Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima, Japan.
Department of Medicinal Pharmacology, Showa Pharmaceutical University, Machida, Tokyo, Japan.
Neurol Res. 2024 Jun;46(6):505-515. doi: 10.1080/01616412.2024.2337512. Epub 2024 Apr 3.
Neuropathic pain is characterized by long-lasting, intractable pain. Sciatic nerve ligation is often used as an animal model of neuropathic pain, and the spared nerve injury (SNI) model, in which the common peroneal nerve (CPN) and tibial nerve (TN) are ligated, is widely used. In the present study, we evaluated the analgesic effect of a cholinergic agonist, carbachol, on a neuropathic pain model prepared by sural nerve (SN) ligation in mice.
The SN was tightly ligated as a branch of the sciatic nerve. Mechanical and thermal allodynia, and hyperalgesia were assessed using von Frey filaments and heat from a hot plate. The analgesic effects of intracerebroventricularly-administered morphine and carbachol were compared.
SN ligation resulted in a significant decrease in pain threshold for mechanical stimulation 1 day after ligation. In response to thermal stimulation, allodynia was observed at 50°C and hyperalgesia at 53 and 56°C 3 days after ligation. Content of thiobarbituric acid reactive substances (TBARS) in the spinal cord increased significantly at 6 and 12 h after ligation. Acetylcholine content of the spinal cord also increased at 5 and 7 days after ligation. Intracerebroventricular administration of carbachol at 7 days after ligation produced a marked analgesic effect against mechanical and thermal stimuli, which was stronger and longer-lasting than morphine at all experimental time points.
These findings suggest that cholinergic nerves are involved in allodynia and hyperalgesia of the SN ligation neuropathic pain model.
神经病理性疼痛的特点是持久的、难治的疼痛。坐骨神经结扎常用于制备动物神经病理性疼痛模型，其中广泛应用的是 spared nerve injury（SNI）模型，即结扎腓总神经（CPN）和胫神经（TN）。在本研究中，我们评估了一种胆碱能激动剂 carbachol 对 SN 结扎小鼠神经病理性疼痛模型的镇痛作用。
将 SN 作为坐骨神经的分支进行紧密结扎。使用 von Frey 纤维和热板评估机械和热感觉过敏和痛觉过敏。比较鞘内给予吗啡和 carbachol 的镇痛效果。
SN 结扎导致结扎后 1 天机械刺激痛阈显著降低。对热刺激的反应，在结扎后 3 天观察到 50°C 的感觉过敏和 53 和 56°C 的痛觉过敏。结扎后 6 和 12 小时脊髓中硫代巴比妥酸反应物质（TBARS）含量显著增加。结扎后 5 和 7 天脊髓乙酰胆碱含量也增加。在结扎后 7 天鞘内给予 carbachol 对机械和热刺激产生明显的镇痛作用，在所有实验时间点均强于吗啡且持续时间更长。
这些发现表明，胆碱能神经参与了 SN 结扎神经病理性疼痛模型的感觉过敏和痛觉过敏。
