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Interstitial Cystitis
Published in Gary W. Jay, Practical Guide to Chronic Pain Syndromes, 2016
Neel Shah, Hossein Sadeghi-Nejad, Robert Moldwin
Two neurotoxins, resiniferatoxin and capsaicin, have been employed as potential treatments for IC. Currently, there is no data supporting the use of capsaicin. In a meta-analysis, Mourtzoukou et al. concluded that, although well tolerated, the efficacy of resiniferatoxin still remains questionable (58). Clorpactin and silver nitrate are two other agents that have been used, but both are caustic. Caution is advised when administering these agents, as they can result in ureteral and bladder scarring. Intravesical bacillus Calmette-Guerin (BCG) has also been investigated as a potential treatment. After 34 weeks in a randomized, controlled trial, overall response rates to both BCG and placebo were low; and there was no statistically significant difference in response rate between the BCG and placebo groups (59).
Coughing induced by drugs
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
The capsaicin receptor is one of a family of irritant receptors, known as the ‘transient receptor potential’ family.2 The importance of this receptor in the production of cough in humans is demonstrated by the exquisite sensitivity of the human cough reflex to specific agonists of this receptor, such as capsaicin3 and resiniferatoxin.4 Indeed, resiniferatoxin is the most potent tussive agent known. The TRPV1 is a non-specific ion channel, which responds not only to vanilloids, such as capsaicin, but also to acidity and a change in temperature. The receptor may be up-regulated by inflammatory mediators,5 and of particular interest it has been demonstrated that lipoxygenase products act intracellularly to increase the opening probability of the receptor.6 Thus, in lung diseases such as asthma, TRPV1 activity is increased and may be responsible for the cough associated with inhaled antiasthmatic medication.7
Proinflammatory Peptides in Sensory Nerves of the Airways
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
Peter Baluk, Donald M. McDonald
A further development that has advanced our understanding of capsaicin-sensitive nerves is the introduction of resiniferatoxin, an ultrapotent analog of capsaicin (222). Although capsaicin and resiniferatoxin are derived from a different genus of plants (Capsicum and Euphorbia, respectively), they share a common homovanillic acid motif, and hence their binding site has been termed the vanilloid receptor (223). Use of radiolabeled resiniferatoxin has permitted the direct visualization of binding sites on sensory nerve fibers in the dorsal horn of the spinal cord (224). Resiniferatoxin has a similar spectrum of actions to capsaicin, for example, it causes the release of peptides from sensory nerves in the airways (162,225), and desensitization and destruction of sensory nerves [20], but it is up to several orders of magnitude more potent. Interestingly, the relative potency of resiniferatoxin compared to capsaicin varies for different actions. Resiniferatoxin is 1000 times more potent at inducing neurogenic inflammation, but does not stimulate pulmonary chemoreceptors or cause apnea, as does capsaicin (20,223). This suggests the possible existence of subtypes of vanilloid receptors. The strong binding of radiolabeled resiniferatoxin to the vanilloid receptor has permitted the direct visualization of binding sites on sensory nerve fibers in the dorsal horn of the spinal cord (224), and offers hope for the isolation and molecular characterization of the receptor (222). It is not yet clear why vanilloid receptors should exist on sensory nerves at all, or whether there is an endogenous ligand that stimulates these receptors.
Capsaicin and cancer: Guilty as charged or innocent until proven guilty?
Published in Temperature, 2023
In the ‘70ies, the mouse ear erythema test was broadly used as a surrogate bioassay to discover putative tumor promoting agents in natural sources. In fact, resiniferatoxin, a phorbol-related diterpene analog of capsaicin, was isolated from the latex of Euphorbia resinifera as a putative tumor promoter based on its extraordinary irritancy in the mouse skin [70]. In a two-stage carcinogenesis model, resiniferatoxin did not promote the formation of tumors in the skin of NMRI mice after 7,12-dimethylbenzanthracene (DMBA) initiation [71], nor did it affect the phorbol 12-myristate 13-acetate (PMA)-induced epidermal hyperplasia [72], though it did block the inflammatory response to PMA [72,73]. In CD1 mice, resiniferatoxin applied to the shaved back skin caused no skin tumors during the lifetime of the animals (Blumberg and Szallasi, unpublished observation).
Emerging injectable therapies for osteoarthritis
Published in Expert Opinion on Emerging Drugs, 2022
In a phase II trial, a single dose of intraarticular CNTX-4975, a synthetic form of capsaicin, resulted in a significant dose-dependent improvement in pain among patients with knee OA after 24 weeks. The most common adverse effect was, unsurprisingly, initial procedural-related pain as might occur with initial exposure to chili [79]. This procedural-related pain was addressed in a phase III trial with cold gel wraps or ice water packs, which was found to be clinically acceptable and well tolerated. This trial is currently underway, and preliminary data has shown high levels of clinical response 8 weeks post a single intraarticular injection of CNTX-4975 [80]. Another phase III trial of repeated doses of CNTX-4975 is also in progress, the effects of which will be measured up to 52 weeks [81]. Resiniferatoxin is an another TRPV1 agonist, and preliminary results of a phase 1b study demonstrate safety and efficacy after intra-articular administration [82].
A patent review of transient receptor potential vanilloid type 1 modulators (2014–present)
Published in Expert Opinion on Therapeutic Patents, 2021
Mengkang Gao, Yusui Wang, Lanqi Liu, Zhenrui Qiao, Lin Yan
In fact, in addition to TRPV1, many other receptors are expressed in nociceptive neurons and play important roles in the development and maintenance of pain. TRPV1 agonists (capsaicin and RTX) not only cause TRPV1-expressing nociceptive neurons desensitization but also make other receptors dormant. This development renewed interest in TRPV1 agonists. Currently, low-concentration capsaicin creams such as Zostrix (0.075%) and Axsain (0.025% capsaicin mixed with lidocaine) are popular over-the-counter (OTC) analgesic agents. Moreover, high-concentration capsaicin dermal patch (NGX-4010), liquid formulations (NGX-1998), and site-specific injections (ALGRX-4975) were also developed. In addition, the safety and clinical efficacy of RTX (with unique pharmacological properties) is also an area of active research. In 2009, a clinical trial was initiated on patients with chronic intractable bone pain caused by cancer metastasis (NCT0252261). In August 2020, resiniferatoxin (NCT04044742) enter Phase 3 clinical trials to evaluate its efficacy and safety in the treatment of pain due to osteoarthritis of the knee. We believe that reasonably developing and improving the drug delivery system of TRPV1 agonists (especially RTX) will be an excellent and safe strategy.