Role of opioid receptors in the spinal antinociceptive effects of neuropeptide FF analogues.
1. Neuropeptide FF (NPFF) has been shown to produce antinociceptive effects and enhance morphine-induced antinociception after intrathecal (i.t.) injection. In this study, the spinal effects of two NPFF analogues, -D-Tyr1,(NMe)Phe3-NPFF (1DMe) and [D-Tyr1,D-Leu2,D-Phe3]NPFF (3D), which are resistant to degradation and exhibit a high affinity for NPFF binding sites, were examined in tests of thermal and mechanical nociception. 2. 1DMe and 3D produced potent dose-dependent spinal antinociception in the tail-flick test. On a molar basis, 1DMe was 20 and 50 times more potent than 3D and morphine, respectively, and high doses of 1DMe and 3D produced a sustained antinociceptive effect without visible signs of motor impairment. 3. Spinal antinociceptive effects produced by 1DMe (0.86 nmol) or 3D (8.6 nmol) were significantly reduced by i.t. co-administration of naloxone (11 nmol) or i.t. pre-administration of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP, 9.25 nmol) or beta-funaltrexamine (beta-FNA, 2 nmol) or naltrindole (2.2 nmol). The doses of the mu-antagonists (CTOP and beta-FNA) or the delta-antagonist (naltrindole) used in 1DMe and 3D experiments blocked the antinociceptive effects of mu- or delta-receptor-selective agonists. 4. When administered in combination with antinociceptive doses of the mu-receptor agonist, morphine (13.2 nmol) or the delta-receptor agonist, [D-Ala2]deltorphin I (20 nmol), sub-effective dose of 1DMe or 3D (0.009 nmol) enhanced and prolonged the spinal effects of these opioid agonists. 5. The results of this study show that spinal mu- and delta-opioid receptors play a role in antinociception produced by NPFF analogues. These results also suggest a role for NPFF in modulation of nociceptive signals at the spinal level.
Gouardères
C
C
Laboratoire de Pharmacologie et de Toxicologie Fondamentales, CNRS, Toulouse, France.
Jhamandas
K
K
Sutak
M
M
Zajac
J M
JM
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects*
D000700:Analgesics; D000701:Analgesics, Opioid; D004745:Enkephalins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011957:Receptors, Opioid; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; C055382:naltrindole