Inhibition of Muscular Nociceptive Afferents via the Activation of Cutaneous Nociceptors in a Rat Model of Inflammatory Muscle Pain

Abstract

Topical irritants such as capsaicin (CAP), peppermint oil (PO), and mustard oil (MO) are effective in relieving inflammatory muscle pain. We investigated the effects of topical irritants in a rat model of inflammatory muscle pain produced by injecting complete Freund's adjuvant (CFA) into the tibialis anterior muscle. CFAinduced mechanical hypersensitivity and the spontaneous activity of muscular nociceptive afferents, and decreased weight-bearing of the hindlimb were relieved by topical application of CAP, PO, or MO on the skin overlying the inflamed muscle. The effects of topical irritants were abolished when applied to the skin on the ipsilateral plantar region or on the contralateral leg, or when the relevant cutaneous nerve or dorsal root was transected. Our results demonstrated that topical irritants may alleviate inflammatory muscle pain via activating cutaneous nociceptors and subsequently inhibiting the abnormal activity of muscular nociceptive neurons.

Electroacupuncture and Moxibustion-Like Stimulation Relieves Inflammatory Muscle Pain by Activating Local Distinct Layer Somatosensory Afferent Fibers

“…Our previous study revealed that noxious MS (> 43 • C) was able to drive long-distance neural reflex by activating peptidergic C-fibers (Su et al, 2015), which was in line with the results that noxious MS (about 50 • C) activated local SP-IR or CGRP-IR cutaneous terminals in the present study. In addition, cutaneous nerve transection abolished the analgesic effect of C-afferents in the skin over the inflamed muscle (Xie et al, 1995;Fang et al, 2020). In this study, cutaneous nociceptor-mediated noxious MS analgesia was also demonstrated, while it disappeared after skin nerve transection.…”

“…Nociceptive transmission could likewise trigger the descending inhibition system to regulate SRD neurons (Pinto et al, 2008). Besides, noxious stimuli on the contralateral side (Fang et al, 2020) or BL57 acupoint area (data not shown) over the inflamed muscle failed to relieve pain behavior, in turn implicating that presynaptic inhibition FIGURE 6 | Diagram of distinct primary afferent pathways of deep electroacupuncture (dEA)-and moxibustion-like stimulation (MS)-induced analgesic effects. dEA activates muscular A-fibers at the BL57 acupoint, while noxious MS or capsaicin (CAP) excites cutaneous C-fibers to improve muscle pain behavior via inhibiting spontaneous activity of muscular C-fibers.…”

“…Also, continuous A-fiber threshold electric stimuli substantially decreased both antidromic C-fiber spontaneous activity and neurogenic inflammation in chronic neuropathic pain (Zhu et al, 2012). Furthermore, topical irritants such as capsaicin (CAP), mustard oil, and peppermint oil could attenuate inflammatory muscle pain by activating cutaneous C-fiber afferents (Fang et al, 2020). These studies shed light on different layers of somatotopic afferent nerves in relieving chronic pain.…”

“…Weight-bearing measurement, a natural spontaneous pain indicator (Xie et al, 1995;Vermeirsch et al, 2007;Fang et al, 2020;Hill and Bautista, 2020), was carried out to observe inflammatory muscle pain behavior induced by CFA. Generally, rats were positioned with the hindlimbs on force plates in an Incapacitance Tester (Life Science, IITC600, United States).…”

Electroacupuncture-Induced Muscular Inflammatory Pain Relief Was Associated With Activation of Low-Threshold Mechanoreceptor Neurons and Inhibition of Wide Dynamic Range Neurons in Spinal Dorsal Horn

“…The receptive fields (RFs) of the neurons were identified with a mechanical press stimulator (ALMEMO2450, Ahlborn, Germany). Muscular nociceptive neurons in CFA rats were evoked by 200-mN pressure stimulation when there was no response to 60-mN pressure stimulation, as described previously ( Fang et al, 2020 ). Therefore, innocuous stimulation (60 mN) and noxious stimulation (200 mN) were chosen to identify WDR neurons and LTM neurons in the spinal dorsal horn, respectively.…”