Investigating Mechanically Activated Currents from Trigeminal Neurons of Non-Human Primates

Abstract

IntroductionPain sensation has predominantly mechanical modalities in many pain conditions. Mechanically activated (MA) ion channels on sensory neurons underly responsiveness to mechanical stimuli. The study aimed to address gaps in knowledge regarding MA current properties in higher order species such as non-human primates (NHP; common marmosets), and characterization of MA currents in trigeminal (TG) neuronal subtypes. MethodsWe employed patch clamp electrophysiology and immunohistochemistry (IHC) to associate MA current types to different marmoset TG neuronal groups. TG neurons were grouped according to presumed marker expression, action potential (AP) width, characteristic AP features, after-hyperpolarization parameters, presence/absence of AP trains and transient outward currents, and responses to mechanical stimuli. ResultsMarmoset TG were clustered into 5 C-fiber and 5 A-fiber neuronal groups. The C1 group likely represent non-peptidergic C-nociceptors, the C2-C4 groups resembles peptidergic C-nociceptors, while the C5 group could be either cold-nociceptors or C-low-threshold-mechanoreceptors (C-LTMR). Among C-fiber neurons only C4 were mechanically responsive. The A1 and A2 groups are likely A-nociceptors, while the A3-A5 groups probably denote different subtypes of A-low-threshold-mechanoreceptors (A-LTMRs). Among A-fiber neurons only A1 was mechanically unresponsive. IHC data was correlated with electrophysiology results and estimates that NHP TG has [~]25% peptidergic C-nociceptors, [~]20% non-peptidergic C-nociceptors, [~]30% A-nociceptors, [~]5% C-LTMR, and [~]20% A-LTMR. ConclusionOverall, marmoset TG neuronal subtypes and their associated MA currents have common and unique properties compared to previously reported data. Findings from this study could be the basis for investigation on MA current sensitizations and mechanical hypersensitivity during head and neck pain conditions.