Articles: neuropathic-pain.
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Retromer, which crucially contributes to endosomal sorting machinery through the retrieval and recycling of signaling receptors away from degradation, has been identified as a critical element for glutamatergic-receptor-dependent neural plasticity at excitatory synapses. We observed it accompanied by behavioral allodynia; neuropathic injury time-dependently enhanced VPS26A and SNX27 expression; VPS26A-SNX27 coprecipitation; and VPS26A-positive, SNX27-positive, and VPS26A-SNX27 double-labeled immunoreactivity in the dorsal horn of Sprague Dawley rats that were all sufficiently ameliorated through the focal knock-down of spinal VPS26A expression. Although the knock-down of spinal SNX27 expression exhibited similar effects, spinal nerve ligation (SNL)-enhanced VPS26A expression remained unaffected. Moreover, SNL also increased membrane-bound and total mGluR5 abundance, VPS26A-bound SNX27 and mGluR5 and mGluR5-bound VPS26A and SNX27 coprecipitation, and mGluR5-positive and VPS26A/SNX27/mGluR5 triple-labeled immunoreactivity in the dorsal horn, and these effects were all attenuated through the focal knock-down of spinal VPS26A and SNX27 expression. Although administration with MPEP adequately ameliorated SNL-associated allodynia, mGluR5 expression, and membrane insertion, SNL-enhanced VPS26A and SNX27 expression were unaffected. Together, these results suggested a role of spinal VPS26A-SNX27-dependent mGluR5 recycling in the development of neuropathic pain. This is the first study that links retromer-associated sorting machinery with the spinal plasticity underlying pain hypersensitivity and proposes the possible pathophysiological relevance of endocytic recycling in pain pathophysiology through the modification of glutamatergic mGluR5 recycling. ⋯ VPS26A-SNX27-dependent mGluR5 recycling plays a role in the development of neuropathic pain. The regulation of the VPS26A-SNX27 interaction that modifies mGluR5 trafficking and expression in the dorsal horn provides a novel therapeutic strategy for pain relief.
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Neuroscience letters · Nov 2015
Regulation of neuropathic pain behavior by amygdaloid TRPC4/C5 channels.
Pain per se may increase anxiety and conversely, anxiety may increase pain. Therefore, a positive feedback loop between anxiety and pain possibly contributes to pain and suffering in some pathophysiological pain conditions, such as that induced by peripheral nerve injury. Recent results indicate that transient receptor channels 4 and 5 (TRPC4/C5) in the amygdala have anxiogenic effects in rodents, while their role in chronic pain conditions is not known. ⋯ In the internal capsule, ML-204 had no effect on hypersensitivity or affective-like pain in SNI animals. In healthy controls, amygdaloid administration of ML-204 failed to influence pain behavior induced by mechanical stimulation or noxious heat. The results indicate that the amygdaloid TRPC4/C5 contribute to maintenance of pain hypersensitivity and pain affect in neuropathy.
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Eur Neuropsychopharmacol · Nov 2015
Comparative StudyRespective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats.
Numerous reported data support the idea that Brain Derived Neurotrophic Factor (BDNF) is critically involved in both depression and comorbid pain. The possible direct effect of BDNF on pain mechanisms was assessed here and compared with behavioral/neurobiological features of neuropathic pain caused by chronic constriction injury to the sciatic nerve (CCI-SN). Sprague-Dawley male rats were either injected intrathecally with BDNF (3.0 ng i.t.) or subjected to unilateral CCI-SN. ⋯ A long lasting spinal BDNF overexpression was also observed in BDNF i.t. rats, indicating an autocrine self-induction, with downstream long lasting TrkB-mediated neuropathic-like pain. Accordingly, TrkB blockade appeared as a relevant approach to alleviate not only i.t. BDNF- but also nerve lesion-evoked neuropathic pain.
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Complex regional pain syndrome (CRPS) is multifactorial condition with complex pathogenesis characterized by spontaneous or stimulus-induced pain that is disproportionate to the inciting event. It is also commonly accompanied by a myriad of autonomic and motor disturbances in highly variable combinations. ⋯ In this retrospective case series, a multidisciplinary management plan is presented in 10 children for whom the standard noninvasive treatment was unsuccessful. Within this management plan, novel drugs were included such as the capsaicin 8% patch, in addition to invasive techniques in patients who did not respond to noninvasive therapies.
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Observational Study
Risk Factors for Chronic Saphenous Neuralgia Following Coronary Artery Bypass Graft Surgery Utilizing Saphenous Vein Grafts.
The aim of this trial was to determine risk factors for chronic saphenous neuralgia (SN) following harvesting of the great saphenous vein (GSV) for coronary artery bypass graft (CABG) surgery. ⋯ Chronic SN after CABG surgery utilizing GSV grafts is not uncommon. Risk factors identified in this trial are younger age, female gender, higher body mass index, diabetes mellitus, distal-to-proximal dissection of the GSV, and closure of the leg wound in two layers.