Receptor mechanism of melatonin's analgesic effect on spinal dorsal horn neurons in mice
YANG Yinjuan
TAN Chaoyang
WANG Jian
JIA Jingchen
YE Xiaolong
CHEN Tao
Abstract：Objective To study whether melatonin(MLT)is involved in the regulation of analgesic effects at the spinal cord level in neuropathic pain,and its possible receptor mechanisms.Methods Male C57BL/6 mice were used to establish a partial spared nerve injury(SNI)model and sham surgery(Sham).After 7 d,MLT and different MLT receptor agonists and/or antagonists were administered intrathecally,respectively.Von Frey filament test was used to compare the changes in paw withdrawal mechanical threshold of mice before and after SNI modeling and Sham surgery administration.Male C57BL/6 and transgenic mice were used as the research objects,and immunofluorescence staining technology was used to determine the expression of MLT receptors on different types of spinal dorsal horn neurons.Patch clamp technique was used to compare the changes in excitability of spinal dorsal horn neurons before and after SNI modeling and Sham surgery drug intervention.Results Compared with Sham group,the mechanical pain threshold in SNI group was significantly reduced(P＜0.05).Intrathecal administration of MLT and Ramelteon(MT1/MT2 receptor agonist)could significantly restore the mechanical pain threshold of SNI group mice(P＜0.05),but the mechanical pain threshold of SNI group mice did not recover after the administration of Ramelteon+4PP(MT2 receptor antagonist).The immunofluorescence results indicated that MT2 was widely distributed in excitatory neurons in spinal dorsal horn in mice.The patch clamp experiment found that,compared with Sham group,the action potential rheobase of excitatory neurons in spinal dorsal horn in SNI group was significantly reduced(P＜0.05),the absolute value of resting potential was reduced(P＜0.05),and MT2 receptor agonist(8MP)could reverse the above changes(P＜0.01).Conclusion Under neuropathic pain conditions,MLT significantly alleviates mechanical hypersensitivity in SNI mice at the spinal cord level,and its analgesic effect is mediated by MT2.
Keywords：neuropathic painmelatoninmelatonin type 2 receptorspinal dorsal horn
Publication Date：2024-08-28
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：6( 907-912 )