Articles: neuropathic-pain.
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Background and aims The clinical management of chronic neuropathic pain remains a global health challenge. Current treatments are either ineffective, or associated with unwanted side-effects. The development of effective, safe therapies requires the identification of novel therapeutic targets using clinically relevant animal models of neuropathic pain. ⋯ Conclusion The observation that levels of PPARα protein were increased in ipsilateral spinal cord of neuropathic rats supports a contribution of spinal sites of action mediating the effects of systemic WY-14643. Our data suggests that the inhibitory effects of a PPARα agonist on spinal neuronal responses may account, at least in part, for their analgesic effects of in neuropathic pain. Implication Selective activation of PPARα in the spinal cord may be therapeutically relevant for the treatment of neuropathic pain.
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Neuroligin-1 (NL1) forms a complex with the presynaptic neurexin-1β (Nrx1b), regulating clustering of N-methyl-D-aspartate receptors with postsynaptic density-95 (PSD-95) to underlie learning-/memory-associated plasticity. Pain-related spinal neuroplasticity shares several common features with learning-/memory-associated plasticity. The authors thereby investigated the potential involvement of NL1-related mechanism in spinal nerve ligation (SNL)-associated allodynia. ⋯ SNL-induced allodynia, which is mediated by the spinal NL1/PSD-95/pNR2B cascade, can be prevented by blockade of transsynaptic Nrx1b-NL1 interactions.
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Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. ⋯ We particularly focus on connexin 43 and pannexin 1 because their regulation vastly attenuates symptoms of neuropathic pain. We hope that the study of gap junction channels eventually leads to the development of a suitable treatment tool for patients with neuropathic pain.
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Neuropathic pain is a common disorder for which patients seek treatment. The most common causes of neuropathic pain are diabetes, herpetic infection and chemotherapy-induced neuropathy. Oral administration of amitriptyline has traditionally been used for treating neuropathic pain; however, it has dose-related anticholinergic effects, which may limit its use in some individuals. Pharmacotherapeutic agents that are commonly used to treat neuropathic pain include antidepressants, anticonvulsants, opioids and opioid-like substances, and topical medications. The objective of this paper is to review the effectiveness of topical amitriptyline in patients with neuropathic pain. ⋯ Although there are reports that describe the benefits of topical amitriptyline for neuropathic pain, data from evidence-based controlled clinical trials do not support efficacy in patients who use topical amitriptyline for neuropathic pain control.
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Brain Behav. Immun. · Oct 2015
Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice.
Spinal cord astrocytes are critical in the maintenance of neuropathic pain. Connexin 43 (Cx43) expressed on spinal dorsal horn astrocytes modulates synaptic neurotransmission, but its role in nociceptive transduction has yet to be fully elaborated. In mice, Cx43 is mainly expressed in astrocytes, not neurons or microglia, in the spinal dorsal horn. ⋯ Intrathecal injection of TNF in naïve mice induced the downregulation of both Cx43 and GLT-1 in spinal dorsal horn, as well as hind paw mechanical hypersensitivity, as observed in PSNL mice. Conversely, intrathecal treatment of PSNL mice with the TNF inhibitor etanercept prevented not only mechanical hypersensitivity but also the downregulation of Cx43 and GLT-1 expression in astrocytes. The current findings indicate that spinal astrocytic Cx43 are essential for the maintenance of neuropathic pain following peripheral nerve injury and suggest modulation of Cx43 as a novel target for developing analgesics for neuropathic pain.