Spinal levels of nonprotein thiols are related to nociception in mice.
Oxidative stress markers are thought to be related to nociception. Because thiolic compounds are important antioxidants, we investigated the relationship between thiols, endogenous or exogenous, and nociception. Systemic or spinal, but not peripheral, administration of the exogenous thiolic compound N-acetyl-L-cysteine (NAC) reduced nociception induced by intraplantar capsaicin injection. Moreover, we detected an increase in lipid peroxidation and 3-nitrotyrosine and a decrease in nonprotein thiolic levels in the lumbar spinal cord of capsaicin-injected animals. All these effects were prevented by NAC treatment (i.p. and i.t.). Our findings confirm a role for the spinal cord in NAC actions because systemic NAC administration also reduced the nociception trigged by intrathecal injection of capsaicin. Moreover, adjuvant-induced arthritis, but not paw incision, also -decreases nonprotein thiol levels in the spinal cord. Similarly, NAC produced antinociception in adjuvant-treated animals, but not in paw-incised animals. Finally, we investigated the role of endogenous thiol compounds in the nociceptive process administrating buthionine-suphoxamine (BSO), an inhibitor of glutathione-synthesis. Intrathecal BSO treatment decreased nonprotein thiol levels in the spinal cord, as well as induced mechanical allodynia and chemical and thermal hyperalgesia. In conclusion, our results indicate a critical role for nonprotein thiols in nociception at the level of the spinal cord.


CONCLUSIONS
The results presented here indicate that the loss of nonprotein thiols in the spinal cord is involved in pain development. Therefore, the administration of thiolic compounds or other strategies allow thiol levels to be maintained and could be a beneficial action in the therapy of painful conditions.
Rossato
Mateus Fortes
MF
Laboratório de Neurotoxicidade e Psicofarmacologia, Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.
Velloso
Nádia Alesso
NA
de Oliveira Ferreira
Ana Paula
AP
de Mello
Carlos Fernando
CF
Ferreira
Juliano
J
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology; D000208:Acute Disease; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002211:Capsaicin; D004195:Disease Models, Animal; D005260:Female; D018409:Foot Injuries / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008159:Lumbar Vertebrae; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology
D000700:Analgesics; D000963:Antimetabolites; D013438:Sulfhydryl Compounds; D019328:Buthionine Sulfoximine; D002211:Capsaicin; D000111:Acetylcysteine