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USE OF ISOFORM SPECIFIC INHIBITORS OF CGMP-DEPENDENT PROTEIN KINASE FOR TREATMENT OF PAIN
USE OF ISOFORM SPECIFIC INHIBITORS OF CGMP-DEPENDENT PROTEIN KINASE FOR TREATMENT OF PAIN
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机译:CGMP依赖性蛋白激酶同工型特异性抑制剂在疼痛治疗中的应用
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摘要
Several lines of evidence have shown a role for the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway in the development of spinal hyperalgesia. However, the roles of effectors for cGMP are not fully understood in the processing of pain in the spinal cord. cGMP-dependent protein kinase (PKG) I alpha but not PKGI beta was localized in the neuronal bodies and processes, and was distributed primarily in the superficial laminae of the spinal cord. Intrathecal administration of an inhibitor of PKGI alpha , Rp-8-[(4-Chlorophenyl)thio]-cGMPS triethylamine, produces significant antinociception. Moreover, PKGI alpha protein expression was dramatically increased in the lumbar spinal cord after noxious stimulation. This upregulation of PKGI alpha expression was completely blocked not only by a neuronal NO synthase inhibitor, and a soluble guanylate cyclase inhibitor, but also by an N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801. Noxious stimulation not only initially activates but also later upregulates PKGI alpha expression in the superficial laminae via an NMDA-NO-cGMP signaling pathway, suggesting that PKGI alpha plays an important role in the central mechanism of inflammatory hyperalgesia in the spinal cord.
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