Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study aimed to investigate the role of spinal p38 mitogen-activated protein kinase (p38 MAPK) activation in chronic constriction injury (CCI) of the sciatic nerve induced neuropathic pain. CCI model was produced by loosely ligating the left sciatic nerve proximal to the sciatica's trifurcation with 4-0 silk thread in male Sprague-Dawley rat. SB203580, a specific inhibitor of the p38 MAPK, was intrathecally administered on day 5 post-CCI. Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal lantency (PWL) to radiant heat and the paw withdrawal threshold (PWT) to von Frey filaments respectively. The protein levels of the phosphorylated p38 MAPK (p-p38 MAPK) and phosphorylated cAMP response element binding protein (pCREB) were assessed by Western blot analysis. The results showed that CCI significantly increased the expressions of cytosolic and nuclear p-p38 MAPK in the spinal cord. Intrathecal administration of SB203580 dose-dependently reversed the established mechanical allodynia and thermal hyperalgesia induced by CCI. Correlated with behavior results, SB203580 dose-dependently inhibited the CCI-induced increase of the expressions of cytosolic and nuclear p-p38 MAPK and nuclear pCREB in the spinal cord. Taken together, these findings suggest that the activation of p38 MAPK pathway contributes to the development of neuropathic pain induced by CCI, and that the function of p-p38 MAPK may partly be accomplished via the CREB-dependent gene expression.
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PMID:Activation of p38 mitogen-activated protein kinase in spinal cord contributes to chronic constriction injury-induced neuropathic pain. 1622 Jan 91

The present study is to investigate whether the extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) signaling pathway contributes to the initiation of chronic constriction injury (CCI)-induced neuropathic pain in rats. Mechanical allodynia was assessed by measuring the hindpaw withdrawal threshold in response to a calibrated series of von Frey hairs. Thermal hyperalgesia was assessed by measuring the latency of paw withdrawal in response to a radiant heat source. The expressions of phosphor-ERK (pERK) and phosphor-CREB (pCREB) were examined using Western blot analysis and immunohistochemistry. An early robust increase in the expression of pERK on the spinal cords ipsilateral to injury was observed on day 1 after CCI, when the CCI-induced behavioral hypersensitivity had not developed yet. Moreover, the upregulation of pERK expression in ipsilateral spinal cord was associated with the increase in pCREB expression in bilateral spinal cord. Intrathecal administration of mitogen-activated protein kinase kinase (MEK) inhibitor U0126 before CCI can efficiently block and delay the CCI-induced mechanical allodynia and thermal hyperalgesia. These data suggest that activation of ERK and CREB in the spinal cord contributes to the initiation of peripheral nerve injury-induced pain hypersensitivity, and an early intervention strategy should be proposed.
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PMID:Early intervention of ERK activation in the spinal cord can block initiation of peripheral nerve injury-induced neuropathic pain in rats. 2150 24