江剑平*, 付艳, 洪炎国
福建师范大学生命科学学院， 福建省发育与神经生物学重点实验室，福州 350108
本研究旨在探讨感觉神经元特异性受体(sensory neuron-specific receptor, SNSR)的内源性激动剂牛肾上腺髓质22 肽(bovine adrenal medulla 22, BAM22 )对完全弗氏佐剂(complete Freund’s adjuvant, CFA)引起的早期炎性痛的影响。在大鼠后足皮下注射CFA形成炎性痛模型，通过撤足反射、脚肿测定和免疫组织化学等方法观察鞘内给予BAM22对炎性痛的影响。结果显示：在撤足反射实验中，BAM22能剂量依赖地延长CFA炎性鼠撤足反射潜伏期基础阈值，增强抗伤害作用，并降低脚肿程度。10 nmol BAM22作用48 h后，撤足反射潜伏期恢复至正常的83.2%，脚肿仅增加60.0%；24 h时延长撤足反射潜伏期达最大可能作用的33.5%，并持续至少1 h。在免疫组织化学实验中，BAM22能显著降低CFA引起的L3-L5脊髓背角神经元型一氧化氮合酶(neuronal nitric oxide synthase, nNOS)阳性细胞和降钙素基因相关肽(calcitonin gene-related peptide, CGRP)样免疫活性物质的表达，与生理盐水组相比分别下降了25.6% (P < 0.01)和25.2% (P < 0.001)；BAM22处理组背根神经节(dorsal root ganglion, DRG)中的小型和中型CGRP阳性细胞分别为57.4%和35.2%，明显低于生理盐水组(P < 0.001)。结果表明，BAM22可能通过SNSR下调nNOS和CGRP的表达来削弱CFA引起的早期热痛觉过敏和恢复抗伤害效力。
关键词： 牛肾上腺髓质 22 肽; 完全弗氏佐剂; 炎性痛; 神经型一氧化氮合酶; 降钙素基因相关肽
[Bovine adrenal medulla 22 attenuates hyperalgesia in the early phase of complete Freund's adjuvant-induced inflammation in rats.] [Article in Chinese]
JIANG Jian-Ping*, FU Yan, HONG Yan-Guo
College of Life Sciences, Fujian Normal University, Fujian Key Laboratory of Developmental and Neuro Biology, Fuzhou 350108, China
The present study investigated the effects of intrathecal (i.t.) application of bovine adrenal medulla 22 (BAM22), an endogenous opioid peptide potently activating opioid receptors and sensory neuron-specific receptor (SNSR), on a model of complete Freund's adjuvant (CFA)-induced inﬂammatory pain. Unilateral, but not bilateral, inﬂammatory pain was induced by intraplantar (i.pl.) injection of CFA in one side, as indicated by the shortened paw withdrawal latency and the increased edema of paw. Paw withdrawal latency test, paw edema determination and immunohistochemistry were used in CFA-induced inﬂammatory pain model after i.t. administration of BAM22 or saline. It was found that administration of BAM22 dose-dependently attenuated CFA-induced hyperalgesia and edema, and resumed antinociceptive effects against thermal stimulation in behavioral test. In 10 nmol BAM22 group, paw withdrawal latency was resumed to 83.2% of normal, and edema increased only by 60% of normal at 48 h. The potency of BAM22 was 33.5% of maximal possible effect (MPE) at 24 h, and the antinociception persisted for at least 1 h. Furthermore, i.t. treatment of 10 nmol BAM22 evidently decreased the expressions of CFA-evoked neuronal nitric oxide synthase (nNOS)-positive cells and calcitonin gene-related peptide (CGRP)-immunoreactivity positive nerve fibers by 25.6% (P<0.01) and 25.2% (P<0.001) compared with saline group, respectively, at L3-L5 segments of the spinal cord. Small and medium CGRP-positive cells were 57.4% and 35.2% in dorsal root ganglion (DRG) in 10 nmol BAM22 group, respectively, which were remarkably lower than those in saline group (P<0.001). The present study suggests that BAM22 relieves CFA-induced thermal hyperalgesia in the early phase and resumes antinociceptive effects through down-regulation of nNOS and CGRP expressions in DRG and spinal cord, which is possibly mediated via SNSR.
Key words: bovine adrenal medulla 22; complete Freund's adjuvant; inflammatory pain; neuronal nitric oxide synthase; calcitonin gene-related peptide
通讯作者：江剑平 E-mail: email@example.com
江剑平, 付艳, 洪炎国. 牛肾上腺髓质22肽削弱完全弗氏佐剂引起的早期痛觉过敏[J]. 生理学报 2011; 63 (1): 9-19.
JIANG Jian-Ping, FU Yan, HONG Yan-Guo. [Bovine adrenal medulla 22 attenuates hyperalgesia in the early phase of complete Freund's adjuvant-induced inflammation in rats.] [Article in Chinese]. Acta Physiol Sin 2011; 63 (1): 9-19 (in Chinese with English abstract).