The journal of pain : official journal of the American Pain Society
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Both pain and mental health conditions are common among young people. They often co-occur, but we wanted to investigate further whether it is pain (abdominal pain, headache, musculoskeletal pain, menstrual pain) that precedes mental health conditions (depression, anxiety, stress, phobia) or whether it is the other way around, mental health conditions that precede pain. Using electronic health records-the Skåne Healthcare Register-we identified and followed young people aged 7 to 18 over a 13-year period and tracked all their registered diagnoses. ⋯ Compared to boys, girls had consistently higher estimates, and the same was found for the younger individuals compared to the older ones. Individuals with pain have a 3-fold increased risk of developing mental health conditions, while the risk of developing pain after mental health conditions was lower although still elevated compared to young people seeking care regardless of cause. PERSPECTIVE: Young people with pain have a 3-fold increased risk of developing mental health conditions, while the reverse risk is lower but still elevated compared to young people without these conditions. Health care professionals must recognize the interplay between pain and mental health in young patients when diagnosing and planning treatment.
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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.