Thermosensitive transient receptor potential melastatin 8 (TRPM8) antagonists are considered to be potential therapeutic agents for the treatment of cold hypersensitivity. The discovery of a new class of TRPM8 antagonists that shows in vivo efficacy in the rat chronic constriction injury (CCI)-induced model of neuropathic pain is described.
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http://dx.doi.org/10.1016/j.bmcl.2012.01.060 | DOI Listing |
bioRxiv
December 2024
Center for Pain Therapeutics and Addiction Research, School of Dentistry, University of Texas Health San Antonio, Texas, 78229, USA.
Truncated TrkB (TrkBT1), traditionally considered a dominant-negative regulator of full-length TrkB (TrkBTK+), remains poorly understood in peripheral sensory neurons, particularly nociceptors. Furthermore, sensory neuronal TrkB expression and function has been traditionally associated with non-nociceptive neurons, particularly Aδ low-threshold mechanoreceptors. This study challenges prevailing assumptions by demonstrating that TrkBT1 is the predominant TrkB isoform expressed in sensory neurons and plays a functional role in modulating neuronal activity.
View Article and Find Full Text PDFExp Eye Res
January 2025
Laboratory of Ocular Immunology, Transplantation and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address:
Substance P (SP) expressed by corneal nerves, is an 11-amino acid long neuropeptide from the tachykinin family, encoded by the Tac1 gene, and binds to neurokinin receptors. SP overexpression is associated with various pathological responses in the cornea including vasodilation, pain, inflammation, and angiogenesis in the normally avascular tissue. This study investigates the role of neurokinin-1 receptor (NK-1R) mediated signaling in nociception, nerve regeneration, and neuronal activation following mechanical corneal injury in mice.
View Article and Find Full Text PDFCont Lens Anterior Eye
January 2025
Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China; Department of Integrative Medicine, Baoshan Campus of Huashan Hospital, Fudan University, Shanghai, China. Electronic address:
Purpose: To investigate the efficacy and safety of transient receptor potential (TRP) channel modulators for dry eye.
Methods: A thorough search for randomized clinical trials was conducted in seven databases up to February 16, 2024. Suitable studies were identified according to inclusion and exclusion criteria, extracted data were synthesized and analyzed using Review Manager 5.
SLAS Discov
December 2024
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; University of Pittsburgh Hillman Cancer Center, Pittsburgh, PA 15232, USA. Electronic address:
Development, optimization, and calibration of human transient receptor potential (TRP) channel Ca mobilization assays for TRPM8, TRPV1, and TRPA1 are described. Heterologous expression of hTRPM8 in HEK293T cells was required for anti-TRPM8 antibody staining and TRPM8 agonist induced Ca mobilization signals which were both used to optimize transfection efficiency. FLIPR Calcium 6 dye concentration, loading time, and TRPM8 transfected cell seeding density were optimized and a DMSO tolerance of ≤0.
View Article and Find Full Text PDFPain
December 2024
Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
The mechanism causing cold pain in humans is unresolved. Animal data suggest a nonredundant contribution to cold pain for transient receptor potential channels TRPM8 and TRPA1 for detection and voltage-gated sodium channels NaV1.7 and NaV1.
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