Antiallodynic effects of intrathecally administered 5-HT2C receptor agonists in rats with nerve injury
Antiallodynic effects of intrathecally administered 5-HT2C receptor agonists in rats with nerve injury
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DOI：
10.1016/j.pain.2003.12.019
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发表时间：
2004-03-01
期刊：
影响因子：
7.4
通讯作者：
Goto, F
中科院分区：
文献类型：
--
作者：
Obata, H;Saito, S;Goto, F
鞘内注射5-羟色胺2型(5-HT2)受体激动剂，α-甲基-5-羟色胺马来酸(α-m-5-HT)或(+/-)-1-(4-iodo-2，5-dimethoxyphenyt)-2-aminopropane盐酸盐(DOI)，在神经病理性疼痛的大鼠模型上产生止痛作用。在本研究中，我们研究了鞘内给药对5-HT2C受体的选择性的抗痛觉过敏作用。通过紧密结扎左侧L5和L6脊神经造成痛觉过敏，并通过将von Frey细丝应用于左侧后爪来测量。给予5-HT2C受体激动剂6-氯-2-(1-哌嗪基)-吡嗪(MK212；3-100µg)、1-(间氯苯基)-哌嗪(mCPP；30-300µg)或1-(三氟甲基苯基)-哌嗪(TFMPP；30-300 g)，可产生剂量依赖性的止痛作用，且不伴随运动无力。MK212、mCPP和TFMPP的ED50值分别为39.2MUG、119.9和191.9 MUG。鞘内注射选择性5-HT2C受体拮抗剂RS-102221(30杯)可减弱最大剂量5-HT2C受体激动剂的作用。优先使用的5-HT2a受体拮抗剂酮色林(30杯)不能逆转这一作用。与5-HT2C受体激动剂相比，鞘内注射α-m-5-HT(30mug)和DOI(100mug)的抗痛觉过敏作用可被酮色林逆转，但不能被RS-102221逆转。这些结果表明，5-HT2C受体在脊髓对神经病理性疼痛的抑制中起作用，鞘内注射5-HT2C受体激动剂的作用机制与α-m-5-HT或DOI不同，后者似乎是通过5-HT2A受体产生作用的。(C)2004年国际疼痛研究协会。爱思唯尔出版，版权所有。
Intrathecal administration of serotonin type 2 (5-HT2) receptor agonists, alpha-methyl-5-hydroxytryptamine maleate (alpha-m-5-HT) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyt)-2-aminopropane hydrochloride (DOI), produces antiallodynic effects in a rat model of neuropathic pain. In the present study, we examined the antiallodynic effects of intrathecally administered agents which are selective for 5-HT2C receptors. Allodynia was produced by tight ligation of the left L5 and L6 spinal nerves, and was measured by applying von Frey filaments to the left hindpaw. Administration of the 5-HT2C receptor agonist, 6-chloro-2-(1-piperazinyl)-pyrazine (MK212; 3-100 mug), 1-(m-chlorophenyl)-piperazine (mCPP; 30-300 mug), or 1-(in-trifluoromethylphenyl)-piperazine (TFMPP; 30-300 jig), produced antiallodynic effects in a dose-dependent manner with no associated motor weakness. The ED50 values of MK212, mCPP, and TFMPP were 39.2, 119.9, and 191.9 mug, respectively. Intrathecal pretreatment with the selective 5-HT2C receptor antagonist RS-102221 (30 mug) diminished the effects of the highest doses of 5-HT2C receptor agonists. The preferential 5-HT2A receptor antagonist ketanserin (30 mug) did not reverse the effects. In contrast to 5-HT2C receptor agonists, the antiallodynic effects of intrathecally administered alpha-m-5-HT (30 mug) and DOI (100 mug) were reversed by ketanserin, but not by RS-102221. These results indicate that 5-HT2C receptors have a role in spinal inhibition of neuropathic pain, and the effects produced by intrathecal administration of 5-HT2C receptor agonists are mediated by a mechanism different from that of alpha-m-5-HT or DOI, which seem to produce their effects through 5-HT2A receptors. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.