Activation of 5-HT2A receptors potentiates pain produced by inflammatory mediators
Activation of 5-HT2A receptors potentiates pain produced by inflammatory mediators
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DOI：
10.1016/0028-3908(95)00136-0
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发表时间：
1996-01-01
影响因子：
4.7
通讯作者：
Blier, P
中科院分区：
文献类型：
--
作者：
Abbott, FV;Hong, Y;Blier, P
我们实验室先前的结果表明，5-羟色胺（5-HT）增强了其他炎症介质产生的疼痛。为了表征介导5-HT协同作用的受体亚型，将选择性5-HT激动剂单独或与去甲肾上腺素（NA）或前列腺素E(2) （PGE(2)）一起注射到大鼠脚掌表面。使用量化福尔马林引起的疼痛的评分量表记录行为反应（偏好、抬高和舔爪）。5-HT1A和5-HT3激动剂8-OH-DPAT和2-甲基-5- ht各自仅产生短暂反应，不与PGE(2)或NA相互作用。5-HT2激动剂α -甲基-5- ht和DOI单独使用也能产生短暂的反应，但当与PGE(2)或NA联合使用时，会引起注射足部的抬起和舔舐，持续时间超过30分钟。5-HT1A和5-HT3拮抗剂bmy7378和托替司酮足底预处理不改变5-HT + PGE(2)产生的举和舔反应，但被5-HT2A/2C拮抗剂酮色林减弱。经5-HT2A/2C拮抗剂酮色林、利坦色林和5-HT2A拮抗剂spiperone （MPE（50）分别为1.4、7.7和0.06 nmol）预处理后，α -甲基-5- ht + PGE(2)产生的疼痛反应被阻断。酮色林、利坦色林和spiperone （MPE（50）分别为11.3、21.8和0.23 nmol）也能减弱足底注射福尔马林的第二阶段反应。这些数据表明，5-HT2A拮抗剂可能是有效的外周镇痛药或镇痛辅助药物，用于与血小板5-HT释放相关的疼痛，如急性损伤和某些慢性疼痛状态。
Previous results from our laboratory indicate that serotonin (5-HT) potentiates pain produced by other inflammatory mediators. To characterize the receptor subtype(s) mediating this synergistic effect of 5-HT, selective 5-HT agonists were injected, alone or with noradrenaline (NA) or prostaglandin E(2) (PGE(2)), into the plantar surface of the paws of rats. The behavioural response (favouring, elevation and licking the paw) was recorded using the rating scale developed to quantify formalin-induced pain. The 5-HT1A and 5-HT3 agonists, 8-OH-DPAT and 2-methyl-5-HT, respectively, produced only transient responses by themselves and did not interact with PGE(2) or NA. The 5-HT2 agonists, alpha-methyl-5-HT and DOI, also produced transient responses alone, but induced lifting and licking of the injected paw lasting more than 30 min when combined with PGE(2) or NA. The lifting and licking response produced by 5-HT plus PGE(2) was not altered by intraplantar pretreatment with the 5-HT1A and 5-HT3 antagonists, BMY 7378 and tropisetron, but was attenuated by the 5-HT2A/2C antagonist ketanserin. The pain response produced by alpha-methyl-5-HT plus PGE(2) was blocked by pretreatment with the 5-HT2A/2C antagonists ketanserin and ritanserin, and the 5-HT2A antagonist spiperone (MPE(50) values 1.4, 7.7 and 0.06 nmol, respectively). The second phase of the response to intraplantar formalin was also attenuated by ketanserin, ritanserin and spiperone (MPE(50) values 11.3, 21.8 and 0.23 nmol, respectively). These data imply that 5-HT2A antagonists may be effective peripherally acting analgesics or analgesic adjuncts in pain associated with 5-HT release from platelets, such as acute injury and, perhaps, some chronic pain states.