title: Subeffective doses of nitroparacetamol (NCX-701) enhance the antinociceptive activity of the α₂-adrenoceptor agonist medetomidine.
abstract: The α₂-adrenergic system is involved in pain processing and inflammation-induced sensitization. α₂-adrenoceptor agonists induce analgesia, and this effect is greater when administered in combination with other analgesics. In the present study, we assessed a possible enhancement of antinociception combining the α₂-adrenoceptor agonist medetomidine with subeffective doses of NCX701 (nitroparacetamol). The effects of the drugs were studied in spinal cord neuronal responses from adult male Wistar rats with carrageenan-induced inflammation, using the recording of single motor unit technique. The experiments showed that the i.v. administration of medetomidine and NCX701 induced a more potent and effective antinociceptive effect than medetomidine when given alone (ID₅₀: 0.47±0.1 vs. 1.1±0.1 μg/kg) or in the presence of paracetamol, in naturally-evoked nociceptive responses. In addition, the duration of antinociception was significantly longer (P<0.001, 100 min after administration). The use of low doses of NCX701 and α₂-adrenoceptor agonists might open new perspectives in the treatment of inflammatory pain.
authors.affiliation: Departamento de Fisiologia, Facultad de Medicina, Campus Universitario, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Molina
authors.forename: Juan F
authors.initials: JF
authors.lastname: Herrero
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D020926:Medetomidine / Q000008:administration & dosage*; D009566:Nitrates / Q000008:administration & dosage*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018712:Analgesics, Non-Narcotic; D009566:Nitrates; D000082:Acetaminophen; C478738:4-(nitroxy)butanoic acid 4-acetylaminophenyl ester; D020926:Medetomidine