Spontaneously Hypertensive Rats Exhibit Reduced Facial Pain Sensitivity with Altered Electrophysiology and Transcriptomics in the Trigeminal Ganglia

J Pain. 2026 Jun 20:106367. doi: 10.1016/j.jpain.2026.106367. Online ahead of print.

ABSTRACT

Hypertension has been associated with altered nociceptive thresholds in humans and animal models, but the relationship between blood pressure (BP) and pain sensitivity remains inconsistent. Here, we investigated trigeminal nociception in male spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats using operant facial pain assays, trigeminal ganglion (TG) electrophysiology, and bulk RNA sequencing with cell-type deconvolution. SHRs exhibited reduced thermal and mechanical facial pain sensitivity relative to WKY controls; however, measured systolic BP did not robustly explain the strain difference in thermal pain behavior. Whole-cell recordings of TG neurons revealed increased hyperpolarization-activated cyclic nucleotide-gated (HCN)-mediated currents and voltage-gated potassium currents in SHRs, while voltage-gated sodium currents were unchanged despite reduced expression of Scn8a, Scn9a, and Scn10a. Transcriptomic analysis further demonstrated broad downregulation of ion channel and sensory transduction genes in SHRs, including Hcn1, Hcn4, Kcnq3, Kcnq4, Piezo2, and Trpm8. Cell-type deconvolution revealed strain-dependent shifts in TG composition, including alterations in sensory neurons and non-neuronal populations such as immune cells, satellite glia, endothelial cells, pericytes, and Schwann cells. Together, these findings show that reduced trigeminal nociception in SHRs is associated with changes in TG ion channel function, sensory gene programs, and cell-type composition, while not being robustly explained by measured systolic BP. PERSPECTIVE: This study shows that reduced trigeminal pain in SHRs is associated with changes in ion channel function, gene expression, and TG cell-type composition, while not being robustly explained by measured systolic BP.

PMID:42323036 | DOI:10.1016/j.jpain.2026.106367