Michael C Rowbotham

California Pacific Medical Center Research Institute, San Francisco, California, United States

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Publications (119)666.5 Total impact

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    ABSTRACT: Sample size calculations are used to determine the number of participants required to have sufficiently high power to detect a given treatment effect. In this review, we examined the reporting quality of sample size calculations in 172 publications of double-blind RCTs of non-invasive pharmacologic or interventional (i.e., invasive) pain treatments published in European Journal of Pain, Journal of Pain, and Pain from January 2006 through June 2013. Sixty-five percent of publications reported a sample size calculation but only 38% provided all elements required to replicate the calculated sample size. In publications reporting at least one element, 54% provided a justification for the treatment effect used to calculate sample size, and 24% of studies with continuous outcome variables justified the variability estimate. Publications of clinical pain condition trials reported a sample size calculation more frequently than experimental pain model trials (77% vs. 33%, P < 0.001), but did not differ in the frequency of reporting all required elements. No significant differences in reporting of any or all elements were detected between publications of trials with industry and non-industry sponsorship. Twenty-eight percent included a discrepancy between the reported number of planned and randomized participants. This study suggests that sample size calculation reporting in analgesic trial publications is usually incomplete. Investigators should provide detailed accounts of sample size calculations in publications of clinical trials of pain treatments, which is necessary for reporting transparency and communication of pre-trial design decisions. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.
    The journal of pain : official journal of the American Pain Society. 12/2014;
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    ABSTRACT: Peer-reviewed publications of randomized clinical trials (RCTs) are the primary means of disseminating research findings. “Spin” in RCT publications is misrepresentation of statistically non-significant research findings to suggest treatment benefit. Spin can influence the way readers interpret clinical trials and use the information to make decisions about treatments and medical policies. The objective of this study was to determine the frequency with which 4 types of spin were used in publications of analgesic RCTs with non-significant primary analyses in 6 major pain journals. In the 76 articles included in our sample, 28% of the Abstracts and 29% of the main texts emphasized secondary analyses with p-values <0.05; 22% of Abstracts and 29% of texts emphasized treatment benefit based on non-significant primary results; 14% of Abstracts and 18% of texts emphasized within-group improvements over time, rather than primary between-group comparisons; and 13% of Abstracts and 10% of texts interpreted a non-significant difference between groups in a superiority study as comparable effectiveness. When considering the article Conclusion sections, 21% did not mention the non-significant primary result, 22% were presented with no uncertainty or qualification, 30% did not acknowledge that future research was required, and 8% recommended the intervention for clinical use. Perspective This article identifies relatively frequent “spin” in analgesic RCTs. These findings highlight a need for authors, reviewers, and editors to be more cognizant of how analgesic RCT results are presented and attempt to minimize spin in future clinical trial publications.
    The Journal of Pain. 10/2014;
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    ABSTRACT: The Intention-to-treat (ITT) principle states that all subjects in a randomized clinical trial (RCT) should be analyzed in the group to which they were assigned regardless of compliance with assigned treatment. Analyses performed according to the ITT principle preserve the benefits of randomization and are recommended by regulators and statisticians for analyses of RCTs. The objective of this study was to determine the frequency with which publications of analgesic RCTs in three major pain journals report an ITT analysis and the percentage of the author-declared ITT analyses that include all randomized subjects and thereby fulfill the most common interpretation of the ITT principle. RCTs investigating non-invasive, pharmacologic and interventional (e.g., nerve blocks, implantable pumps, spinal cord stimulators, surgery) treatments for pain, published between January 2006 and June 2013 (n =173), were included. None of the trials using experimental pain models reported an ITT analysis; 47% of trials investigating clinical pain conditions reported an ITT analysis and 5% reported a modified ITT analysis. Of the analyses reported as ITT, 67% reported reasons for excluding subjects from the analysis and 18% of those listing reasons for exclusion did not do so in the Methods section. Such mislabeling can make it difficult to identify traditional ITT analyses for inclusion in meta-analyses. We hope that deficiencies in reporting identified in this study will encourage authors, reviewers, and editors to promote more consistent use of the phrase ITT for more accurate reporting of RCT-based evidence for pain treatments.
    Pain 10/2014; · 5.64 Impact Factor
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    Faustine L Dufka, Robert H Dworkin, Michael C Rowbotham
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    ABSTRACT: Transparency in research requires public access to unbiased information prior to trial initiation and openly available results upon study completion. The Repository of Registered Migraine Trials is a global snapshot of registered migraine clinical trials and scorecard of results availability via the peer-reviewed literature, registry databases, and gray literature. The 295 unique clinical trials identified employed 447 investigational agents, with 30% of 154 acute migraine trials and 11% of 141 migraine prophylaxis trials testing combinations of agents. The most frequently studied categories in acute migraine trials were triptans, nonsteroidal anti-inflammatory drugs, antiemetics, calcitonin gene-related peptide antagonists, and acetaminophen. Migraine prophylaxis trials frequently studied anticonvulsants, β-blockers, complementary/alternative therapies, antidepressants, and botulinum toxin. Overall, 237 trials were eligible for a results search. Of 163 trials completed at least 12 months earlier, 57% had peer-reviewed literature results, and registries/gray literature added another 13%. Using logistic regression analysis, studies with a sample size below the median of 141 subjects were significantly less likely to have results, but the dominant factor associated with availability of results was time since study completion. In unadjusted models, trials registered on ClinicalTrials.gov and trials with industry primary sponsorship were significantly more likely to have results. Recently completed trials rarely have publicly available results; 2 years after completion, the peer-reviewed literature contains results for fewer than 60% of completed migraine trials. To avoid bias, evidence-based therapy algorithms should consider factors affecting results availability. As negative trials are less likely to be published, special caution should be exercised before recommending a therapy with a high proportion of missing trial results.
    Neurology 09/2014; · 8.30 Impact Factor
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    ABSTRACT: This article presents general considerations discussed at an IMMPACT consensus meeting regarding proof-of-concept (POC) clinical trials and major POC trial designs and their advantages and limitations when used to evaluate chronic pain treatments. Abstract Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine if a treatment is likely to be efficacious for a given indication and thus if it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge of designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost effective manner. An IMMPACT consensus meeting was convened to discuss design considerations for POC trials in analgesia with a focus on maximizing power with limited resources and participants. We present general design aspects to consider including patient population, active comparators and placebos, study power, pharmacokinetic-pharmacodynamic relationships, and minimization of missing data. Efficiency of single dose studies for treatments with rapid onset is discussed. The trade-off between parallel-group and cross-over designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages of more recent trial designs including (1) N-of-1 designs, (2) enriched designs, (3) adaptive designs, and (4) sequential parallel comparison designs are summarized and recommendations for consideration are provided. More attention to identifying efficient yet powerful designs for POC clinical trials of chronic pain treatments may increase the percentage of truly efficacious pain treatments that are advanced to confirmatory trials while decreasing the percentage of ineffective treatments that continue to be evaluated rather than abandoned.
    Pain 05/2014; · 5.64 Impact Factor
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    ABSTRACT: The degree of variability in the patient baseline 7-day diary of pain ratings has been hypothesized to have a potential effect on the assay sensitivity of randomized clinical trials of pain therapies. To address this question, we obtained clinical trial data from the Food and Drug Administration (FDA) through the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership, and harmonized patient level data from 12 clinical trials (4 gabapentin and 8 pregabalin) in postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Models were developed using exploratory logistic regression to examine the interaction between available baseline factors and treatment (placebo vs. active-medication) in predicting patient response to therapy (i.e., >30% improvement). Our analysis demonstrated an increased likelihood of response in the placebo-treated group for patients with a higher standard deviation in the baseline 7-day diary without affecting the likelihood of a response in the active-medication treated group, confirming our hypothesis. In addition, there was a small but significant age-by-treatment interaction in the PHN model, and small weight-by-treatment interaction in the DPN model. The patient's sex, baseline pain level, and the study protocol only had an effect on the likelihood of response overall. Our results suggest the possibility that at least in some disease processes excluding patients with a highly variable baseline 7-day diary has the potential to improve the assay sensitivity of these analgesic clinical trials, although reductions of external validity must be considered when increasing the homogeneity of the investigated sample.
    Pain 05/2014; · 5.64 Impact Factor
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    ABSTRACT: Eliminating publication bias requires ensuring public awareness of studies and access to results. clinical trial registries provide basic trial information, but access to unbiased trial results is inadequate. nearly all studies of trial registration and results reporting have been limited to the clinicaltrials.gov registry. we analyzed trial registration, registry functionality, cross-registry harmonization, and results reporting on all fifteen primary registries in the who international clinical trials registry platform (ictrp) for post-herpetic neuralgia, painful diabetic neuropathy, and fibromyalgia. a total of 447 unique trials were identified, with 86 trials listed on more than one registry. a comprehensive search algorithm was used to find trial results in the peer-reviewed literature and the grey literature. creating a global database of registered trials and trial results proved surprisingly difficult for several reasons: 1) ictrp does not reliably identify trials listed on multiple registries; manual searches are necessary. 2) searching ictrp yields different results than searching individual registries. 3) outcome measure descriptions for multiply-registered trials vary between registries. 4) registry-publication pairings are often inaccurate or incomplete. 5) grey literature results are not permanent. overall, only 46% of all trials had results available. trials registered on clinicaltrials.gov were significantly more likely to have results (52% vs 18%, p<0.001), partly due to the ability to post results directly to the registry. in addition to the simple remedy of including trial registration numbers on all meeting abstracts and peer-reviewed papers, specific strategies are offered to facilitate identifying multiply-registered studies, and ensuring accurate pairing of results and publications.
    Pain 04/2014; · 5.64 Impact Factor
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    ABSTRACT: Studies on complications related to chronic nerve injury following sentinel lymph node biopsy (SLNB) and complete lymph node dissection (CLND) for melanoma are sparse. This review summarizes the existing literature on pain and neuropathic complications in melanoma patients undergoing SLNB with or without CLND. The Cochrane Central Register of Controlled Trials and the Embase and PubMed databases were searched. Full-text English language articles published before June 2013 were included. Prospective and retrospective studies assessing persistent (>1 month) sensory nerve injury, postoperative pain, neuropathic pain, and sensory disturbances following SLNB with or without CLND in melanoma patients were eligible. Nine studies (six prospective and three retrospective) including data for 3632 patients met our inclusion criteria. Outcome parameters were too heterogeneous to conduct a quantitative analysis, and few studies systematically evaluated pain and sensory abnormalities. Persistent postoperative pain was reported in 1-14% of patients following SLNB and in 6-34% following CLND and sensory abnormalities in 0.1-32 and 2-82%, respectively. In the one study that assessed the type of pain, neuropathic pain was suggested to explain persistent pain in 31-66% of patients with SLNB and 82-89% of patients with CLND. Sensory-nerve-related complications in melanoma patients seem to be less pronounced following SLNB compared with CLND. Prospective observational studies are necessary to identify predictors of persistent pain, to evaluate the prevalence and impact of pain and sensory abnormalities, and to develop strategies for prevention of long-term complications.
    Melanoma research 12/2013; · 2.06 Impact Factor
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    ABSTRACT: Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Analgesics have traditionally been assessed in randomized clinical trials (RCTs) designed to demonstrate analgesic efficacy relative to placebo or an active comparator. In these trials, rigorous, prospectively designed assessment for AL is generally not performed. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) convened a consensus meeting to review the available evidence and discuss methods for improving the assessment of the AL of analgesics in clinical trials in patients with pain. Recommendations for improved assessment include: (1) performing trials that include individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out of the trial). The authors also propose a research agenda for improving the assessment of AL in future trials.
    Pain 11/2013; 154(11):2324-34. · 5.64 Impact Factor
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    ABSTRACT: The National Institutes of Health released the trial registry ClinicalTrials.gov in 2000 to increase public reporting and clinical trial transparency. This systematic review examined whether registered primary outcome specifications (POSs; i.e., definitions, timing, and analytic plans) in analgesic treatment trials correspond with published POSs. Trials with accompanying publications (n=87) were selected from the Repository of Registered Analgesic Clinical Trials (RReACT) database of all postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia clinical trials registered at ClinicalTrials.gov as of 12/1/2011. POSs never matched precisely; discrepancies occurred in 79% of the registry-publication pairs (21% failed to register or publish POs). These percentages did not differ significantly between industry and non-industry sponsored trials. Thirty percent of the trials contained unambiguous POS discrepancies (e.g., omitting a registered primary outcome [PO] from the publication, "demoting" a registered PO to a published secondary outcome), with a statistically significantly higher percentage of non-industry sponsored than industry-sponsored trials containing unambiguous POS discrepancies. POS discrepancies due to ambiguous reporting included vaguely worded PO registration, or failing to report the timing of PO assessment, statistical analysis used for the PO, or method to address missing PO data. At best, POS discrepancies may be attributable to insufficient registry requirements, carelessness (e.g., failing to report PO assessment timing), or difficulty uploading registry information. At worst, discrepancies could indicate investigator impropriety (e.g., registering imprecise POs ["pain"], then publishing whichever pain assessment produced statistically significant results). Improvements in PO registration, as well as journal policies requiring consistency between registered and published PO descriptions, are needed.
    Pain 08/2013; · 5.64 Impact Factor
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    ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows for effects in surface cortical structures. The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients. Part 1: Different coil configurations were tested in a placebo-controlled crossover design in volunteers (N = 16). Tonic pain was induced using a capsaicin/thermal pain model and functional brain imaging was performed by means of H215O positron emission tomography -- computed tomography (PET/CT) scans. Differences in NRS pain ratings between TMS and sham treatment (NRSTMS-NRSplacebo) which were recorded each minute during the 10 minute PET scans. Part 2: 16 fibromyalgia patients were subjected to 20 multi-coil rTMS treatments over 4 weeks and effects on standard pain scales (Brief Pain Inventory, item 5, i.e. average pain NRS over the last 24 hours) were recorded. A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers. In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz. This degree of pain control was maintained for at least 4 weeks after the final session. Multi-coil rTMS may be a safe and effective treatment option for acute as well as for chronic pain, such as that accompanying fibromyalgia. Further studies are necessary to optimize configurations and settings as well as to elucidate the mechanisms that lead to the long-lasting pain control produced by these treatments.
    Molecular Pain 07/2013; 9(1):33. · 3.77 Impact Factor
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    ABSTRACT: OBJECTIVE: Our objective was to identify patient, study, and site factors associated with assay sensitivity in placebo-controlled neuropathic pain trials. METHODS: We examined the associations between study characteristics and standardized effect size (SES) in a database of 200 publicly available randomized clinical trials of pharmacologic treatments for neuropathic pain. RESULTS: There was considerable heterogeneity in the SESs among the examined trials. Univariate meta-regression analyses indicated that larger SESs were significantly associated with trials that had 1) greater minimum baseline pain inclusion criteria, 2) greater mean subject age, 3) a larger percentage of Caucasian subjects, and 4) a smaller total number of subjects. In a multiple meta-regression analysis, the associations between SES and minimum baseline pain inclusion criterion and age remained significant. CONCLUSIONS: Our analyses have examined potentially modifiable correlates of study SES and shown that a minimum pain inclusion criterion of 40 or above on a 0 to 100 scale is associated with a larger SES. These data provide a foundation for investigating strategies to improve assay sensitivity and thereby decrease the likelihood of falsely negative outcomes in clinical trials of efficacious treatments for neuropathic pain.
    Neurology 05/2013; · 8.30 Impact Factor
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    ABSTRACT: Postherpetic neuralgia (PHN) is a common complication after herpes zoster (HZ). Subjects who completed a longitudinal observational 6-month study (4 visits) of the natural history of HZ were recontacted for 2 additional follow-up visits that included pain and sensory symptom assessment, quantitative sensory testing, capsaicin response test, and 3-mm punch skin biopsies in HZ-affected, mirror-image, and control skin sites. Forty-three subjects (14 with PHN at 6months) of the original 94 subjects in the cohort were comprehensively assessed at a median 3.9years after HZ onset (visit 5), and 10 subjects underwent a final assessment at a median 7.7years after HZ onset (visit 6). At 3.9years, none of the 29 subjects who had been pain free at 6months had a recurrence of pain. Only 2 of the 14 subjects with PHN at 6months still had pain at 3.9years. One subject with PHN at 6months was free of symptoms at 3.9years but had very mild pain at 7.7years. Sensory function continued on a path toward normalization, but was still abnormal in many subjects, especially those who met criteria for PHN at 6months. Even at 7.7years, reinnervation of HZ-affected skin was not apparent.
    Pain 04/2013; · 5.64 Impact Factor
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    ABSTRACT: The development of valid and informative treatment risk-benefit profiles requires consistent and thorough information about adverse event (AE) assessment and participants' AEs during randomized controlled trials (RCTs). Despite a 2004 extension of the Consolidated Standards of Reporting Trials (CONSORT) statement recommending the specific AE information that investigators should report, there is little evidence that analgesic RCTs adequately adhere to these recommendations. This systematic review builds on prior recommendations by describing a comprehensive checklist for AE reporting developed to capture clinically important AE information. Using this checklist, we coded AE assessment methods and reporting in all 80 double-blind RCTs of noninvasive pharmacologic treatments published in the European Journal of Pain, Journal of Pain, and PAIN® from 2006 to 2011. Across all trials, reports of AEs were frequently incomplete, inconsistent across trials, and, in some cases, missing. For example, >40% of trials failed to report any information on serious adverse events. Trials of participants with acute or chronic pain conditions and industry-sponsored trials typically provided more and better-quality AE data than trials involving pain-free volunteers or trials that were not industry sponsored. The results of this review suggest that improved AE reporting is needed in analgesic RCTs. We developed an ACTTION (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks) AE reporting checklist that is intended to assist investigators in thoroughly and consistently capturing and reporting these critically important data in publications.
    Pain 03/2013; · 5.64 Impact Factor
  • Pain 03/2013; · 5.64 Impact Factor
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    European journal of pain (London, England) 01/2013; · 3.37 Impact Factor
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    ABSTRACT: Informed consent is the cornerstone of human research subject protection. Many subjects sign consent documents without understanding the study purpose, procedures, risks, benefits, and their rights. Proof of comprehension is not required and rarely obtained. Understanding might improve by using an interactive system with multiple options for hearing, viewing and reading about the study and the consent form at the subject's own pace with testing and immediate feedback. This prospective randomized study compared the IRB-approved paper ICF for an actual clinical research study with an interactive presentation of the same study and its associated consent form using an iPad device in two populations: clinical research professionals, and patients drawn from a variety of outpatient practice settings. Of the 90 participants, 69 completed the online test and survey questions the day after the session (maximum 36 hours post-session). Among research professionals (n = 14), there was a trend (p = .07) in the direction of iPad subjects testing better on the online test (mean correct = 77%) compared with paper subjects (mean correct = 57%). Among patients (n = 55), iPad subjects had significantly higher test scores than standard paper consent subjects (mean correct = 75% vs 58%, p < .001). For all subjects, the total time spent reviewing the paper consent was 13.2 minutes, significantly less than the average of 22.7 minutes total on the three components to be reviewed using the iPad (introductory video, consent form, interactive quiz). Overall satisfaction and overall enjoyment slightly favored the interactive iPad presentation. This study demonstrates that combining an introductory video, standard consent language, and an interactive quiz on a tablet-based system improves comprehension of research study procedures and risks.
    PLoS ONE 01/2013; 8(3):e58603. · 3.53 Impact Factor
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    ABSTRACT: Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models. We performed post-hoc analyses of 10 completed healthy volunteer studies (n = 342 [409 repeated measurements]). Three different models were used to induce secondary hyperalgesia to monofilament stimulation: the heat/capsaicin sensitization (H/C), the brief thermal sensitization (BTS), and the burn injury (BI) models. Three studies included both the H/C and BTS models. Within-subject compared to between-subject variability was low, and there was substantial strength of agreement between repeated induction-sessions in most studies. The intraclass correlation coefficient (ICC) improved little with repeated testing beyond two sessions. There was good agreement in categorizing subjects into 'small area' (1(st) quartile [<25%]) and 'large area' (4(th) quartile [>75%]) responders: 56-76% of subjects consistently fell into same 'small-area' or 'large-area' category on two consecutive study days. There was moderate to substantial agreement between the areas of secondary hyperalgesia induced on the same day using the H/C (forearm) and BTS (thigh) models. Secondary hyperalgesia induced by experimental heat pain models seem a consistent measure of sensitization in pharmacodynamic and physiological research. The analysis indicates that healthy volunteers can be phenotyped based on their pattern of sensitization by the heat [and heat plus capsaicin] pain models.
    PLoS ONE 01/2013; 8(5):e62733. · 3.53 Impact Factor
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    ABSTRACT: Development of secondary hyperalgesia following a cutaneous injury is a centrally mediated, robust phenomenon. The pathophysiological role of endogenous opioid signalling to the development of hyperalgesia is unclear. Recent animal studies, carried out after the resolution of inflammatory pain, have demonstrated reinstatement of tactile hypersensitivity following administration of μ-opioid-receptor-antagonists. In the present study in humans, we analyzed the effect of naloxone when given after the resolution of secondary hyperalgesia following a first-degree burn injury. Twenty-two healthy volunteers were included in this placebo-controlled, randomized, double-blind, cross-over study. Following baseline assessment of thermal and mechanical thresholds, a first-degree burn injury (BI; 47°C, 7 minutes, thermode area 12.5 cm(2)) was induced on the lower leg. Secondary hyperalgesia areas around the BI-area, and separately produced by brief thermal sensitization on the contralateral thigh (BTS; 45°C, 3 minutes, area 12.5 cm(2)), were assessed using a polyamide monofilament at pre-BI and 1, 2, and 3 hours post-BI. At 72 hrs, BI and BTS secondary hyperalgesia areas were assessed prior to start of a 30 minutes intravenous infusion of naloxone (total dose 21 microg/kg) or placebo. Fifteen minutes after start of the infusion, BI and BTS secondary hyperalgesia areas were reassessed, along with mechanical and thermal thresholds. Secondary hyperalgesia areas were demonstrable in all volunteers 1-3 hrs post-BI, but were not demonstrable at 72 hrs post-burn in 73-86% of the subjects. Neither magnitude of secondary hyperalgesia areas nor the mechanical and thermal thresholds were associated with naloxone-treated compared to placebo-treated subjects. Naloxone (21 microg/kg) did not reinstate secondary hyperalgesia when administered 72 hours after a first-degree burn injury and did not increase BTS-generated hyperalgesia. The negative results may be due to the low dose of naloxone or insufficient tissue injury to generate latent sensitization.
    PLoS ONE 01/2013; 8(5):e64608. · 3.53 Impact Factor

Publication Stats

5k Citations
666.50 Total Impact Points

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Institutions

  • 2010–2014
    • California Pacific Medical Center Research Institute
      San Francisco, California, United States
  • 2013
    • University of Rochester
      Rochester, New York, United States
  • 1989–2012
    • University of California, San Francisco
      • • Department of Neurology
      • • Division of Hospital Medicine
      San Francisco, California, United States
  • 2011
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 1997–2011
    • CSU Mentor
      • • Department of Neurology
      • • Department of Medicine
      Long Beach, California, United States
  • 2009
    • Oxford University Hospitals NHS Trust
      Oxford, England, United Kingdom
  • 2008
    • Oregon Health and Science University
      • Comprehensive Pain Center
      Los Angeles, CA, United States
    • University of San Francisco
      San Francisco, California, United States
  • 2002
    • Endo Pharmaceuticals
      Philadelphia, Pennsylvania, United States
  • 2001
    • Rigshospitalet
      • Department of Anaesthesiology
      Copenhagen, Capital Region, Denmark
  • 2000–2001
    • Herlev Hospital
      • Department of Anaesthesiology
      Herlev, Capital Region, Denmark
    • Beth Israel Medical Center
      • Department of Pain Medicine and Palliative Care
      New York City, New York, United States
  • 1999
    • Christian-Albrechts-Universität zu Kiel
      • UKSH Klinik für Neurologie
      Kiel, Schleswig-Holstein, Germany
    • Rabin Medical Center
      Tell Afif, Tel Aviv, Israel
  • 1995
    • Erasmus MC
      • Daniel den Hoed Centre
      Rotterdam, South Holland, Netherlands