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

ABSTRACT

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 micromol.L(-1)), menthol (200 micromol.L(-1)) and capsaicin (1 micromol.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 degrees C), 3 micromol.L(-1) icilin (EC50 1.5 micromol.L(-1)) and menthol (EC50 263 micromol.L(-1)) increased the rate of spontaneous miniature EPSCs. In the majority of lamina I and II neurones, 100 micromol.L(-1) icilin (EC50 79 micromol.L(-1)), allyl isothiocyanate (EC50 226 micromol.L(-1)), cinnamaldehyde (EC50 38 micromol.L(-1)) and capsaicin (1 micromol.L(-1)) increased miniature EPSC rate. The response to 100 micromol.L(-1), but not 3 micromol.L(-1) icilin, was abolished by ruthenium red, while neither was affected by iodoresiniferatoxin. Responsiveness to 3 micromol.L(-1), but not to 100 micromol.L(-1) icilin, was highly predictive of innocuous cold responsiveness. Neurones responding to 3 micromol.L(-1) icilin and innocuous cold were located more superficially than those responding to 100 micromol.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.