title: Antinociception induced by intravenous dipyrone (metamizol) upon dorsal horn neurons: involvement of endogenous opioids at the periaqueductal gray matter, the nucleus raphe magnus, and the spinal cord in rats.
abstract: Microinjection of dipyrone (metamizol) into the periaqueductal gray matter (PAG) in rats causes antinociception. This is mediated by endogenous opioidergic circuits located in the PAG itself, in the nucleus raphe magnus and adjacent structures, and in the spinal cord. The clinical relevance of these findings, however, is unclear. Therefore, in the present study, dipyrone was administered intravenously, and the involvement of endogenous opioidergic circuits in the so-induced antinociception was investigated. In rats, responses of dorsal spinal wide-dynamic range neurons to mechanical noxious stimulation of a hindpaw were strongly inhibited by intravenous dipyrone (200 mg/kg). This effect was abolished by microinjection of naloxone (0.5 microg/0.5 microl) into the ventrolateral and lateral PAG or into the nucleus raphe magnus or by direct application of naloxone (50 microg/50 microl) onto the spinal cord surface above the recorded neuron. These results show that dipyrone, a non-opioid analgesic with widespread use in Europe and Latin America, when administered in a clinically relevant fashion causes antinociception by activating endogenous opioidergic circuits along the descending pain control system.
authors.affiliation: Instituto Venezolano de Investigaciones Cientificas (IVIC), Centro Biofisica/Bioquimica, 8424 NW 56th Street, Suite CCS 00202, Miami, FL 33166, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Vazquez
authors.forename: Norma
authors.initials: N
authors.lastname: Hernandez
authors.forename: William
authors.initials: W
authors.lastname: Escobar
authors.forename: Horacio
authors.initials: H
authors.lastname: Vanegas
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004177:Dipyrone / Q000008:administration & dosage*; D004347:Drug Interactions; D007276:Injections, Intraventricular / Q000379:methods; D035002:Lower Extremity / Q000294:innervation; D008297:Male; D008845:Microinjections / Q000379:methods; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009270:Naloxone; D004177:Dipyrone