Pain
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Dorsal root ganglion field stimulation (GFS) relieves evoked and spontaneous neuropathic pain by use-dependent blockade of impulse trains through the sensory neuron T-junction, which becomes complete within less than 1 minute for C-type units, also with partial blockade of Aδ units. We used this tool in the spinal nerve ligation (SNL) rat model to selectively block sensory neuron spontaneous activity (SA) of axotomized neurons at the fifth lumbar (L5) level vs blockade of units at the L4 level that remain uninjured but exposed to inflammation. In vivo dorsal root single-unit recordings after SNL showed increased SA in L5 units but not L4 units. ⋯ In addition, L5 GFS, but not L4 GFS, increased mechanical threshold of DH units during cutaneous mechanical stimulation, while L5 GFS exceeded L4 GFS in reducing evoked firing rates. Our results indicate that SA in injured neurons supports increased firing of DH wide-dynamic-range neurons, contributing to hyperalgesia, allodynia, and ongoing pain. Ganglion field stimulation analgesic effects after nerve injury are at least partly attributable to blocking propagation of this SA.
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This study investigated the association between COVID-related myalgia experienced by patients at hospital admission and the presence of post-COVID symptoms. A case-control study including patients hospitalised due to COVID-19 between February 20 and May 31, 2020, was conducted. Patients reporting myalgia and patients without myalgia at hospital admission were scheduled for a telephone interview 7 months after hospital discharge. ⋯ The presence of myalgia at hospital admission was associated with preexisting history of musculoskeletal pain (OR 1.62, 95% confidence interval 1.10-2.40). In conclusion, myalgia at the acute phase was associated with musculoskeletal pain as long-term post-COVID sequelae. In addition, half of the patients with preexisting pain conditions experienced a persistent exacerbation of their previous syndromes.
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Brain biomarkers of pain, including pain-predictive "signatures" based on brain activity, can provide measures of neurophysiological processes and potential targets for interventions. A central issue relates to the specificity of such measures, and understanding their current limits will both advance their development and explore potentially generalizable properties of pain to other states. Here, we used 2 data sets to test the neurologic pain signature (NPS), an established pain neuromarker. ⋯ Local NPS patterns in anterior or midinsula, S2, and dorsal anterior cingulate responded to breathlessness and finger opposition and were reduced by remifentanil. Local NPS responses in the dorsal posterior insula did not respond to any manipulations. Therefore, significant global NPS activity alone is not specific for pain, and we offer insight into the overlap between NPS responses, breathlessness, and somatomotor demand.
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Randomized Controlled Trial
Internet-delivered cognitive behavioral therapy for youth with functional abdominal pain: a randomized clinical trial testing differential efficacy by patient subgroup.
Inconsistent results of psychological treatments for pediatric functional abdominal pain (FAP) may be due to heterogeneity of patients' pain-related psychological characteristics. This randomized controlled trial tested whether statistically derived patient subgroups (high pain dysfunctional [HPD], high pain adaptive [HPA], and low pain adaptive [LPA]) moderated response to cognitive behavior therapy (CBT) for adolescents with FAP and their parents (n = 278 dyads; patients were 66% female, mean [SD] age was 14.62 [1.88] years, and parents were 95% female). Randomization to Internet-delivered CBT vs Internet-delivered pain education (EDU) was stratified by patient subgroup. ⋯ Furthermore, among all patients assigned to CBT, HPD youth demonstrated significantly greater reductions in GI symptoms compared with HPA and LPA youth and greater reductions in abdominal pain compared with LPA youth. All subgroups maintained symptom reductions throughout the follow-up period. Results suggest that subgrouping FAP patients may inform treatment allocation and optimize treatment response.
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Tricyclic antidepressants that inhibit serotonin and noradrenaline reuptake, such as amitriptyline, are among the first-line treatments for neuropathic pain, which is caused by a lesion or disease affecting the somatosensory nervous system. These treatments are, however, partially efficient to alleviate neuropathic pain symptoms, and better treatments are still highly required. Interactions between neurons and glial cells participate in neuropathic pain processes, and importantly, connexins-transmembrane proteins involved in cell-cell communication-contribute to these interactions. ⋯ Another connexin blocker, carbenoxolone, also improved amitriptyline action. Additional in vitro studies suggested that mefloquine may also directly act on serotonin transporters and on adenosine A1 and A2A receptors, but drugs acting on these other targets failed to amplify amitriptyline action. Together, our data indicate that pharmacological blockade of connexins potentiates the therapeutic effect of amitriptyline in neuropathic pain.