (NDPH)
- Chronic Daily Headache
- Postural Orthostatic Tachycardia Syndrome (POTS)
- Pseudotumor Cerebri
- Cluster Headache
- Trigeminal Neuralgia
- Occipital Neuralgia
Assistant Professor - Med Center Line, Anesthesiology, Perioperative and Pain Medicine
Member, Stanford Cancer Institute
Honors & Awards
Stanford Department of Anesthesiology Departmental Research Award, Stanford Department of Anesthesiology (2008)
Award for Teaching Excellence, Stanford Department of Anesthesiology (2004-2005)
Chief Resident, Stanford Department of Anesthesiology (2001-2002)
Best Anesthesia-Resident Teacher Award, Stanford Department of Anesthesiology (2001)
Best Anesthesia-Resident Teacher Award, Stanford Department of Anesthesiology (2000)
Intramural Research Training Award Fellowship-Pre-doctoral, National Cancer Institute, National Institutes of Health (1996-1997)
Phi Beta Kappa, Columbia University (1993)
Summa Cum Laude, Columbia University (1993)
Edwin Robbins Scholarship for Public Service, Columbia University (1991)
Boards, Advisory Committees, Professional Organizations
Medical Advisory Board Member, Spinal CSF Leak Foundation (2016 - Present)
Board Certification: Headache Medicine, United Council for Neurologic Subspecialties (2016)
Fellowship:Stanford University School of Medicine Registrar (2004) CA
Residency:Stanford University School of Medicine Registrar (2002) CA
Board Certification, United Council for Neurologic Subspecialties (UCNS), Headache Medicine (2016)
Board Certification, American Board of Addiction Medicine, Addiction Medicine (2009)
M.S., Stanford University, Clinical Epidemiology (2006)
Board Certification: Pain Medicine, American Board of Anesthesiology (2004)
Board Certification: Anesthesia, American Board of Anesthesiology (2003)
Internship:Stanford School of Medicine (1999) CA
M.D., Columbia University; College of Physicians and Surgions (1998)
Current Research and Scholarly Interests
Cerebrospinal fluid (CSF) leaks are a treatable disease that can cause a myriad of symptoms including chronic head pain, headache, migraine, neck pain, nausea, vomiting, ringing in the ears (tinnitus), difficulty concentrating, difficulty with memory, and fatigue. One of the cardinal features of cerebrospinal fluid leaks is that symptoms tend to be worse depending on the posture of the body-with headaches being more prominent when upright, and relieved when lying down (orthostatic headaches). Among people who are leaking chronically, a person may need to be upright or flat for a protracted period of time in order for symptoms to be exacerbated or relieved. Therefore, many patients with cerebrospinal fluid leaks experience a typical daily pattern in which the mornings are better-especially before arising from bed, but things get progressively worse as the day goes on with prolonged upright activity.
Because patients with cerebrospinal fluid leaks often feel significantly worse when they are upright, patients with cerebrospinal fluid leaks may be misdiagnosed with an alternative diagnosis associated with increased symptoms depending on body posture such as postural orthostatic tachycardia syndrome (POTS). In addition because of reduced spinal fluid pressure the brain may sag resulting in a misdiagnosis of Chiari malformation. Toher patients have been diagnosed with New Daily persistent Headache (NDPH), Chronic migraine, Occipital Neuralgia,and Chronic Fatigue Syndrome.
Cerebrospinal fluid leaks should be considered as a diagnostic possibility in any patient who has previously undergone an injection into the spine, or the placement of a needle into the spinal fluid and is then experiencing symptoms that are worse when the patient is upright and relieved when the patient is flat. In addition, it is well recognized that spine surgery can precipitate cerebrospinal fluid leaks related to the surgery.
CSF leaks are understood to be much more frequent among people with genes that make their connective tissue less strong. These patients may be notably flexible, unusually tall or unusually short, may appear to be double-jointed, or have unusually stretchy skin. Clinically, these patients often have multiple joint dislocations, or joint sprains at different times of their life, may have early arthritis in multiple joints, and may have multilevel spine pain from degenerative joint disease or degenerative disc disease. Subsequently many patients have been misdiagnosed as having fibromyalgia, chronic fatigue syndrome, and other conditions. Some hereditary disorders of connective tissue are named such as Marfan syndrome, or Ehlers-Danlos syndrome (EDS), but other people may have a number of signs and symptoms associated with hereditary disorders of connective tissue, and are more likely to experience spinal fluid leaks, but don't have these named syndromes.
Dr. Carroll's current clinical and research work are oriented towards ensuring that all patients with cerebrospinal fluid leaks receive prompt diagnosis and effective treatment.
Patients and physicians may find the following lecture on cerebrospinal fluid leaks helpful and informative:
Dr. Carroll shares a library of articles on CSF leaks:
Giving: Gifts to support innovative patient care, research and education programs will make a difference in the lives of patients now and in the future. If you need assistance or more information on giving options such as a gift of securities or a planned gift, please call Medical Center Development at (650) 725-2504 or email us at email@example.com. In the memo line indicate For Dr. Ian Carroll CSF Leak Research.
[18F]FTC-146 PET/MRI in Healthy Volunteers and in CRPS and Sciatica
Chronic pain can result from injured or inflamed nerves, as occurs in people suffering from sciatica and CRPS. These nerve injuries or regions of nerve irritation are often the cause of pain in these conditions, but the current diagnostic tools are limited in pinpointing the area of origin. Several studies have implicated involvement of sigma-1 receptors in the generation and perpetuation of chronic pain conditions, others are investigating anti sigma-1 receptor drugs for the treatment of chronic pain. Using the sigma-1 receptor (S1R) detector and experimental radiotracer [18F]FTC-146 and positron emission tomography/magnetic resonance imaging (PET/MRI) scanner, the researchers may potentially identify the source of pain generation in patients suffering from complex regional pain syndrome (CRPS) and chronic sciatica. The ultimate goal is to assist in the optimization of pain treatment regimens using an [18F]FTC-146 PET/MRI scan. The study is not designed to induce any physiological/pharmacological effect.
Stanford is currently not accepting patients for this trial. For more information, please contact Sandip Biswal, MD, 650-725-8018.
Stanford Accelerated Recovery Trial (START)
The goal of this study is to determine whether administering Gabapentin prior to surgery affects duration of pain and opioid use post-surgery. The investigators aim to compare gabapentin to placebo in a prospective, randomized clinical trial in which patients will be followed post-surgery until pain resolves and opioid use ceases.
Stanford is currently not accepting patients for this trial. For more information, please contact Debra Clay, 650-724-1753.
- Independent Studies (5)
Ondansetron Does Not Reduce Withdrawal in Patients With Physical Dependence on Chronic Opioid Therapy.
Journal of addiction medicine
Individuals taking opioids for an extended period of time may become physically dependent, and will therefore experience opioid withdrawal should they stop taking the medication. Previous work in animal and human models has shown that the serotonin (5-HT3) receptor may be implicated in opioid withdrawal. In this study, we investigated if ondansetron, a 5-HT3-receptor antagonist, could reduce the symptoms of opioid withdrawal after chronic opioid exposure in humans.In this double-blinded, randomized, crossover study, 33 chronic back pain patients (N = 33) were titrated onto sustained-release oral morphine for 30 days. After titration, participants attended 2 study sessions, 1 week apart, in which opioid withdrawal was induced with intravenous naloxone, with or without 8 mg intravenous ondansetron pretreatment. Opioid withdrawal symptoms were assessed by a blinded research assistant (objective opioid withdrawal score [OOWS]) and by the research participant (subjective opioid withdrawal score [SOWS]).Clinically significant signs of withdrawal were observed during both the ondansetron (ΔOOWS = 3.58 ± 2.22, P < 0.0001; ΔSOWS = 12.48 ± 11.18, P < 0.0001) and placebo sessions (ΔOOWS = 3.55 ± 2.39, P < 0.0001; ΔSOWS = 12.21 ± 10.72, P < 0.0001), but no significant differences were seen between the treatment sessions in either the OOWS or SOWS scores.We hypothesized that ondansetron would reduce opioid withdrawal symptoms in human subjects, but found no difference in withdrawal severity between ondansetron and placebo sessions. These findings suggest that more investigation may be necessary to determine if 5-HT3-receptor antagonists are suitable treatment options for opioid withdrawal.
View details for DOI 10.1097/ADM.0000000000000321
View details for PubMedID 28514235
A Double-Blind Placebo Randomized Controlled Trial of Minocycline to Reduce Pain After Carpal Tunnel and Trigger Finger Release.
journal of hand surgery
2017; 42 (3): 166-174
Minocycline is a microglial cell inhibitor and decreases pain behaviors in animal models. Minocycline might represent an intervention for reducing postoperative pain. This trial tested whether perioperative administration of minocycline reduced time to pain resolution (TPR) after standardized hand surgeries with known prolonged pain profiles: carpal tunnel release (CTR) and trigger finger release (TFR).This double-blinded randomized controlled trial included patients undergoing CTR or TFR under local anesthesia. Before surgery, participants recorded psychological and pain measures. Participants received oral minocycline, 200 mg, or placebo 2 hours prior to procedure, and then 100 mg of minocycline or placebo 2 times a day for 5 days. After surgery, participants were called daily assessing their pain. The primary end point of TPR was when participants had 3 consecutive days of 0 postsurgical pain. Futility analysis and Kaplan-Meier analyses were performed.A total of 131 participants were randomized and 56 placebo and 58 controls were analyzed. Median TPR for CTR was 3 weeks, with 15% having pain more than 6 weeks. Median TPR for TFR was 2 weeks with 18% having pain more than 6 weeks. The overall median TPR for the placebo group was 2 weeks (10% pain > 6 weeks) versus 2.5 weeks (17% pain > 6 weeks) for the minocycline group. Futility analysis found that the likelihood of a true underlying clinically meaningful reduction in TPR owing to minocycline was only 3.5%. Survival analysis found minocycline did not reduce TPR. However, subgroup analysis of those with elevated posttraumatic distress scores found the minocycline group had longer TPR.Oral administration of minocycline did not reduce TPR after minor hand surgery. There was evidence that minocycline might increase length of pain in those with increased posttraumatic stress disorder symptoms.Therapeutic I.
View details for DOI 10.1016/j.jhsa.2016.12.011
View details for PubMedID 28259273
- Pharmacologic Management of Upper Extremity Chronic Nerve Pain. Hand clinics 2016; 32 (1): 51-61
- Pain Duration and Resolution following Surgery: An Inception Cohort Study PAIN MEDICINE 2015; 16 (12): 2386-2396
Pain Duration and Resolution following Surgery: An Inception Cohort Study.
2015; 16 (12): 2386-2396
Preoperative determinants of pain duration following surgery are poorly understood. We identified preoperative predictors of prolonged pain after surgery in a mixed surgical cohort.We conducted a prospective longitudinal study of patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured pain and opioid use after surgery until patients reported the cessation of both opioid consumption and pain. The primary endpoint was time to opioid cessation, and those results have been previously reported. Here, we report preoperative determinants of time to pain resolution following surgery in Cox proportional hazards regression.Between January 2007 and April 2009, we enrolled 107 of 134 consecutively approached patients undergoing the aforementioned surgical procedures. In the final multivariate model, preoperative self-perceived risk of addiction predicted more prolonged pain. Unexpectedly, anxiety sensitivity predicted more rapid pain resolution after surgery. Each one-point increase (on a four point scale) of self-perceived risk of addiction was associated with a 38% (95% CI 3-61) reduction in the rate of pain resolution (P = 0.04). Furthermore, higher anxiety sensitivity was associated with an 89% (95% CI 23-190) increased rate of pain resolution (P = 0.004).Greater preoperative self-perceived risk of addiction, and lower anxiety sensitivity predicted a slower rate of pain resolution following surgery. Each of these factors was a better predictor of pain duration than preoperative depressive symptoms, post-traumatic stress disorder symptoms, past substance use, fear of pain, gender, age, preoperative pain, or preoperative opioid use.
View details for DOI 10.1111/pme.12842
View details for PubMedID 26179223
- [18F]FDG PET/MRI of patients with chronic pain alters management: early experience. EJNMMI physics 2015; 2: A84-?
Factors Associated with Opioid Use in a Cohort of Patients Presenting for Surgery.
Pain research and treatment
2015; 2015: 829696-?
Objectives. Patients taking opioids prior to surgery experience prolonged postoperative opioid use, worse clinical outcomes, increased pain, and more postoperative complications. We aimed to compare preoperative opioid users to their opioid naïve counterparts to identify differences in baseline characteristics. Methods. 107 patients presenting for thoracotomy, total knee replacement, total hip replacement, radical mastectomy, and lumpectomy were investigated in a cross-sectional study to characterize the associations between measures of pain, substance use, abuse, addiction, sleep, and psychological measures (depressive symptoms, Posttraumatic Stress Disorder symptoms, somatic fear and anxiety, and fear of pain) with opioid use. Results. Every 9-point increase in the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) score was associated with 2.37 (95% CI 1.29-4.32) increased odds of preoperative opioid use (p = 0.0005). The SOAPP-R score was also associated with 3.02 (95% CI 1.36-6.70) increased odds of illicit preoperative opioid use (p = 0.007). Also, every 4-point increase in baseline pain at the future surgical site was associated with 2.85 (95% CI 1.12-7.27) increased odds of legitimate preoperative opioid use (p = 0.03). Discussion. Patients presenting with preoperative opioid use have higher SOAPP-R scores potentially indicating an increased risk for opioid misuse after surgery. In addition, legitimate preoperative opioid use is associated with preexisting pain.
View details for DOI 10.1155/2015/829696
View details for PubMedID 26881072
- In reply. Anesthesiology 2014; 121 (2): 424-426
- Self-Loathing Aspects of Depression Reduce Postoperative Opioid Cessation Rate PAIN MEDICINE 2014; 15 (6): 954-964
- Perioperative Gabapentinoids Choice of Agent, Dose, Timing, and Effects on Chronic Postsurgical Pain ANESTHESIOLOGY 2013; 119 (5): 1215-1221
Management of Chronic Pain Following Nerve lnjuries/CRPS Type II
2013; 29 (3): 401-?
Chronic pain affects quality of life and adversely affects functional outcomes. Chronic postoperative pain is a frustrating problem for the surgeon because it ruins a technically perfect procedure, and the surgeon may be unsure of treatment strategies. There is much information on chronic pain and its treatment, but it is often published outside of surgery and diffusion of this information across disciplines is slow. This article synthesizes some of this literature and provides a systematic presentation of the evidence on pain associated with peripheral nerve injury. It highlights the use of perioperative and early intervention to decrease this debilitating problem.
View details for DOI 10.1016/j.hcl.2013.04.009
View details for Web of Science ID 000323627800009
View details for PubMedID 23895720
Perioperative interventions to reduce chronic postsurgical pain.
Journal of reconstructive microsurgery
2013; 29 (4): 213-222
Approximately 10% of patients following a variety of surgeries develop chronic postsurgical pain. Reducing chronic postoperative pain is especially important to reconstructive surgeons because common operations such as breast and limb reconstruction have even higher risk for developing chronic postsurgical pain. Animal studies of posttraumatic nerve injury pain demonstrate that there is a critical time frame before and immediately after nerve injury in which specific interventions can reduce the incidence and intensity of chronic neuropathic pain behaviors-so called "preventative analgesia." In animal models, perineural local anesthetic, systemic intravenous local anesthetic, perineural clonidine, systemic gabapentin, systemic tricyclic antidepressants, and minocycline have each been shown to reduce pain behaviors days to weeks after treatment. The translation of this work to humans also suggests that brief perioperative interventions may protect patients from developing new chronic postsurgical pain. Recent clinical trial data show that there is an opportunity during the perioperative period to dramatically reduce the incidence and severity of chronic postsurgical pain. The surgeon, working with the anesthesiologist, has the ability to modify both early and chronic postoperative pain by implementing an evidence-based preventative analgesia plan.
View details for DOI 10.1055/s-0032-1329921
View details for PubMedID 23463498
- Perioperative Interventions to Reduce Chronic Postsurgical Pain JOURNAL OF RECONSTRUCTIVE MICROSURGERY 2013; 29 (4): 213-222
- Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology JOURNAL OF TRANSLATIONAL MEDICINE 2013; 11
Exploratory factor analysis of the beck depression inventory: predictors of delayed opioid cessation after surgery in a pilot cohort study
CHURCHILL LIVINGSTONE. 2013: S25–S25
View details for Web of Science ID 000317639400100
Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology.
Journal of translational medicine
2013; 11: 93-?
Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.Our results support the role of cytokines in the pathophysiology of CFS.
View details for DOI 10.1186/1479-5876-11-93
View details for PubMedID 23570606
A Pilot Cohort Study of the Determinants of Longitudinal Opioid Use After Surgery
ANESTHESIA AND ANALGESIA
2012; 115 (3): 694-702
Determinants of the duration of opioid use after surgery have not been reported. We hypothesized that both preoperative psychological distress and substance abuse would predict more prolonged opioid use after surgery.Between January 2007 and April 2009, a prospective, longitudinal inception cohort study enrolled 109 of 134 consecutively approached patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured the daily use of opioids until patients reported the cessation of both opioid consumption and pain. The primary end point was time to opioid cessation. All analyses were controlled for the type of surgery done.Overall, 6% of patients continued on new opioids 150 days after surgery. Preoperative prescribed opioid use, depressive symptoms, and increased self-perceived risk of addiction were each independently associated with more prolonged opioid use. Preoperative prescribed opioid use was associated with a 73% (95% confidence interval [CI] 0.51%-87%) reduction in the rate of opioid cessation after surgery (P = 0.0009). Additionally, each 1-point increase (on a 4-point scale) of self-perceived risk of addiction was associated with a 53% (95% CI 23%-71%) reduction in the rate of opioid cessation (P = 0.003). Independent of preoperative opioid use and self-perceived risk of addiction, each 10-point increase on a preoperative Beck Depression Inventory II was associated with a 42% (95% CI 18%-58%) reduction in the rate of opioid cessation (P = 0.002). The variance in the duration of postoperative opioid use was better predicted by preoperative prescribed opioid use, self-perceived risk of addiction, and depressive symptoms than postoperative pain duration or severity.Preoperative factors, including legitimate prescribed opioid use, self-perceived risk of addiction, and depressive symptoms each independently predicted more prolonged opioid use after surgery. Each of these factors was a better predictor of prolonged opioid use than postoperative pain duration or severity.
View details for DOI 10.1213/ANE.0b013e31825c049f
View details for Web of Science ID 000307942900028
View details for PubMedID 22729963
Sensory Pain Qualities in Neuropathic Pain
JOURNAL OF PAIN
2012; 13 (1): 58-63
The qualities of chronic neuropathic pain (NeP) may be informative about the different mechanisms of pain. We previously developed a 2-factor model of NeP that described an underlying structure among sensory descriptors on the Short-Form McGill Pain Questionnaire. The goal of this study was to confirm the correlated 2-factor model of NeP. Individual descriptive scores from the Short-Form McGill Pain Questionnaire were analyzed. Confirmatory factor analysis was used to test a correlated 2-factor model. Factor 1 (stabbing pain) was characterized by high loadings on stabbing, sharp, and shooting sensory items; factor 2 (heavy pain) was characterized by high loadings on heavy, gnawing, and aching items. Results of the confirmatory factor analysis strongly supported the correlated 2-factor model.This article validates a model that describes the qualities of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. These data suggest that specific pain qualities may be associated with pain mechanisms or may be useful for predicting treatment response.
View details for DOI 10.1016/j.jpain.2011.10.002
View details for Web of Science ID 000299198300007
View details for PubMedID 22172451
Human Response to Unintended Intrathecal Injection of Botulinum Toxin
2011; 12 (7): 1094-1097
Describe the first reported human intrathecal (IT) botulinum toxin injection.Case report.We report here the sequelae to an unintended IT injection of botulinum toxin type B (BTB) in a 60-year-old woman with chronic back pain.Following the IT administration of BTB, the patient experienced the onset of symmetric ascending stocking distribution painful dysesthesias, which persisted for approximately 6 months before receding. Objective neurologic deficits were not appreciated, and analgesic effects were prominently absent.Analgesic actions of botulinum toxins in animals and in humans have led to speculation that IT botulinum toxin might exert significant analgesic effects. The unusual and unexpected subsequent clinical course, neurologic sequelae, dysesthesias, and absence of analgesia suggest that botulinum toxin will not be a therapeutic modality to treat pain as proposed by those studying botulinum toxin in animal models.
View details for DOI 10.1111/j.1526-4637.2011.01135.x
View details for Web of Science ID 000292697100016
View details for PubMedID 21627762
Variable expression of soluble fms-like tyrosine kinase 1 in patients at high risk for preeclampsia
JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
2010; 23 (7): 705-711
To explore angiogenic factor differences in preeclamptic patients according to the absence or presence of underlying vascular disease.We prospectively compared serum soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin, and placental growth factor (PlGF) from 41 normal-risk and 32 high-risk (preexisting conditions) subjects at serial gestational ages.Median sFlt1 was lower at delivery in preeclamptic patients with underlying chronic hypertension and/or chronic proteinuria (5115 pg/ml) compared with normal risk preeclamptic patients (16375 pg/ml). PlGF was consistently low in patients who developed preeclampsia.Effects of sFlt1 may be contextual, varying according to the health or disease state of vascular endothelium.
View details for DOI 10.3109/14767050903258753
View details for Web of Science ID 000279865300024
View details for PubMedID 19895348
Pain Quality Predicts Lidocaine Analgesia among Patients with Suspected Neuropathic Pain
2010; 11 (4): 617-621
Oral sodium channel blockers have shown mixed results in randomized controlled trials despite the known importance of sodium channels in generating pain. We hypothesized that differing baseline pain qualities (e.g. "stabbing" vs "dull") might define specific subgroups responsive to intravenous (IV) lidocaine-a potent sodium channel blocker.A prospective cohort study of 71 patient with chronic pain suspected of being neuropathic were recruited between January 2003 and July 2007 and underwent lidocaine infusions at Stanford University Hospital in a single-blind nonrandomized fashion. Baseline sensory pain qualities were measured with the Short-Form McGill Pain Questionnaire (SF-MPQ). Pain intensity was measured with a visual analog scale (VAS).Factor analysis demonstrated two underlying pain quality factors among SF-MPQ sensory items: a heavy pain and a stabbing pain. Baseline heavy pain quality, but not stabbing quality predicted subsequent relief of pain intensity in response to lidocaine. In contrast, these factors did not predict divergent analgesic responses to placebo infusions. In response to each 1 mcg/mL increase in lidocaine plasma level, patients with high heavy pain quality drop their VAS 0.24 (95% CI 0.05-0.43) more points than those with low heavy pain quality (P < 0.013)."Heavy" pain quality may indentify patients with enhanced lidocaine responsiveness. Pain quality may identify subgroups among patients with suspected neuropathic pain responsive to IV lidocaine. Further investigation is warranted to validate and extend these findings.
View details for Web of Science ID 000276223500020
View details for PubMedID 20210867
A Novel CT-Guided Transpsoas Approach to Diagnostic Genitofemoral Nerve Block and Ablation
2010; 11 (5): 785-789
Inguinal hernia repair is associated with a high incidence of chronic postsurgical pain. This pain may be caused by injury to the iliohypogastric, ilioinguinal, or genitofemoral nerves. It is often difficult to identify the specific source of the pain, in part, because these nerves are derived from overlapping nerve roots and closely colocalize in the area of surgery. It is therefore technically difficult to selectively block these nerves individually proximal to the site of surgical injury. In particular, the genitofemoral nerve is retroperitoneal before entering the inguinal canal, a position that puts anterior approaches to the proximal nerve at risk of transgressing into the peritoneum. We report a computed tomography (CT)-guided transpsoas technique to selectively block the genitofemoral nerve for both diagnostic and therapeutic purposes while avoiding injury to the nearby ureter and intestines.A 39-year-old woman with chronic lancinating right groin pain after inguinal hernia repair underwent multiple pharmacologic interventions and invasive procedures without relief. Using CT and Stimuplex nerve stimulator guidance, the genitofemoral nerve was localized on the anterior surface of the psoas muscle and a diagnostic block with local anesthetic block was performed. The patient had immediate relief of her symptoms for 36 hours, confirming the diagnosis of genitofemoral neuralgia. She subsequently underwent CT-guided radiofrequency and phenol ablation of the genitofemoral nerve but has not achieved long-term analgesia.CT-guided transpsoas genitofemoral nerve block is a viable option for safely and selectively blocking the genitofemoral nerve for diagnostic or therapeutic purposes proximal to injury caused by inguinal surgery.
View details for Web of Science ID 000277206200018
View details for PubMedID 20546515
- Cutaneous neuroma physiology and its relationship to chronic pain. journal of hand surgery 2009; 34 (7): 1334-1336
- Cutaneous Neuroma Physiology and Its Relationship to Chronic Pain JOURNAL OF HAND SURGERY-AMERICAN VOLUME 2009; 34A (7): 1334-1336
Sympathetic Block with Botulinum Toxin to Treat Complex Regional Pain Syndrome
ANNALS OF NEUROLOGY
2009; 65 (3): 348-351
Complex regional pain syndrome is a refractory pain condition with few tested therapies. We hypothesized that botulinum toxin A (BTA) would prolong analgesia after sympathetic blocks in patients with complex regional pain syndrome. We compared the duration of standard lumbar sympathetic block (LSB) with bupivacaine to LSB with bupivacaine and BTA in nine patients with refractory complex regional pain syndrome. Median time to analgesic failure was 71 (95% confidence interval, 12-253) days after LSB with BTA compared with fewer than 10 days (95% confidence interval, 0-12) after standard LSB (log-rank, p < 0.02). BTA profoundly prolonged the analgesia from sympathetic block in this preliminary study.
View details for DOI 10.1002/ana.21601
View details for Web of Science ID 000264779600016
View details for PubMedID 19334078
Factors contributing to pain chronicity
CURRENT PAIN AND HEADACHE REPORTS
2009; 13 (1): 7-11
The chronicity of pain is the feature of pain that is least understood and most directly linked with our inability to effectively manage pain. Acute pain is relatively responsive to our current pharmacologic and interventional armamentarium. However, as pain persists, our ability to treat effectively diminishes and the patient's frustration and resource utilization increases. This article explores our current understanding of the factors linked to pain duration and the transition from acute to chronic pain in both human and animal models, and across a spectrum of human chronic pain conditions.
View details for DOI 10.1007/s11916-009-0003-3
View details for Web of Science ID 000263064900003
View details for PubMedID 19126364
Serratus muscle stimulation effectively treats notalgia paresthetica caused by long thoracic nerve dysfunction: a case series.
Journal of brachial plexus and peripheral nerve injury
2009; 4: 17-?
Currently, notalgia paresthetica (NP) is a poorly-understood condition diagnosed on the basis of pruritus, pain, or both, in the area medial to the scapula and lateral to the thoracic spine. It has been proposed that NP is caused by degenerative changes to the T2-T6 vertebrae, genetic disposition, or nerve entrapment of the posterior rami of spinal nerves arising at T2-T6. Despite considerable research, the etiology of NP remains unclear, and a multitude of different treatment modalities have correspondingly met with varying degrees of success. Here we demonstrate that NP can be caused by long thoracic nerve injury leading to serratus anterior dysfunction, and that electrical muscle stimulation (EMS) of the serratus anterior can successfully and conservatively treat NP. In four cases of NP with known injury to the long thoracic nerve we performed transcutaneous EMS to the serratus anterior in an area far lateral to the site of pain and pruritus, resulting in significant and rapid pain relief. These findings are the first to identify long thoracic nerve injury as a cause for notalgia paresthetica and electrical muscle stimulation of the serratus anterior as a possible treatment, and we discuss the implications of these findings on better diagnosing and treating notalgia paresthetica.
View details for DOI 10.1186/1749-7221-4-17
View details for PubMedID 19772656
Postoperative Pain Following Foot and Ankle Surgery: A Prospective Study
FOOT & ANKLE INTERNATIONAL
2008; 29 (11): 1063-1068
Orthopaedic procedures have been reported to have the highest incidence of pain compared to other types of operations. There are limited studies in the literature that investigate postoperative pain.A prospective study of 98 patients undergoing orthopedic foot and ankle operations was undertaken to evaluate their pain experience. A Short-Form McGill Pain Questionnaire (SF-MPQ) was administered preoperatively and postoperatively.The results showed that patients who experienced pain before the operation anticipated feeling higher pain intensity immediately postoperatively. Patients, on average, experienced higher pain intensity 3 days after the operation than anticipated. The postoperative pain intensity at 3 days was the most severe, while postoperative pain intensity at 6 weeks was the least severe. Age, gender and preoperative diagnosis (acute versus chronic) did not have a significant effect on the severity of pain that patients experienced. Six weeks following the operation, the majority of patients felt no pain. In addition, the severity of preoperative pain was highly predictive of their anticipated postoperative pain and 6-week postoperative pain, and both preoperative pain and anticipated pain predict higher immediate postoperative pain.The intensity of patients' preoperative pain was predictive of the anticipated postoperative pain. Patients' preoperative pain and anticipated postoperative pain were independently predictive of the 3-day postoperative pain. The higher pain intensity a patient experienced preoperatively suggested that their postoperative pain severity would be greater. Therefore, surgeons should be aware of these findings when treating postoperative pain after orthopaedic foot and ankle operations.
View details for DOI 10.3113/FAI.2008.1063
View details for Web of Science ID 000260714000002
View details for PubMedID 19026197
View details for PubMedCentralID PMC2743476
Reduced Cold Pain Tolerance in Chronic Pain Patients Following Opioid Detoxification
2008; 9 (8): 1158-1163
One potential consequence of chronic opioid analgesic administration is a paradoxical increase of pain sensitivity over time. Little scientific attention has been given to how cessation of opioid medication affects the hyperalgesic state. In this study, we examined the effects of opioid tapering on pain sensitivity in chronic pain patients.Twelve chronic pain patients on long-term opioid analgesic treatment were observed in a 7- to 14-day inpatient pain rehabilitation program, with cold pain tolerance assessed at admission and discharge. The majority of participants were completely withdrawn from their opioids during their stay.We hypothesized that those patients with the greatest reduction in daily opioid use would show the greatest increases in pain tolerance, as assessed by a cold pressor task.A linear regression revealed that the amount of opioid medication withdrawn was a significant predictor of pain tolerance changes, but not in the direction hypothesized. Greater opioid reduction was associated with decreased pain tolerance. This reduction of pain tolerance was not associated with opioid withdrawal symptoms or changes in general pain.These findings suggest that the withdrawal of opioids in a chronic pain sample leads to an acute increase in pain sensitivity.
View details for DOI 10.1111/j.1526-4637.2008.00475.x
View details for Web of Science ID 000261106100026
View details for PubMedID 18564998
View details for PubMedCentralID PMC2751584
Prenatal diagnosis of placenta accreta - Sonography or magnetic resonance imaging?
JOURNAL OF ULTRASOUND IN MEDICINE
2008; 27 (9): 1275-1281
The purpose of this study was to compare the accuracy of transabdominal sonography and magnetic resonance imaging (MRI) for prenatal diagnosis of placenta accreta.A historical cohort study was undertaken at 3 institutions identifying women at risk for placenta accreta who had undergone both sonography and MRI prenatally. Sonographic and MRI findings were compared with the final diagnosis as determined at delivery and by pathologic examination.Thirty-two patients who had both sonography and MRI prenatally to evaluate for placenta accreta were identified. Of these, 15 had confirmation of placenta accreta at delivery. Sonography correctly identified the presence of placenta accreta in 14 of 15 patients (93% sensitivity; 95% confidence interval [CI], 80%-100%) and the absence of placenta accreta in 12 of 17 patients (71% specificity; 95% CI, 49%-93%). Magnetic resonance imaging correctly identified the presence of placenta accreta in 12 of 15 patients (80% sensitivity; 95% CI, 60%-100%) and the absence of placenta accreta in 11 of 17 patients (65% specificity; 95% CI, 42%-88%). In 7 of 32 cases, sonography and MRI had discordant diagnoses: sonography was correct in 5 cases, and MRI was correct in 2. There was no statistical difference in sensitivity (P = .25) or specificity (P = .5) between sonography and MRI.Both sonography and MRI have fairly good sensitivity for prenatal diagnosis of placenta accreta; however, specificity does not appear to be as good as reported in other studies. In the case of inconclusive findings with one imaging modality, the other modality may be useful for clarifying the diagnosis.
View details for Web of Science ID 000258853200002
View details for PubMedID 18716136
View details for PubMedCentralID PMC2743470
Urinalysis vs urine protein-creatinine ratio to predict significant proteinuria in pregnancy
JOURNAL OF PERINATOLOGY
2008; 28 (7): 461-467
To compare the urine protein-creatinine ratio with urinalysis to predict significant proteinuria (>or=300 mg per day).A total of 116 paired spot urine samples and 24-h urine collections were obtained prospectively from women at risk for preeclampsia. Urine protein-creatinine ratio and urinalysis were compared to the 24-h urine collection.The urine protein-creatinine ratio had better discriminatory power than urinalysis: the receiver operating characteristic curve had a greater area under the curve, 0.89 (95% confidence interval (CI) 0.83 to 0.95) vs 0.71 (95% CI 0.64 to 0.77, P<0.001). When matched for clinically relevant specificity, urine protein-creatinine ratio (cutoff >or=0.28) is more sensitive than urinalysis (cutoff >or=1+): 66 vs 41%, P=0.001 (with 95 and 100% specificity, respectively). Furthermore, the urine protein-creatinine ratio predicted the absence or presence of proteinuria in 64% of patients; urinalysis predicted this in only 19%.The urine protein-creatinine ratio is a better screening test. It provides early information for more patients.
View details for DOI 10.1038/jp.2008.4
View details for Web of Science ID 000257271500003
View details for PubMedID 18288120
Mexiletine therapy for chronic pain: Survival analysis identifies factors predicting clinical success
JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
2008; 35 (3): 321-326
Mexiletine, a sodium channel blocker, treats neuropathic pain but its clinical value has been questioned due to its significant side effects and limited efficacy. We hypothesized that ongoing therapy with mexiletine would have limited patient acceptance, but that an analgesic response to intravenous (IV) lidocaine (a pharmacologically similar drug) would identify patients most likely to choose ongoing therapy with mexiletine. We identified a cohort of 37 patients with neuropathic pain who underwent IV lidocaine infusions at our institution and were subsequently prescribed mexiletine. Time until discontinuation of mexiletine was used as the primary endpoint. Time until discontinuation is a clinically relevant, discrete, objective endpoint gaining acceptance as a metric for assessing clinical performance of drugs with significant side effects and limited efficacy. We used the techniques of survival analysis to determine factors that predicted continued therapy with mexiletine. Median time to discontinuation of mexiletine was only 43 days. A stronger analgesic response to IV lidocaine significantly predicted continued acceptance of mexiletine therapy. Decreasing age and male gender also predicted continued acceptance of mexiletine therapy. Analyzing time to mexiletine discontinuation uncovers important limitations in mexiletine's clinical performance missed by studies with conventional endpoints, such as change in pain score. Despite claims of efficacy, acceptance of mexiletine therapy is poor overall. Test infusions with lidocaine identify patients most likely to continue mexiletine therapy. Further work is needed to confirm these results and evaluate the relative acceptance of mexiletine vs. other treatments of neuropathic pain.
View details for DOI 10.1016/j.jpainsymman.2007.04.022
View details for Web of Science ID 000253919000016
View details for PubMedID 18222627
View details for PubMedCentralID PMC2925416
Multivariate analysis of chronic pain patients undergoing lidocaine infusions: Increasing pain severity and advancing age predict likelihood of clinically meaningful analgesia
CLINICAL JOURNAL OF PAIN
2007; 23 (8): 702-706
The proportion of chronic pain patients with suspected neuropathic pain who will have clinically meaningful pain relief with intravenous (IV) lidocaine and the clinical characteristics that identify these patients have not been described previously.We conducted a cohort study of 99 patients who underwent IV lidocaine infusions for suspected neuropathic pain. An 11-point Numerical Rating Score (NRS) of pain intensity was recorded at the beginning and end of each infusion. A predefined literature-based criteria for "clinically meaningful" reductions in pain score was used to classify patients as responders or nonresponders. Multivariate logistic regression was used to determine clinical variables that predicted an increased likelihood of being a lidocaine responder.The mean reduction in NRS during lidocaine infusions was 2.34 (95% confidence interval 2.83-1.85, P<0.001). Forty-two percent of patients (95% confidence interval 32.5%-52.8%) had NRS reductions of 30% or greater and met the predefined criteria as lidocaine responders. Univariate and multivariate analyses indicated that advancing age and pain severity significantly increased the odds of being a lidocaine responder. Controlled for all other factors, each decade of advancing age increased the odds of being a lidocaine responder by 36%. Each 1-point increase, on an 11-point scale of baseline pain severity, increased the odds of being a lidocaine responder by 29%.IV lidocaine effectively reduces pain in a minority of patients suspected of having neuropathic pain. Pain severity and patient age can be used to target therapy to those most likely to respond.
View details for Web of Science ID 000249743000009
View details for PubMedID 17885349
Intravenous lidocaine for neuropathic pain: diagnostic utility and therapeutic efficacy.
Current pain and headache reports
2007; 11 (1): 20-24
Lidocaine is a use-dependent sodium channel blocker that produces analgesia when administered intravenously to patients with neuropathic pain. This article reviews the role and limitations of intravenous lidocaine infusions for neuropathic pain. Lidocaine infusions rarely provide relief that persists significantly beyond the duration of the infusion. Diagnostically, systemic lidocaine may help establish the presence of neuropathic pain and the responsivity to oral sodium channel blockade. However, the data supporting diagnostic infusions remain sparse. Therapeutically, infusions should generally be restricted to patients with neuropathic pain who are unable to take oral medication.
View details for PubMedID 17214917
Celiac plexus block for visceral pain.
Current pain and headache reports
2006; 10 (1): 20-25
Celiac plexus block has long been used to provide analgesia for upper abdominal pain. In particular, neurolytic celiac plexus block has been advocated for pancreatic cancer pain. In this article, recent advances clarifying the role and limitations of neurolytic celiac plexus block are reviewed. Neurolytic celiac plexus block provides persistent augmented analgesia when used as an adjunct to systemic opiates, but does not reliably decrease opiate requirements. In addition, neurolytic celiac plexus block may prolong survival, but the data supporting this remain controversial. The optimal technique for accomplishing neurolytic celiac plexus block remains undetermined.
View details for PubMedID 16499826
- A vaccine to prevent herpes zoster NEW ENGLAND JOURNAL OF MEDICINE 2005; 353 (13): 1414-1415
Management of perioperative pain in patients chronically consuming opioids
REGIONAL ANESTHESIA AND PAIN MEDICINE
2004; 29 (6): 576-591
The prevalence of licit and illicit opioid use is growing, and a greater percentage of chronically opioid-consuming patients are presenting for surgery. These patients can be expected to experience increased postoperative pain, greater postoperative opioid consumption, and prolonged use of healthcare resources for managing their pain.Achieving adequate pain control in these patients can be challenging because commonly used strategies for alleviating postoperative pain may have diminished effectiveness. We explore the prevalence and characteristics of opioid use in the United States and discuss its impact on the perioperative management of pain. We examine mechanistically why adequate perioperative pain control in chronically opioid-consuming patients may be difficult.We present strategies for providing adequate analgesia to these patients that include the optimal use of opioids, adjuvant medications, and regional anesthetic techniques.
View details for DOI 10.1016/j.rapm.2004.06.009
View details for Web of Science ID 000226144300011
View details for PubMedID 15635517
HIV Tat represses transcription of the beta(2)-microglobulin promoter
1998; 35 (18): 1171-1178
The MHC class I complex, which binds and presents peptide antigen, is composed of a class I heavy chain and the beta2-microglobulin light chain. HIV-1, which induces a profound immunodeficiency in infected individuals, encodes proteins that cause decreased expression of class I heavy chain. We now report that the HIV Tat protein, which is a potent transactivator of viral transcription, is also a potent repressor of the beta2-microglobulin gene. Repression is mediated through the basal promoter of the beta2-microglobulin gene, which is shown to be predominantly regulated by an initiator element. Tat repression is further augmented by the short viral transcript, TAR, which interacts with Tat. Tat-mediated repression of beta2-microglobulin expression, together with its known repression of class I gene transcription, provides an effective mechanism by which HIV could prevent cell surface expression of the MHC class I complex and avoid immune surveillance.
View details for Web of Science ID 000079458800003
View details for PubMedID 10199391