Role of 5-HT1 receptor subtypes in the modulation of pain and synaptic transmission in rat spinal superficial dorsal horn
Role of 5-HT1 receptor subtypes in the modulation of pain and synaptic transmission in rat spinal superficial dorsal horn
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DOI：
10.1111/j.1476-5381.2011.01685.x
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发表时间：
2012-03-01
影响因子：
7.3
通讯作者：
Vaughan, Christopher W.
中科院分区：
文献类型：
--
作者：
Jeong, Hyo-Jin;Mitchell, Vanessa A.;Vaughan, Christopher W.
背景和结论5-HT受体激动剂在脊髓内具有可变的伤害性作用。虽然有一些证据表明5-HT 1A脊髓介导的镇痛，其他5-HT 1受体亚型的作用仍不清楚。在本研究中，我们检查了一系列5-HT 1激动剂（包括舒马曲坦）对急性疼痛的脊髓作用，以及它们对传入诱发的突触传递到浅表背角神经元的作用。5-通过长期植入的脊髓导管注射HT激动剂，以使用爪压镇痛仪和热刺激仪检查它们在急性机械和热疼痛测定中的作用。哈洛夫的装置。在体外实验中，从大鼠腰段脊髓切片中的板层II神经元进行初级传入诱发的神经元兴奋性EPSC的全细胞膜片钳记录。5-HT 1A激动剂R +/- 8-OH-DPAT（30-300 nmol）的递送产生剂量依赖性的热镇痛，但不产生机械镇痛。舒马曲坦和5-HT 1B、5-HT 1D、5-HT 1F激动剂CP 93129、PNU 109291和LY 344864（100 nmol）对任一急性疼痛试验均无影响。R +/- 8-OH-DPAT（1 μ M）和舒马曲坦（3 mM）均降低诱发的EPSC的幅度。相反，CP 93129、PNU 109291和LY 344864（0.3-3 μ M）对诱发的EPSC没有影响。5-HT 1A受体拮抗剂WAY 100635（3 μ M）可阻断R +/- 8-OH-DPAT和舒马曲坦的作用。结论和意义这些发现表明5-HT 1A受体亚型主要介导大鼠浅背角内5-HT 1配体的急性抗伤害性和细胞作用。
BACKGROUND AND PURPOSE5-HT receptor agonists have variable nociceptive effects within the spinal cord. While there is some evidence for 5-HT1A spinally-mediated analgesia, the role of other 5-HT1 receptor subtypes remains unclear. In the present study, we examined the spinal actions of a range of 5-HT1 agonists, including sumatriptan, on acute pain, plus their effect on afferent-evoked synaptic transmission onto superficial dorsal horn neurons.EXPERIMENTAL APPROACHFor in vivo experiments, 5-HT agonists were injected via chronically implanted spinal catheters to examine their effects in acute mechanical and thermal pain assays using a paw pressure analgesymeter and a Hargreave's device. For in vitro experiments, whole-cell patch-clamp recordings of primary afferent-evoked glutamatergic EPSC were made from lamina II neurons in rat lumbar spinal slices.KEY RESULTSIntrathecal (i.t.) delivery of the 5-HT1A agonist R +/- 8-OH-DPAT (30-300 nmol) produced a dose-dependent thermal, but not mechanical, analgesia. Sumatriptan and the 5-HT1B, 5-HT1D, 5-HT1F agonists CP93129, PNU109291 and LY344864 (100 nmol) had no effect on either acute pain assay. R +/- 8-OH-DPAT (1 mu M) and sumatriptan (3 mM) both reduced the amplitude of the evoked EPSC. In contrast, CP93129, PNU109291 and LY344864 (0.3-3 mu M) had no effect on the evoked EPSC. The actions of both R +/- 8-OH-DPAT and sumatriptan were abolished by th e 5-HT1A antagonist WAY100635 (3 mu M).CONCLUSIONS AND IMPLICATIONSThese findings indicate that the 5-HT1A receptor subtype predominantly mediates the acute antinociceptive and cellular actions of 5-HT1 ligands within the rat superficial dorsal horn.