In spinal cord neurons in anesthetized rats, the role on
neurokinin A and
neurokinin-2 receptors in the processing of nociceptive information from the knee joint was studied. The specific non-
peptide antagonist at the
neurokinin-2 receptor,
SR48968, its inactive R-enantiomer, SR48965,
neurokinin A,
substance P and (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
acid (
AMPA), were administered ionophoretically close to neurons with input from the knee joint.
SR48968 reduced the effects of exogenous
neurokinin A, but not those of exogenous
substance P and
AMPA, indicating selective blockade of
neurokinin-2 receptors. In most neurons with input from the normal knee joint,
SR48968 reduced dose-dependently the responses to noxious pressure with applied to the knee, and in approximately 50% of the neurons the responses to innocuous pressure. The administration of
SR48968 during the induction of an experimental joint
inflammation markedly attenuated the development of
inflammation-evoked hyperexcitability. In hyperexcitable neurons with input from the inflamed joint,
SR48968 reduced the responses to noxious and innocuous pressure. The relative reduction of the responses was more pronounced than in neurons with input from the normal joint. None of the effects of
SR48968 was mimicked by SR48965. These data show that
neurokinin-2 receptors are involved in the spinal processing of nociceptive information from the normal joint. Furthermore,
neurokinin-2 receptors must be coactivated at an early stage of
inflammation, to allow the generation of hyperexcitability. Finally,
neurokinin-2 receptors are involved in maintenance of hyperexcitability during
inflammation. In summary, spinal
neurokinin-2 receptors are important in the generation of
pain in the normal and inflamed joint.