Effects of Se-phenyl thiazolidine-4-carboselenoate on mechanical and thermal hyperalgesia in brachial plexus avulsion in mice: mediation by cannabinoid CB1 and CB2 receptors.
In this study, we investigated the therapeutic effects of treatment with (R)-Se-phenyl thiazolidine-4-carboselenoate (Se-PTC), an organic selenium compound with antinociceptive properties, against mechanical and thermal hyperalgesia induced by brachial plexus avulsion (BPA), a neuropathic model in mice. The involvement of cannabinoid CB(1) and CB(2) receptors in the Se-PTC anti-hyperalgesic effect was also investigated. Se-PTC treatment at (25 and 50mg/kg, per oral, p.o.) lowered (BPA model) induced mechanical and thermal hyperalgesia in mice. Pretreatment with cannabinoid CB(1) (AM251; 1mg/kg, intraperitoneally, i.p.), or CB(2) (AM630; 3mg/kg, i.p.) receptor antagonists reverted the mechanical and thermal anti-hyperalgesic effect of Se-PTC (25mg/kg) in the BPA model. Selective CB(1) (ACEA, 10mg/kg, i.p.) and CB(2) (JWH-133, 10mg/kg, i.p.) receptor agonists lowered mechanical and thermal hyperalgesia in the BPA model, and this effect was prevented by selective CB(1) and CB(2) receptor antagonists. Gabapentin (70mg/kg, p.o.), positive control administration also lowered mechanical and thermal hyperalgesia in the BPA model. The results suggest that the mechanical and thermal hyperalgesia observed following BPA in mice is dependent on cannabinoid receptors. The results indicate that modulating cannabinoid receptors represent a valuable approach for the treatment of neuropathic pain. In conclusion, the results suggested that Se-PTC produces pronounced mechanical and thermal anti-hyperalgesic effects in neuropathic models in mice by modulating CB(1) and CB(2) receptors.
Laboratório de avaliações farmacológicas e toxicológicas aplicadas às moléculas bioativas-LaftamBio Pampa-Universidade Federal do Pampa, CEP 97650-000 Itaqui, RS, Brazil.
Lucian
L
Del Fabbro
Carlos
C
Borges Filho
Leandro
L
Cattelan Souza
Lucielli
L
Savegnago
Diego
D
Alves
Paulo
P
Henrique Schneider
Helena Domingues
HD
de Salles
Cristiano R
CR
Jesse
D000818:Animals; D001917:Brachial Plexus / Q000187:drug effects* / Q000293:injuries*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016566:Organoselenium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010812:Physical Stimulation / Q000009:adverse effects; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D053778:Thiazolidines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D063387:Cannabinoid Receptor Antagonists; D016566:Organoselenium Compounds; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C568847:Se-phenyl thiazolidine-4-carboselenoate; D053778:Thiazolidines