Abstract
Temperature sensing is a crucial feature of the nervous system, enabling organisms to avoid physical danger and choose optimal environments for survival. TRPM8 (Transient Receptor Potential Melastatin type 8) belongs to a select group of ion channels which are gated by changes in temperature, are expressed in sensory nerves and/or skin cells and may be involved in temperature sensing. This channel is activated by a moderate decrease in temperature, with a threshold of ∼25 °C in heterologous expression systems, and by a variety of natural and synthetic compounds, including menthol. While the physiological role of TRPM8 as a transducer of gentle cooling is widely accepted, its involvement in acute noxious cold sensing in healthy tissues is still under debate. Although accumulating evidence indicates that TRPM8 is involved in neuropathic cold allodynia, in some animal models of nerve injury peripheral and central activation of TRPM8 is followed by analgesia. A variety of inflammatory mediators, including bradykinin and prostaglandin E2, modulate TRPM8 by inhibiting the channel and shifting its activation threshold to colder temperatures, most likely counteracting the analgesic action of TRPM8. While important progress has been made in unraveling the biophysical features of TRPM8, including the revelation of its voltage dependence, the precise mechanism involved in temperature sensing by this channel is still not completely understood. This article will review the current status of knowledge regarding the (patho)physiological role(s) of TRPM8, its modulation by inflammatory mediators, the signaling pathways involved in this regulation, and the biophysical properties of the channel.
Keywords: Cold, pain, inflammation, neuropathy, cancer, TRPM8, bradykinin, prostaglandin, lung epithelia, cold allodynia, CMR1, trigeminal ganglion, cDNA, geniculate ganglia, TRPV1, DRG neurons, TRP channels, cysteines C929, CPS-369, Coolact P, PMD-38, orthologue, mutagenesis, HEK293 cells, S4-S5 linker, GPCRs, prostaglandin E2, PKC phosphorylation, C-fibres, thermal grill illusion, innocuous cold nociception, micturition reflex, Brain-Derived Neurotrophic Factor, TRPM8 mRNA, CCI model
Current Pharmaceutical Biotechnology
Title: TRPM8, a Sensor for Mild Cooling in Mammalian Sensory Nerve Endings
Volume: 12 Issue: 1
Author(s): Alexandru Babes, Alexandru Cristian Ciobanu, Cristian Neacsu and Ramona-Madalina Babes
Affiliation:
Keywords: Cold, pain, inflammation, neuropathy, cancer, TRPM8, bradykinin, prostaglandin, lung epithelia, cold allodynia, CMR1, trigeminal ganglion, cDNA, geniculate ganglia, TRPV1, DRG neurons, TRP channels, cysteines C929, CPS-369, Coolact P, PMD-38, orthologue, mutagenesis, HEK293 cells, S4-S5 linker, GPCRs, prostaglandin E2, PKC phosphorylation, C-fibres, thermal grill illusion, innocuous cold nociception, micturition reflex, Brain-Derived Neurotrophic Factor, TRPM8 mRNA, CCI model
Abstract: Temperature sensing is a crucial feature of the nervous system, enabling organisms to avoid physical danger and choose optimal environments for survival. TRPM8 (Transient Receptor Potential Melastatin type 8) belongs to a select group of ion channels which are gated by changes in temperature, are expressed in sensory nerves and/or skin cells and may be involved in temperature sensing. This channel is activated by a moderate decrease in temperature, with a threshold of ∼25 °C in heterologous expression systems, and by a variety of natural and synthetic compounds, including menthol. While the physiological role of TRPM8 as a transducer of gentle cooling is widely accepted, its involvement in acute noxious cold sensing in healthy tissues is still under debate. Although accumulating evidence indicates that TRPM8 is involved in neuropathic cold allodynia, in some animal models of nerve injury peripheral and central activation of TRPM8 is followed by analgesia. A variety of inflammatory mediators, including bradykinin and prostaglandin E2, modulate TRPM8 by inhibiting the channel and shifting its activation threshold to colder temperatures, most likely counteracting the analgesic action of TRPM8. While important progress has been made in unraveling the biophysical features of TRPM8, including the revelation of its voltage dependence, the precise mechanism involved in temperature sensing by this channel is still not completely understood. This article will review the current status of knowledge regarding the (patho)physiological role(s) of TRPM8, its modulation by inflammatory mediators, the signaling pathways involved in this regulation, and the biophysical properties of the channel.
Export Options
About this article
Cite this article as:
Babes Alexandru, Cristian Ciobanu Alexandru, Neacsu Cristian and Babes Ramona-Madalina, TRPM8, a Sensor for Mild Cooling in Mammalian Sensory Nerve Endings, Current Pharmaceutical Biotechnology 2011; 12 (1) . https://dx.doi.org/10.2174/138920111793937835
DOI https://dx.doi.org/10.2174/138920111793937835 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Epoxyeicosatrienoic Acids as a Therapeutic Target for Nephropathy Associated with Diabetes and Hypertension
Current Hypertension Reviews Efficacy of HGF Gene Transfer for Various Nervous Injuries and Disorders
Central Nervous System Agents in Medicinal Chemistry Recent Advances in Pharmacological Interventions of Chronic Prostatitis/ Chronic Pelvic Pain Syndrome
Current Pharmaceutical Design Vitamins B1, B2, B3 and B9 – Occurrence, Biosynthesis Pathways and Functions in Human Nutrition
Mini-Reviews in Medicinal Chemistry A Current Update on the Use of Alpha Lipoic Acid in the Management of Type 2 Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias
Current Pharmaceutical Design Phosphodiesterase Type 5 Inhibitors: Unmet Needs
Current Pharmaceutical Design Neurodegeneration in the Pathogenesis of Diabetic Retinopathy: Molecular Mechanisms and Therapeutic Implications
Current Medicinal Chemistry Novel Methods of Genetic Modification of Human Pluripotent Stem Cells
Recent Patents on Regenerative Medicine Advances in Drug Discovery and Development for Pediatric Tuberculosis
Mini-Reviews in Medicinal Chemistry Efficacy of Duloxetine in Patients with Chronic Pain Conditions
Current Drug Therapy A Comprehensive Review on Pharmacology and Toxicology of Bioactive Compounds of <i>Lagerstroemia Speciosa(L.</i>) Pers.
Current Traditional Medicine Mining for Protein Kinase Substrates: Integration of Biochemistry, Genetics and Proteomics
Current Proteomics Molecular Genetics and Epidemiology of Japanese Type 1 Diabetes
Current Pharmacogenomics Evaluation of the Fibromyalgia and Related Risk Factors in Patients with Advanced Kidney Failure Undergoing Hemodialysis
Current Rheumatology Reviews Essentials of Daflon 500 mg: From Early Valve Protection to Long-Term Benefits in the Management of Chronic Venous Disease
Current Pharmaceutical Design Various Non-Injectable Delivery Systems for the Treatment of Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Role of NFAT5 in Inflammatory Disorders Associated with Osmotic Stress
Current Genomics Meet Our Editorial Board Member
Current Drug Targets Fibrates and Statins in the Treatment of Diabetic Retinopathy
Current Pharmaceutical Biotechnology