The journal of pain : official journal of the American Pain Society
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This study examines the influence of body mass index (BMI) on the relationship between quantitative sensory testing measures and clinical characteristics in fibromyalgia syndrome (FMS). Utilizing BMI as a categorical covariate (≥25 or ≥30 kg/m²) in associations between quantitative sensory testing metrics (pain-60, conditioned pain modulation, and temporal summation of pain [TSP]) and FMS clinical features, we explored BMI's role as both a confounder (change-in-estimate criterion-change equal or higher than 10%) and effect modifier (interaction term). Significant interactions revealed overweight/obese BMI as a modifier in the relationship between conditioned pain modification and both depression and symptom impact, with a homeostatic relationship between better clinical profile and pain inhibitory response observed solely in the normal-weight group. ⋯ We discuss the mechanistic and therapeutic implications of targeting BMI in FMS clinical trials and the potential impact of this important relationship. PERSPECTIVE: This investigation highlights the disruptive influence of high BMI on pain inhibitory control in fibromyalgia, unbalancing clinical symptoms such as pain and depression. It underscores the necessity of integrating BMI considerations into therapeutic approaches to enhance pain management and patient outcomes.
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Thalamic pain can be understood as a network reorganization disorder. This study aimed to investigate functional connectivity (FC) in human patients and a macaque model of thalamic pain. In humans, resting-state FC was compared between patients with thalamic pain and healthy individuals. ⋯ Therefore, the present results suggest that the FC changes in the regions associated with emotion, memory, motivation, and reward are part of the underlying mechanisms of thalamic pain onset present in both human patients and model macaques. This cross-species convergence provides new insights into the neurological mechanisms underlying thalamic pain, paving the way for further studies and the development of therapeutic strategies. PERSPECTIVE: This article presents that the FC changes in the regions associated with emotion, motivation, and reward are part of the underlying mechanisms of thalamic pain in humans and macaques.
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Altered nociception, a key feature of nociplastic pain, often involves central sensitization. We previously found that central sensitization underlying a nociplastic pain state in female mice depends on the ongoing activity of TRPA1 agonist-responsive afferents. Here, we investigated how the activity of these afferents induces and maintains central sensitization at the spinal level. ⋯ These results suggest that the activity of TRPA1 agonist-responsive afferents induces and maintains central sensitization by activating dorsal horn SSTn and suppressing GABAn via SST2A-R, resulting in altered nociception that manifests as mechanical hypersensitivity. PERSPECTIVE: This article presents experimental evidence that TRPA1 agonist-responsive afferents induce and maintain central sensitization at the spinal level by activating SST-expressing excitatory interneurons and suppressing GABAergic inhibitory interneurons via SST2A-R. Spinal SST2A-R may represent a promising target for treating mechanical pain hypersensitivity due to central sensitization by TRPA1 agonist-responsive afferents.
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Osteoarthritis (OA) represents a significant pain challenge globally, as current treatments are limited and come with substantial and adverse side effects. Voltage-gated calcium channels have proved to be pharmacologically effective targets, with multiple Food and Drug Administration-approved CaV2.2 modulators available for the treatment of pain. Although effective, drugs targeting CaV2.2 are complicated by the same obstacles facing other pain therapeutics-invasive routes of administration, narrow therapeutic windows, side effects, and addiction potential. ⋯ Together, these studies suggest that CBD3063 is an effective analgesic for OA pain. PERSPECTIVE: Despite the high prevalence of OA pain worldwide, current treatment options remain limited. We demonstrate that CBD3063-mediated disruption of the CaV2.2-collapsin response mediator protein 2 interaction alleviates pain in a preclinical joint pain model, providing a promising basis for the development of new OA pain treatments.