Effects of cooling on the excitability of trigeminal Aβ-afferent nociceptors in mice: Involvement of temperature-sensitive K2P channels
Year: 2026
Type: article
Abstract: Aβ-afferents are traditionally believed to be low-threshold mechanoreceptors (LTMRs) involved in sensing innocuous mechanical stimuli such as gentle touch; however, emerging evidence indicates that a subset of Aβ-afferents functions as high-threshold mechanoreceptors (HTMRs) involved in mechanical pain and termed Aβ-afferent nociceptors. While cooling is known to usually suppress neuronal excitability, its effects on the excitability of Aβ-afferent nociceptors remain unclear. Here, we used Nav1.8 ChR2/eYFP mice and patch-clamp recordings to examine how cooling affects intrinsic membrane properties, excitability, and ionic currents in Aβ-afferent nociceptors in the trigeminal ganglia (TG). Aβ-afferent nociceptors were identified as Nav1.8-positive (eYFP-positive) large-diameter (34–43 μm) TG neurons with their axon conduction velocities >13 m/s at 33°C. Cooling from 33 to 10°C progressively reduced axon conduction velocity and increased their stimulation threshold. However, at the soma of Aβ-afferent nociceptors, cooling decreased the action potential (AP) rheobase, increased AP amplitude and input resistance, and depolarized the resting membrane potential, although it increased the AP threshold and width. Voltage-clamp recordings showed that cooling suppressed both inward Na + and outward K + currents at the soma. Interestingly, the cooling-induced reduction in outward K + currents was largely mediated by temperature-sensitive two-pore-domain potassium (K2P) channels at the soma, suggesting a role in shifting intrinsic membrane properties toward increased excitability. Enhancing intrinsic membrane excitability at the soma of Aβ-afferent nociceptors raises the possibility that cooling may similarly affect excitability at their endings.
Source: Molecular Pain
Authors: Amit Raj Sharma, Jennifer Ling, Saurav Gupta, Jianguo Gu
Institutions: University of Alabama at Birmingham, UAB Medicine
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,650
OpenAlex ID: W7165150841
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