Sluka K A, Willis W D
Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston 77555-1069, USA.
Pain. 1997 Jun;71(2):165-78. doi: 10.1016/s0304-3959(97)03371-x.
This study was designed to assess the role of G-proteins and protein kinases in the spinal cord in the behavioral manifestations induced by intradermal injection of capsaicin in rats. A microdialysis fiber was implanted in the spinal cord dorsal horn for administration of G-protein and protein kinase inhibitors to decipher the role of signal transduction cascades in mechanical allodynia induced by intradermal injection of capsaicin. Animals were tested for responses to graded mechanical stimuli using von Frey filaments and for responses to radiant heat stimuli outside the area of injection. The present study demonstrated that intradermal injection of capsaicin results in changes consistent with secondary mechanical allodynia without secondary heat hyperalgesia. Infusion of a G-protein inhibitor (GDP-beta-S), a general protein kinase inhibitor (H7), or selective inhibitors of protein kinase C (NPC15437), protein kinase A (H89), or protein kinase G (KT5823) into the spinal cord dorsal horn reversed the mechanical allodynia induced by intradermal injection of capsaicin in a dose-dependent manner by increasing the threshold to mechanical stimulation towards baseline. This suggests that multiple signal transduction pathways in the spinal cord are involved in the secondary allodynia that occurs following activation of C-fiber afferents by capsaicin.
本研究旨在评估G蛋白和蛋白激酶在大鼠脊髓中对皮内注射辣椒素所诱导行为表现的作用。将一根微透析纤维植入脊髓背角，用于给予G蛋白和蛋白激酶抑制剂，以阐明信号转导级联在皮内注射辣椒素诱导的机械性异常性疼痛中的作用。使用von Frey细丝测试动物对分级机械刺激的反应，并测试其对注射区域外辐射热刺激的反应。本研究表明，皮内注射辣椒素会导致与继发性机械性异常性疼痛一致的变化，而无继发性热痛觉过敏。向脊髓背角注入G蛋白抑制剂（GDP-β-S）、一种通用蛋白激酶抑制剂（H7）或蛋白激酶C（NPC15437）、蛋白激酶A（H89）或蛋白激酶G（KT5823）的选择性抑制剂，可通过将机械刺激阈值提高至基线水平，以剂量依赖的方式逆转皮内注射辣椒素诱导的机械性异常性疼痛。这表明脊髓中的多种信号转导途径参与了辣椒素激活C纤维传入神经后发生的继发性异常性疼痛。
