Experiments were designed to examine the
analgesic effects induced by selective
tachykinin receptor agonists microinfused into either the ventral tegmental area (VTA) or nucleus accumbens septi (
NAS). Rats were tested in the
formalin test for tonic
pain following an injection of 0.05 ml of 2.5%
formalin into one hind paw immediately after bilateral intra-VTA infusions of either the NK-1 agonist,
GR-73632 (0.005, 0.05 or 0.5 nmol/side), the NK-3 agonist,
senktide (0.005, 0.5 or 1.5 nmol/side), or saline. Two weeks later, the saline-treated rats were assessed in the tail-flick test for phasic
pain after infusions of the
tachykinin agonists. Tail-flick latencies were recorded following immersion of the tail in 55 degrees C hot water
at 10 min intervals for 1 h immediately after intra-VTA infusions of either
GR-73632 (0.5 nmol/side),
senktide (1.5 nmol/side) or saline. In a second group of rats, the same effects were studied after infusions into the nucleus accumbens (
NAS) of
GR-73632 (0.005, 0.5 or 1.5 nmol/side),
senktide (0.005, 0.5 or 1.5 nmol/side), or saline. In both the VTA and
NAS, the NK-1 and the NK-3 agonists caused significant
analgesia in the
formalin test, although the NK-1 agonist appeared to be more effective.
Naltrexone (2.0 mg/kg) pretreatment failed to reverse the
analgesic effects in the
formalin test induced by intra-VTA infusions of the
substance P (SP) analog,
DiMe-C7 (3.0 microg/side),
GR-73632 (0.5 nmol/side), or
senktide (1.5 nmol/side). Neither compound given at either site was effective in the tail-flick test. These findings suggest that SP-
dopamine (DA) interactions within the mesolimbic DA system play an important role in the inhibition of tonic
pain. Furthermore, they support our earlier ideas that activation of midbrain DA systems by SP might play a role in stress- and/or
pain-induced
analgesia.