Electroacupuncture Attenuates Induction of Inflammatory Pain by Regulating Opioid and Adenosine Pathways in Mice

Abstract

Although inflammatory pain is a common clinical condition, its mechanisms are still unclear. Electroacupuncture (EA), a well-known method of pain management, may reduce inflammatory pain by regulating neurons, astrocytes, and inflammatory signaling pathways. Injections of complete Freund’s adjuvant (CFA), which can initiate cell-mediated inflammatory pain, resulted in significant hyperalgesia, which was subsequently prevented by EA. In CFA-injected mice, a dramatic increase was observed in the expression of the following proteins in the dorsal root ganglion and spinal cord dorsal horn: the astrocytic marker GFAP, S100B, RAGE, pPKCε, COX-2, pERK, and pNFκB. These effects were reversed by EA. In addition, mechanical hyperalgesia was significantly reduced in the N6-cyclopentyladenosine (CPA) i.p. or i.m. and endomorphin (EM) i.p. groups. Neither EM i.m. nor EM i.p. exhibited any analgesic effect on thermal hyperalgesia. However, both CPA i.m. and CPA i.p. attenuated thermal hyperalgesia in the mouse inflammatory pain model. We showed that CPA reduced COX-2 and pPKCε expression. However, EM administration did not reduce COX-2 levels. Combined administration of naloxone and rolofylline increased pPKCε and COX-2 pathways. Taken together, our study results revealed a novel and detailed mechanism of EA-induced analgesia that involves the regulation of the opioid and adenosine pathways.

Effects and Mechanisms of Electroacupuncture on Chronic Inflammatory Pain and Depression Comorbidity in Mice

“…EA treatment was applied by stainless steel acupuncture needles (1.5″ inches, 30G, YU KUANG, Taiwan) that were inserted into the muscle layer at a depth of 3-4 mm at the ST36 acupoint. Several articles indicated the analgesic effect and pathway of EA on the ST36 acupoint [10,11]. Electrical square pulses generated by the stimulator were delivered for 15 min-at 2 Hz, with 100 μs between each pulse and a 1 mA amplitude.…”

“…MDD and pain share biological pathways and neurotransmitters, which suggests that simultaneous treatment of both conditions may be effective [9]. Our previous animal model studies have illustrated the therapeutic effects of EA against inflammatory pain via neuronal and nonneuronal pathways [10,11]. EA stimulated secretion of endogenous opioids through the anesthesia pain descending pathway in the central neural system [12].…”

Effect of Acupuncture on the p38 Signaling Pathway in Several Nervous System Diseases: A Systematic Review

“…Furthermore, overexpression of the voltage-gated sodium channel (Na v ), TRPV1, and acid-sensing ion channel 3 (ASIC3) in DRG neurons in response to proinflammatory cytokines is a key component of inflammatory pain [ 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 ]. Low-frequency (2-Hz) EA at acupoint ST36 can reduce inflammatory pain by attenuating ASIC3 overexpression in peripheral DRG neurons.…”

(E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential

“…Due to in vitro data which suggested the anti-inflammatory potential of ICMD-01, in vivo studies were carried out in order to assess the interference of biological systems and possible changes in pharmacological activity using paw inflammation models induced by Freund's complete adjuvant (CFA). CFA is a complex consisting of a suspension of Mycobacterium tuberculosis and mineral oil which guarantees both deposition action and formation of granulomas rich in macrophages and immunocompetent cells [35][36][37].…”