Distinct roles of ASIC3 and TRPV1 receptors in electroacupuncture-induced segmental and systemic analgesia

Abstract

Previous studies have demonstrated the effects of different afferent fibers on electroacupuncture (EA)-induced analgesia. However, contributions of functional receptors expressed on afferent fibers to the EA analgesia remain unclear. This study investigates the roles of acid-sensing ion channel 3 (ASIC3) and transient receptor potential vanilloid 1 (TRPV1) receptors in EA-induced segmental and systemic analgesia. Effects of EA at acupoint ST36 with different intensities on the C-fiber reflex and mechanical and thermal pain thresholds were measured among the ASIC3, TRPV1, and C57BL/6 mice. Compared with C57BL/6 mice, the ipsilateral inhibition of EA with 0.8 C-fiber threshold (0.8Tc) intensity on C-fiber reflex was markedly reduced in ASIC3 mice, whereas the bilateral inhibition of 1.0 and 2.0Tc EA was significantly decreased in TRPV1 mice. The segmental increase in pain thresholds induced by 0.3 mA EA was significantly reduced in ASIC3 mice, whereas the systemic enhancement of 1.0 mA EA was markedly decreased in TRPV1 mice. Thus, segmental analgesia of EA with lower intensity is partially mediated by ASIC3 receptor on Aβ-fiber, whereas systemic analgesia induced by EA with higher intensity is more likely induced by TRPV1 receptor on Aδ- and C-fibers.

Inhibition of electroacupuncture on nociceptive responses of dorsal horn neurons evoked by noxious colorectal distention in an intensity-dependent manner

“…As a result, it is evident that, on visceral pain, EA-induced segmental analgesia is mediated by both A- and C-fibers, and extrasegmental analgesia is mediated only by C-fibers. Our results are consistent with previous studies on somatic pain that show that EA with a high enough intensity to excite Aβ-fibers is capable of producing local analgesia, but excitation of Aδ- and some C-fibers induces a more potent and extensive analgesia 7,20,21…”

“…It is well known that the antinociceptive effects of EA treatment are different when EA is applied to acupoints with the same or different segmental innervation with the pain organs 7–9. For these experiments, EA stimulation was applied at contralateral PC 6, which innervates different segments of rectum and colon, to study the dose–effect relationship of EA at heterotopic acupoints on visceral nociception.…”

“…Consequently, we speculate that current intensity is important for effective analgesia. In fact, many human and animal studies have shown that EA with different intensities can excite different types of peripheral afferent fibers and produce different extents of analgesia 7–9. However, a comprehensive understanding of the relationship between current intensity and EA-induced analgesia on visceral pain is still unknown.…”

Electroacupuncture Inhibits Visceral Nociception via Somatovisceral Interaction at Subnucleus Reticularis Dorsalis Neurons in the Rat Medulla

“…The mechanisms underlying EA induced segmental and extrasegmental analgesia are differ. Electrophysiological studies on somatic pain have shown that segmental analgesia of homotopic EA stimulation can be elicited by the activation of Aβ- and part of Aδ – fibers, whereas extrasegmental analgesia of heterotopic EA stimulation is only effective with intensities strong enough to excite Aδ–or C–fibers ( Xu et al, 2003 ; Zhu et al, 2004 ; Xin et al, 2016 ). It is very likely that SRD neurons are involved in the mechanism of the widespread extrasegmental antinociceptive effects of EA.…”

Orofacial antinociceptive activity and anchorage molecular mechanism in silico of geraniol

“…This experiment followed the protocol described by Beirith et al, 17 Experiments (ARRIVE). 20,21 Molecular docking analysis: in silico The structure of geraniol was obtained from PubChem (https://pubchem.ncbi.nlm.nih.gov/ compound/637566#section=Top) as a .sdf file. All receptors are coupled with an inhibitory ligand previously described in enzyme activity studies in vitro.…”