Ablation of TRPV11 afferent terminals by capsaicin mediates long-lasting analgesia for trigeminal neuropathic pain
PublisherSociety for Neuroscience
MetadataShow full item record
AbstractTrigeminal neuropathic pain (TNP) is often resistant to current pharmacotherapy, and there is a pressing need to develop more efficacious treatments. Capsaicin is a pungent ingredient of chili peppers and specifically activates transient receptor potential vanilloid subtype 1 (TRPV1), a Ca21-permeable ion channel. Topical capsaicin invariably induces burning pain. Paradoxically, the transient pain is often followed by prolonged attenuation of the preexisting pathologic pain from the same region. However, the mechanisms underlying capsaicin-induced analgesia are not well understood. Although the reports of the involvement of TRPV1 and TRPV11 afferents in neuropathic pain are controversial, we recently demonstrated that TRPV1 and TRPV11 afferents are involved in mechanical hyperalgesia in mice with chronic constriction injury of the infraorbital nerve (ION-CCI). Consistently, chemogenetic inhibition of TRPV1-lineage (TRPV1-LN) afferents attenuated mechanical hyperalgesia and ongoing pain. In mice with ION-CCI, we found that a single focal injection of capsaicin into facial skin led to attenuation of mechanical hyperalgesia over two weeks. Capsaicin treatment also attenuated secondary hyperalgesia in extraterritorial mandibular skin. Furthermore, capsaicin treatment decreased ongoing pain. Longitudinal in vivo two-photon imaging of cutaneous nerve fibers showed that such capsaicin-induced analgesia is correlated with cutaneous nerve terminal density. Furthermore, preventing capsaicin-induced ablation of afferent terminals by co-administration of capsaicin with MDL28170, an inhibitor of calpain, abolished capsaicin-induced analgesia. These results suggest that a single focal injection of capsaicin induces long-lasting analgesia for neuropathic pain via selective ablation of TRPV11 afferent terminals and that TRPV11 afferents contribute to the maintenance of TNP.
SponsorsThis work was supported by National Institutes of Health Grants DE023846 and DE027731.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85085618371&doi=10.1523%2fENEURO.0118-20.2020&partnerID=40&md5=ef6deeae59ebbfb9fed1f05c8a5d5cfe; http://hdl.handle.net/10713/12995
- Ca<sup>2+</sup> and calpain mediate capsaicin-induced ablation of axonal terminals expressing transient receptor potential vanilloid 1.
- Authors: Wang S, Wang S, Asgar J, Joseph J, Ro JY, Wei F, Campbell JN, Chung MK
- Issue date: 2017 May 19
- Fight fire with fire: Neurobiology of capsaicin-induced analgesia for chronic pain.
- Authors: Arora V, Campbell JN, Chung MK
- Issue date: 2021 Apr
- Vitamin B complex attenuated heat hyperalgesia following infraorbital nerve constriction in rats and reduced capsaicin in vivo and in vitro effects.
- Authors: Kopruszinski CM, Reis RC, Bressan E, Reeh PW, Chichorro JG
- Issue date: 2015 Sep 5
- Palvanil, a non-pungent capsaicin analogue, inhibits inflammatory and neuropathic pain with little effects on bronchopulmonary function and body temperature.
- Authors: Luongo L, Costa B, D'Agostino B, Guida F, Comelli F, Gatta L, Matteis M, Sullo N, De Petrocellis L, de Novellis V, Maione S, Di Marzo V
- Issue date: 2012 Sep
- Cytokine activin C ameliorates chronic neuropathic pain in peripheral nerve injury rodents by modulating the TRPV1 channel.
- Authors: Huang YK, Lu YG, Zhao X, Zhang JB, Zhang FM, Chen Y, Bi LB, Gu JH, Jiang ZJ, Wu XM, Li QY, Liu Y, Shen JX, Liu XJ
- Issue date: 2020 Dec