Pain
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A well-recognized molecular entity involved in pain-related neuroplasticity is the N-methyl-D-aspartate receptor (NMDAR), which is crucial for developing chronic pain. Likewise, the pannexin 1 (Panx1) channel has been described as necessary for initiating and maintaining neuropathic pain, driving nociceptive signals dependent on spinal NMDAR through several possible mechanisms. Through behavioral, pharmacological, and molecular approaches, our study in male rats has revealed several key findings: (1) neurons located in spinal cord laminae I and II express functional Panx1 channels in both neuropathic and sham rats. ⋯ Notably, while 10Panx successfully alleviates hyperalgesia, it does not alter pSrc expression; and (4) NMDA-stimulated YOPRO-1 uptake in neurons of laminae I-II of spinal cord slices were prevented by the NMDAR antagonist D-AP5, the Src inhibitor PP2 (but not PP3), as well as with the 10Panx and carbenoxolone. Therefore, NMDAR activation in dorsal horn neurons triggers an NMDAR-Src-Panx1 signaling pathway, where Panx1 acts as an enhancing effector in neuropathic pain. This implies that disrupting the NMDAR-Panx1 communication (eg, through Src inhibitors and/or Panx1 blockers) may offer a valuable strategy for managing some forms of chronic pain.
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The spread of pain across body locations remains poorly understood but may provide important insights into the encoding of sensory features of noxious stimuli by populations of neurons. In this psychophysical experiment, we hypothesized that more intense noxious stimuli would lead to spread of pain, but more intense light stimuli would not produce perceptual radiation. Fifty healthy volunteers (27 females, 23 males, ages 14-44 years) participated in this study wherein noxious stimuli (43, 45, 47, and 49°C) were applied to glabrous (hand) and hairy skin (forearm) skin with 5-second and 10-second durations. ⋯ Pain radiation was more pronounced in hairy than glabrous skin (P < 0.05) and was more pronounced with longer stimulus duration (P < 0.001). Pain intensity explained only 14% of the pain radiation variability. The relative independence of the pain radiation from pain intensity indicates that distinct components of population coding mechanisms may be involved in the spatial representation of pain vs intensity coding.
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The urocortin 1 (UCN1)-expressing centrally projecting Edinger-Westphal (EWcp) nucleus is influenced by circadian rhythms, hormones, stress, and pain, all known migraine triggers. Our study investigated EWcp's potential involvement in migraine. Using RNAscope in situ hybridization and immunostaining, we examined the expression of calcitonin gene-related peptide (CGRP) receptor components in both mouse and human EWcp and dorsal raphe nucleus (DRN). ⋯ Targeted ablation of EWcp/UCN1 neurons induced hyperalgesia. A positive functional connectivity between EW and STN as well as DRN has been identified by functional magnetic resonance imaging. The presented data strongly suggest the regulatory role of EWcp/UCN1 neurons in migraine through the STN and DRN with high translational value.
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Data were obtained from the Global Burden of Disease study 2019. Joinpoint regression model was used to analyze the temporal trends from 1990 to 2019 of neck pain burden, focusing on age-standardized incidence rates, age-standardized prevalence rates, and age-standardized years lived with disability (YLDs) rates at the global, regional, and national levels. The age-period-cohort analysis was used to estimate the effects of age (5-99 years), period (1990-2019), and cohort (1893-2012) at the global, regional, and national levels. ⋯ Compared with 2019, the incident cases, prevalent cases, and YLDs counts of neck pain were projected to increase by 134%, 142%, and 140% by 2044. The global burden of neck pain has persisted at a relatively elevated level from 1990 to 2019, with projections indicating a continuing upward trend. Future research is urgently needed to better understand the predictors and clinical course of neck pain and to enhance prevention and management strategies.
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Pain-related motor adaptations may be enacted predictively at the mere threat of pain, before pain occurrence. Yet, in humans, the neurophysiological mechanisms underlying motor adaptations in anticipation of pain remain poorly understood. We tracked the evolution of changes in corticospinal excitability (CSE) as healthy adults learned to anticipate the occurrence of lateralized, muscle-specific pain to the upper limb. ⋯ Finally, stronger corticospinal inhibition correlated with greater trait anxiety. These results advance the mechanistic understanding of pain processes showing that pain-related motor adaptations are enacted at the mere threat of pain, as sets of anticipatory, topographically organized motor changes that are associated with the expected pain and are shaped by individual anxiety levels. Including such anticipatory motor changes into models of pain may lead to new treatments for pain-related disorders.