Electroacupuncture may alleviate neuropathic pain via suppressing P2X7R expression

Abstract

Neuropathic pain is a severe problem that is difficult to treat clinically. Reducing abnormal remodeling of dendritic spines/synapses and increasing the anti-inflammatory effects in the spinal cord dorsal horn are potential methods to treat this disease. Previous studies have reported that electroacupuncture (EA) could increase the pain threshold after peripheral nerve injury. However, the underlying mechanism is unclear. P2X7 receptors (P2X7R) mediate the activation of microglia and participate in the occurrence and development of neuropathic pain. We hypothesized that the effects of EA on relieving pain may be related to the downregulation of the P2X7R. Spinal nerve ligation (SNL) rats were used as a model in this experiment, and 2'(3')-O-(4-benzoyl)benzoyl ATP (BzATP) was used as a P2X7R agonist. We found that EA treatment decreased dendritic spine density, inhibited synaptic reconstruction and reduced inflammatory response, which is consistent with the decrease in P2X7R expression as well as the improved neurobehavioral performance. In contrast to the beneficial effects of EA, BzATP enhanced abnormal remodeling of dendritic spines/synapses and inflammation. Furthermore, the EA-mediated positive effects were reversed by BzATP, which is consistent with the increased P2X7R expression. These findings indicated that EA improves neuropathic pain by reducing abnormal dendritic spine/synaptic reconstruction and inflammation via suppressing P2X7R expression.

Mechanism Underlying Acupuncture Therapy in Spinal Cord Injury: A Narrative Overview of Preclinical Studies

“…The purinergic receptors P2X4 and P2X7 are overexpressed on the cell surface of spinal dorsal horn microglia involved in microglial activation, which significantly contributes to the inflammation after SCI ( Deng et al, 2018 ; Du et al, 2019 ; Kobayakawa et al, 2019 ; Song et al, 2022 ). Electroacupuncture can inhibit P2X7 receptor-mediated microglial activation and attenuate neuropathic pain ( Wu et al, 2021a ). It can also relieve pain hypersensitivity by inhibiting P2X7 receptor-positive microglia after chronic constriction injury ( Xu et al, 2016 ).…”

Role of nerve signal transduction and neuroimmune crosstalk in mediating the analgesic effects of acupuncture for neuropathic pain

“…Studies have shown that the EA at ST36 and BL60 in SNL and DNP models can reduce P2X3 receptors in L4–6 DRGs ( 37 , 43 , 44 , 46 ). EA also reduces P2X4 ( 36 , 45 ) and P2X7 receptors ( 38 ) in L4–6 DRGs, inhibits excitatory postsynaptic potentials, neural loops excitability from the periphery to the spinal cord, abnormal dendritic/spinous synaptic reconstructions and inflammation to improve NP. EA modulates three main types of P2X receptors: the P2X3 receptors located in sensory neurons themselves, the P2X4 receptors located in microglia, and the P2X7 receptors located in glial cells (microglia, astrocytes, and oligodendrocytes) ( 73 ).…”

From Low-Grade Inflammation in Osteoarthritis to Neuropsychiatric Sequelae: A Narrative Review

“…Its blockage has been shown to alleviate neuropathic pain [132]. Furthermore, P2X7 agonists were shown to reduce electroacupuncture-related neuropathic pain-alleviating effects, as well as enhance morphological changes in the neurons of the spinal dorsal horn [133].…”