title: Analgesic and anti-edematogenic effects of oral trypsin were abolished after subdiaphragmatic vagotomy and spinal monoaminergic inhibition in rats.
abstract: OBJECTIVE
  Rheumatoid arthritis brings great burdens to the patients. In addition to the highly expensive treatment, they are commonly associated with severe side effects. In such context, the research for safe and affordable treatments is needed.
  
  
  METHODS
  Arthritis was induced by CFA (0.5mg/mL) in female wistar rats. Trypsin was given p.o. (2.95mg/kg; 2mL) 24h after the intra-articular CFA injection. Articular incapacitation was measured daily by counting the paw elevation time (PET; s) during 1-min periods of stimulated walk, throughout the 7-days after intra-articular CFA injection. Articular diameter (AD) was accessed just after each PET measurement, taken the difference between naïve and diseased knee-joint diameter (cm).
  
  
  RESULTS
  The present study showed that orally administered trypsin was able to reduce nociception and edema, effects that could be observed throughout the evaluation period. These effect, however, were not observed in animals underwent subdiaphragmatic vagotomy, suggesting a vagal mediation for trypsin effects. Likewise, these effects were blocked in rats which received intrathecal injection of the neurotoxins 5,7-dihydroxytryptamine or 6-hydroxydopamine, suggesting the involvement of spinal amines from axon terminals.
  
  
  CONCLUSIONS
  The present study proposes that oral trypsin may cause vagal activation, followed by the activation of descending inhibitory pathways and such mechanism may lead to a novel approach for the treatment of arthritis.
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Flora
authors.initials: F
authors.lastname: Lucena
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Foletto
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Lucas Zanon
authors.initials: LZ
authors.lastname: Mascarin
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC 88040-900, Brazil. Electronic address: c.r.tonussi@ufsc.br.
authors.forename: Carlos Rogério
authors.initials: CR
authors.lastname: Tonussi
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage / Q000494:pharmacology; D000284:Administration, Oral; D018663:Adrenergic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D004487:Edema / Q000150:complications / Q000188:drug therapy*; D005260:Female; D007278:Injections, Spinal; D059225:Nociception / Q000187:drug effects*; D016627:Oxidopamine / Q000008:administration & dosage / Q000494:pharmacology; D017208:Rats, Wistar; D018490:Serotonin Agents / Q000008:administration & dosage / Q000494:pharmacology; D014357:Trypsin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014628:Vagotomy
chemical_list: D018663:Adrenergic Agents; D000700:Analgesics; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D016627:Oxidopamine; D014357:Trypsin
keywords: Arthritis; Enteropeptidase; Inflammation; Monoamines; Pain control; Vagus nerve