Primary afferents with TRPM8 and TRPA1 profiles target distinct subpopulations of rat superficial dorsal horn neurones

• Published in: British journal of pharmacology 2009-06, Vol.157 (3), p.371-380
• Main Authors: Wrigley, Paul J, Jeong, Hyo‐Jin, Vaughan, Christopher W
• Format: Article
• Language: English
• Subjects: Afferent Pathways - drug effects; Animals; Ankyrins; Biological and medical sciences; Calcium Channels - physiology; cold; Cold Temperature; Excitatory Postsynaptic Potentials; Glutamic Acid - physiology; In Vitro Techniques; Male; Medical sciences; Menthol - pharmacology; pain; Patch-Clamp Techniques; Pharmacology. Drug treatments; Posterior Horn Cells - physiology; Pyrimidinones - pharmacology; Rats; Rats, Sprague-Dawley; Research Papers; spinal cord; synaptic transmission; Synaptic Transmission - drug effects; TRP ion channel; TRPA1 Cation Channel; TRPC Cation Channels; TRPM Cation Channels - agonists; TRPM Cation Channels - physiology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2009.00167.x

Background and purpose:  The transient receptor potential (TRP) channels, transient receptor potential melastatin‐1 (TRPM8) and transient receptor potential ankyrin‐1 (TRPA1), are expressed in subpopulations of sensory neurones and have been proposed to mediate innocuous and noxious cold sensation respectively. The aim of this study was to compare TRPM8 and TRPA1 modulation of glutamatergic afferent transmission within the spinal dorsal horn. Experimental approach:  Whole cell patch clamp recordings were made from rat spinal cord slices in vitro to examine the effect of TRP agonists and temperature on glutamatergic excitatory postsynaptic currents (EPSCs). Key results:  Icilin (3 or 100 µmol·L−1), menthol (200 µmol·L−1) and capsaicin (1 µmol·L−1) reduced the amplitude of primary afferent evoked EPSCs in subpopulations of lamina I and II neurones. In a subpopulation of superficial neurones, innocuous cold (threshold 29°C), 3 µmol·L−1 icilin (EC50 1.5 µmol·L−1) and menthol (EC50 263 µmol·L−1) increased the rate of spontaneous miniature EPSCs. In the majority of lamina I and II neurones, 100 µmol·L−1 icilin (EC50 79 µmol·L−1), allyl isothiocyanate (EC50 226 µmol·L−1), cinnamaldehyde (EC50 38 µmol·L−1) and capsaicin (1 µmol·L−1) increased miniature EPSC rate. The response to 100 µmol·L−1, but not 3 µmol·L−1 icilin, was abolished by ruthenium red, while neither was affected by iodoresiniferatoxin. Responsiveness to 3 µmol·L−1, but not to 100 µmol·L−1 icilin, was highly predictive of innocuous cold responsiveness. Neurones responding to 3 µmol·L−1 icilin and innocuous cold were located more superficially than those responding to 100 µmol·L−1 icilin. Conclusions and implications:  Activation of TRPM8 and TRPA1 presynaptically modulated glutamatergic transmission onto partially overlapping but distinct populations of superficial dorsal horn neurones. Spinal TRPM8 and TRPA1 channels may therefore provide therapeutic targets in cold hyperesthesia.