The journal of pain : official journal of the American Pain Society
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The facet joint is a common source of pain, especially from mechanical injury. Although chronic pain is associated with altered spinal glial and neuronal responses, the contribution of specific spinal cells to joint pain is not understood. This study used the neurotoxin [Sar(9),Met(O2)(11)]-substance P-saporin (SSP-SAP) to selectively eliminate spinal cells expressing neurokinin-1 receptor (NK1R) in a rat model of painful facet joint injury to determine the role of those spinal neurons in pain from facet injury. Following spinal administration of SSP-SAP or its control (blank-SAP), a cervical facet injury was imposed and behavioral sensitivity was assessed. Spinal extracellular recordings were made on day 7 to classify neurons and quantify evoked firing. Spinal glial activation and interleukin 1αα (IL1α) expression also were evaluated. SSP-SAP prevented the development of mechanical hyperalgesia that is induced by joint injury and reduced NK1R expression and mechanically evoked neuronal firing in the dorsal horn. SSP-SAP also prevented a shift toward wide dynamic range neurons that is seen after injury. Spinal astrocytic activation and interleukin 1α (IL1α) expression were reduced to sham levels with SSP-SAP treatment. These results suggest that spinal NK1R-bearing cells are critical in initiating spinal nociception and inflammation associated with a painful mechanical joint injury. ⋯ Results demonstrate that cells expressing NK1R in the spinal cord are critical for the development of joint pain, spinal neuroplasticity, and inflammation after trauma to the joint. These findings have utility for understanding mechanisms of joint pain and developing potential targets to treat pain.
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Previous research describes an inconsistent relation between temporal changes in transversus abdominis or lumbar multifidus and temporal changes in clinical outcomes. Unfortunately, a relevant systematic review is unavailable. As a result, this systematic review was designed to summarize evidence regarding the association between temporal changes in muscle morphometry and activity in response to treatment, and temporal changes in clinical outcomes. Candidate publications were identified from 6 electronic databases. Fifteen articles were included after scrutinization by 2 reviewers using predetermined selection criteria. The methodological quality of these articles was appraised using a standard tool. These methods revealed strong evidence that temporal alterations in transversus abdominis thickness change during contraction (as measured by B-mode or M-mode ultrasound) or feedforward activation of transversus abdominis (assessed via electromyography, tissue Doppler imaging, or M-mode ultrasound) were unrelated to temporal changes in low back pain (LBP)/LBP-related disability. There was limited evidence that temporal changes in transversus abdominis lateral sliding or lumbar multifidus endurance were unrelated to temporal changes in LBP intensity. Conflicting evidence was found for the relation between temporal changes in lumbar multifidus morphometry and temporal changes in LBP/LBP-related disability. This review highlights that temporal changes in transversus abdominis features tend to be unrelated to the corresponding LBP/LBP-related disability improvements, whereas the relation between multifidus changes and clinical improvements remains uncertain. ⋯ This systematic review highlighted that changes in morphometry or activation of transversus abdominis following conservative treatments tend not to be associated with the corresponding changes in clinical outcomes. The relation between posttreatment changes in characteristics of lumbar multifidus and clinical improvements remains uncertain.
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The purpose of this study was to investigate possible racial differences in opioid prescriptions among primary care patients with chronic noncancer pain receiving care in the Veterans Affairs health care system. This was a retrospective cohort study of 99,903 veterans with diagnoses of low back, neck, or joint pain selected to participate in the Veterans Affairs Survey of the Healthcare Experiences of Patients in fiscal year 2006. The outcome was prescription of opioids in the year following the first pain diagnosis, obtained through electronic medical record data. Analyses incorporated fixed effects for race, most recent pain intensity rating, new or established primary care patient status, and an interaction between race and most recent pain intensity rating, together with random effects for health care facility and race within facility. The association between patient race and prescription of opioids was moderated by baseline level of pain intensity scores (assessed on a 0-10 scale) and patient age. Among patients under 65 years of age, blacks with moderate (4-6) or high (7-10) levels of pain were less likely to receive opioids than whites (P = .0025, P = .0011); however, there were no significant differences between black and white patients with low levels of pain intensity (1-3) and those with pain intensity ratings of 0 (no pain). Among patients 65 and older with pain intensity ratings of zero, blacks were more likely than whites to receive opioid prescriptions (P = .0087), but there were no significant racial differences in opioid prescriptions in those with low to high levels of pain. ⋯ Among veterans under age 65 reporting moderate to high levels of chronic noncancer pain, blacks were less likely to be prescribed opioids than whites, even after controlling for clinical and system-level factors. Results underscore the challenges of eliminating racial differences in pain treatment, despite comprehensive systemwide improvement initiatives.
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Central neuropathic pain (CNP) is a debilitating consequence of central nervous system damage for which current treatments are ineffective. To explore mechanisms underlying CNP, we developed a rat model involving T13/L1 dorsal root avulsion. The resultant dorsal horn damage creates bilateral below-level (L4-L6) mechanical allodynia. This allodynia, termed spinal neuropathic avulsion pain, occurs in the absence of confounding paralysis. To characterize this model, we undertook a series of studies aimed at defining whether spinal neuropathic avulsion pain could be reversed by any of 3 putative glial activation inhibitors, each with distinct mechanisms of action. Indeed, the phosphodiesterase inhibitor propentofylline, the macrophage migration inhibitory factor inhibitor ibudilast, and the toll-like receptor 4 antagonist (+)-naltrexone each reversed below-level allodynia bilaterally. Strikingly, none of these impacted spinal neuropathic avulsion pain upon first administration but required 1 to 2 weeks of daily administration before pain reversal was obtained. Given reversal of CNP by each of these glial modulatory agents, these results suggest that glia contribute to the maintenance of such pain and enduring release of macrophage migration inhibitory factor and endogenous agonists of toll-like receptor 4 is important for sustaining CNP. The markedly delayed efficacy of all 3 glial modulatory drugs may prove instructive for interpretation of apparent drug failures after shorter dosing regimens. ⋯ CNP that develops after trauma is often described by patients as severe and intolerable. Unfortunately, current treatments are not effective. This work suggests that using pharmacologic treatments that target glial cells could be an effective clinical treatment for CNP.
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The number of deaths associated with methadone use increased dramatically in parallel with marked increases in its use, particularly for treatment of chronic pain. To develop a clinical guideline on methadone prescribing to reduce potential harms, the American Pain Society commissioned a review of various aspects related to methadone safety. This article summarizes evidence related to unintentional overdose due to methadone and harms related to cardiac arrhythmia potential. We searched Ovid MEDLINE, the Cochrane Library, and PsycINFO databases through January 2014 for studies assessing harms associated with methadone use; we judged 70 studies to be relevant and to meet inclusion criteria. The majority of studies on overdose and cardiac arrhythmia risk are observational and provide weak evidence on which to base clinical guidelines. In patients prescribed methadone for treatment of opioid dependence, data suggest that mortality benefits related to reduction in illicit drug use outweigh harms. Despite epidemiologic data showing marked increases in the numbers of methadone-related deaths that have been primarily attributed to increased use of methadone for chronic pain, evidence on methadone and mortality risk in this population has been somewhat contradictory. There is some evidence that recent initiation of methadone, psychiatric admissions, and concomitant use of benzodiazepines are associated with a higher risk for overdose. Evidence on cardiac risks is primarily limited to case reports of torsades de pointes, primarily in patients on high doses of methadone, and to studies showing an association between methadone use and prolongation of QTc intervals. Research is needed to understand the effectiveness of dosing methods, electrocardiogram monitoring, and other risk mitigation strategies in patients prescribed methadone. ⋯ This systematic review synthesizes the evidence related to methadone use and risk for overdose and cardiac arrhythmia. Findings regarding the association between methadone use and QTc interval prolongation and risk factors for methadone-associated overdose suggest potential targets for risk mitigation strategies, though research is needed to determine the effectiveness of such strategies at reducing adverse outcomes.