title: NSAIDs induce peripheral antinociception by interaction with the adrenergic system.
abstract: OBJECTIVE
  We evaluated the role of adrenergic systems on the peripheral antinociception induced by dipyrone and diclofenac. Mainmethods: The rat pawpressure test, inwhich sensitivity is increased by intraplantar injection of prostaglandin E2, was used to examine the peripheral effects of locally administered drugs.
  
  
  RESULTS
  Dipyrone (10, 20 and 40 μg) and diclofenac (5, 10 and 20 μg) administered locally into the right paw elicited a dose-dependent antinociceptive effect, which was demonstrated to be local; the injection of drugs into the ipsilateral and contralateral hindpaws demonstrated an effect only in the ipsilateral paw because only the treated paw produced an antinociceptive effect. To test the adrenergic system, we used guanethidine (30 mg/kg) to deplete noradrenalin from noradrenergic vesicles. Guanethidine antagonized the peripheral antinociception induced by diclofenac and dipyrone. Yohimbine (2.5, 5, 10, or 20 μg/paw) a nonselective α2-adrenergic receptor antagonist antagonized the peripheral antinociception induced by diclofenac (20 μg/paw) and dipyrone (40 μg/paw). Rauwolscine (Rau; 10, 15, 20 μg), a selective α2C-adrenoreceptor, was able to block the peripheral antinociception induced by NSAIDs. The other specific α2A,B and D-adrenoreceptor antagonists (BRL 44480, imiloxan and RX 821002, respectively) did not modify the peripheral antinociception. However, prazosin (0.5, 1, and 2 μg/paw), an α1 receptor antagonist, and propranolol (0.3, 0.6 or 1.2 μg/paw), a β-adrenoreceptor antagonist, antagonized the antinociception induced by diclofenac (20 μg/paw) and dipyrone (40 μg/paw).
  
  
  CONCLUSIONS
  Dipyrone and diclofenac produce peripheral antinociception, which involves the release of NA and interaction with α1, α2C and β-adrenoreceptors.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, CEP 31.270-100 Belo Horizonte, MG, Brazil.
authors.forename: Lívia Caroline Resende
authors.initials: LC
authors.lastname: Silva
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, CEP 31.270-100 Belo Horizonte, MG, Brazil.
authors.forename: Marina Gomes
authors.initials: MG
authors.lastname: Miranda e Castor
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, CEP 31.270-100 Belo Horizonte, MG, Brazil.
authors.forename: Tâmara Cristina
authors.initials: TC
authors.lastname: Souza
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, CEP 31.270-100 Belo Horizonte, MG, Brazil.
authors.forename: Igor Dimitri Gama
authors.initials: ID
authors.lastname: Duarte
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, CEP 31.270-100 Belo Horizonte, MG, Brazil. Electronic address: thiromero@ufmg.br.
authors.forename: Thiago Roberto Lima
authors.initials: TR
authors.lastname: Romero
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology*; D004177:Dipyrone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006145:Guanethidine / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004008:Diclofenac; D015016:Yohimbine; D004177:Dipyrone; D009638:Norepinephrine; D011224:Prazosin; D006145:Guanethidine
keywords: Adrenergic mechanisms; Anti-inflammatory drugs (NSAIDs); Peripheral antinociception