Analgesia with 5' extracellular nucleotidase-mediated electroacupuncture for neuropathic pain

Abstract

Background: Acupuncture is a treatment for neuropathic pain, but its mechanism remains unclear. Previous studies showed that analgesia was induced in rats with neuropathic pain when their spinal cord adenosine content increased after electroacupuncture (EA); however, the mechanism behind this electroacupuncture-induced increase has not been clarified. Objective: This study aimed to determine the role that ecto-5’-nucleotidase plays in EA-induced analgesia for neuropathic pain. Methods: We performed electroacupuncture at the Zusanli acupoint on the seventh day after establishing a rat model of neuropathic pain induced through chronic constriction injuries. We observed the mechanical withdrawal threshold and thermal pain threshold and detected the expression of ecto-5’-nucleotidase in the spinal cord using Western blot. Chronic constriction injury rat models were intraperitoneally injected with α,β-methyleneadenosine 5'-diphosphate, an ecto-5’-nucleotidase inhibitor, 30 min before electroacupuncture. The adenosine content of the spinal cord was detected using high-performance liquid chromatography. Lastly, the adenosine A1 receptor agonist N6-cyclopentyladenosine was intrathecally injected into the lumbar swelling of the rats, and the mechanical withdrawal and thermal pain thresholds were reevaluated. Results: Analgesia and increased ecto-5’-nucleotidase expression and adenosine content in the spinal cord were observed 1 h after electroacupuncture. α,β-methyleneadenosine 5'-diphosphate was able to inhibit upregulation of adenosine content and electroacupuncture-induced analgesia. After administration of N6-cyclopentyladenosine, electroacupuncture-induced analgesia was restored. Conclusions: Our results suggest that electroacupuncture at Zusanli can produce analgesia in chronic constriction injury rat models, possibly via the increased ecto-5’-nucleotidase expression induced through electroacupuncture, thus leading to increased adenosine expression in the spinal cord.

Comprehensive landscape-style investigation of the molecular mechanism of acupuncture at ST36 single acupoint on different systemic diseases

“…Specifically, acupuncture at ST36 can cause a short-term increase in local eATP at the acupoint, and subsequently accelerate ATP hydrolysis by regulating the levels of the Nucleoside triphosphate diphosphohydrolases (NTPDase)-2/3 in the DRG and ecto-5′NT in the spinal cord, and the sequence of hydrolysis is in the following order: "ATP→ADP→AMP→ADO" [ 140 , 141 ]. Eventually, ADO can bind to A1 receptors to affect purinergic signaling, inhibit ATP binding to purinergic P2 receptors, reduce neurotransmission between neurons, and exert analgesic effects [ [142] , [143] , [144] ]. Evidence suggests [ 145 ] that acupuncture at ST36 single point also induces a localized increase in acupoint macrophage elevation, and the acupuncture signal promotes macrophage differentiation to M2 type and reduces the production of M1 type macrophages.…”

The Effectiveness and Safety of Acupuncture on Occipital Neuralgia: A Study Protocol for Systematic Review and/or Meta-Analysis

“…Recent studies, such as the study of Luo et al [13] in 2021 were not included, thus updates on this topic are being requested. Moreover, an emerging body of research has reported the potential roles of various acupuncture treatment types, including manual acupuncture [14], electroacupuncture [15], acupotomy [16], and pharmacopuncture [17] in pain and related disorder management. However, to date, none of the previous research has investigated the effect of each specific acupuncture treatment method.…”