Pain
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Focal nerve injuries are often associated with neuropathic pain. Preclinical research suggests altered neuroimmune signalling underlies such neuropathic pain; however, its cause remains poorly understood in humans. In this multicentre cohort study, we describe the local cellular and molecular signature of neuropathic pain at the lesion site, using Morton's neuroma as a human model system of neuropathic pain (n = 22; 18 women) compared with nerves from participants without nerve injury (n = 11; 4 women). ⋯ Targeted immunofluorescent analyses confirmed higher densities of intraneural CD163+MARCO+ macrophage subsets in Morton's neuroma. Our findings provide detailed insight into the local molecular signature in the context of human focal nerve injury. There is clear evidence for an ongoing role of the immune system in chronic peripheral neuropathic pain in humans, with macrophages and specifically the M(GC) MARCO+ subset implicated.
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Traumatic orthopedic injuries are common and frequently associated with persistent pain, disability, and emotional distress. Risk factors of persistent pain and disability include pain catastrophizing and pain anxiety, though most interventions for orthopedic injuries are primarily biomedical (eg, surgeries, pharmacology, physiotherapy/exercise). The Toolkit for Optimal Recovery (TOR) is a brief, live video mind-body program designed to directly target pain catastrophizing and anxiety in patients with recent traumatic orthopedic injury to prevent persistent disability. ⋯ A multiple mediation analysis using multilevel structural equation modeling (MSEM) demonstrated that pain catastrophizing (b = -5.22, SE = 3.02, Bootstrapped 95% CIs = -0.04, -12.37) and pain anxiety (b = -8.45, SE = 3.59, Bootstrapped 95% CIs = -0.04, -12.37) each significantly mediated improvement in physical function. Overall, findings elucidate the mechanistic role of TOR's primary treatment targets (ie, reductions in pain catastrophizing and anxiety) in improving physical function. Findings highlight the importance of targeting pain catastrophizing and pain anxiety early after orthopedic injury through psychosocial interventions such as TOR.
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The perception of pain and ability to cope with it varies widely amongst people, which in part could be due to the presence of inhibitory (antinociceptive) or facilitatory (pronociceptive) effects in conditioned pain modulation (CPM). This study examined whether individual differences in CPM reflect functional connectivity (FC) strengths within nodes of the descending antinociceptive pathway (DAP). A heat-based CPM paradigm and resting-state functional magnetic resonance imaging (rs-fMRI) were used to test the hypothesis that an individual's capacity to exhibit inhibitory CPM (changes in test stimuli [TS] pain due to a conditioning stimulus [CS]) reflects FC of the subgenual anterior cingulate cortex (sgACC), periaqueductal gray (PAG), and rostral ventromedial medulla (RVM). ⋯ Furthermore, only the Antinociceptive subgroup exhibited a correlation of both left and right sgACC-RVM FC (medium effect sizes) with CPM effect magnitude. Women, compared with men were more likely to be categorized as pronociceptive. These data support the proposition that FC of the DAP reflects or contributes to inhibitory CPM.