ArticlePain2014
Anti-hyperalgesic effects of a novel TRPM8 agonist in neuropathic rats: a comparison with topical menthol.
Article in Pain, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Osteoarthritis: molecular pathogenesis and potential therapeutic options.Signal transduction and targeted therapy · 2026Review
- Suppression of neuropathic pain hypersensitivity by TRPM8 is mediated by mGluR group II and III receptors acting differentially on distinct nociceptor inputs to spinal cord.Frontiers in pharmacology · 2026Article
- Cold- and TRPM8-dependent shaking in mammals and birds.Communications biology · 2025Article
- Borneol's Pre-Clinical Analgesic Efficacy: Mediated by Receptor and Immune Mechanisms.Journal of pain research · 2025Review
- TRPM8's Role in the Shift Between Opioid and Cannabinoid Pathways in Electroacupuncture for Inflammatory Pain in Mice.International journal of molecular sciences · 2024Article
- Review
- TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine.Nature communications · 2022Article
- Glucocorticoid Receptor/HCN4 Channels Interaction in Spinal Dorsal Horn Participates in the Regulation of Neuropathic Pain after Peripheral Nerve Injury in Rats.Bulletin of experimental biology and medicine · 2022Article
- The cation channel TRPM8 influences the differentiation and function of human monocytes.Journal of leukocyte biology · 2022Article
- The distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances.Frontiers in molecular neuroscience · 2022Review
- Structural and in Vitro Functional Characterization of a Menthyl TRPM8 Antagonist Indicates Species-Dependent Regulation.ACS medicinal chemistry letters · 2021Article
- Expression of transient receptor potential cation channel subfamily M member 8 in gastric cancer and its clinical significance.Experimental and therapeutic medicine · 2021Article
- Trigeminal Neuralgia TRPM8 Mutation: Enhanced Activation, Basal [CaNeurology. Genetics · 2021Article
- Anti-Hyperalgesic Properties of Menthol and Pulegone.Frontiers in pharmacology · 2021Article
- Chronicling changes in the somatosensory neurons after peripheral nerve injury.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Exploration of TRPM8 Binding Sites by β-Carboline-Based Antagonists and Their In Vitro Characterization and In Vivo Analgesic Activities.Journal of medicinal chemistry · 2020Article
- Structure-Based Design of Novel Biphenyl Amide Antagonists of Human Transient Receptor Potential Cation Channel Subfamily M Member 8 Channels with Potential Implications in the Treatment of Sensory Neuropathies.ACS chemical neuroscience · 2020Article
- Characterization of New TRPM8 Modulators in Pain Perception.International journal of molecular sciences · 2019Article
- Efficacy of the Game ReadyEuropean spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2019Article
- Modality selective roles of pro-nociceptive spinal 5-HTNeuropharmacology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Menthol has historically been used topically to alleviate various pain conditions. At low concentrations, this non-selective TRPM8 agonist elicits a cooling sensation, however higher concentrations result in cold hyperalgesia in normal subjects and paradoxically analgesia in neuropathic patients. Through behavioural and electrophysiological means, we examined whether this back-translated into a pre-clinical rodent model. Menthol was applied topically to the hind paws of naive and spinal nerve-ligated (SNL) rats. In behavioural assays, menthol did not affect withdrawal thresholds to mechanical stimulation and 10% and 40% menthol rarely sensitised withdrawals to innocuous cooling in naïve rats. However, in SNL rats, 10% and 40% menthol alleviated cold hypersensitivity. This was partly corroborated by in vivo electrophysiological recordings of dorsal horn lamina V/VI neurones. As several studies have implicated TRPM8 in analgesia, we examined whether a novel systemically available TRPM8 agonist, M8-Ag, had more potent anti-hyperalgesic effects than menthol in neuropathic rats. In vitro, M8-Ag activates TRPM8, expressed in HEK293 cells, with an EC50 of 44.97 nM. In vivo, M8-Ag inhibited neuronal responses to innocuous and noxious cooling in SNL rats with no effect in sham-operated rats. This effect was modality selective; M8-Ag did not alter neuronal responses to mechanical, heat or brush stimulation. In addition, M8-Ag attenuated behavioural hypersensitivity to innocuous cooling but not mechanical stimulation. These data suggest that menthol induced hyperalgesia is not consistently replicable in the rat and that the analgesic properties are revealed by injury. Systemic TRPM8 agonists might be beneficial in neuropathy without affecting normal cold sensitivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.