Diphenyl diselenide attenuates acute thermal hyperalgesia and persistent inflammatory and neuropathic pain behavior in mice.
Experiments were designed to address whether diphenyl diselenide (PhSe)(2) has antiallodynic and antihyperalgesic properties. The neuropathic pain was caused by a partial tying (2/3) of sciatic nerve and the inflammatory pain was induced by an intraplantar (i.pl.) injection of 20 microl of Freund's Complete Adjuvant (CFA) in mice. Seven days after sciatic nerve constriction and 24 h after CFA intraplantar (i.pl.) injection, mouse pain threshold was evaluated through tactile allodynia, using Von Frey Hair (VHF) filaments. The acute thermal hyperalgesia was induced by intrathecal (i.t.) injection of glutamate, N-methyl-d-aspartate (NMDA), bradykinin (BK) and prostaglandin E(2) (PGE(2)), and the nociceptive response was assessed using hot-plate test. (PhSe)(2) administered by oral route (p.o.) (10 mg/kg) decreased the paw withdrawal response on the ipsilateral side of the partial sciatic nerve ligation 30 min after drug administration (64+/-7%) and this effect was kept for 1 h after treatment. (PhSe)(2) (10 mg/kg, p.o.) produced a reduction in mechanical allodynia induced by CFA started 30 min after (PhSe)(2) administration (71+/-5%) and this effect was maintained for up 4 h. (PhSe)(2) (0.1-50 mg/kg, p.o.) caused a significant inhibition of glutamate-, NMDA- and BK-(PGE(2))-induced acute thermal hyperalgesia in mice. Together, the present results indicate that (PhSe)(2) produces systemic antiallodynic action when assessed in mechanical stimulus (VHF) in the hindpaw and also attenuates acute thermal hyperalgesia. Thus, this compound might be potentially interesting in the development of new clinically relevant drugs for the management of pain.
Savegnago
Lucielli
L
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Jesse
Cristiano R
CR
Pinto
Larissa G
LG
Rocha
Joao B T
JB
Nogueira
Cristina W
CW
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001555:Benzene Derivatives / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005620:Freund's Adjuvant; D018698:Glutamic Acid / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D018836:Inflammation Mediators; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D020078:Neurogenic Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001555:Benzene Derivatives; D018836:Inflammation Mediators; D016566:Organoselenium Compounds; C061132:diphenyldiselenide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D005620:Freund's Adjuvant; D015232:Dinoprostone; D001920:Bradykinin