Electroacupuncture Regulates Pain Transition Through Inhibiting PKCε and TRPV1 Expression in Dorsal Root Ganglion

Abstract

Many cases of acute pain can be resolved with few side effects. However, some cases of acute pain may persist beyond the time required for tissue injury recovery and transit to chronic pain, which is hard to treat. The mechanisms underlying pain transition are not entirely understood, and treatment strategies are lacking. In this study, the hyperalgesic priming model was established on rats to study pain transition by injection of carrageenan (Car) and prostaglandin E2 (PGE2). The expression levels of protein kinase C epsilon (PKCε) and transient receptor potential vanilloid 1 (TRPV1) in the L4–L6 dorsal root ganglion (DRG) were investigated. Electroacupuncture (EA) is a form of acupuncture in which a small electric current is passed between a pair of acupuncture needles. EA was administrated, and its effect on hyperalgesia and PKCε and TRPV1 expression was investigated. The PKCε–TRPV1 signaling pathway in DRG was implicated in the pain transition. EA increased the pain threshold of model animals and regulated the high expression of PKCε and TRPV1. Moreover, EA also regulated hyperalgesia and high TRPV1 expression induced by selective PKCε activation. We also found that EA partly increased chronic pain threshold, even though it was only administered between the Car and PGE2 injections. These findings suggested that EA could prevent the transition from acute to chronic pain by inhibiting the PKCε and TRPV1 expression in the peripheral nervous system.

Satellite glial cells drive the transition from acute to chronic pain in a rat model of hyperalgesic priming

“…Previous studies have demonstrated that PKCε activation in the DRG is a molecular marker of pain transition initiation (Wang et al, 2021). Our previous studies also showed that inhibition of high PKCε expression reverses chronic pain in HP model rats (Fang et al, 2021). Here, we tested whether blocking the induction of SGC reactivity affects PKCε expression in the L5 DRG.…”

“…Fc injection also decreased the expression level of PKCε, as well as GFAP, in the DRG in this study. Our previous research demonstrated that preventing PKCε activation in the lumbar DRG regulates pain transition ( Fang et al, 2021 ). All of the above results indicate that SGC activation is involved in the transition from acute to chronic pain.…”

“…Most importantly, a previous study demonstrated that short-term application of CXCL1 is able to modulate the activity of TRPV1+/IB4+ DRG neurons ( Deftu et al, 2017 , 2018 ). In addition, PKCε activation in IB4+ DRG neurons and increased TRPV1 expression play an important role in pain transition ( Wang et al, 2018 ; Fang et al, 2021 ). Therefore, we hypothesized that CXCL1 may be involved in the transition from acute to chronic pain.…”

“…In this animal model, intraplantar PGE2 injection after recovery from acute inflammatory stimulation was found to produce long-lasting hyperalgesia that was significantly beyond its ability to lead to acute pain ( Ferrari et al, 2013 ). Protein kinase C epsilon (PKCε) has been identified as the key molecule involved in this phenomenon, and its activation in dorsal root ganglion (DRG) neurons induces the transition from acute pain to chronic pain ( Fang et al, 2021 ; Wang et al, 2021 ). Our group recently found that in this model, changes in the expression of some receptors on neurons, such as upregulation of mGluR5 and downregulation of GABAAR, are involved in the activation of PKCε in the DRG ( Wang et al, 2020 , 2021 ).…”

Shared nociceptive dorsal root ganglion neurons participating in acupoint sensitization

“…Many works of literature have reported that the efficacy of acupuncture is related to the C-type fibers innervating acupoints or DRG neurons expressing TRPV1 ( Wang et al, 1996 ; Tjen et al, 2005 ; Qin et al, 2014 ; Gao X. et al, 2015 ; Chen et al, 2018 ; Guo et al, 2018 ; Liu et al, 2018 ; Li et al, 2019 ; Du et al, 2021 ; Fang et al, 2021 ; Song et al, 2021 ). However, the TRPV1-expressing shared DRG neurons in this study are unlikely to be involved in the analgesia produced by acupuncture at the ST36 acupoint.…”