Pain
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The basal ganglia modulate somatosensory pain pathways, but it is unclear whether a common circuit exists to mitigate hyperalgesia in pain states induced by peripheral nociceptive stimuli. As a key output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNr) may be a candidate for this role. To test this possibility, we optogenetically modulated SNr GABAergic neurons and examined pain thresholds in freely behaving male mice in inflammatory and neuropathic pain states as well as comorbid depression in chronic pain. ⋯ However, SNr modulation did not affect baseline pain thresholds. We also found that SNr-STN GABAergic projection was attenuated in pain states, resulting in disinhibition of STN neurons. Thus, impairment of the SNr-STN GABAergic circuit may be a common pathophysiology for the maintenance of hyperalgesia in both inflammatory and neuropathic pain states and the comorbid depression in chronic pain; compensating this circuit has potential to effectively treat pain related conditions.
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The interest and the rationale for meaningful engagement of patients as partners in clinical trials of pain treatments has been increasing. No specific guidance on patient engagement for pain research studies currently exists; thus, the goal of this narrative review was to provide a historical perspective and a current evaluation of the literature on engaging patients as partners in clinical studies in general and in pain-related studies more specifically. ⋯ We provided an overview on key practices of patient recruitment and engagement as partners in clinical research and highlighted the perceived benefits and challenges of such partnerships. We summarized factors that can facilitate or hinder meaningful patient engagement in clinical trials of pain treatments and outlined gaps that future research should address to optimize patient-centered clinical research.
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Following surgical repair after peripheral nerve injury, neuropathic pain diminishes in most patients but can persist in a small proportion of cases, the mechanism of which remains poorly understood. Based on the spared nerve injury (SNI), we developed a rat nerve repair (NR) model, where a delayed reconstruction of the SNI-injured nerves resulted in alleviating chronic pain-like behavior only in a subpopulation of rats. Multiple behavioral measures were assayed over 11-week presurgery and postsurgery periods (tactile allodynia, pain prick responses, sucrose preference, motor coordination, and cold allodynia) in SNI (n = 10), sham (n = 8), and NR (n = 12) rats. ⋯ By contrast, large brain functional connectivity differences were observed between NR groups, where corticolimbic reorganization paralleled with pain recovery (repeated-measures analysis of variance, false discovery rate, P < 0.05), and functional connectivity between accumbens and medial frontal cortex was related both to tactile allodynia (nociception) and to sucrose preference (anhedonia) in the NR group. Our study highlights the importance of brain circuitry in the reversal of neuropathic pain as a natural pain-relieving mechanism. Further studies regarding the therapeutic potentials of these processes are warranted.
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Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic condition in which mutations in the type VII collagen gene ( COL7A1 ) lead to decreased expression of this anchoring protein of the skin, causing the loss of stability at the dermo-epidermal junction. Most patients with RDEB experience neuropathic pain and itch due to the development of a small fibre neuropathy, characterised by decreased intraepidermal innervation and thermal hypoaesthesia. To understand the physiopathology of this neuropathy, we used a mouse model of RDEB (Col7a1 flNeo/flNeo ) and performed a detailed characterisation of the somatosensory system. ⋯ This axonal damage was not associated with inflammation of the dorsal root ganglion or central projection targets at the time of assessment. These results suggest that in RDEB, there is a distal degeneration of axons produced by exclusive damage of small fibres in the epidermis, and in contrast with traumatic and acute neuropathies, it does not induce sustained neuroinflammation. Thus, this animal model emphasizes the importance of a healthy cutaneous environment for maintenance of epidermal innervation and faithfully replicates the pathology in humans, offering the opportunity to use this model in the development of treatments for pain for patients with RDEB.
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Data are equivocal on the consequences of COVID-19 pandemic on pain and well-being for individuals with chronic pain. Furthermore, little is known regarding its impact on the health of young adults with chronic pain. We conducted a longitudinal study to compare pain, psychological functioning, and substance use before and during the pandemic of 196 young adults with chronic pain. ⋯ Mixed linear models revealed that COVID-19 exposure and impact were not associated with changes in pain intensity or interference, with female sex associated with increased pain intensity (β = 0.86, P = 0.02) and pain interference (β = 0.87, P = 0.02). Our findings indicated relative stability of pain symptoms experienced by young adults with chronic pain. However, the increases in anxiety highlight the need to facilitate treatment access for mental health services to mitigate downstream impact.