Zhou S, Komak S, Du J, Carlton S M
Department of Anatomy and Neurosciences, Marine Biomedical Institute, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA.
Brain Res. 2001 Sep 14;913(1):18-26. doi: 10.1016/s0006-8993(01)02747-0.
Several lines of evidence indicate that Group I metabotropic glutamate (mGlu) 1alpha receptors are involved in the processing of nociceptive information in the spinal cord. The goals of the present study are to document the role of mGlu1alpha receptors in peripheral nociception. To accomplish this we investigate the presence of mGlu1alpha receptors on peripheral primary afferent fibers and determine the behavioral effects of (S)-3,5-dihydroxyphenylglycine (S-DHPG), which is an mGlu1/5 receptor agonist and (RS)-1-aminoindan-1, 5-dicarboxylic acid (AIDA), a selective mGluR1alpha antagonist, on mechanical and thermal sensitivity and formalin-induced nociceptive behaviors. The anatomical studies at the electron microscopic level demonstrate that 32.4+/-2.9% of the unmyelinated axons and 21.6+/-4.7% of the myelinated axons are positively immunostained for mGlu1alpha receptors. Intraplantar injection of 0.1 or 1 mM S-DHPG results in a significant increase in mechanical sensitivity that persists for more than 60 min and this effect is blocked by co-injection of S-DHPG with 1 mM AIDA. Intraplantar injection of 40 microM AIDA+2% formalin significantly attenuates phase 2 lifting/licking and flinching behavior and this AIDA-induced effect is blocked with co-injection of 1 microM S-DHPG. In behavioral tests, intraplantar S-DHPG (0.1, 1.0, 10 mM) does not change tail flick latencies or paw withdrawal latencies to heat stimulation. These data indicate that mGlu1alpha receptors are present on peripheral cutaneous axons and activation of peripheral mGlu1alpha receptors contributes to mechanical allodynia and inflammatory pain but not thermal hyperalgesia.
多项证据表明，I 型代谢型谷氨酸（mGlu）1α 受体参与脊髓伤害性信息的处理。本研究的目的是记录 mGlu1α 受体在外周伤害感受中的作用。为实现这一目标，我们研究外周初级传入纤维上 mGlu1α 受体的存在情况，并确定 mGlu1/5 受体激动剂（S）-3,5-二羟基苯甘氨酸（S-DHPG）和选择性 mGluR1α 拮抗剂（RS）-1-氨基茚满-1,5-二羧酸（AIDA）对机械和热敏感性以及福尔马林诱导的伤害性行为的行为学影响。电子显微镜水平的解剖学研究表明，32.4±2.9% 的无髓轴突和 21.6±4.7% 的有髓轴突对 mGlu1α 受体呈阳性免疫染色。足底注射 0.1 或 1 mM 的 S-DHPG 会导致机械敏感性显著增加，这种增加持续超过 60 分钟，并且这种作用会被 S-DHPG 与 1 mM AIDA 共同注射所阻断。足底注射 40 μM AIDA + 2% 福尔马林可显著减轻第二阶段的抬起/舔舐和退缩行为，并且这种 AIDA 诱导的作用会被 1 μM S-DHPG 共同注射所阻断。在行为测试中，足底注射 S-DHPG（0.1、1.0、10 mM）不会改变对热刺激的甩尾潜伏期或爪退缩潜伏期。这些数据表明，mGlu1α 受体存在于外周皮肤轴突上，外周 mGlu1α 受体的激活会导致机械性异常性疼痛和炎性疼痛，但不会导致热痛觉过敏。
