Pain
-
Brain structure, psychosocial, and physical factors underpin back pain conditions; however, less is known about how these factors differ based on pain duration and location. We examined, cross-sectionally, 11,106 individuals from the UK Biobank who (1) were pain-free (n = 5616), (2) had acute back pain (n = 1746), (3) had chronic localised back pain (CBP; n = 1872), or (4) had chronic back pain and additional chronic pain sites (CWP; n = 1872). We found differences in structural brain measures in the chronic pain groups alone. ⋯ Psychosocial factors and body mass index differed between all groups and affected those with widespread pain the most (all, P < 0.001), whereas grip strength was only compromised in individuals with widespread pain (-1.0 [-1.4, -0.5] kg, P < 0.001) compared with pain-free controls. Longitudinal research is necessary to confirm these interactions to determine the process of pain development in relation to assessed variables and covariates. However, our results suggest that categorised pain duration and the number of pain sites warrant consideration when assessing markers of brain structure, psychosocial, and physical health.
-
The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. ⋯ Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16-binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves. Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.
-
Top-down processes allow the selection and prioritization of information by limiting attentional capture by distractors, and these mechanisms depend on task demands such as working memory (WM) load. However, bottom-up processes give salient stimuli a stronger neuronal representation and provoke attentional capture. The aim of this study was to examine the effect of salient nociceptive stimuli on WM while manipulating task demands. ⋯ Moreover, compared with control stimuli, nociceptive stimuli abolished the increase in contralateral delay activity amplitude for set size 4 vs set size 2 (P = 0.04). Consistent with these results, laser-evoked potential amplitude was not decreased when task demands were high (P = 0.5). These findings indicate that WM may shield cognition from nociceptive stimuli, but nociceptive stimuli disrupt WM and alter task performance when cognitive resources become insufficient to process all task-relevant information.
-
Mutations in the alpha subunit of voltage-gated sodium channel 1.7 (NaV1.7), encoded by SCN9A gene, play an important role in the regulation of nociception and can lead to a wide range of clinical outcomes, ranging from extreme pain syndromes to congenital inability to experience pain. To expand the phenotypic and genotypic spectrum of SCN9A-related channelopathies, we describe the proband, a daughter born from consanguineous parents, who had pain insensitivity, diminished temperature sensation, foot burns, and severe loss of nociceptive nerve fibers in the epidermis. Next-generation sequencing of SCN9A (NM_002977.3) revealed a novel homozygous substitution (c.377+7T>G) in the donor splice site of intron 3. ⋯ A functional study on proband RNA showed different aberrant transcripts, where exon 3 was missing and an intron fragment was included. A quantification study using real-time polymerase chain reaction showed a significant reduction of the NaV1.7 canonical transcript. Collectively, these data widen the spectrum of SCN9A-related insensitivity to pain by describing a mutation causing NaV1.7 deficiency, underlying the nociceptor dysfunction, and highlight the importance of molecular investigation of U12 introns' mutations despite the silent prediction.
-
Neuropathic pain is a common condition experienced by older adults. Prevalence estimates of neuropathic pain and descriptive data of pharmacologic management among nursing home residents are unavailable. We estimated the prevalence of neuropathic pain diagnoses and described the use of pain medications among nursing home residents with possible neuropathic pain. ⋯ Resident characteristics associated with lack of medications included advanced age, dependency in activities of daily living, cognitive impairment, and diagnoses of comorbid conditions. A diagnosis of neuropathic pain is common among nursing home residents, yet many lack pharmacologic treatment for their pain. Future epidemiologic studies can help develop a more standard approach to identifying and managing neuropathic pain among nursing home residents.