Analgesic effect of a cholinergic agonist (carbachol) in a sural nerve ligation-induced hypersensitivity mouse model

ABSTRACT

Objectives

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.

Methods

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.

Results

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.

Conclusion

These findings suggest that cholinergic nerves are involved in allodynia and hyperalgesia of the SN ligation neuropathic pain model.

KEYWORDS:

• Neuropathic pain
• spared nerve injury (SNI) model
• allodynia
• hyperalgesia
• acetylcholine
• mouse

Acknowledgments

This study was supported in part by a fund for joint research from Ohu University.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution statement

KT and KA conceived and designed the research. NK and TC conducted experiments and analyzed data. NK and TK wrote the original draft manuscript. KT and KA reviewed and edited the manuscript. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Supplemental material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/01616412.2024.2337512

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.