Bennett A D, Chastain K M, Hulsebosch C E
Marine Biomedical Institute, Anatomy and Neurosciences, University of Texas Medical Branch, Galveston 77555-1069, USA.
Pain. 2000 May;86(1-2):163-75. doi: 10.1016/s0304-3959(00)00242-6.
CGRP(8-37) is a truncated version of calcitonin gene-related peptide (CGRP) that binds to the CGRP receptor with similar affinity but does not activate the receptor and is a highly selective CGRP receptor antagonist. CGRP and activation of its receptor appear to play a role in peripheral inflammatory and neuropathic models of pain although there is considerable controversy. The aim of this study was to examine possible anti-nociceptive effects of CGRP(8-37) on a model of chronic central neuropathic pain known to develop weeks after spinal hemisection. Adult male Sprague-Dawley rats were given a spinal hemisection (N=34) or a sham surgery (N=10) at the T13 spinal segment. An externally accessible PE-10 intrathecal catheter that terminated at T13 was used for drug delivery. Animals were allowed to recover for 4 weeks at which time the hemisected animals displayed mechanical and thermal allodynia bilaterally, in both forelimbs and hindlimbs. CGRP(8-37) was delivered just prior to a testing session in 1, 5, 10, or 50 nM doses in artificial cerebral spinal fluid in 10 microl volumes. CGRP(8-37) was effective in alleviating mechanical and thermal allodynia in a dose-dependent manner (P<0.05). The 50 nM dose was most efficacious for both forelimb and hindlimb responses (P<0.05). The period of efficacy was 10 min to onset for a duration of 20 min. Post-drug washout responses were not statistically significant compared to pre-drug responses. The sham control groups demonstrated no statistically significant difference at any dose of CGRP(8-37) when compared to pre-surgical baseline values. In conclusion, CGRP(8-37) is effective in abolishing mechanical and thermal allodynia produced by spinal hemisection. Consequently, the CGRP receptor may play a role in chronic central neuropathic pain and offers a novel therapeutic approach to managing chronic central pain.
降钙素基因相关肽（CGRP）（8 - 37）是降钙素基因相关肽（CGRP）的截短形式，它以相似的亲和力与CGRP受体结合，但不激活该受体，是一种高度选择性的CGRP受体拮抗剂。尽管存在相当大的争议，但CGRP及其受体的激活似乎在周围炎症性和神经性疼痛模型中起作用。本研究的目的是研究CGRP（8 - 37）对一种已知在脊髓半切术后数周发展的慢性中枢神经性疼痛模型可能的抗伤害感受作用。成年雄性Sprague - Dawley大鼠在T13脊髓节段接受脊髓半切术（N = 34）或假手术（N = 10）。一根终止于T13的可外部接入的PE - 10鞘内导管用于给药。动物恢复4周，此时接受脊髓半切术的动物双侧前肢和后肢均表现出机械性和热性痛觉过敏。在测试前，以10微升体积的人工脑脊液，分别以1、5、10或50纳摩尔的剂量给予CGRP（8 - 37）。CGRP（8 - 37）能以剂量依赖性方式有效减轻机械性和热性痛觉过敏（P < 0.05）。50纳摩尔剂量对前肢和后肢反应最有效（P < 0.05）。起效时间为10分钟，持续时间为20分钟。与给药前反应相比，给药后冲洗后的反应无统计学意义。与手术前基线值相比，假手术对照组在任何剂量的CGRP（8 - 37）下均无统计学显著差异。总之，CGRP（8 - 37）能有效消除脊髓半切术产生的机械性和热性痛觉过敏。因此，CGRP受体可能在慢性中枢神经性疼痛中起作用，并为治疗慢性中枢性疼痛提供了一种新的治疗方法。
