Year: 2026
Type: article
Abstract: Cold sensation is gaining clinical significance in the diagnosis, prognosis, and treatment of chronic pain. Despite this, mechanisms responsible for normal and abnormal cool/cold detection remain underexplored compared to other sensory modalities. This narrative review presents a synthesis of innocuous cool and noxious cold processing in a standard stepwise framework spanning five stages of transduction, transmission, spinal modulation, projection, and ascending/descending cortical activity. Synthesizing molecular, anatomical, functional, and behavioral evidence, this review suggests that cold sensation relies on highly specialized, though still emerging, molecular and circuit-level frameworks. Specifically, we propose the possibility of P2Y1 role in noxious cold signaling and re-evaluate the potential mechanistic contribution of Nav1.3 to neuropathic cold hypersensitivity. The narrative translates these molecular findings for potential clinical application, advancing the case for cold-specific quantitative sensory testing (QST) as a vital biomarker for assessing descending pain modulation and chronic pain phenotypes.
Source: Discover Neuroscience
Authors: Alexander F. G. Hagström, Rania Nuwailati
Institution: University of Minnesota
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funder: University of Minnesota
OpenAlex ID: W7204938556