The
TRPV1 receptor functions as a molecular integrator, and blockade of this receptor modulates enhanced somatosensitivity across several animal models of pathological
pain, including models of osteoarthritic (OA)
pain. In order to further characterize the contributions of TRPV1 to OA-related
pain, we investigated the systemic effects of a selective
TRPV1 receptor antagonist,
A-889425, on grip force behavior, and on the evoked and spontaneous firing of spinal wide dynamic range (WDR) and nociceptive specific (NS) neurons in the monoiodoacetate (MIA) model of OA. Administration of
A-889425 (10-300 μmol/kg, p.o.) alleviated grip force impairment in OA rats 3 weeks after the MIA injection. Also at 3 weeks post-MIA injection, the responses of WDR and NS neurons to 300 g von Frey hair stimulation of the knee joint were significantly reduced by
A-889425 administration (10 and 30 μmol/kg, i.v.) in OA, but not
sham-OA rats. Spontaneous firing of WDR neurons was elevated in the OA rats compared to
sham-OA rats and may reflect ongoing discomfort in the OA animal. In addition to an effect on mechanotransmission, systemic administration of
A-889425 reduced the elevated spontaneous firing of WDR neurons in OA rats but did not alter spontaneous firing in
sham rats. The present data demonstrate that blockade of TRPV1 receptors modulates the firing of two important classes of spinal nociceptive neurons in a rat model of OA. The effect of
A-889425 on neuronal responses to intense mechanical stimulation of the knee and on the spontaneous firing of WDR neurons adds to the growing appreciation for the role of TRPV1 receptors in pathological mechanotransmission and possibly non-evoked discomfort, respectively.