The journal of pain : official journal of the American Pain Society
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Incongruence of pain severity ratings among people experiencing pain and their observers has been linked to psychological distress. Previous studies have measured pain rating congruence through static self-report, involving a single rating of pain; however, this method does not capture changes in ratings over time. The present study examined the extent to which partners were congruent on multiple ratings of a participants' pain severity during the cold pressor task. ⋯ On average, observers rated participants' pain as less severe than participants' rated their own pain. In addition, congruence between partners increased over time because of observers' ratings becoming more similar to participant's ratings. Finally, pain catastrophizing and perceived threat independently and jointly influenced the degree to which partners similarly rated the participant's pain.
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We have recently shown that spinal sigma-1 receptor (Sig-1R) activation facilitates nociception via an increase in phosphorylation of the N-methyl-D-aspartate (NMDA) receptor GluN1 subunit (pGluN1). The present study was designed to examine whether the Sig-1R-induced facilitative effect on NMDA-induced nociception is mediated by D-serine, and whether D-serine modulates spinal pGluN1 expression and the development of neuropathic pain after chronic constriction injury (CCI) of the sciatic nerve. Intrathecal administration of the D-serine degrading enzyme, D-amino acid oxidase attenuated the facilitation of NMDA-induced nociception induced by the Sig-1R agonist, 2-(4-morpholinethyl)1-phenylcyclohexane carboxylate. Exogenous D-serine increased protein kinase C (PKC)-dependent (Ser896) pGluN1 expression and facilitated NMDA-induced nociception, which was attenuated by preteatment with the PKC inhibitor, chelerythrine. In CCI mice, administration of the serine racemase inhibitor, L-serine O-sulfate potassium salt or D-amino acid oxidase on postoperative days 0 to 3 suppressed CCI-induced mechanical allodynia (MA) and pGluN1 expression on day 3 after CCI surgery. Intrathecal administration of D-serine restored MA as well as the GluN1 phosphorylation on day 3 after surgery that was suppressed by the Sig-1R antagonist, N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide or the astrocyte inhibitor, fluorocitrate. In contrast, D-serine had no effect on CCI-induced thermal hyperalgesia or GluN1 expression. These results indicate that spinal D-serine: 1) mediates the facilitative effect of Sig-1R on NMDA-induced nociception, 2) modulates PKC-dependent pGluN1 expression, and 3) ultimately contributes to the induction of MA after peripheral nerve injury. ⋯ This report shows that reducing D-serine suppresses central sensitization and significantly alleviates peripheral nerve injury-induced chronic neuropathic pain and that this process is modulated by spinal Sig-1Rs. This preclinical evidence provides a strong rationale for using D-serine antagonists to treat peripheral nerve injury-induced neuropathy.
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Multicenter Study
Higher Prescription Opioid Dose is associated with Worse Patient-Reported Pain Outcomes and More Health Care Utilization.
Some previous research has examined pain-related variables on the basis of prescription opioid dose, but data from studies involving patient-reported outcomes have been limited. This study examined the relationships between prescription opioid dose and self-reported pain intensity, function, quality of life, and mental health. Participants were recruited from 2 large integrated health systems, Kaiser Permanente Northwest (n = 331) and VA Portland Health Care System (n = 186). ⋯ A statistically significant trend emerged where higher prescription opioid dose was associated with moderately sized effects including greater pain intensity, more impairments in functioning and quality of life, poorer self-efficacy for managing pain, greater fear avoidance, and more health care utilization. Rates of potential alcohol and substance use disorders also differed among groups. Findings from this evaluation reveal significant differences in pain-related and substance-related factors on the basis of prescription opioid dose.
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The nature of the transition from acute to chronic pain still eludes explanation, but chronic pain resulting from surgery provides a natural experiment that invites clinical epidemiological investigation and basic scientific inquiry into the mechanisms of this transition. The primary purpose of this article is to review current knowledge and hypotheses on the transition from acute to persistent postsurgical pain, summarizing literature on clinical epidemiological studies of persistent postsurgical pain development, as well as basic neurophysiological studies targeting mechanisms in the periphery, spinal cord, and brain. The second purpose of this article is to integrate theory, information, and causal reasoning in these areas. ⋯ These propose that chronic pain results from: 1) persistent noxious signaling in the periphery; 2) enduring maladaptive neuroplastic changes at the spinal dorsal horn and/or higher central nervous system structures reflecting a multiplicity of factors, including peripherally released neurotrophic factors and interactions between neurons and microglia; 3) compromised inhibitory modulation of noxious signaling in medullary-spinal pathways; 4) descending facilitatory modulation; and 5) maladaptive brain remodeling in function, structure, and connectivity. The third purpose of this article is to identify barriers to progress and review opportunities for advancing the field. This review reveals a need for a concerted, strategic effort toward integrating clinical epidemiology, basic science research, and current theory about pain mechanisms to hasten progress toward understanding, managing, and preventing persistent postsurgical pain.
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We explored causal mediation of sleep quality and perceived stress in development of painful temporomandibular disorder (TMD). Sleep quality and perceived stress were assessed at baseline and quarterly intervals thereafter in 2,737 initially TMD-free adults in the Orofacial Pain Prospective Evaluation and Risk Assessment study (OPPERA) prospective cohort study. During follow-up, incident TMD cases were classified using research diagnostic criteria. Mediation analysis was conducted using a weighted Cox proportional hazards regression model that estimated hazard ratios (HRs) and 95% confidence limits (CL) of first-onset TMD. Models determined whether: 1) poor sleep quality during follow-up mediated the effect of baseline perceived stress on first-onset TMD, and 2) perceived stress during follow-up mediated the effect of baseline poor sleep quality on first-onset TMD. In both analyses, the total effect was decomposed into natural direct and indirect effects. Poor baseline sleep quality led to heightened perceived stress that then contributed to TMD development. When the total effect of poor sleep quality (HR = 2.10, CL = 1.76, 2.50) was decomposed, 34% of its effect was mediated by perceived stress (indirect effect HR = 1.29, CL = 1.06, 1.58). The effect of perceived stress on first-onset TMD was not mediated by sleep quality. Improving sleep may avert escalation of stress, limiting effects of both factors on TMD development. ⋯ Causal mediation analysis highlights mechanisms by which poor sleep quality promotes development of TMD. First, poor sleep quality exerts a direct effect on pain. Second, it triggers a heightened perception of stress, which acts as an intermediate factor in the causal pathway between poor sleep quality and first-onset TMD pain.