Department of CNS Diseases Research, Birkendorfer Strasse 65, Boehringer Ingelheim Pharma GmbH & Co KG, 88397 Biberach, Germany.
Pain. 2013 May;154(5):700-707. doi: 10.1016/j.pain.2013.01.002. Epub 2013 Jan 11.
Calcitonin gene-related peptide (CGRP) is known to play a major role in the pathogenesis of pain syndromes, in particular migraine pain. Here we focus on its implication in a rat pain model of inflammation, induced by injection of complete Freund adjuvant (CFA). The nonpeptide CGRP receptor antagonist BIBN4096BS reduces migraine pain and trigeminal neuronal activity. Here we demonstrate that the compound reduces inflammatory pain and spinal neuronal activity. Behavioural experiments reveal a reversal of the CFA-induced mechanical hypersensitivity and monoiodoacetate (MIA)-induced weight-bearing deficit in rats after systemic drug administration. To further investigate the mechanism of action of the CGRP antagonist in inflammatory pain, in vivo electrophysiological studies were performed in CFA-injected rats. Recordings from wide dynamic range neurons in deep dorsal horn layers of the lumbar spinal cord confirmed a reduction of neuronal activity after systemic drug application. The same amount of reduction occurred after topical administration onto the paw, with resulting systemic plasma concentrations in the low nanomolar range. However, spinal administration of BIBN4096BS did not modify the neuronal activity in the CFA model. Peripheral blockade of CGRP receptors by BIBN4096BS significantly alleviates inflammatory pain.
降钙素基因相关肽（CGRP）在疼痛综合征的发病机制中起着重要作用，特别是偏头痛疼痛。在这里，我们重点研究它在完全弗氏佐剂（CFA）诱导的炎症大鼠疼痛模型中的作用。非肽 CGRP 受体拮抗剂 BIBN4096BS 可减轻偏头痛疼痛和三叉神经神经元活动。在这里，我们证明该化合物可减轻炎症性疼痛和脊髓神经元活动。行为实验表明，在全身给予药物后，该化合物可逆转 CFA 诱导的机械性超敏反应和单碘乙酸（MIA）诱导的大鼠负重缺陷。为了进一步研究 CGRP 拮抗剂在炎症性疼痛中的作用机制，在 CFA 注射大鼠中进行了体内电生理研究。来自腰椎脊髓背角深层的宽动态范围神经元的记录证实，全身给药后神经元活动减少。在爪子上局部给药后也会发生相同程度的减少，导致全身血浆浓度在纳摩尔范围内。然而，脊髓给予 BIBN4096BS 并没有改变 CFA 模型中的神经元活动。BIBN4096BS 对 CGRP 受体的外周阻断可显著缓解炎症性疼痛。
