Related Experiment Video
Updated: May 6, 2026
A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice
Published on: March 17, 2015
TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons
Mohammad-Reza Ghovanloo1, Philip R Effraim1, Sidharth Tyagi1
1From the Department of Neurology (M.-R.G., S.T., A.M.A., X.C., J.-H.Y., B.R.S., S.D.D.-H., S.G.W.), Yale University School of Medicine, New Haven; Center for Neuroscience and Regeneration Research (M.-R.G., P.R.E., S.T., A.M.A., X.C., J.-H.Y., B.R.S., S.D.D.-H., S.G.W.), Yale University, New Haven; Neuro-Rehabilitation Research Center (M.-R.G., P.R.E., S.T., A.M.A., X.C., J.-H.Y., B.R.S., S.D.D.-H., S.G.W.), Veterans Affairs Connecticut Healthcare System, West Haven; Department of Anesthesiology (P.R.E.), Yale University School of Medicine, New Haven, CT; and Department of Ophthalmology (D.S.J.), Massachusetts Eye and Ear, Harvard Medical School, Boston.
Rare TRPM8 gene variants may cause persistent ocular pain after LASIK surgery by increasing nerve cell activity. These findings suggest TRPM8 channel inhibitors could be a future treatment for chronic pain.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Persistent pain after corneal refractive surgery (LASIK) is a complex condition.
- LASIK severs trigeminal nerve axons, offering a model for axonal injury and pain.
- Genomic analysis revealed rare variants in ion channel genes, including TRPM8, in patients with persistent pain.
Purpose of the Study:
- Investigate the functional impact of two TRPM8 variants (D665N and V915M) found in patients with persistent postoperative ocular pain.
- Determine how these mutations affect the biophysical and pharmacological properties of the TRPM8 channel.
Main Methods:
- Utilized patch-clamp electrophysiology to analyze mutant TRPM8 channel function.
- Employed multielectrode array (MEA) recordings in transfected trigeminal ganglion neurons.
- Compared the activity of wild-type (WT) TRPM8 channels with D665N and V915M mutant channels.
Main Results:
- Mutations D665N and V915M shifted TRPM8 channel activation curves hyperpolarized.
- Both mutations increased TRPM8 channel sensitivity to menthol.
- Mutant TRPM8 channels led to increased spontaneous activity in trigeminal ganglion neurons.
Conclusions:
- Proexcitatory TRPM8 mutations contribute to trigeminal nerve hyperexcitability and persistent ocular pain post-LASIK.
- This study provides further evidence for TRPM8's role in human pain.
- TRPM8 channel inhibitors warrant investigation as potential treatments for this type of chronic pain.
