Analgesic Effect of Intrathecal 2R， 6R-HNK on Neuropathic Pain in Female Mice
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20230523.002
- VernacularTitle:鞘内注射2R， 6R-HNK缓解雌性小鼠的神经病理性疼痛
- Author:
An-ran LIU
1
;
Zhen-jia LIN
2
;
Xiang-ge PENG
2
;
Ying LI
2
;
Yu-fan ZHENG
2
;
Zhi TAN
2
;
Li-jun ZHOU
2
;
Xia FENG
1
Author Information
1. Department of Anesthesiology and Pain Clinic， The First Affiliated Hospital of Sun Yat-sen University， Guangzhou 510080， China
2. Department of Physiology， Zhongshan School of Medical， Sun Yat-sen University //Center for Pain Research， Sun Yat-sen University， Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
neuropathic pain;
2R， 6R-hydroxynorketamine （2R， 6R-HNK）;
dorsal root ganglion;
calcitonin gene-related peptide （CGRP）
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2023;44(4):607-616
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the analgesic action and mechanism of intrathecal 2R， 6R-hydroxynorketamine （2R， 6R-HNK） on spared nerve injury （SNI）-induced chronic neuropathic pain （CNP） in female mice. MethodsSNI was used to establish acute and chronic CNP models in female mice. The mice were randomly divided into different groups with administration of vehicle， 2R， 6R-HNK or S-ketamine （10 mg/kg intraperitoneal injection/i.p. or 7， 21 μmol/L intrathecal injection/i.t.） at 3 weeks after or 30 min/1 d before operation （n = 3 - 7 mice/group）. The curative or preventive effect of 2R， 6R-HNK was evaluated by mechanical paw withdrawal threshold （PWT） and the analgesic efficiency. Finally， immunofluorescence and RT-PCR of dorsal root ganglion （DRG） and spinal dorsal horn （SDH） were used to explore the possible mechanisms. ResultsCompared with vehicle， intrathecal injection of 2R， 6R-HNK largely reversed SNI-induced bilateral mechanical allodynia in a delayed-and-dose-dependent way. Among them， 21 μmol/L 2R， 6R-HNK reached its maximum analgesic efficiency （75.32±7.69） % at 2 d. Pre-intrathecal delivery of 2R， 6R-HNK also delayed the development of bilateral mechanical hypersensitivity 2 - 3 d induced by SNI. Mechanically， 2R， 6R-HNK reversed not only the abnormal excitability of neurons in bilateral DRG and superficial SDH， but also the upregulation of calcitonin gene-related peptide （CGRP） and brain-derived nerve growth factor （BDNF） in DRG. ConclusionIntrathecal administration of 2R， 6R-HNK exerts an analgesic effect against CNP， probably via suppressing abnormal neuronal excitability in ascending pain pathway as well as down-regulating CGRP and BDNF expression in DRG neurons.
