Wei Hong, Pertovaara Antti
Biomedicum Helsinki, Institute of Biomedicine/Physiology, POB 63, 00014 University of Helsinki, Finland.
Eur J Pharmacol. 2006 Dec 3;551(1-3):41-9. doi: 10.1016/j.ejphar.2006.08.064. Epub 2006 Sep 8.
Descending noradrenergic pathways contribute to feedback inhibition of pain by releasing norepinephrine in the spinal cord. Noradrenergic nuclei in the pons contain abundant alpha(2)-adrenoceptors. We assessed the contribution of pontine alpha(2)-adrenoceptors to endogenous regulation of pain in nerve-injured rats. Tactile allodynia and mechanical hyperalgesia were assessed in the injured dermatome and heat nociception in an uninjured dermatome. Atipamezole, an alpha(2)-adrenoceptor antagonist, or saline was administered systemically or microinjected into the locus coeruleus, the lateral parabrachial nucleus, the central nucleus of the amygdala, the midbrain periaqueductal gray, and/or through an intrathecal (i.t.) catheter to the spinal cord. Atipamezole administered systemically, into the amygdala or the periaqueductal gray had no significant effects on pain behavior. Atipamezole (0.3-5 microg) microinjected into the pons, the locus coeruleus or the lateral parabrachial nucleus, produced a selective and dose-related antiallodynia, which was reversed by i.t. administration of atipamezole (5 microg). I.t. administration of atipamezole alone (5 microg) produced thermal hypersensitivity in the non-neuropathic segment (tail) of nerve-injured animals. In sham-operated controls, i.t. administration of atipamezole had no effect. Suppression of heat nociception in uninjured dermatomes of nerve-injured but not the control animals following i.t. administration of atipamezole indicates that nerve injury produced a tonic activation of noradrenergic feedback inhibition acting on spinal alpha(2)-adrenoceptors. In parallel, antiallodynia induced by pontine administration of atipamezole indicates that nerve injury induces a tonic activation of pontine alpha(2)-adrenoceptors that promotes neuropathic hypersensitivity by attenuating descending inhibition. Thus, spinal and pontine alpha(2)-adrenoceptors have opposite effects on pain-related behavior in neuropathic animals.
下行去甲肾上腺素能通路通过在脊髓中释放去甲肾上腺素来对疼痛进行反馈抑制。脑桥中的去甲肾上腺素能核团含有丰富的α₂肾上腺素能受体。我们评估了脑桥α₂肾上腺素能受体对神经损伤大鼠内源性疼痛调节的作用。在损伤的皮节评估触觉异常性疼痛和机械性痛觉过敏，在未损伤的皮节评估热痛觉。将α₂肾上腺素能受体拮抗剂阿替美唑或生理盐水全身给药，或微量注射到蓝斑、外侧臂旁核、杏仁核中央核、中脑导水管周围灰质，和/或通过鞘内（i.t.）导管注入脊髓。全身给药、注入杏仁核或导水管周围灰质的阿替美唑对疼痛行为无显著影响。微量注射到脑桥、蓝斑或外侧臂旁核的阿替美唑（0.3 - 5微克）产生了选择性且与剂量相关的抗异常性疼痛作用，鞘内注射阿替美唑（5微克）可逆转此作用。单独鞘内注射阿替美唑（5微克）在神经损伤动物的非神经病变节段（尾巴）产生热超敏反应。在假手术对照组中，鞘内注射阿替美唑无作用。鞘内注射阿替美唑后，神经损伤但非对照动物的未损伤皮节热痛觉受到抑制，这表明神经损伤导致作用于脊髓α₂肾上腺素能受体的去甲肾上腺素能反馈抑制出现紧张性激活。同时，脑桥给药阿替美唑诱导的抗异常性疼痛表明，神经损伤诱导脑桥α₂肾上腺素能受体出现紧张性激活，通过减弱下行抑制促进神经病理性超敏反应。因此，脊髓和脑桥的α₂肾上腺素能受体对神经病变动物与疼痛相关的行为具有相反作用。
