Experiments were designed to examine the
analgesic effects of SP injected into the ventral tegmental area (VTA). Rats received bilateral intra-VTA infusions of 3.0 micrograms/0.5 microliter/side of the SP analogue,
DiMe-C7, or the vehicle, either immediately prior to or 25 min following an injection of 0.05 ml of 2.5%
formalin into one hind paw.
Formalin-induced
pain responses were continuously recorded for 75 min.
DiMe-C7 attenuated
pain responses for approximately 30 min; the
analgesia was more potent and longer-lasting when
DiMe-C7 was infused after, rather than prior to, the early
pain phase. In another set of experiments, rats were tested in the
formalin test immediately following bilateral infusions of
amphetamine (1.5 or 2.5 micrograms/0.05 microliter/side) into either the medial prefrontal cortex (mPFC) or the nucleus accumbens septi (
NAS).
Amphetamine failed to alter
pain responses when infused into the mPFC, but both doses attenuated
pain responses during 25 min when infused into the
NAS. There was no evidence for
pain inhibition in the tail-flick test for phasic
pain following either intra-VTA
DiMe-C7 or intra-
NAS amphetamine. The finding that intra-VTA
DiMe-C7 and intra-
NAS amphetamine produces
analgesia in the
formalin, but not the tail-flick test, suggests that activation of mesolimbic
dopamine (DA) neurons contributes to suppression of tonic
pain. Because stressors attenuate tonic
pain responses, and are known to cause SP release in the VTA, we speculate that SP-induced activation of midbrain DA systems may mediate a form of
pain- or stress-induced
pain inhibitory system.