Spinal effect of a neuropeptide FF analogue on hyperalgesia and morphine‐induced analgesia in mononeuropathic and diabetic rats

• Published in: British journal of pharmacology Vol. 127; no. 6; pp. 1454 - 1462
• Main Authors: Courteix, Christine, Coudoré‐Civiale, Marie‐Ange, Privat, Anne‐Marie, Zajac, Jean‐Marie, Eschalier, Alain, Fialip, Joseph
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.1999; Nature Publishing
• Subjects: Analgesia; Analgesics; Analgesics - pharmacology; Analgesics, Opioid - pharmacology; Animals; Behavior, Animal - drug effects; Biological and medical sciences; chronic pain; Diabetes Mellitus, Experimental - physiopathology; diabetic rats; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hyperalgesia - physiopathology; Hyperalgesia - prevention & control; Injections, Spinal; intrathecal; Male; Medical sciences; mononeuropathic rats; Morphine - pharmacology; morphine analgesia; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Nervous System Diseases - physiopathology; neuropathy; Neuropeptide FF; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Oligopeptides - chemistry; Oligopeptides - pharmacology; Pain - prevention & control; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Somatostatin - analogs & derivatives; Somatostatin - pharmacology; Time Factors; Vocalization, Animal - drug effects; μ‐ and δ‐opioid; Endocrinopathy; Drug combination; Nervous system diseases; Intravenous administration; Rat; Diabetes mellitus; Rodentia; μ Opioid receptor; Morphine; Opiates; Neuropathy; Narcotic analgesic; δ Opioid receptor; Intrathecal administration; Hyperalgesia; Vertebrata; Mammalia; Pain; Animal; Drug interaction; Neuropeptide FF
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702682

1DMe, a neuropeptide FF (NPFF) analogue, has been shown to produce antinociception and to enhance morphine analgesia in rats after intrathecal administration. To determine whether 1DMe could correct hyperalgesia and restore morphine efficacy in mononeuropathic (MN) and diabetic (D) rats we examined the spinal effect of 1DMe in MN and D rats without and after spinal blockade of μ‐ and δ‐opioid receptors with CTOP and naltrindole, respectively. The influence of 1DMe on morphine‐induced antinociception was assessed in the two models using isobolographic analysis. Whereas 1DMe intrathecally injected (0.1, 1, 7.5 μg rat−1) was ineffective in normal (N) rats, it suppressed mechanical hyperalgesia (decrease in paw pressure‐induced vocalisation thresholds) in both MN and D rats. This effect was completely cancelled by CTOP (10 μg rat−1) and naltrindole (1 μg rat−1) suggesting that it requires the simultaneous availability of μ‐ and δ‐opioid receptors. The combinations of morphine : 1DMe (80.6 : 19.4% and 99.8 : 0.2%, in MN and D rats, respectively) followed by isobolographic analysis, showed a superadditive interaction, relative to the antinociceptive effect of single doses, in D rats only. In N rats, the combination of morphine : 1DMe (0.5 mg kg−1, i.v.: 1 μg rat−1, i.t., ineffective doses) resulted in a weak short‐lasting antinociceptive effect. These results show a different efficacy of 1DMe according to the pain model used, suggesting that the pro‐opioid effects of the NPFF in neuropathic pain are only weak, which should contribute to hyperalgesia and to the impaired efficacy of morphine. British Journal of Pharmacology (1999) 127, 1454–1462; doi:10.1038/sj.bjp.0702682