Articles: neuropathic-pain.
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Studies have demonstrated that the cerebrospinal fluid-contacting nucleus (CSF-CN) is involved in neuropathic pain, but the underlying molecular mechanisms still largely remain obscure. Emerging evidence suggests that spinal Wnt5a plays a crucial role in regulation of chronic pain. However, little is known about the potential role of the supraspinal Wnt5a in the development of chronic pain. ⋯ In the present study, we demonstrated that Wnt5a is distributed in the CSF-CN and the Wnt5a protein was up-regulated by nerve injury-induced nociceptive stimuli. Furthermore, lateral intracerebroventricular injection of Wnt5a antagonist Box5 attenuated the chronic constriction injury (CCI)-induced neuropathic pain and down-regulated the expression of Wnt5a in the CSF-CN. These data extend our understanding of the role of Wnt5a in supraspinal site and demonstrate that the CSF-CN participates in nerve injury-induced neuropathic pain via the regulation of Wnt5a.
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Interactions of opioid receptors with other receptor families can be made use of to improve analgesia and reduce adverse effects of opioid analgesics. We investigated interactions of the α2-adrenergic receptor (α2AR) with opioid receptors of the mu (MOR) and delta (DOR) types in the spinal dorsal horn in an animal model of neuropathic pain induced by spinal nerve ligation. Nine days after nerve injury, immunoreactivity for the α2AR subtype A (α2AAR) was increased both in tissue homogenates and at pre- and post-synaptic sites in transverse sections. ⋯ Such an effect was dramatically enhanced by co-administration of a low dose of guanfacine, which reversed thermal and mechanical thresholds to levels near those prior to injury. The results suggest that spinal, α2AAR-mediated antinociception is increased after nerve injury and based on DOR co-activation. We demonstrate in vivo that α2AAR/DOR interaction can be exploited to provide effective behavioral antinociception during neuropathic pain.
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Chronic pain is still a basic science and clinical challenge. Unraveling of the neurobiological mechanisms involved in chronic pain will offer novel targets for the development of therapeutic strategies. It is well known that central sensitization in the anterior cingulate cortex (ACC) plays a critical role in initiation, development, and maintenance of chronic pain. ⋯ Disrupting the interaction of Cav-1 and NR2B through microinjection of a short peptide derived from the C-terminal of NR2B into the ACC exhibited a significant anti-nociception effect associated with decrease of surface NR2B expression. Moreover, Cav-1 increased intracellular Ca(2+) concentration and activated the ERK/CREB signaling pathway in an NR2B-dependent manner in the ACC. Our findings implicate that Cav-1 in the ACC neurons modulates chronic neuropathic pain via regulation of NR2B and subsequent activation of ERK/CREB signaling, suggesting a possible caveolin-mediated process would participate in neuronal transmission pathways implicated in pain modulation.
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The aims were to determine whether individuals with a past history of pain exhibit (i) altered jaw movement (e.g. reduced amplitude, increased jaw movement variability) in comparison with matched asymptomatic controls, and (ii) correlations between psychological measures (e.g. catastrophising) and altered jaw movement variables. Sixteen participants with a history of trigeminal neuropathic pain (TNP) and 15 age- and gender-matched healthy controls had jaw movements recorded during open/close, free gum chewing and chewing at standardised rates. All completed the Pain Catastrophising Scale (PCS), the Pain Self-Efficacy Questionnaire (PSEQ), and the Depression, Anxiety and Stress Scales (DASS). ⋯ In comparison with control, the TNP participants exhibited significantly greater variability, bias and/or mean square error during slow and/or fast opening, and significantly greater variance in velocity and/or amplitude during free and standardised chewing. There were significant negative correlations between PCS scores and velocity and/or amplitude of free and/or standardised chewing. This exploratory study suggests that individuals with a history of pain have altered patterns of jaw movements in comparison with asymptomatic control participants and that catastrophising may play a role in the manifestation of these altered jaw movements.
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Complex regional pain syndrome (CRPS) is the current consensus-derived name for a syndrome usually triggered by limb trauma. Required elements include prolonged, disproportionate distal-limb pain and microvascular dysregulation (e.g., edema or color changes) or altered sweating. CRPS-II (formerly "causalgia") describes patients with identified nerve injuries. ⋯ Investigational treatments include ketamine, botulinum toxin, immunoglobulins, and transcranial neuromodulation. Nonrecovering patients should be re-evaluated for neurosurgically treatable causal lesions (nerve entrapment, impingement, infections, or tumors) and treatable potentiating medical conditions, including polyneuropathy and circulatory insufficiency. Earlier impressions that CRPS represents malingering or psychosomatic illness have been replaced by evidence that CRPS is a rare complication of limb injury in biologically susceptible individuals.