The Journal of Pain

Opioid Pharmacotherapy for Chronic Non-Cancer Pain in the United States: A Research Guideline for Developing an Evidence-Base

2010-04-29

Abstract: This document reports the consensus of an interdisciplinary panel of research and clinical experts charged with reviewing the use of opioids for chronic noncancer pain (CNCP) and formulating guidelines for future research. Prescribing opioids for chronic noncancer pain has recently escalated in the United States. Contrasting with increasing opioid use are: 1) The lack of evidence supporting long-term effectiveness; 2) Escalating misuse of prescription opioids including abuse and diversion; and 3) Uncertainty about the incidence and clinical salience of multiple, poorly characterized adverse drug events (ADEs) including endocrine dysfunction, immunosuppression and infectious disease, opioid-induced hyperalgesia and xerostomia, overdose, falls and fractures, and psychosocial complications. Chief among the limitations of current evidence are: 1) Sparse evidence on long-term opioid effectiveness in chronic pain patients due to the short-term time frame of clinical trials; 2) Insufficiently comprehensive outcome assessment; and 3) Incomplete identification and quantification of ADEs. The panel called for a strategic interdisciplinary approach to the problem domain in which basic scientists and clinicians cooperate to resolve urgent issues and generate a comprehensive evidence base. It offered 4 recommendations in 3 areas: 1) A research strategy for studying the effectiveness of long-term opioid pharmacotherapy; 2) Improvements in evidence-generation methodology; and 3) Potential research topics for generating new evidence.Perspective: Prescribing opioids for CNCP has outpaced the growth of scientific evidence bearing on the benefits and harms of these interventions. The need for a strong evidence base is urgent. This guideline offers a strategic approach to creating a comprehensive evidence base to guide safe and effective management of CNCP.

Is Lack of Evidence the Problem?

Jane C. Ballantyne — 2010-07-23

Whatever successes there have been for chronic opioid therapy, they are currently overshadowed by the consequences of indiscriminate prescribing. Lest anyone doubt that there is an urgent need to moderate opioid prescribing in the U.S., consider the following. Opioid prescribing in the U.S. increased 200-fold over a single decade, largely because of new prescribing for chronic pain. Efforts to identify an evidence base for chronic opioid therapy revealed only that the evidence supporting effectiveness for the therapy is weak. Prescription opioid abuse in the U.S. has increased in parallel, to the extent that it has overtaken illicit opioid (heroin) abuse, and is regarded by the regulatory authorities as a significant societal problem.

Hiding in Plain Sight: A Case of Tarlov Perineural Cysts

Reta Honey Hiers, Donlin Long, Richard B. North, Anne Louise Oaklander — 2010-09-01

A 52-year-old woman sought help for intractable lumbosacral pain, which began after she lifted a heavy object and fell onto her back more than 2 decades ago. Additional symptoms included burning, numbness, tingling, and pain in her right hip, posterior thigh, leg, and toes, and diminished sensation and sensitivity throughout her right leg and foot. Muscle spasms/cramps, which often interrupted sleep, were intermittently present in her right buttock and right lower extremity. Right-foot drop impaired her ability to walk, and she used a wheeled walker with a seat because she could not walk more than a few steps without sitting. Other problems included: Severe pressure-type headaches, chronic abdominal and pelvic pain, cervical and thoracic back pain, frequent urinary tract infections, and urinary incontinence. Her pain increased with sitting, standing, and walking, and had been refractory to ibuprofen 800 mg tid, gabapentin 300 mg tid, oxycodone/acetaminophen 5/325 mg q4h PRN, and cyclobenzaprine 10 mg tid.

Central Sensitization in the Trigeminal Nucleus Caudalis Produced by a Conjugate of Substance P and the A Subunit of Cholera Toxin

2010-07-12

Abstract: Individuals with chronic craniofacial pain experience symptoms that are consistent with central sensitization. In fact, central sensitization may constitute the major disease process in these conditions, particularly if the original injury has healed or the condition is idiopathic. To understand central sensitization we have developed a conjugate of substance P and cholera toxin (SP-CTA). SP-CTA is selectively taken up by cells that express neurokinin receptors. Twenty-four hours following intracisternal administration of SP-CTA, wild-type rats and mice demonstrated signs of persistent background nociception, but when tested for facial cold sensitivity, they did not differ from controls. However, treating the SP-CTA–injected animals with naloxone exposed cold hypersensitivity in the face. Mu-opioid receptor knockout mice treated with SP-CTA demonstrated hypersensitivity without naloxone treatment. These findings suggest that central sensitization leads to activation of an endogenous opioid system. The data also demonstrate that the intracisternal administration of SP-CTA in rodents is a useful model for studying central sensitization as a disease process without having to induce a peripheral injury.Perspective: Central sensitization is a concern in many craniofacial pain conditions. In this project, we utilize a conjugate of substance P and the catalytic subunit of cholera toxin to induce central sensitization in the nucleus caudalis of rodents. The data indicate that the injected animals become hypersensitive in the face.

Hyperbaric Oxygen Treatment Induces a 2-Phase Antinociceptive Response of Unusually Long Duration in Mice

2010-04-26

Abstract: Hyperbaric oxygen (HBO2) therapy is approved by the FDA for limited clinical indications but is reported to produce pain relief in several chronic pain conditions. However, there have been no studies to explain this apparent analgesic effect of HBO2. Research conducted in our laboratory demonstrates that 4 daily 60-minute HBO2 treatments at 3.5 absolute atmospheres induced an unparalleled antinociceptive response that consists of 1) an early phase that lasted at least 6 hours after the HBO2 treatment before dissipating; and 2) a late phase that emerged about 18 hours after the early phase and lasted for up to 3 weeks. The early phase was sensitive to antagonism by acutely intracerebroventricular (i.c.v.)-administered opioid antagonist naltrexone and the nitric oxide synthase (NOS)-inhibitor L-NAME. The late phase was inhibited by treatment with i.c.v. naltrexone or L-NAME during the 4 daily HBO2 treatments but was not antagonized by either naltrexone or L-NAME following acute pretreatment 2 weeks after HBO2 treatment. These experimental results implicate a novel mechanism that is activated by HBO2, resulting in an antinociceptive response of unusually long duration that is of potential interest in the clinical management of pain.Perspective: Hyperbaric oxygen treatment of mice can induce a 2-phase antinociceptive response of unusually long duration. Nitric oxide and opioid receptors appear to initiate or mediate both phases of the antinociceptive response. Further elucidation of the underlying mechanism may potentially identify molecular targets that cause long-lasting activation of endogenous analgesic systems.

Pediatric Nurses' Cognitive Representations of Children's Pain

Catherine Van Hulle Vincent, Diana J. Wilkie, Laura Szalacha — 2010-04-26

Abstract: The aim of this mixed methods exploratory study was to describe pediatric nurses' cognitive representations (CRs) of the assessment and management of children's pain and to determine the relationships between their CRs and their choices about pain assessment and morphine administration. We recruited a convenience sample of 87 nurses caring for hospitalized children at 4 institutions. We measured the CRs with the Conceptual Content Cognitive Map (3CM) technique and pain assessment and morphine administration with smiling and grimacing child vignettes. We used content analyses for the 3CM data and fit logistic regression models to predict participants' analgesic choice for each vignette. Nearly all (91%) participants identified the child's behavior as an assessment approach; 48% indicated it as most important. Participants (92%) identified pharmacologic as a management approach; 47% indicated it as most important. Participants' CRs did not predict assessment or morphine administration choices. Significantly more participants chose the appropriate analgesic response for the grimacing child than they did for the smiling child. Nurses with more years of pediatric experience were less likely to select administration of the appropriate morphine dose. The 3CM method provided insights into nurses' thinking about pain that are indicative of gaps, which may be amenable to interventions.Perspective: Findings are from an innovative, unique measure of nurses' knowledge and beliefs about the complex phenomenon of children's pain management. Extensive details about the thought processes of pediatric nurses regarding pain assessment and management surfaced through this analysis, which provide excellent information for direction of future research and practice innovations.

Spinal Cord Injuries Containing Asymmetrical Damage in the Ventrolateral Funiculus Is Associated With a Higher Incidence of At-Level Allodynia

2010-03-25

Abstract: Approximately 70% of male rats receiving severe T8 spinal contusions develop allodynia in T5-7 dermatomes (at-level) beginning 2 weeks after injury. In contrast, rats having either complete transections or dorsal hemisections do not develop allodynia at-level after chronic spinal cord injury (SCI). In the present study, incomplete laceration and contusion injuries were made to test for neuroanatomical correlates between areas of white matter damage/sparing at the lesion epicenter and the presence/absence of allodynia. After incomplete laceration lesions and 6 weeks of behavioral testing, histological reconstruction and analysis of the lesion epicenters revealed a significant difference (P < .001) in the amount of ventrolateral funiculus (VLF) asymmetry between rats showing pain-like responses evoked by touch (74.5% ± 8.4% side-to-side difference in VLF damage) versus those not responding to touch (11.3% ± 4.4% side-to-side difference in VLF damage). A 5-week mean allodynia score for each rat that incorporates a full range of forces that are all innocuous in intact controls revealed that the degree of hypersensitivity at level is related to the extent of VLF asymmetry after SCI. No other damaged spinal white matter or gray matter area was correlated with sensitivity to touch. Similar findings were obtained for rats receiving T8 contusions, a more clinically relevant injury. These data suggest that different extents of damage/sparing between the 2 sides of VLF probably are a requisite for the development of allodynia after SCI.Perspective: A side-to-side lesion asymmetry after chronic SCI in a rodent model was found to be highly correlated with the presence and degree of allodynia. Greater insight of key factors contributing to the development and maintenance of chronic neuropathic pain is important for improving quality of life.

Changes in Situation-Specific Pain Catastrophizing Precede Changes in Pain Report During Capsaicin Pain: A Cross-Lagged Panel Analysis Among Healthy, Pain-Free Participants

2010-05-20

Abstract: Considerable evidence has linked catastrophizing to pain responses, and recent experimental pain research has suggested that situational catastrophizing, measured during or immediately after laboratory pain procedures, is strongly related to pain ratings of standardized noxious stimuli. However, given that most experimental pain protocols involve “static” assessments of pain ratings and catastrophizing at a single time point, the direction by which these factors may affect each other remains unclear. Does catastrophizing influences one's subsequent pain responses or do individual differences in the perceived severity of pain lead to differential rates of catastrophizing? Little is known regarding the course of these variables. Using a cross-lagged panel analysis, we evaluated whether changes in situation-specific catastrophizing preceded changes in laboratory-induced pain responses, or vice versa, during tonic capsaicin pain stimulation. Topical application of a 10% capsaicin cream was applied to the dorsal aspect of the nondominant hand of 38 healthy participants. Situation-specific catastrophizing and pain ratings were obtained at Early (0 to 15 minutes), Mid (15 to 30 minutes), and Final (30 to 35 minutes) periods during capsaicin pain. Analyses revealed that Early-to-Mid changes in catastrophizing ratings prospectively accounted for unique variance in subsequent Mid-to-Final changes in pain ratings, whereas Early-to-Mid changes in pain ratings did not account for unique variance in Mid-to-Final changes in catastrophizing ratings. That is, participants who showed the largest initial increases in catastrophizing reported the greatest subsequent increases in pain. Controlling for the reported change in stress did not affect this pattern of results. These findings provide empirical evidence that a situation-specific catastrophizing process might precede and contribute to subsequent increases in pain experience. Limitations of the present study and possible future research directions are discussed.Perspective: The present study adds to a growing literature on prospective associations between catastrophizing and pain. These results provide initial evidence, in healthy individuals, that changes in catastrophizing may precede changes in pain response.

Actigraphy-Based Physical Activity Monitoring in Adolescents With Juvenile Primary Fibromyalgia Syndrome

2010-04-26

Abstract: Juvenile primary fibromyalgia syndrome (JPFS) is a chronic pain condition associated with significant impairment in physical functioning, but no studies have used newer technologies such as actigraphy to document objective physical activity levels in JPFS. This is the first study to objectively describe physical activity in JPFS patients and examine the relationship of pain, perceived functional impairment, and depressive symptoms on physical activity. One hundred four clinically referred adolescents with JPFS (ages 11 to 18 years) wore a hip-mounted actigraph for 1 week. Data on pain intensity, functional disability, depressive symptoms, and psychiatric diagnoses were obtained using self- and parent-report measures and a standardized psychiatric interview. Results showed that younger patients were more active. Pain intensity was not significantly associated with physical activity levels overall, but the most highly active group of adolescents reported lower levels of pain and disability than the least active. Parent report of adolescents' physical functioning and depressive symptoms were significantly correlated with adolescents' physical activity levels. Actigraphy provides a unique source of information about physical functioning which is distinct from adolescents' self-report of physical functioning in JPFS. Preliminary findings suggest that further study of factors that predict perceived and actual physical functioning in JPFS is warranted.Perspective: This study presents the results of physical activity monitoring in adolescents with JPFS using actigraphy. Results indicate that actigraphy provides a unique source of objective information that can advance our understanding of physical disability in JPFS and the factors associated with physical impairment.

Ginger (Zingiber officinale) Reduces Muscle Pain Caused by Eccentric Exercise

Christopher D. Black, Matthew P. Herring, David J. Hurley, Patrick J. O'Connor — 2010-04-26

Abstract: Ginger has been shown to exert anti-inflammatory effects in rodents, but its effect on human muscle pain is uncertain. Heat treatment of ginger has been suggested to enhance its hypoalgesic effects. The purpose of this study was to examine the effects of 11 days of raw (study 1) and heat-treated (study 2) ginger supplementation on muscle pain. Study 1 and 2 were identical double-blind, placebo controlled, randomized experiments with 34 and 40 volunteers, respectively. Participants consumed 2 grams of either raw (study 1) or heated (study 2) ginger or placebo for 11 consecutive days. Participants performed 18 eccentric actions of the elbow flexors to induce pain and inflammation. Pain intensity, perceived effort, plasma prostaglandin E2, arm volume, range-of-motion and isometric strength were assessed prior to and for 3 days after exercise. Results Raw (25%, –.78 SD, P = .041) and heat-treated (23%, –.57 SD, P = .049) ginger resulted in similar pain reductions 24 hours after eccentric exercise compared to placebo. Smaller effects were noted between both types of ginger and placebo on other measures. Daily supplementation with ginger reduced muscle pain caused by eccentric exercise, and this effect was not enhanced by heat treating the ginger.Perspective: This study demonstrates that daily consumption of raw and heat-treated ginger resulted in moderate-to-large reductions in muscle pain following exercise-induced muscle injury. Our findings agree with those showing hypoalgesic effects of ginger in osteoarthritis patients and further demonstrate ginger's effectiveness as a pain reliever.

High Levels of Vicarious Exposure Bias Pain Judgments

Kenneth M. Prkachin, Elizabete M. Rocha — 2010-03-15

Abstract: The present study evaluated the effects of exposure to facial expression of pain, on observers' perceptions of pain expression. Participants were undergraduates shown brief video clips of the facial expressions of shoulder-pain patients displaying no pain or moderate pain. Participants were randomly allocated to either a high preexposure condition in which each clip was preceded by 10 other clips showing strong pain or a no-exposure control. On each test trial, participants indicated whether they thought the person they saw was in pain or not. Data were analyzed using signal detection theory methods. High prior exposure to pain was unrelated to sensitivity to pain expression, but did significantly diminish the likelihood of judging the other to be in pain. Results are discussed in terms of their implications for pain judgments of health-care professionals, adaptation-level theory, and the psychophysical method of selective adaptation.Perspective: This paper provides an experimental demonstration that, when people have large amounts of exposure to others' expressions of pain, their estimation of others' pain is reduced. The findings offer 1 explanation for the widely observed underestimation bias in pain judgments and may suggest ways of changing it.

The Association of Single Nucleotide Polymorphisms in the Catechol-O-Methyltransferase Gene and Pain Scores in Female Patients With Major Depressive Disorder

Bonnie Fijal, Roy H. Perlis, Alexandra N. Heinloth, John P. Houston — 2010-06-07

Abstract: We tested the hypothesis that single nucleotide polymorphisms (SNPs) in the catechol-O-methyltransferase (COMT) gene are associated with baseline pain levels in patients with major depressive disorder (MDD). Pain levels were quantified using a visual analog scale (VAS) for pain. Data from 159 female and 93 male self-reported white patients with MDD were analyzed. The associations between a haplotype previously associated with pain sensitivity created using COMT SNPs rs6269, rs4633, rs4818, and rs4680, and the proportion of female patients with “Pain While Awake” and “Overall Pain” at baseline were statistically significant (P < .05). In male patients, no statistically significant associations between COMT haplotypes and baseline pain scores were seen. The rs165599 SNP, which has previously been associated with response of depressive symptoms to treatment in patients with MDD, did not impact baseline pain in either gender. In conclusion, baseline pain levels appear to be associated with the COMT pain sensitivity haplotype in female patients with MDD.Perspective: This article presents associations of the COMT pain sensitivity haplotype and baseline pain levels in female patients with MDD. This finding could potentially help clinicians who seek to assess how genetic polymorphisms may contribute to a patient's pain experience.

Erratum

2010-09-01

In the December 2008 issue of The Journal of Pain (Volume 9, Issue 12), Peter Dalton was inadvertently excluded from the list of authors for “Trends in funding for research on pain: a report on the National Institutes Of Health grant awards over the years 2003 to 2007,” in J Pain 9:1077-1087. Mr Dalton is from the University of Utah, Department of Anesthesiology, Salt Lake City, Utah, and the correct author list is as follows: David H. Bradshaw, Court Empy, Phillip Davis, David Lipschitz, Peter Dalton, Yoshio Nakamura, and C. Richard Chapman.

Masthead

2010-09-01

Editorial Board

2010-09-01

Instructions to Authors

2010-09-01

Submission Form

2010-09-01

The Journal of Pain

Opioid Pharmacotherapy for Chronic Non-Cancer Pain in the United States: A Research Guideline for Developing an Evidence-Base

Is Lack of Evidence the Problem?

Hiding in Plain Sight: A Case of Tarlov Perineural Cysts

Central Sensitization in the Trigeminal Nucleus Caudalis Produced by a Conjugate of Substance P and the A Subunit of Cholera Toxin

Hyperbaric Oxygen Treatment Induces a 2-Phase Antinociceptive Response of Unusually Long Duration in Mice

Pediatric Nurses' Cognitive Representations of Children's Pain

Spinal Cord Injuries Containing Asymmetrical Damage in the Ventrolateral Funiculus Is Associated With a Higher Incidence of At-Level Allodynia

Changes in Situation-Specific Pain Catastrophizing Precede Changes in Pain Report During Capsaicin Pain: A Cross-Lagged Panel Analysis Among Healthy, Pain-Free Participants

Actigraphy-Based Physical Activity Monitoring in Adolescents With Juvenile Primary Fibromyalgia Syndrome

Ginger (Zingiber officinale) Reduces Muscle Pain Caused by Eccentric Exercise

High Levels of Vicarious Exposure Bias Pain Judgments

The Association of Single Nucleotide Polymorphisms in the Catechol-O-Methyltransferase Gene and Pain Scores in Female Patients With Major Depressive Disorder

Erratum

Masthead

Editorial Board

Table of Contents

Instructions to Authors

Submission Form