Abstract
Transient receptor potential melastatin 8 (TRPM8) is a non-selective cation channel activated by cold temperature and cooling agents. TRPM8 is expressed in peripheral cold thermoreceptors and plays a fundamental role in sensing mild, cool temperatures. In addition, cumulative evidence obtained in humans and different animals models, combined with pharmacological and gene silencing techniques, suggest that TRPM8 may also play a role in cold discomfort and the pathophysiology of cold pain. This article reviews the available evidence in a critical fashion. In addition, the article reviews the possible role of TRPM8 in basal tearing, cold urticaria and airway irritation. Collectively, these results suggest that pharmacological modulators of TRPM8 could have potential indications in a variety of conditions, including dry eye disease, airway irritation, teeth hypersensitivity, migraine and neuropathic pain. However, additional studies, especially in humans, are needed to verify these preliminary observations. The paucity of potent, specific pharmacological TRPM8 antagonists available is a current limitation for further progress in this field.
Highlights
Hypersensitivity to cold temperature, manifested clinically as cold hyperalgesia or cold allodynia, is a frequent, disabling, symptom in patients suffering with neuropathic pain [1,2,3,4]
This review focuses on the role of Transient receptor potential melastatin 8 (TRPM8) in cold pain, we should briefly discuss the possible role of transient receptor potential ankyrin 1 (TRPA1) in cold nociception, a controversial issue in the literature [reviewed by 165]
A couple of years ago we compared the therapeutic prospects of TRPM8 channel modulators in the treatment of cold pain to the tip of a floating iceberg, showing some promise but with much of this potential still hidden beneath the surface [22]
Summary
Hypersensitivity to cold temperature, manifested clinically as cold hyperalgesia or cold allodynia, is a frequent, disabling, symptom in patients suffering with neuropathic pain [1,2,3,4]. The threshold of activation, the expression within peptidergic nociceptors and behavioural results suggest that TRPA1 is a noxious cold sensor [15,16]. The nerve endings of TRPM8-containing fibers terminate in peripheral zones mediating distinct perceptions of cold and pain, suggesting that TRPM8 expressing neurons may be responsible for a wide range of sensory functions [50].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
