TRPV1 is a Responding Channel for Acupuncture Manipulation in Mice Peripheral and Central Nerve System

Abstract

Background/Aims: Acupuncture involves inserting a fine needle into a specific point, often called an acupoint, thereby initiating a therapeutic effect accompanied by phenomena such as soreness, heaviness, fullness, and numbness. Acupoints are characterized as points located in deep tissues with abundant sensory nerve terminals, which suggests that there is a strong relationship between acupoints and peripheral sensory afferents. In this study, we determined whether manual acupuncture (MA) or different frequencies of electroacupuncture (EA) share similar mechanisms for activating excitatory neurotransmission. Methods: We performed MA or EA at acupoint ST36 and we also used western blot and immunostaining techniques to determine neural changes at the peripheral dorsal root ganglion (DRG), spinal cord (SC), and somatosensory cortex (SSC) levels. Results: Our results show that either MA or EA at the ST36 acupoint significantly increased components of the TRPV1-related signaling pathway, such as pPKA, pPI3K, pPKC-pERK, and pAKT (but not pp38 or pJNK) at the peripheral DRG and central SC-SSC levels. Furthermore, excitatory phosphorylated N-methyl-D-aspartate receptor (pNMDA) and pCaMKIIα (but not pNR2B, pCaMKIIδ, or pCaMKIIγ) also increased. These molecules could not increase in the DRG and SC-SSC of TRPV1^–/–mice. Conclusion: Our data demonstrates that both MA and EA can activate excitatory signals in either peripheral or central levels. We also define that TRPV1 is crucial for an acupuncture effect and then initiate excitatory pNR1-pCaMKII pathway, at peripheral DRG and central SC-SSC level. We suggest that the TRPV1 signaling pathway is highly correlated to Acupuncture effect that implies the real clinical significance.

Neuromechanism of acupuncture regulating gastrointestinal motility

“…Components of calcium wave propagation (CWP, the proposed downstream sensing pathway) were also co-expressed with TRPV1. However, only TRPV1 is regarded as a responding channel for acupuncture by sensing peripheral information and conducting signaling via the CWP and the excitatory phosphorylated glutamate ionotropic receptor NMDA type subunit 1-phosphorylated calcium/calmodulin dependent protein kinase II pathway, offering a comprehensive understanding of the physical stimulation by acupuncture of neurological signaling[ 31 ].…”

“…However, the literature on the central role of acupuncture on ghrelin secretion is limited. It has been confirmed that acupuncture can activate the TRPV1 receptor[ 21 , 23 , 30 , 31 ], which can also be activated by capsaicin during GI motility, i.e ., acupuncture has a similar effect to capsaicin. Capsaicin regulates the central action of ghrelin[ 194 - 196 ]; therefore, we speculated that acupuncture also has a central regulatory effect on ghrelin, which requires further data to prove this.…”

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

“…Other studies have reported that delivering EA at acupoints GV14 and GV20 exerts neuroprotective effects by activating CREB, BDNF [161], and α7 nicotinic acetylcholine receptor (α7 nAChR) [162] while simultaneously reducing S100B-mediated neurotoxicity [163]. Moreover, EA at acupoint ST36 can evoke excitatory signals in either the peripheral nervous system or CNS in vivo [163].…”

“…By contrast, high-frequency (100 Hz) EA induces long-term potentiation (LTP) of endogenous GABAergic (GABA B ) and the serotonergic inhibitory systems through modulation of μ-opioid and 5-hydroxytryptamine 1 (5-HT1) receptors [ 25 , 160 ]. Other studies have reported that delivering EA at acupoints GV14 and GV20 exerts neuroprotective effects by activating CREB, BDNF [ 161 ], and α7 nicotinic acetylcholine receptor (α7 nAChR) [ 162 ] while simultaneously reducing S100B-mediated neurotoxicity [ 163 ]. Moreover, EA at acupoint ST36 can evoke excitatory signals in either the peripheral nervous system or CNS in vivo [ 163 ].…”

“…Protein kinase C (PKC) is rapidly activated by heat or bradykinin and translocates, assisted by scaffolding proteins, from intracellular compartments to the plasma membrane. In rat DRG, the TRPV1 signaling pathways involve the phosphatidylinositol 3-kinases (PI3K), PKC, and calmodulin-dependent protein kinase II (CaMKII) [ 143 , 163 ]. The p38α MAPK was first recognized for its role in inflammation where it regulates the biosynthesis of proinflammatory cytokines IL-1 and TNFα [ 77 , 78 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 115 , 164 , 165 , 166 , 167 , 168 , 169 ].…”