Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons

Pecze, László; Viskolcz, Béla; Oláh, Zoltán

doi:10.3389/fphys.2017.00378

Cited by 16 publications

(10 citation statements)

References 91 publications

(160 reference statements)

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“…This has both clinical and basic implications. In a clinical context, chemical ablation of nociceptive primary afferents is now a promising molecular neurosurgical approach for pain management 49 . Our present results indicate that if the ablation is extended to the brain, the effect of analgesia might be attenuated.…”

Section: Discussionmentioning

confidence: 99%

Supraspinal-selective TRPV1 desensitization induced by intracerebroventricular treatment with resiniferatoxin

Fukushima

Mamada

Iimura

et al. 2017

Sci Rep

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The transient receptor potential vanilloid type 1 (TRPV1) is a thermosensitive cation channel that triggers heat pain in the periphery. Long-term desensitization of TRPV1, which can be induced by excess amounts of agonists, has been a method for investigating the physiological relevance of TRPV1-containing neuronal circuits, and desensitization induced by various routes of administration, including systemic, intrathecal and intraganglionic, has been demonstrated in rodents. In the present study, we examined the effect of intracerebroventricular (i.c.v.) treatment with an ultrapotent TRPV1 agonist, resiniferatoxin (RTX), on nociception and the analgesic effect of acetaminophen, which is known to mediate the activation of central TRPV1. I.c.v. administration of RTX a week before the test did not affect the licking/biting response to intraplantar injection of RTX (RTX test), suggesting that such i.c.v. treatment spares the function of TRPV1 at the hindpaw. Mice that had been i.c.v.-administered RTX also exhibited normal nociceptive responses in the formalin test and the tail pressure test, but acetaminophen failed to induce analgesia in those mice in any of the tests. These results suggest that i.c.v. administration of RTX leads to brain-selective TRPV1 desensitization in mice.

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Section: Discussionmentioning

confidence: 99%

Supraspinal-selective TRPV1 desensitization induced by intracerebroventricular treatment with resiniferatoxin

Fukushima

Mamada

Iimura

et al. 2017

Sci Rep

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“…TRPV1 is a nonselective cation channel that can be activated by different physical and chemical stimuli, including temperatures over 43°C, acidic conditions (pH <6), and vanilloids [8,9,16]. The activation of TRPV1 induces the cellular influx of Ca 2+ and Na + ions [17][18][19], and the excess intracellular Ca 2+ and Na + leads to cell death [20]. Numerous putative endogenous and exogenous agonists and antagonists of TRPV1 have been identified and summarized (Table 1).…”

Section: What Is Trpv1mentioning

confidence: 99%

The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review

Li¹,

Chen²,

Chiang³

et al. 2021

Int. J. Biol. Sci.

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The transient receptor potential cation channel subfamily V member 1 (TRPV1) is a transmembrane protein that can be activated by various physical and chemical stimuli and is associated with pain transduction. In recent years, TRPV1 was discovered to play essential roles in cancer tumorigenesis and development, as TRPV1 expression levels are altered in numerous cancer cell types. Several investigations have discovered direct associations between TRPV1 and cancer cell proliferation, cell death, and metastasis. Furthermore, about two dozen TRPV1 agonists/antagonists are under clinical trial, as TRPV1 is a potential drug target for treating various diseases. Hence, more researchers are focusing on the effects of TRPV1 agonists or antagonists on cancer tumorigenesis and development. However, both agonists and antagonists may reveal anti-cancer effects, and the effect may function via or be independent of TRPV1. In this review, we provide an overview of the impact of TRPV1 on cancer cell proliferation, cell death, and metastasis, as well as on cancer therapy and the tumor microenvironment, and consider the implications of using TRPV1 agonists and antagonists for future research and potential therapeutic approaches.

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“…Resiniferatoxin is an ultrapotent TRPV1 agonist with substantially greater selectivity and efficacy than capsaicin. Topical application of resiniferatoxin induces reversible analgesia, and injection produces irreversible analgesia through highly selective neuronal cytotoxic- (31). Intraarticular administration of resiniferatoxin has demonstrated long-lasting analgesic effect and functional improvement in canine osteoarthritis models (32).…”

Section: Trpv1 Targetsmentioning

confidence: 99%

Receptor and Molecular Targets for the Development of Novel Opioid and Non-Opioid Analgesic Therapies

2021

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BACKGROUND: Although conventional pain relief therapeutics have centered around μ-opioid agonists, these drugs are limited by adverse side effects, including respiratory depression and addiction potential. The ongoing opioid epidemic has galvanized research into novel analgesic therapies with more favorable profiles. New pharmacologic agents have been developed to target neuronal pathways involved in pain sensation. Certain receptors have been recognized to mediate nociceptive transmission, central sensitization, and the development of chronic pain states. OBJECTIVES: We conducted a literature review to identify potential targets for novel analgesic therapies. STUDY DESIGN: This study is a narrative review of potential analgesic targets. We characterize their antinociceptive mechanisms of action and evaluate their therapeutic potential. METHODS: A systemized search of available literature on novel analgesics was performed. A search was performed through the PubMed database to identify articles with key words of “novel analgesics,” “novel non-opioid analgesics,” “novel pain targets,” and “non-opioid analgesics.” Potential drug classes were identified and researched through corresponding keywords, with an emphasis on publications from 2018 to 2020. Older articles were included if frequently referenced by current literature. RESULTS: Potential novel analgesic targets include Nav1.7, Nav1.8, CaV2.2, and transient receptor potential vanilloid-1 (TRPV1) cation channel receptors in the peripheral nervous system. Other approaches disrupt the synthesis of pronociceptive signaling molecules such as nitric oxide, prostaglandin E2, and interleukin-6 (IL-6). Within central pain pathways, modification of -opioid, -opioid, N-methyl-D-aspartate, and cannabinoid receptors have been investigated in chronic pain and hyperalgesia models. Recent advances in molecular technology have also presented opportunities to modify protein expression or the cellular genome altogether. LIMITATIONS: Several analgesic targets have only demonstrated efficacy in preclinical trials. There are limited data evaluating the long-term safety profiles of therapies further on in development. CONCLUSIONS: We provide an overview of potential analgesic therapies in various stages of development, which may become clinically relevant in the near future. Some drugs such as TRPV1 agonists, anti-IL-6, and anti-nerve growth factor antibodies have demonstrated analgesic effect in specific clinical pain states. KEY WORDS: Nav1.7, Cav2.2, TRPV1, mPGES-1, IL-6, FAAH, NGF, gene therapy

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Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons

Cited by 16 publications

References 91 publications

Supraspinal-selective TRPV1 desensitization induced by intracerebroventricular treatment with resiniferatoxin

Supraspinal-selective TRPV1 desensitization induced by intracerebroventricular treatment with resiniferatoxin

The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review

Receptor and Molecular Targets for the Development of Novel Opioid and Non-Opioid Analgesic Therapies

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