Cold
allodynia is a poorly understood symptom of
neuropathic pain. Two members of the transient receptor potential (TRP) family of
proteins, TRPM8 and TRPA1, may contribute to cold somatosensation. The aim of the present study was to investigate the usefulness of
icilin as a pharmacological tool to study primary afferent fibre responses to cold stimuli and to determine whether there are differences in the responses of spinal neurones to cooling of peripheral receptive fields in control versus neuropathic rats. The effects of
icilin, a TRPM8 and TRPA1 agonist, on intracellular Ca(2+) ([Ca(2+)](i)) responses of small diameter adult dorsal root ganglia (DRG) neurones were determined.
Icilin (10 nM-10 microM) produced a concentration-related increase in [Ca(2+)](i) in DRG neurones, which was attenuated by the non-selective TRP channel antagonist
ruthenium red (10 microM). In vivo electrophysiology in naïve,
sham-operated and SNL rats demonstrated that application of
ice to receptive fields evoked firing of wide dynamic range (WDR) neurones, which was significantly greater in SNL rats than naïve and
sham-operated rats. Intraplantar injection of
icilin did not evoke firing of WDR neurones in naïve,
sham-operated or SNL rats but inhibited mechanically-evoked responses of WDR neurones in naïve and
sham-operated rats, whilst facilitating mechanically-evoked responses in SNL rats.
Icilin increased both innocuous (
sham-operated and SNL rats) and noxious (SNL rats) receptive field sizes of WDR neurones. Our data suggests that
icilin modulates the mechanosensitivity of dorsal horn neurones. The differing effects of
ice and
icilin on dorsal horn neurones indicate different mechanisms of action.