Progress in the development of TRPV1 small-molecule antagonists: Novel Strategies for pain management

Zhu, Kun; Wang, Lin; Liao, TingTing; Li, Wen; Zhou, Jing; You, Yaodong; Shi, Jianyou

doi:10.1016/j.ejmech.2023.115806

Cited by 9 publications

(3 citation statements)

References 171 publications

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“…Although many TRPV1 antagonists have been developed, none have received clinical approval, which may indicate that targeting only the TRPV1 channel may not be the optimal strategy for developing analgesic drugs. The development of multi-targeted or multifunctional TRPV1 antagonists may enable multilevel modulation of multiple TRP subtypes, other pain-related targets, and synergize with other drugs or therapies to achieve better analgesic effects [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

Research trends and frontier hotspots of TRPV1 based on bibliometric and visualization analyses

Zeng,

Lu,

Chu

et al. 2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

Research trends and frontier hotspots of TRPV1 based on bibliometric and visualization analyses

Zeng,

Lu,

Chu

et al. 2024

Heliyon

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“…There is increasing evidence that TRPV1 plays a major role in cancer pain [ 86 ]. In preclinical studies, selective TRPV1 inactivation through genetic manipulation [ 87 , 88 ] or pharmacological blockade [ 89 ] was shown to ameliorate cancer pain. Ehrlich tumor cells injected into the paw of mice cause nociception [ 90 ].…”

Section: Can Selective Trpv1 Antagonism Ameliorate Cancer Pain?mentioning

confidence: 99%

Targeting TRPV1 for Cancer Pain Relief: Can It Work?

Szallasi

2024

Cancers

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Chronic intractable pain affects a large proportion of cancer patients, especially those with metastatic bone disease. Blocking sensory afferents for cancer pain relief represents an attractive alternative to opioids and other drugs acting in the CNS in that sensory nerve blockers are not addictive and do not affect the mental state of the patient. A distinct subpopulation of sensory afferents expresses the capsaicin receptor TRPV1. Intrathecal resiniferatoxin, an ultrapotent capsaicin analog, ablates TRPV1-expressing nerve endings exposed to the cerebrospinal fluid, resulting in permanent analgesia in women with cervical cancer metastasis to the pelvic bone. High-dose capsaicin patches are effective pain killers in patients with chemotherapy-induced peripheral neuropathic pain. However, large gaps remain in our knowledge since the mechanisms by which cancer activates TRPV1 are essentially unknown. Most important, it is not clear whether or not sensory denervation mediated by TRPV1 agonists affects cancer progression. In a murine model of breast cancer, capsaicin desensitization was reported to accelerate progression. By contrast, desensitization mediated by resiniferatoxin was found to block melanoma growth. These observations imply that TRPV1 blockade for pain relief may be indicated for some cancers and contraindicated for others. In this review, we explore the current state of this field and compare the analgesic potential of TRPV1 antagonism and sensory afferent desensitization in cancer patients.

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“…pH values below 6, a level easily reached by tissue injury such as infection and inflammation, also show this activity [ 11 ], giving TRPV1 an important role in the process of injury-related hyperalgesia, inflammation, and pain [ 12 ]. Activation of TRPV1 by vanilloids is followed by rapid and sustained desensitization [ 13 , 14 ], resulting in a particular form of analgesia, thus making TRPV1 a potential pharmacological target in pain therapy [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Association between Variants of the TRPV1 Gene and Body Composition in Sub-Saharan Africans

Giannì,

Antinucci,

Bertoncini

et al. 2024

Genes

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In humans, the transient receptor potential vanilloid 1 (TRPV1) gene is activated by exogenous (e.g., high temperatures, irritating compounds such as capsaicin) and endogenous (e.g., endocannabinoids, inflammatory factors, fatty acid metabolites, low pH) stimuli. It has been shown to be involved in several processes including nociception, thermosensation, and energy homeostasis. In this study, we investigated the association between TRPV1 gene variants, sensory perception (to capsaicin and PROP), and body composition (BMI and bioimpedance variables) in human populations. By comparing sequences deposited in worldwide databases, we identified two haplotype blocks (herein referred to as H1 and H2) that show strong stabilizing selection signals (MAF approaching 0.50, Tajima’s D > +4.5) only in individuals with sub-Saharan African ancestry. We therefore studied the genetic variants of these two regions in 46 volunteers of sub-Saharan descent and 45 Italian volunteers (both sexes). Linear regression analyses showed significant associations between TRPV1 diplotypes and body composition, but not with capsaicin perception. Specifically, in African women carrying the H1-b and H2-b haplotypes, a higher percentage of fat mass and lower extracellular fluid retention was observed, whereas no significant association was found in men. Our results suggest the possible action of sex-driven balancing selection at the non-coding sequences of the TRPV1 gene, with adaptive effects on water balance and lipid deposition.

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Progress in the development of TRPV1 small-molecule antagonists: Novel Strategies for pain management

Cited by 9 publications

References 171 publications

Research trends and frontier hotspots of TRPV1 based on bibliometric and visualization analyses

Research trends and frontier hotspots of TRPV1 based on bibliometric and visualization analyses

Targeting TRPV1 for Cancer Pain Relief: Can It Work?

Association between Variants of the TRPV1 Gene and Body Composition in Sub-Saharan Africans

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