Perfil longitudinal clínico-comportamental da neuropatia diabética dolorosa experimental

Abstract

Diabetes Mellitus is a chronic disease of energy metabolism and chronic complications are one of its major caracteristics. Neuropathy is the most prevalent chronic complication of Diabetes Mellitus. Its physiopathology still remains as a challenge to be solved. The diabetic neuropathy shows several clinicai pictures. In one of these, the diabetic neuropathy manifests itself as a chronic neuropathic pain of difficult control, provoking a great anguish in its bearers. Among the several types of painfiil diabetic neuropathies, the sensorimotor symmetric polyneuropathy outstands for its greatest frequency. Animal models that faithfiilly represent this painfiil clinicai condition are lacking, and this is one of the reasons why we know very little about the physiopathology and treatment of the painfi.il diabetic neuropathy. The literature about experimental pain in diabetic rats is conflicting, and in its majority concems only painful evoked behaviors. Moreover, the majority of these works was accomplished in short periods of disease. With the purpose of studying not yet reported spontaneous behavioral changes in diabetic rats, we induced diabetes in 32 rats with an intraperitoneal injection of streptozotocin in a dose of 75 mg/Kg. The animais were then followed during 27 weeks. In this study, we looked for changes similar to human diabetes, and for sensorimotor neuropathy evidences, through the utilizatioii of clinicai observations, sciatic functional Index parameters, and thermal tests with non-noxious (40° C) and noxious (46° C) stimulus, respectively. Nevertheless, the aim of our study was to characterize the spontaneous behavioral changes that could sugest signs of chronic pain, particularly the scratching behavior, that has been proclaimed as a parameter of nociceptive chronic pain in arthritic rats, and of neuropathic pain in rats with compressed sciatic mononeuropathy. With the aim of testing these possible results, we have tried to revert such behavioral changes utilizing a potent analgesic (morphine), and to antagonize the analgesic effects over the behaviors with a specific antagonist (naloxone). Oiir results evidenced a clinicai syndrome similar to hiiman diabetes (with polyuria, cataract, and weight loss), motor neuropathy of distai predominance, sensory neuropathy (hypoalgesia in some animais, and hyperalgesia in others). The behavioral analysis revealed an increase of scratching and resting behaviors, and a decrease of motor, eating, and grooming behaviors. The pharmacological tests with morphine showed an inhibition of scratching behavior with reciprocai increase in the motor and eating activities, and decrease of resting behavior. Naloxone antagonized the effects induced by morphine. The results allowed us to conclude that the diabétic animais showed during 27 weeks, general clinicai changes and neurological changes similar to the changes found in diabétic patients, such as polyuria, cataract, disautonomy, weight loss, and painful sensorimotor neuropathy. This confirms the similarity of the model with the clinicai condition found in human Diabetes Mellitus. Moreover, the diabétic rats showed behavioral signs of chronic pain, evidenced by decrease in sniffing, rearing, eating, and grooming behaviors, and an increase of scratching and resting behaviors. Morphine decreased the time spent in scratching behavior by the diabétic animais and this was antagonized by naloxone, thereby confírming that this behavior, possibly, is also manifestation of pain in this model of painfiil diabétic neuropathy in rats.