Anti-hyperalgesic effects of a novel TRPM8 agonist in neuropathic rats: A comparison with topical menthol

Patel, Ryan; Gonçalves, Leônor; Leveridge, Mathew; Mack, Stephen R.; Hendrick, Alan G.; Brice, Nicola; Dickenson, Anthony H.

doi:10.1016/j.pain.2014.07.022

Cited by 39 publications

(48 citation statements)

References 71 publications

(60 reference statements)

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“…He observed that topical ointment with peppermint oil (containing L-menthol) reduced pain in patients suffering from post-herpetic neuralgia and several studies have since substantiated the claim. 15,19,39,44,45,65 Today, L-menthol is widely used in ointments to counteract local inflammation, eczema and joint aches, in lozenges to relieve throat soreness and also in nasal sprays to decongest and de-inflame the upper airways in case of common colds and fl. Moreover, FDA has listed L-menthol as a local anesthetic, antipruritic and antitussive compound.…”

Section: Introductionmentioning

confidence: 99%

“…The relative promiscuity among the natural transient receptor potential (TRP) channels agonists is also applicable for L-menthol, which interacts with several TRP-channels besides TRPM8 as well as other receptors often in a concentration-dependent manner. 20,33,44,45 . However, a recent preclinical study convincingly ascertained TRPM8 to be the principal mediator of L-menthol-induced analgesia.…”

Section: Introductionmentioning

confidence: 99%

“…However, a recent preclinical study convincingly ascertained TRPM8 to be the principal mediator of L-menthol-induced analgesia. 45 Despite the widespread recognition of L-menthol's moderate pain-relieving properties to pre-existing painful or pruritic conditions, very little is known with regards to the characteristics of these anti-irritant effects and potential underlying mechanisms in humans.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

High-Concentration L-Menthol Exhibits Counter-Irritancy to Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde

Andersen

Gazerani

Arendt-Nielsen

2016

The Journal of Pain

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Drugs interacting with transient receptor potential channels are of great therapeutic potential. In the present study we established cutaneous pain and hyperalgesia using the TRPA1 agonist CA. Subsequently, we showed that the frequently used topical counterirritant and TRPM8 agonist, L-menthol, decreased evoked pain, hyperalgesia, and inflammation, indicating direct and indirect antinociceptive mechanisms.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High-Concentration L-Menthol Exhibits Counter-Irritancy to Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde

Andersen

Gazerani

Arendt-Nielsen

2016

The Journal of Pain

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“…This observation was confirmed in a recent study with spinal nerve-ligated (SNL) rats treated with a topical TRPM8 agonist, a 1,2,4-triazole derivative (M8-Ag). 66 This agonist inhibited neuronal responses to innocuous and noxious cooling in SNL rats, with no effect in the control group, and did not alter neuronal responses to mechanical, heat or brush stimulation.…”

Section: Trpm8 Inflammation and Painmentioning

confidence: 89%

“…66 This compound activates TRPM8 channels with a 45 nM EC 50 value and also TRPA1 thermoreceptors, although with lower potency (4 M). It attenuates neuronal responses after innocuous and noxious cooling, and reverses hypersensitivity to acetone-induced cooling in spinal nerve-ligated (SNL) rats.…”

Section: Five-membered Heterocycle Derivativesmentioning

confidence: 99%

Transient Receptor Potential Melastatin 8 Channel (TRPM8) Modulation: Cool Entryway for Treating Pain and Cancer

et al. 2016

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Abstract. TRPM8 ion channels, the primary cold sensors in humans, are activated by innocuous cooling (< 28 ºC) and cooling compounds (menthol, icilin), and are implicated in sensing unpleasant cold stimuli, as well as in mammalian thermoregulation. Over-expression of these thermoregulators in prostate cancer and in other life-threatening tumors, along with their contribution to an increasing number of pathological conditions, opens a plethora of medicinal chemistry opportunities to develop receptor modulators. This Perspective seeks to compile current known modulators for this ion channel, since both agonists and antagonists may be useful for the treatment of most TRPM8-mediated pathologies. We primarily focus on SAR data for the different families of compounds and the pharmacological properties of the most promising ligands. Furthermore, we also address the knowledge about the channel structure, although still in its infancy, and the role of the TRPM8 protein signalplex to channel function and dysfunction. We finally outline the potential future prospects of the challenging TRPM8 drug discovery field.

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Multidisciplinary Advances Address the Challenges in Developing Drugs against Transient Receptor Potential Channels to Treat Metabolic Disorders

Wang

2023

ChemMedChem

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Transient receptor potential (TRP) channels are cation channels that regulate key physiological and pathological processes in response to a broad range of stimuli. Moreover, they systemically regulate the release of hormones, metabolic homeostasis, and complications of diabetes, which positions them as promising therapeutic targets to combat metabolic disorders. Nevertheless, there are significant challenges in the design of TRP ligands with high potency and durability. Herein we summarize the four challenges as hydrophobicity, selectivity, mono‐target therapy, and interspecies discrepancy. We present 1134 TRP ligands with diversified modes of TRP‐ligand interaction and provide a detailed discussion of the latest strategies, especially cryogenic electron microscopy (cryo‐EM) and computational methods. We propose solutions to address the challenges with a critical analysis of advances in membrane partitioning, polypharmacology, biased agonism, and biochemical screening of transcriptional modulators. They are fueled by the breakthrough from cryo‐EM, chemoinformatics and bioinformatics. The discussion is aimed to shed new light on designing next‐generation drugs to treat obesity, diabetes and its complications, with optimal hydrophobicity, higher mode selectivity, multi‐targeting and consistent activities between human and rodents.

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Anti-hyperalgesic effects of a novel TRPM8 agonist in neuropathic rats: A comparison with topical menthol

Abstract: SummaryAn in vivo electrophysiological characterisation of the pro- and anti-nociceptive effects of TRPM8 agonists reveals menthol and a novel TRPM8 agonist have selective inhibitory effects on cold sensitivity in neuropathic rats.

Cited by 39 publications

References 71 publications

High-Concentration L-Menthol Exhibits Counter-Irritancy to Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde

High-Concentration L-Menthol Exhibits Counter-Irritancy to Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde

Transient Receptor Potential Melastatin 8 Channel (TRPM8) Modulation: Cool Entryway for Treating Pain and Cancer

Multidisciplinary Advances Address the Challenges in Developing Drugs against Transient Receptor Potential Channels to Treat Metabolic Disorders

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