Pain
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Posttraumatic widespread pain (PTWP) and posttraumatic stress symptoms (PTSS) are frequent comorbid sequelae of trauma that occur at different rates in women and men. We sought to identify microRNA (miRNA) that may contribute to sex-dependent differences in vulnerability to these outcomes. Monte Carlo simulations (x10,000) identified miRNA in which predicted targeting of PTWP or PTSS genes was most enriched. ⋯ Furthermore, in support of increasing evidence indicating a role for the circadian rhythm (CR) in PTWP and PTSS pathogenesis, miR-19b targets were enriched in CR gene transcripts. Human cohort and in vitro analyses assessing miR-19b regulation of key CR transcripts, CLOCK and RORA, supported the potential importance of miR-19b to regulating the CR pathway. Together, these results highlight the potential role that sex-dependent expression of miR-19b might play in PTWP and PTSS development after trauma/stress exposure.
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Postamputation stump and phantom pain are highly prevalent but remain a difficult condition to treat. The underlying mechanisms are not fully clarified, but growing evidence suggests that changes in afferent nerves, including the formation of neuromas, play an important role. The main objective of this cross-sectional study was to investigate whether ultrasound-verified neuroma swellings are more frequent in amputees with postamputation pain than in amputees without pain (primary outcome). ⋯ No difference was found in stump pain intensity (P = 0.42) during the last week or in phantom pain intensity in the last month (P = 0.74) between amputees with and without swollen neuromas. Our findings suggest that it is not the presence of swollen neuromas itself that drives postamputation pain. However, changes in the transected nerve endings may still be crucial for driving postamputation pain because a positive Tinel sign was significantly more frequent in amputees with pain, irrespectively of the degree of neuroma swelling.
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Early life stress (ELS) can significantly influence biological pathways associated with nociception, increasing vulnerability to future heightened pain sensitivity and subsequent risk of pain events. However, very little human research has investigated the association of ELS, measured across multiple domains, with future pain sensitivity. Data from Gen1 and Gen2 of the Raine Study were used to assess the association between a wide range of early life stressors, including antenatally, and pressure and cold pain sensitivity at young adulthood. ⋯ More problematic behaviour at age 2 years was associated with less pressure pain sensitivity at 22 years (13.7 kPa, 95% CI: 1.0-27.0, P = 0.037), with no interaction between problematic behaviour and pain experience at 22 years. For those reporting a moderate/high pain experience at 22 years, poor family functioning increased the odds ratio for high cold pain sensitivity (3.0, 95% CI: 1.6-5.6), but for those reporting no/low pain experience, it did not (OR:1.2, 95% CI: 0.8-1.8). This study provides the most comprehensive investigation of the relationship between ELS and pressure and cold pain sensitivity in young adults supporting early life as a critical period of development influencing future nociceptive processing.
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Brain-derived neurotrophic factor (BDNF) and the high-affinity receptor tropomyosin receptor kinase B (TrkB) have important roles in neuronal survival and in spinal sensitization mechanisms associated with chronic pain. Recent clinical evidence also supports a peripheral role of BDNF in osteoarthritis (OA), with synovial expression of TrkB associated with higher OA pain. The aim of this study was to use clinical samples and animal models to explore the potential contribution of knee joint BDNF/TrkB signalling to chronic OA pain. ⋯ Intra-articular injection of BDNF augmented established OA pain behaviour in MIA rats, but had no effect in controls. Intra-articular injection of the TrkB-Fc chimera acutely reversed pain behaviour to a similar extent in both models of OA pain (weight-bearing asymmetry MIA: -11 ± 4%, MNX: -12 ± 4%), compared to vehicle treatment. Our data suggesting a contribution of peripheral knee joint BDNF/TrkB signalling in the maintenance of chronic OA joint pain support further investigation of the therapeutic potential of this target.