Up-regulation of preprotachykinin and calcitonin gene-related peptide messenger RNA in L4 dorsal root ganglion neurons following L5 spinal nerve ligation; a rat neuropathic pain model

Abstract

The anti-emetic mechanism of action of fentanyl to inhibit nicotine (5 mg/kg, s.c.)-induced emesis was investigated in Suncus murinus. The anti-emetic action of fentanyl (40 μg/kg, s.c.) was antagonised by the opioid receptor antagonists naltrexone (1 mg/kg, s.c.), naloxone (1 mg/kg, s.c.), M8008 (16S-methylcyprenorphine; 1 mg/kg, s.c.) and MR 2266 (5,9-diethyl-2-(3-furylmethyl)2′-hydroxy-7,7-benzomorphan; 1 mg/kg) but not by naloxone methylbromide (1 mg/kg, s.c.), naloxone methyliodide (1 mg/kg, s.c.), naltrindole (1 mg/kg, s.c.), DIPPA (2-(3,4-dichlorophenyl)-N-methyl-N-[1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide; 3 mg/kg, i.p.) or naloxonazine (35 mg/kg, i.p.). This indicates an involvement of μ2-opioid receptors within the brain to mediate the anti-emetic effect of fentanyl. In other studies, naloxone 10–60 mg/kg, s.c. induced dose-related emesis but naltrexone was only emetic at 60 mg/kg, s.c. and naloxone methylbromide failed to induce emesis at doses up to 60 mg/kg, s.c. The emesis induced by a high dose of naloxone 60 mg/kg, s.c. was antagonized by CP-99,994 ((+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine; 3–30 mg/kg, i.p.), 8-OH-DPAT, ((±)-8-hydroxy-dipropylaminotetralin; 0.003–0.3 mg/kg, s.c.), buspirone (3 mg/kg, s.c.) and fluphenazine (1–3 mg/kg, i.p.) but not by naltrexone (1–30 mg/kg, s.c.), metoclopramide (0.3–3 mg/kg, i.p.), sulpiride (0.3–3 mg/kg, i.p.), domperidone (0.1–3 mg/kg, i.p.), ondansetron (0.3–3 mg/kg, i.p.), granisetron (0.3–3 mg/kg, i.p.), scopolamine (0.3–3 mg/kg, i.p.) or promethazine (0.3–3 mg/kg, i.p.). The data is discussed in relation to opioid receptor mechanisms moderating emesis and the identification of potential sites of drug action available to inhibit the emetic reflex.