The targeting treatment for prevention and restoration in patients with neuro-degenerative disease

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The neuro-glia activation in the spinal cord may mediate neuropathic pain. However, little is known about the roles of brain-derived neurotrophic factor (BDNF) and mitogen-activated protein kinase (MAPKs) in chronic pain. Although it is well documented that MAPK pathways can increase pain sensitivity via peripheral mechanisms, the present study focused on central mechanisms of MAPKs, especially ERK. In the present study, we characterized neuro-glia and evaluated pERK and c-FOS immunoreactivity after administration of 4-methylcatechol (4-MC), a BDNF inducer, can modify these derangements in relation to chronic pain. A chronic constriction injury (CCI) model as for neuropathic pain model was prepared in SD rats and pain was assessed by a reduction in paw withdrawal latency (PWL) to heat stimuli. 4-MC was injected chronically after CCI. On day 14, k252a (Trk-B receptor inhibitor) or SP600125 (JNK-1 inhibitor) was injected to determine if the analgesic effects of 4-MC could be reversed. The animals were perfused with 4% paraformaldehyde followed by fixation for immunohistochemistry (c-FOS, pERK). The rats showed a persistent decrease in PWL after CCI. On day 14, there was increase in pERK and c-FOS in regions related to pain pathways and regions associated with emotion. 4-MC reduced the decrease in PWL and this effect was reversed by k252a and SP600125, but not by minocyclin, microglial inactivator.These results suggest that the derangement of neuro-glia associated with pERK in pain-emotion system are responsible for chronic pain Neurotrophic factor related compound ameliorates chronic pain by preventing abnormal intracellular signaling via induction of BDNF and normalization of cell responses.