Okamoto Keiichiro, Imbe Hiroki, Morikawa Yoshihiro, Itoh Masayuki, Sekimoto Masashi, Nemoto Kiyomitsu, Senba Emiko
Department of Anatomy and Neurobiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City 641-8509, Japan.
Pain. 2002 Sep;99(1-2):133-43. doi: 10.1016/s0304-3959(02)00070-2.
One of the major serotonin (5-HT) receptor subtypes expressed in the rat dorsal root ganglion (DRG) neurons is the 5-HT2A receptor. We have previously shown that 5-HT2A receptors in the peripheral sensory terminals are responsible for 5-HT-induced pain and hyperalgesia. In the present study, we characterized neurons expressing 5-HT2A receptors in the rat DRG neurons by means of in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and behavioral tests. In situ hybridization on consecutive sections revealed that 5-HT2A receptor mRNA is colocalized with calcitonin-gene related peptide (CGRP) mRNA (100/104; 96.2%) but not with c-Ret mRNA (1/115; 0.9%). Signals for 5-HT2A receptor mRNA were found in 9.4 +/- 2.2% of normal DRG (L5) neurons, most of which were small to medium in size. Four days of complete Freund's adjuvant-induced inflammation of the hindpaw doubled the incidence of 5-HT2A receptor mRNA-expressing neurons to 19.3 +/- 2.8%. The level of 5-HT2A receptor mRNA in DRGs of normal and various pathological conditions was then determined by RT-PCR. The level was up-regulated by peripheral inflammation, but not by axotomy or chronic constriction of the peripheral nerve. Systemic administration of 5-HT2A receptor antagonist (Sarpogrelate HCI) produced analgesic effects on thermal hyperalgesia caused by peripheral inflammation, but failed to attenuate thermal hyperalgesia in chronic constriction injury model. These findings suggest that 5-HT2A receptors are mainly expressed in CGRP-synthesizing small DRG neurons and may be involved in the potentiation of inflammatory pain in the periphery.
5-羟色胺2A（5-HT2A）受体是大鼠背根神经节（DRG）神经元中表达的主要5-羟色胺（5-HT）受体亚型之一。我们之前已经表明，外周感觉神经末梢中的5-HT2A受体介导5-HT诱导的疼痛和痛觉过敏。在本研究中，我们通过原位杂交、免疫组化、逆转录-聚合酶链反应（RT-PCR）和行为测试对大鼠DRG神经元中表达5-HT2A受体的神经元进行了特性分析。连续切片的原位杂交显示，5-HT2A受体mRNA与降钙素基因相关肽（CGRP）mRNA共定位（100/104；96.2%），但不与c-Ret mRNA共定位（1/115；0.9%）。在9.4±2.2%的正常DRG（L5）神经元中发现了5-HT2A受体mRNA信号，其中大多数为中小尺寸。后爪完全弗氏佐剂诱导的炎症持续4天，使表达5-HT2A受体mRNA的神经元发生率增加一倍，达到19.3±2.8%。然后通过RT-PCR测定正常和各种病理条件下DRG中5-HT2A受体mRNA的水平。该水平在外周炎症时上调，但在轴突切断或外周神经慢性压迫时未上调。全身给予5-HT2A受体拮抗剂（盐酸沙格雷酯）对外周炎症引起的热痛觉过敏产生镇痛作用，但在慢性压迫损伤模型中未能减轻热痛觉过敏。这些发现表明，5-HT2A受体主要在合成CGRP的小DRG神经元中表达，可能参与外周炎症性疼痛的增强。
