Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain
Fu-Jun Zhai1,2,3 • Song-Ping Han4 • Tian-Jia Song1,2,3 • Ran Huo1,2,3 • Xing-Yu Lan1,2,3 • Rong Zhang1,2,3,5 • Ji-Sheng Han1,2,3
1 Neuroscience Research Institute, Peking University, Beijing 100191, China
2 Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
3 Key Laboratory for Neuroscience, Ministry of Education, National Health Commission, Peking University, Beijing 100191, China
4 Wuxi HANS Health Medical Technology Co., Ltd., Wuxi 214122, China 5 Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China
Abstract
Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.
Keywords
SCS; Analgesia; Opioid receptors; Methionine-Enkephalin; Dynorphin; Endorphins
