Articles: neuropathic-pain.
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Mitochondrial dysfunction is observed in various neuropathic pain phenotypes, such as chemotherapy induced neuropathy, diabetic neuropathy, HIV-associated neuropathy, and in Charcot-Marie-Tooth neuropathy. To investigate whether mitochondrial dysfunction is present in trauma-induced painful mononeuropathy, a time-course of mitochondrial function and bioenergetics was characterized in the mouse partial sciatic nerve ligation model. ⋯ Traumatic peripheral nerve injury induces persistent mitochondrial and bioenergetic dysfunction which implies that pharmacological agents which seek to normalize mitochondrial and bioenergetic dysfunction could be expected to be beneficial for pain treatment. Increases in both glycolytic acidification and non-glycolytic acidification suggest that pH sensitive drugs which preferentially act on acidic tissue will have the ability to preferential act on injured nerves without affecting healthy tissues.
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Lamiophlomis rotata (Benth.) Kudo (L. rotata) is a medical plant that has been traditionally used for centuries for the treatment of pain, such as bone and muscle pain, joint pain and dysmenorrhea. Although iridoid glycosides of L. rotata (IGLR) are the major active components of it according to reports, it still remains poorly understood about the molecular mechanisms underlying analgesic effects of IGLR. The aim of the present study was to investigate the analgesic effect of IGLR on a spared nerve injury (SNI) model of neuropathic pain. ⋯ These results indicated IGLR could produce an anti-neuropathic pain effect that might partly be related to the inhibition of the NO/cGMP/PKG and NMDAR/PKC pathways and the level of TNF-α, IL-1β as well as to the increase of the level of IL-10 in spinal cord.
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Neuroscience letters · Sep 2015
Early treatment with UR13870, a novel inhibitor of p38α mitogenous activated protein kinase, prevents hyperreflexia and anxiety behaviors, in the spared nerve injury model of neuropathic pain.
Microglia cell activation plays a role in the development of neuropathic pain partly due to the activation of the p38α MAPK signaling pathway after nerve injury. In this study we assessed the effect of UR13870, a p38α MAPK inhibitor, in the "spared nerve injury" (SNI) model, to study its effects on modulation of spinal microglial activation and to test behavioral hyperreflexia responses and cerebral-mediated pain behavior. The effect of daily administration of UR13870 (10mg/kg p.o.) and Pregabalin (50mg/kg p.o.) on reflex hypersensitivity to mechanical and cold test stimuli and on affective related pain responses measured with the place escape avoidance paradigm and the open field-induced anxiety test, were evaluated after SNI in Sprague Dawley rats. ⋯ UR13870 treatment significantly decreased hindlimb hyperreflexia to both mechanical and cold stimuli after SNI without loss of general motor function, in addition to a reduction in pain-related anxiety behavior at day 21 after SNI, accompanied by normalization of OX-42 immunoreactivity within the ipsilateral lumbar dorsal horn. Pregabalin treatment only reduced mechanical hyperreflexia and affected general motor function. Oral administration of the p38α MAPK inhibitor, UR13870, mediates antinociception to both mechanical and cold stimuli, and significantly restored inner-zone exploration in the open field test, accompanied by normalization in dorsal horn microglial activation in the SNI model.
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Plastic changes in the anterior cingulate cortex (ACC) are critical in the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. Cdh1, a co-activator subunit of anaphase-promoting complex/cyclosome (APC/C) regulates synaptic differentiation and transmission. Based on this, we hypothesised that the APC/C-Cdh1 played an important role in long-term plastic changes induced by neuropathic pain in ACC. ⋯ These results provide evidence that Cdh1 in ACC synapses may offer a novel therapeutic strategy for treating chronic neuropathic pain.
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It has been shown that chronic pain is able to induce depressive disorders in humans, in part, due to peripheral inflammation that reaches the central nervous system. However, the mechanisms involved remain to be established. The purpose of this study was to investigate whether sciatic nerve crush could produce depression-like behaviors, in addition to pain-related behaviors, in mice. Once confirmed, this model was used to investigate tumor necrosis factor-α (TNF-α) as a key mediator involved in the pathophysiology of both pain and depression. ⋯ The sciatic nerve crush model represents a good model to study to mechanisms underlying both pain and depressive-like behaviors. Furthermore, inhibitors of TNF-α synthesis, like thalidomide, have a potential to treat depressive disorders associated with neuropathic pain.