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 Ad- and C-fibers.

Keywords

electroacupuncture / analgesia / ASIC3 / TRPV1 / C-fiber reflex

References

[1] Zhang R, Lao L, Ren K, Berman BM. Mechanisms of acupuncture-electroacupuncture on persistent pain. Anesthesiology 2014; 120(2): 482–503

[2] Zhao ZQ. Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 2008; 85(4): 355–375

[3] Kagitani F, Uchida S, Hotta H. Afferent nerve fibers and acupuncture. Auton Neurosci 2010; 157(1-2): 2–8

[4] Li WG, Xu TL. ASIC3 channels in multimodal sensory perception. ACS Chem Neurosci 2011; 2(1): 26–37

[5] Price MP, McIlwrath SL, Xie J, Cheng C, Qiao J, Tarr DE, Sluka KA, Brennan TJ, Lewin GR, Welsh MJ. The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. Neuron 2001; 32(6): 1071–1083

[6] Borzan J, Zhao C, Meyer RA, Raja SN. A role for acid-sensing ion channel 3, but not acid-sensing ion channel 2, in sensing dynamic mechanical stimuli. Anesthesiology 2010; 113(3): 647–654

[7] Jara-Oseguera A, Simon SA, Rosenbaum T. TRPV1: on the road to pain relief. Curr Mol Pharmacol 2008; 1(3): 255–269

[8] Amaya F, Oh-hashi K, Naruse Y, Iijima N, Ueda M, Shimosato G, Tominaga M, Tanaka Y, Tanaka M. Local inflammation increases vanilloid receptor 1 expression within distinct subgroups of DRG neurons. Brain Res 2003; 963(1-2): 190–196

[9] Ma QP. Expression of capsaicin receptor (VR1) by myelinated primary afferent neurons in rats. Neurosci Lett 2002; 319(2): 87–90

[10] Abraham TS, Chen ML, Ma SX. TRPV1 expression in acupuncture points: response to electroacupuncture stimulation. J Chem Neuroanat 2011; 41(3): 129–136

[11] Guirimand F, Strimbu-Gozariu M, Willer JC, Le Bars D. Effects of mu, delta and kappa opioid antagonists on the depression of a C-fiber reflex by intrathecal morphine and DAGO in the rat. J Pharmacol Exp Ther 1994; 269(3): 1007–1020

[12] Zhu B, Xu WD, Rong PJ, Ben H, Gao XY. A C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic and heterotopic acupoints in rats selectively destructive effects on myelinated and unmyelinated afferent fibers. Brain Res 2004; 1011(2): 228–237

[13] Obata K, Yamanaka H, Kobayashi K, Dai Y, Mizushima T, Katsura H, Fukuoka T, Tokunaga A, Noguchi K. Role of mitogen-activated protein kinase activation in injured and intact primary afferent neurons for mechanical and heat hypersensitivity after spinal nerve ligation. J Neurosci 2004; 24(45): 10211–10222

[14] Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988; 32(1): 77–88

[15] Zotova EG, Arezzo JC. Non-invasive evaluation of nerve conduction in small diameter fibers in the rat. Physiol J 2013; 2013: 254789

[16] Kawakita K, Funakoshi M. Suppression of the jaw-opening reflex by conditioning a-δ fiber stimulation and electroacupuncture in the rat. Exp Neurol 1982; 78(2): 461–465

[17] Noguchi E, Ohsawa H, Kobayashi S, Shimura M, Uchida S, Sato Y. The effect of electro-acupuncture stimulation on the muscle blood flow of the hindlimb in anesthetized rats. J Auton Nerv Syst 1999; 75(2-3): 78–86

[18] Ohsawa H, Yamaguchi S, Ishimaru H, Shimura M, Sato Y. Neural mechanism of pupillary dilation elicited by electro-acupuncture stimulation in anesthetized rats. J Auton Nerv Syst 1997; 64(2-3): 101–106

[19] Xu WD, Zhu B, Rong PJ, Bei H, Gao XY, Li YQ. The pain-relieving effects induced by electroacupuncture with different intensities at homotopic and heterotopic acupoints in humans. Am J Chin Med 2003; 31(5): 791–802

[20] Lumpkin EA, Caterina MJ. Mechanisms of sensory transduction in the skin. Nature 2007; 445(7130): 858–865

[21] Usoskin D, Zilberter M, Linnarsson S, Hjerling-Leffler J, Uhlén P, Harkany T, Ernfors P. En masse in vitro functional profiling of the axonal mechanosensitivity of sensory neurons. Proc Natl Acad Sci USA 2010; 107(37): 16336–16341

[22] Gillespie PG, Walker RG. Molecular basis of mechanosensory transduction. Nature 2001; 413(6852): 194–202

[23] Goodman MB, Lumpkin EA, Ricci A, Tracey WD, Kernan M, Nicolson T. Molecules and mechanisms of mechanotransduction. J Neurosci 2004; 24(42): 9220–9222

[24] Lumpkin EA, Bautista DM. Feeling the pressure in mammalian somatosensation. Curr Opin Neurobiol 2005; 15(4): 382–388

[25] Tsunozaki M, Bautista DM. Mammalian somatosensory mechanotransduction. Curr Opin Neurobiol 2009; 19(4): 362–369

[26] Zhang ZJ, Wang XM, McAlonan GM. Neural acupuncture unit: a new concept for interpreting effects and mechanisms of acupuncture. Evid Based Complement Alternat Med 2012; 2012: 429412

[27] Taylor JS, Neal RI, Harris J, Ford TW, Clarke RW. Prolonged inhibition of a spinal reflex after intense stimulation of distant peripheral nerves in the decerebrated rabbit. J Physiol 1991; 437(1): 71–83

[28] Willer JC, Roby A, Le Bars D. Psychophysical and electrophysiological approaches to the pain-relieving effects of heterotopic nociceptive stimuli. Brain 1984; 107(Pt 4): 1095–1112

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