Injectable Capsaicin for the Management of Pain Due to Osteoarthritis

Abstract

Capsaicin is a potent agonist of the TRPV1 channel, a transduction channel that is highly expressed in nociceptive fibers (pain fibers) throughout the peripheral nervous system. Given the importance of TRPV1 as one of several transduction channels in nociceptive fibers, much research has been focused on the potential therapeutic benefits of using TRPV1 antagonists for the management of pain. However, an antagonist has two limitations. First, an antagonist in principle generally only affects one receptor. Secondly, most antagonists must have an ongoing presence on the receptor to have an effect. Capsaicin overcomes both liabilities by disrupting peripheral terminals of nociceptive fibers that express TRPV1, and thereby affects all of the potential means of activating that pain fiber (not just TRPV1 function). This disruptive effect is dependent on the dose and can occur within minutes. Thus, unlike a typical receptor antagonist, continued bioavailability at the level of the receptor is not necessary. By disrupting the entire terminal of the TRPV1-expressing nociceptive fiber, capsaicin blocks all the activation mechanisms within that fiber, and not just TRPV1 function. Topical capsaicin, an FDA approved treatment for neuropathic pain, addresses pain from abnormal nociceptor activity in the superficial layers of the skin. Effects after a single administration are evident over a period of weeks to months, but in time are fully reversible. This review focuses on the rationale for using capsaicin by injection for painful conditions such as osteoarthritis (OA) and provides an update on studies completed to date.

Single cell RNA-seq analysis identifies ferroptotic chondrocyte cluster and reveals TRPV1 as an anti-ferroptotic target in osteoarthritis

“… 45 , 57 It has been reported that CPS exhibited pain management effects on OA by disrupting the entire terminal of TRPV1-expressing nociceptive fibers. 58 Topical application of CPS has been included in the 2019 American College of Rheumatology/Arthritis Foundation Guideline for the pain management of knee OA. 59 Moreover, we previously showed that TRPV1 was highly expressed by infiltrated M1 macrophages in OA synovium and its activation played an inhibitory role of M1 macrophage polarization by Ca 2+ /CaMKII/Nrf2 signaling pathway.…”

Capsaicin-induced depolymerization of axonal microtubules mediates analgesia for trigeminal neuropathic pain

“… 15 Injectable capsaicin is also under development for the treatment of chronic pain from knee osteoarthritis. 6 Although the peripheral administration of capsaicin provides nonaddictive, nonopioidergic treatment for chronic pain, mechanisms underlying capsaicin-induced analgesia are poorly understood, and further improvement of the therapy is hindered.…”

2022 WSAVA guidelines for the recognition, assessment and treatment of pain

“…Transient receptor potential vanilloid 1 (TRPV1) agonists are predominantly expressed in nociceptive sensory neurons and are promising targets for chronic pain management. Resiniferatoxin and capsaicin are potent TRPV1 agonists currently under investigation, but not yet commercially available, that show promising results in dogs with OA (Iadarola et al 2018, Campbell et al 2021.…”