RESUMEN
The neuromodulatory interactions of sex steroids with the opioid system may result in sex differences in pain and analgesia. Dynorphin is an endogenous kappa-opioid peptide that is upregulated in an animal model of peripheral inflammation and hyperalgesia and is possibly regulated by circulating levels of sex steroids. The present study compared behavioral responses of male, cycling female, and gonadectomized Sprague-Dawley rats in a model of persistent pain. Cycling female rats were behaviorally tested over a 14-day period, and their estrous cycles were monitored by daily vaginal smears. Thermal hyperalgesia was measured by paw withdrawal latencies taken prior to and 24-72 h after rats received a unilateral hindpaw injection of complete Freund's adjuvant (CFA). Prior to CFA administration, there was no significant difference in paw withdrawal latencies between male rats, cycling female rats, and ovariectomized female rats. Following CFA administration, female rats in proestrus exhibited significantly increased hyperalgesia compared with male rats, ovariectomized female rats, and female rats in other estrous stages (P=0.05). Levels of spinal preprodynorphin (PPD) mRNA induction in the L4-L5 segments were assessed by Northern blot analysis. PPD mRNA expression ipsilateral to the injected paw was significantly higher in female rats in diestrus (P=0.05) and proestrus (P=0.01) compared with rats in estrus and intact male rats. Ovariectomized rats had significantly higher levels of PPD mRNA expression compared with intact male rats (P=0.05). However, castrated male rats had significantly lower levels of PPD mRNA expression than intact male rats (P=0.05). PPD mRNA expression was not altered on the contralateral side of the spinal cord in any group. These results suggest a hormonal regulatory influence on the response of spinal cord dynorphin neurons to chronic inflammation and furthermore, that the association of the endocrine and opioid systems have the ability to influence an animal's sensitivity to pain.
Asunto(s)
Dinorfinas/fisiología , Estro/fisiología , Hiperalgesia/patología , Inflamación/patología , Neuronas/patología , Médula Espinal/patología , Animales , Autorradiografía , Conducta Animal/fisiología , Northern Blotting , Dinorfinas/biosíntesis , Femenino , Adyuvante de Freund , Hiperalgesia/inducido químicamente , Hiperalgesia/psicología , Inflamación/inducido químicamente , Inflamación/psicología , Masculino , Precursores de Proteínas/biosíntesis , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Caracteres SexualesRESUMEN
Glucocorticoids (GC) play important roles in response to stressful stimuli, including pain. This study examined the effects of bilateral adrenalectomy (ADX) and dexamethasone (DEX) replacement on the hyperalgesia and spinal preprodynorphin (PPD) mRNA expression induced by injecting complete Freund's adjuvant (CFA) into rats' hind paws. The results demonstrated that CFA induced more intense hyperalgesia and up-expression of spinal PPD mRNA in ADX rats than in control rats, while both of these intensified reactions could be significantly suppressed by subcutaneous pretreatment with DEX. This leads to the conclusion that both exogenous (pharmacological) and endogenous (physiological) GC suppresses the behavioral hyperalgesia and the up-regulation of spinal PPD mRNA induced by sustained peripheral inflammation. The results also suggest that spinal PPD mRNA suppression may partially underlie the inhibition of behavioral hyperalgesia.