Pain
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Randomized Controlled Trial
Are endogenous opioid mechanisms involved in the effects of aerobic exercise training on chronic low back pain?: a randomized controlled trial.
Aerobic exercise is believed to be an effective chronic low back pain (CLBP) intervention, although its mechanisms remain largely untested. This study evaluated whether endogenous opioid (EO) mechanisms contributed to the analgesic effects of an aerobic exercise intervention for CLBP. Individuals with CLBP were randomized to a 6-week, 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 44). ⋯ Enhanced EO analgesia (MPQ-Total) was associated with a significantly greater improvement in average chronic pain intensity (P = 0.009). Aerobic exercise training in the absence of other interventions appears effective for CLBP management. Aerobic exercise-related enhancements in endogenous pain inhibition, in part EO-related, likely contribute to these benefits.
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Randomized Controlled Trial
A digital health psychological intervention (WebMAP Mobile) for children and adolescents with chronic pain: results of a hybrid effectiveness-implementation stepped wedge cluster randomized trial.
Although psychological treatments benefit youth with chronic pain, treatment is not accessible in most communities. Digital health interventions offer promise for expanding access and reach to this population. Using a stepped-wedge cluster randomized trial design, we evaluated effectiveness and implementation of a digital health delivered psychological intervention for pediatric chronic pain. ⋯ Greater engagement (number of completed modules) was associated with significantly greater reductions in pain and disability from pre-treatment to follow-up (d's = -0.57 and -0.38, P < 0.05). Parents, youth, and providers found treatment acceptable; providers had positive attitudes and demonstrated referrals over a maintenance period. Further research is needed to understand how to enhance treatment engagement with digital health interventions and optimize implementation.
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The chronification of pain can be attributed to changes in membrane receptors and channels underlying neuronal plasticity and signal transduction largely within nociceptive neurons that initiate and maintain pathological pain states. These proteins are subject to dynamic modification by posttranslational modifications, creating a code that controls protein function in time and space. Phosphorylation is an important posttranslational modification that affects ∼30% of proteins in vivo. ⋯ This narrative review discusses the molecular mechanisms of Cdk5-mediated regulation of target proteins involved in neuropathic pain. We focus on Cdk5 substrates that have been linked to nociceptive pathways, including channels (eg, transient receptor potential cation channel and voltage-gated calcium channel), proteins involved in neurotransmitter release (eg, synaptophysin and collapsin response mediator protein 2), and receptors (eg, glutamate, purinergic, and opioid). By altering the phosphoregulatory "set point" of proteins involved in pain signaling, Cdk5 thus appears to be an attractive target for treating neuropathic pain conditions.
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Chronic posttraumatic headache (PTH) is among the most common and disabling sequelae of traumatic brain injury (TBI). Current PTH treatments are often only partially effective and have problematic side effects. We previously showed in a small randomized trial of patients with chronic nontraumatic headaches that manipulation of dietary fatty acids decreased headache frequency, severity, and pain medication use. ⋯ Statistical analyses assessed the association of oxylipins with headache severity (primary outcome, measured by headache question on NSI) as well as associations between oxylipins and total NSI or satisfaction with life survey scores. Among oxylipins, 4-hydroxy-DHA and 19,20-epoxy-docosapentaenoate (DHA derivatives) were inversely associated with headache severity, and 11-hydroxy-9-epoxy-octadecenoate (a linoleic acid derivative) was positively associated with headache severity. These findings support a potential for DHA-derived oxylipins as prognostic biomarkers for development of chronic PTH.
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Offset analgesia identifies impaired endogenous pain modulation in pediatric chronic pain disorders.
Offset analgesia (OA), a psychophysical test of endogenous pain inhibition, is diminished in many adult chronic pain disorders but OA has not been investigated in youth with chronic pain disorders. This study assessed OA responses in 30 youth with chronic primary and secondary pain disorders and 32 healthy controls. The OA, control, and constant thermal tests were evoked with an individualized noxious heat stimulus of approximately 50/100 mm on a visual analogue scale followed by 1°C offset temperature. ⋯ Central Sensitization Inventory scores showed excellent predictive accuracy in differentiating patients from controls (area under the curve = 0.95; 95% CI: 0.91-0.99) and CSI score ≥30 was identified as an optimal cutoff value. Pain Sensitivity Questionnaire scores did not differentiate patients from controls nor correlate with OA. In this study, 60% of youth with chronic pain showed reduced capacity for endogenous pain inhibition.