Articles: neuralgia.
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Introduction Neuropathic pain is a debilitating condition. The importance of neuroimmune interactions in neuropathic pain has been evidenced by the involvement of different immune cells in peripheral and central sensitization of pathological pain. Macrophages and microglia are the most abundant immune cells activated in injured nerves and spinal cord, respectively. ⋯ Microglia activation in dorsal horn of lumbar spinal cord following partial sciatic nerve ligation was significantly inhibited with PLX5622 treatment in both preventive and reversal paradigms. Conclusion Macrophages in peripheral nerve and microglia in the spinal cord are required in the generation and maintenance of injury-associated neuropathic pain. Blocking macrophage-colony stimulating factor/colony stimulating factor 1 receptor signaling on these myeloid cells along the pain transmission pathway is an effective strategy to alleviate neuropathic pain.
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Our previous study reported the translocator protein to play a critical role in neuropathic pain and the possible mechanisms in the spinal cord. However, its mechanism in the peripheral nervous system is poorly understood. This study was undertaken to explore the distribution of translocator protein in the dorsal root ganglion and the possible mechanisms in peripheral nervous system in a rat model of spared nerve injury. ⋯ Our results suggested Ro5-4864 could alleviate neuropathic pain and attenuate p-ERK and brain-derived neurotrophic factor activation in dorsal root ganglion. Furthermore, Ro5-4864 stimulated the expression of myelin regeneration proteins which may also be an important factor against neuropathic pain development. Translocator protein may present a novel target for the treatment of neuropathic pain both in the central and peripheral nervous systems.
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Extracellular regulated protein kinase (ERK) pathway activation in astrocytes and neurons has been reported to be critical for neuropathic pain development after chronic constriction injury. TGN-020 was found to be the most potent aquaporin 4 inhibitor among the agents studied. ⋯ Additionally, TGN-020 suppressed ERK phosphorylation in astrocytes and neurons after injury. The findings suggested that the analgesic effects of TGN-020 in neuropathic pain were mediated mainly by the downregulation of chronic constriction injury-induced astrocytic activation and inflammation, which is via the inhibition of ERK pathway in the spinal dorsal horn and dorsal root ganglion.
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Diabetic peripheral neuropathy is a major debilitating late complication of diabetes, which significantly reduces the quality of life in patients. Diabetic peripheral neuropathy is associated with a wide spectrum of sensory abnormalities, where in loss of sensation or hypoalgesia to applied external stimuli is paradoxically accompanied by debilitating tonic spontaneous pain. In numerous studies on animal models of diabetic peripheral neuropathy, behavioural measurements have been largely confined to analysis of evoked withdrawal to mechanical and thermal stimuli applied to dermatomes, whereas spontaneous, on-going pain has not been widely studied. ⋯ Neither early hypersensitivity nor late hypoalgesia were associated with markers of cellular stress in the dorsal root ganglia. Whereas significant neutrophil infiltration was observed in the dorsal root ganglia over both early and late stages post-Streptozotocin, T-cell infiltration in the dorsal root ganglia was prominent at late stages post-Streptozotocin. Thus, longitudinal analyses reveal that similar to patients with chronic diabetic peripheral neuropathy, mice show tonic pain despite sensory loss after several months in the Streptozotocin model, which is accompanied by neuroimmune interactions in the dorsal root ganglia.
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An experimental animal study. ⋯ 5.