Clinical-behavioral long-term profile of painful experimental diabetic neuropathy

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 pathophysiology still remains as a challenge to be solved. The diabetic neuropathy shows several clinical 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 painful diabetic neuropathies, the sensorimotor symmetric polyneuropathy outstands for its greatest frequency.Animal models that faithfully represent this painful clinical condition are lacking, and this is one of the reasons why we know very little about the pathophysiology and treatment of the painful diabetic neuropathy. The literature about experimental pain in diabetic rats is conflicting, and in its majority concerns only painful evoked behaviors. Moreover, the majority of these studies 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 animals were then followed during 27 weeks. In this study, we looked for changes similar to human diabetes, and for sensorimotor neuropathy evidences, through the utilization of clinical 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 compressive 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).Our results evidenced a clinical syndrome similar to human diabetes (with polyuria, cataract, and weight loss), motor neuropathy of distal predominance, sensory neuropathy (hypoalgesia in some animals, 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 reciprocal 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 diabetic animals showed, during 27 weeks, general clinical changes and neurological changes similar to the changes found in diabetic patients, such as polyuria, cataract, disautonomy, weight loss, and painful sensorimotor neuropathy. This confirms the similarity of the model with the clini...