SUBSTANCE-P RELEASE IN THE RAT PERIAQUEDUCTAL GRAY AND PREOPTIC-ANTERIOR HYPOTHALAMUS AFTER NOXIOUS COLD STIMULATION - EFFECT OF SELECTIVE MU AND KAPPA-OPIOID AGONISTS

Intracerebral microdialysis was used to measure changes in the extrace llular level of substance P (SP) released from the periaqueductal gray (PAG) and the preoptic anterior hypothalamus (POAH) of freely moving Sprague-Dawley rats after noxious cold stimulation. Artificial cerebro spinal fluid was perfused into the dialysis probe in the PAG or POAH a nd samples were collected every 30 min for 4 hr. SP-like immunoreactiv ity in the samples was measured by radioimmunoassay. In the PAG, SP ba se-line release was 0.43 +/- 0.08 fmol/fraction. SP release was increa sed to 1.3 +/- 0.4 fmol/fraction during the first collection period af ter noxious cold. Pretreatment with the selective mu opioid receptor a gonist PL017 (0.8-3.4 nmol) or the kappa opioid receptor agonist dynor phin A1-17 (4.6-9.2 nmol), administered into the PAG by microinjection , produced dose-related inhibition of the cold-evoked SP release. Nalo xone (10 mg/kg s.c.) administration 10 min before these opioid agonist s reduced the inhibition of SP release. In the POAH, SP base-line rele ase was 0.45 +/- 0.06 fmol/fraction and noxious cold did not cause any significant change in SP release. Microdialysis of SP (271 fmol-271 p mol/mu l/min, for 30 min) into the PAG, but not the POAH, induced dose -related analgesia (35-68% MPA) in the cold-water tail-flick test. How ever, microdialysis of SP into the POAH or PAG failed to induce any si gnificant change in body temperature. These data suggest that 1) SP re leased from the PAG acts as a neuromodulator to transmit nociceptive i nformation; 2) opioid receptor agonists can suppress this information by inhibiting SP release; 3) SP evoked by noxious cold may have a role in triggering the antinociceptive function of the PAG; and 4) SP does not appear to act as a neuromodulator for thermoregulatory responses in the POAH.