Activation of the cAMP transduction cascade contributes to the mechanical hyperalgesia and allodynia induced by intradermal injection of capsaicin
Activation of the cAMP transduction cascade contributes to the mechanical hyperalgesia and allodynia induced by intradermal injection of capsaicin
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DOI：
10.1038/sj.bjp.0701486
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发表时间：
1997-11-01
影响因子：
7.3
通讯作者：
Sluka, KA
中科院分区：
文献类型：
--
作者：
Sluka, KA
1在清醒行为大鼠（雄性，Sprague-Dawley）中，通过激活或抑制脊髓cAMP转导级联途径，研究了脊髓cAMP转导级联在伤害性处理中的作用。将微透析纤维植入背角，将药物直接输注到脊髓。2在没有外周组织损伤的情况下，测试动物对重复应用（10次试验）von Frey细丝的反应以及输注8-溴-cAMP前后对机械刺激的阈值。在用8-br-cAMP（1-10 mM）脊髓处理的这组动物中，产生了剂量依赖性痛觉过敏和异常性疼痛。这表现为对10次von Frey细丝（10、50、150、250 mN）试验的反应次数增加和机械阈值降低。3第二系列实验研究了皮内注射辣椒素诱导的组织损伤模型中cAMP通路脊髓的操纵。用腺苷酸环化酶抑制剂四氢呋喃腺嘌呤（THFA）或蛋白激酶A抑制剂豆蔻酰化蛋白激酶（14-22）酰胺（PKI）对动物进行脊髓预处理或后处理。注射辣椒素会导致对重复应用von Frey细丝的反应次数增加，并且对注射部位以外的机械刺激、继发性机械性痛觉过敏和异常性疼痛的阈值降低。4用THFA（1 mM）或PKI预处理（5 mM）对辣椒素诱发的继发性痛觉过敏和异常性疼痛没有影响。5相反，用THFA（0.01-1 mM）或PKI（0.05-50 mM）脊髓后处理剂量依赖性地减少由辣椒素注射产生的机械性痛觉过敏和异常性疼痛。此外，腺苷酸环化酶抑制剂THFA（1 mM）阻断的机械性痛觉过敏和异常性疼痛可被8-溴-cAMP逆转（0.01-10 mM）。6因此，这项研究表明，在脊髓水平激活cAMP转导级联导致机械性痛觉过敏和异常性疼痛，并且皮内注射后继发性机械性痛觉过敏和异常性疼痛辣椒素的注射是由这种相同的转导级联介导的。
1 The spinal role of the cAMP transduction cascade in nociceptive processing was investigated in awake behaving rats (male, Sprague-Dawley) by activating or inhibiting this pathway spinally. Microdialysis fibres were implanted into the dorsal horn to infuse drugs directly to the spinal cord.2 Animals, without peripheral tissue injury, were tested for responses to repeated applications (10 trials) of von Frey filaments and threshold to mechanical stimulation before and after infusion of 8-bromo-cAMP. In this group of animals treated spinally with 8-br-cAMP (1-10 mM) a dose-dependent hyperalgesia and allodynia were produced. This was manifested as an increased number of responses to 10 trials of von Frey filaments (10, 50, 150, 250 mN) and a decrease in mechanical threshold.3 A second series of experiments studied the manipulation of the cAMP pathway spinally in a model of tissue injury induced by intradermal injection of capsaicin. Animals were either pre-or post-treated spinally with the adenylate cyclase inhibitor, tetrahydrofuryl adenine (THFA) or the protein kinase A inhibitor, myrosilated protein kinase (14-22) amide (PKI). Injection of capsaicin resulted in an increased number of responses to repeated applications of von Frey filaments and a decrease in threshold to mechanical stimuli outside the site of injection, secondary mechanical hyperalgesia and allodynia.4 Pre-treatment with either THFA (1 mM) or PKI (5 mM) had no effect on the capsaicin-evoked secondary hyperalgesia and allodynia.5 In contrast, post-treatment spinally with THFA (0.01-1 mM) or PKI (0.05-50 mM) dose-dependently reduced the mechanical hyperalgesia and allodynia produced by capsaicin injection. Furthermore, the mechanical hyperalgesia and allodynia blocked by the adenylate cyclase inhibitor, THFA (1 mM), was reversed by infusion of 8-bromo-cAMP (0.01-10 mM) in a dose-dependent manner.6 Thus, this study demonstrates that activation of the cAMP transduction cascade at the spinal cord level results in mechanical hyperalgesia and allodynia and that the secondary mechanical hyperalgesia and allodynia following intradermal injection of capsaicin is mediated by this same transduction cascade.