Abstract / Description of output
TRPM8 is a cation channel expressed in a small subpopulation of sensory neurons, which
detect innocuous cooling and mostly lack characteristics of nociceptors. Whether TRPM8
normally contributes to noxious cold sensing is debatable as few TRPM8-positive neurons
co-express nociceptive markers. TRPM8 is a promising analgesic target. TRPM8 agonists
cause analgesia in chronic pain states, by TRPM8-expressing afferents gating-out a wide
range of hypersensitive pain responses in spinal cord. TRPM8 antagonists may attenuate
exaggerated responses to mild cooling during chronic pain but will not achieve generalised
analgesia as they can only block cool detection, not the clinically problematic
hypersensitivity to other sensory modalities. Biochemical and physiological properties of
TRPM8, the chemistry of TRPM8 ligands, intracellular modulation of TRPM8 and the
neurobiological consequences of TRPM8 activation are discussed, with a view to future
improvements in therapeutic targeting.
detect innocuous cooling and mostly lack characteristics of nociceptors. Whether TRPM8
normally contributes to noxious cold sensing is debatable as few TRPM8-positive neurons
co-express nociceptive markers. TRPM8 is a promising analgesic target. TRPM8 agonists
cause analgesia in chronic pain states, by TRPM8-expressing afferents gating-out a wide
range of hypersensitive pain responses in spinal cord. TRPM8 antagonists may attenuate
exaggerated responses to mild cooling during chronic pain but will not achieve generalised
analgesia as they can only block cool detection, not the clinically problematic
hypersensitivity to other sensory modalities. Biochemical and physiological properties of
TRPM8, the chemistry of TRPM8 ligands, intracellular modulation of TRPM8 and the
neurobiological consequences of TRPM8 activation are discussed, with a view to future
improvements in therapeutic targeting.
| Original language | English |
|---|---|
| Title of host publication | TRP channels as therapeutic targets - from basic science to clinical use |
| Editors | Arpad Szallasi |
| Place of Publication | Waltham, MA, USA |
| Publisher | Academic Press |
| Pages | 239-262 |
| Number of pages | 24 |
| ISBN (Print) | 978-0-12-420024-1 |
| Publication status | Published - 17 Nov 2015 |
Keywords / Materials (for Non-textual outputs)
- TRPM8, pain, analgesia, cool sensing, 5-HT1B receptor, intracellular signalling