Pain
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Chronic pain is the most commonly reported physical symptomology of cerebral palsy (CP) and spina bifida (SB) throughout the lifespan, and yet, pain is perhaps the least understood comorbidity in these populations. The objective of this study was to compare the prevalence and types of pain diagnosed among adults living with and without CP or SB. In this retrospective cohort study, we analyzed data from a nationwide commercial insurance claims database. ⋯ We found that adults living with CP or SB had a higher prevalence of any pain disorders (55.9% vs 35.2%), nociceptive pain (44.0% vs 26.7%), nociplastic pain (26.1% vs 11.9%), neuropathic pain (9.6% vs 5.6%), and pain multimorbidity (21.1% vs 8.4%), as compared to adults without CP or SB, and differences were to a clinically meaningful extent. Adjusted odds ratios of nociceptive pain (odds ratio [OR]: 2.20; 95% confidence interval [CI]: 2.15-2.24), nociplastic pain (OR: 2.47; 95% CI: 2.41-2.53), neuropathic pain (OR: 2.71; 95% CI: 2.54-2.89), and other pain (OR: 3.92; 95% CI: 3.67-4.19) were significantly higher for adults living with CP or SB. In conclusion, adults with CP or SB have a significantly higher prevalence and odds of common peripheral, central, and neuropathic pain disorders and pain multimorbidity, as compared to adults without CP or SB.
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Randomized Controlled Trial
An implantable restorative-neurostimulator for refractory mechanical chronic low back pain: a randomized sham-controlled clinical trial.
Chronic low back pain can be caused by impaired control and degeneration of the multifidus muscles and consequent functional instability of the lumbar spine. Available treatment options have limited effectiveness and prognosis is unfavorable. We conducted an international randomized, double-blind, sham-controlled trial at 26 multidisciplinary centers to determine safety and efficacy of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms (clinicaltrials.gov identifier: NCT02577354). ⋯ Prespecified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related adverse events (3.9%) compared favorably with other neuromodulation therapies for chronic pain.
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Migraine is one of the most common neurological disorders characterized by recurrent attacks of typically throbbing and unilateral headaches, affecting up to 20% of the population worldwide. Despite the high prevalence and severity of this primary headache disorder, it remains to be a challenge to fully understand and treat migraine headaches. By characterizing and validating a mouse migraine model, this study aimed to investigate the functional contribution of protein kinase C (PKC) isoforms in migraine. ⋯ In response to repeated administration of NTG, ongoing spontaneous pain was not developed in mice lacking the specific PKC isoform. This study identified the presence of ongoing pain in mice treated with NTG, a known human migraine trigger that closely resembles the common manifestation of spontaneous migraine attacks in humans. These findings demonstrated a critical regulatory role of PKCδ in migraine pathophysiology, which may offer new pharmacological targets for antimigraine treatment.
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Damage to thinly myelinated and unmyelinated nerve fibers causes small fiber pathology, which is increasingly found in pain syndromes such as small fiber neuropathy (SFN) and fibromyalgia syndrome (FMS). The peripheral nerve endings of the small nerve fibers terminate within the epidermis, where they are surrounded by keratinocytes that may act as primary nociceptive transducers. We performed RNA sequencing of keratinocytes obtained from patients with SFN, FMS, and healthy controls. ⋯ Further analysis revealed enriched inflammatory pathways. Validation of selected candidates in an independent cohort confirmed higher expression of the proinflammatory mediators interleukin-8, C-X-C motif chemokine 3, endothelin receptor type A, and the voltage-gated sodium channel 1.7 in SFN compared with patients with FMS. We provide a diverse keratinocyte transcriptome signature between patients with SFN and patients with FMS, which may hint toward distinct pathomechanisms of small fiber sensitization in both entities and lay the basis for advanced diagnostics.