Activation of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM) can facilitate
pain transmission in conditions such as
inflammation, and thereby contribute to
hyperalgesia. Since blockade of
NK-1 receptors in the RVM can attenuate
hyperalgesia produced by prolonged
inflammation, we examined the role of
NK-1 receptors in changes of response properties of RVM neurons following four days of hind paw
inflammation with complete
Freund's adjuvant. Recordings were made from functionally identified ON, OFF and NEUTRAL cells in the RVM. Spontaneous activity and responses evoked by a series of mechanical (10, 15, 26, 60, 100, and 180 g) and heat (34-50 °C) stimuli applied to the inflamed and non-inflamed hind paws were determined before and at 15 and 60 min after injection of the NK-1-antagonist
L-733,060 or vehicle into the RVM. Prolonged
inflammation did not alter the proportions of functionally-identified ON, OFF and NEUTRAL cells. ON cells exhibited enhanced responses to mechanical (60-100g) and heat (48-50 °C) stimuli applied to the inflamed paw, which were attenuated by
L-733,060 but not by vehicle. Inhibitory responses of OFF cells evoked by mechanical stimuli applied to the inflamed paw were also inhibited by
L-733,060, but responses evoked by stimulation of the contralateral paw were increased. Heat-evoked responses of OFF cells were not altered by
L-733,060. Also, neither
L-733,060 nor vehicle altered spontaneous ongoing discharge rate of RVM neurons. These data indicate that
NK-1 receptors modulate excitability of ON cells which contribute to both mechanical and heat
hyperalgesia, whereas NK-1 modulation of OFF cells contributes to
mechanical hyperalgesia during prolonged
inflammation.