<p>Electroacupuncture decreases Netrin-1-induced myelinated afferent fiber sprouting and neuropathic pain through &mu;-opioid receptors</p>

Abstract

Purpose: We determined whether electroacupuncture (EA) reduces Netrin-1-induced myelinated primary afferent nerve fiber sprouting in the spinal cord and pain hypersensitivity associated with postherpetic neuralgia (PHN) through activation of μ-opioid receptors. Methods: PHN was induced by systemic injection of resiniferatoxin (RTX) in rats. Thirty-six days after RTX injection, a μ-opioid receptor antagonist, beta-funaltrexamine (β-FNA) or a κ-opioid receptor antagonist, nor Binaltorphimine (nor-BNI), was injected intrathecally 30 mins before EA, once every other day for 4 times. Mechanical allodynia was tested with von Frey filaments. The protein expression level of Netrin-1 and its receptors (DCC and UNC5H2) were quantified by using western blotting. The myelinated primary afferent nerve fiber sprouting was mapped with the transganglionic tracer cholera toxin B-subunit (CTB). Results: Treatment with 2 Hz EA at “Huantiao” (GB30) and “Yanglingquan” (GB34) decreased the mechanical allodynia at 22 days and the myelinated primary afferent nerve fiber preternatural sprouting into the lamina II of the spinal dorsal horn at 42 days after RTX injection. Also, treatment with 2 Hz EA reduced the protein levels of DCC and Netrin-1 and promoted the expression of UNC5H2 in the spinal dorsal horn 42 days after RTX injection. Furthermore, the μ-opioid receptor antagonist β-FNA, but not the κ-opioid receptor antagonist nor-BNI, reversed the effect of EA on neuropathic pain caused by RTX. In addition, morphine inhibited the Netrin-1 protein level induced by RTX in SH-SY5Y cells. Conclusions: Through activation of μ-opioid receptors, treatment with EA reduces the expression level of DCC and Netrin-1 and changes a growth-permissive environment in spinal dorsal horn into an inhibitory environment by increasing UNC5H2, thus decreasing RTX-caused primary afferent nerve sprouting in the spinal dorsal horn and neuropathic pain.

Effects of Acupuncture on Behavioral Stereotypies and Brain Dopamine System in Mice as a Model of Tourette Syndrome

“…The time of acupuncture treatment varies from disease to disease. For example, chronic itch model mice are effective for acupuncture treatment for 9 days, while postherpetic neuralgia model mice need acupuncture treatment for 2 weeks to alleviate mechanical allodynia (Li et al, 2019). In a mouse model of TS, we determined that 4 weeks was the optimal treatment duration to alleviate the behavioral stereotypies.…”

A Simulation Study on Selective Stimulation of C-Fiber Nerves for Chronic Pain Relief

“…Endogenous opioids have the same analgesic effect as synthetic opioid drugs but lack addictive properties [7]. Later, researchers found that electroacupuncture stimulation could release endogenous opioids [8] and that needle electrodes could be used to stimulate peripheral nociceptive afferent nerves [9], prompting the nervous system to secrete opioids that act on the μ-receptor for analgesia [10]. Since then, treatments using endogenous opioid theory for sustained analgesia, such as using laser [11], heat [12], and electrical stimulation [13] to induce endogenous opioids, have been developed.…”

Electroacupuncture-Related Metabolic Brain Connectivity in Neuropathic Pain due to Brachial Plexus Avulsion Injury in Rats

“…There also have been some researches in the mechanism of acupuncture/EA in treating neuropathic pain. Li et al (2019) found that 6 weeks of EA intervention could activate µ-opioid receptors, inhibit spinal dorsal horn neuron, and thus release pain. Low frequency of EA inhibits neuropathic pain more effectively than high frequency.…”