Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, Ribeirão Preto, SP 14049-900, Brazil.
Mol Pain. 2010 Mar 23;6:17. doi: 10.1186/1744-8069-6-17.
Descending pronociceptive pathways may be implicated in states of persistent pain. Paw skin incision is a well-established postoperative pain model that causes behavioral nociceptive responses and enhanced excitability of spinal dorsal horn neurons. The number of spinal c-Fos positive neurons of rats treated intrathecally with serotonin, noradrenaline or acetylcholine antagonists where evaluated to study the descending pathways activated by a surgical paw incision.
The number of c-Fos positive neurons in laminae I/II ipsilateral, lamina V bilateral to the incised paw, and in lamina X significantly increased after the incision. These changes: remained unchanged in phenoxybenzamine-treated rats; were increased in the contralateral lamina V of atropine-treated rats; were inhibited in the ipsilateral lamina I/II by 5-HT1/2B/2C (methysergide), 5-HT2A (ketanserin) or 5-HT1/2A/2C/5/6/7 (methiothepin) receptors antagonists, in the ipsilateral lamina V by methysergide or methiothepin, in the contralateral lamina V by all the serotonergic antagonists and in the lamina X by LY 278,584, ketanserin or methiothepin.
We conclude: (1) muscarinic cholinergic mechanisms reduce incision-induced response of spinal neurons inputs from the contralateral paw; (2) 5-HT1/2A/2C/3 receptors-mediate mechanisms increase the activity of descending pathways that facilitates the response of spinal neurons to noxious inputs from the contralateral paw; (3) 5-HT1/2A/2C and 5-HT1/2C receptors increases the descending facilitation mechanisms induced by incision in the ipsilateral paw; (4) 5-HT2A/3 receptors contribute to descending pronociceptive pathways conveyed by lamina X spinal neurons; (5) alpha-adrenergic receptors are unlikely to participate in the incision-induced facilitation of the spinal neurons.
下行敏化传入通路可能与持续性疼痛状态有关。足底皮肤切开是一种成熟的术后疼痛模型,会引起行为性伤害感受反应和脊髓背角神经元兴奋性增强。鞘内给予 5-羟色胺、去甲肾上腺素或乙酰胆碱拮抗剂的大鼠脊髓背角 c-Fos 阳性神经元的数量评估用于研究手术足底切口激活的下行通路。
足底切口后,同侧 I/II 层、对侧 V 层和 X 层的 c-Fos 阳性神经元数量明显增加。这些变化:在酚苄明处理的大鼠中保持不变;在阿托品处理的大鼠对侧 V 层中增加;在同侧 I/II 层中被 5-HT1/2B/2C(美西麦角)、5-HT2A(酮色林)或 5-HT1/2A/2C/5/6/7(甲硫噻吩)受体拮抗剂抑制,在同侧 V 层中被美西麦角或甲硫噻吩抑制,在对侧 V 层中被所有 5-羟色胺能拮抗剂抑制,在 X 层中被 LY 278、酮色林或甲硫噻吩抑制。
我们得出结论:(1)毒蕈碱能胆碱能机制减少来自对侧足底的伤害性输入引起的切口反应;(2)5-HT1/2A/2C/3 受体介导的机制增加了促进来自对侧足底伤害性输入的脊髓神经元反应的下行通路的活性;(3)5-HT1/2A/2C 和 5-HT1/2C 受体增加了同侧足底切口诱导的下行易化机制;(4)5-HT2A/3 受体有助于 X 层脊髓神经元传递的下行伤害性通路;(5)α-肾上腺素能受体不太可能参与切口诱导的脊髓神经元易化。