EVALUATION OF THE CONTINUOUS BUPRENORPHINE DELIVERY ANALGESIC EFFECT IN AN EXPERIMENTAL RAT MODEL OF PAINFUL DIABETIC NEUROPATHY

Diabetic neuropathy (DN) can induce loss of nociception, as well as mechanical hyperalgesia and tactile allodynia. Recent pharmacological and clinical studies have shown that buprenorphine, a low molecular weight, lipophilic, opioid analgesic, acts not only on nociceptive and visceral pain, but also on neuropathic pain. To assess the analgesic effect of buprenorphine we used a well-established experimental rat model of painful DN in which two buprenorphine doses were administered by implantable Alzet® osmotic pumps for 3 weeks. Diabetic rats developed severe hyperglycaemia, a marked weight gain reduction and a decrease in soleum and extensor digitorum longus muscles weight vs. control rats. Buprenorphine treatment did not modify all these diabetes-induced alterations. Na+,K+-ATPase activity was significantly reduced in diabetic animals and buprenorphine administration increased this activity. After 6 weeks of diabetes, nerve conduction velocity (NCV) and behavioural responses to noxious mechanical and thermal stimuli were assessed. Diabetic rats showed an impairment of NCV, mechanical allodynia and thermal hypoalgesia. Both doses of buprenorphine significantly reverted the DN-induced allodynia up to day 7 of treatment. Buprenorphine did not alter either thermal perception or NCV. In conclusion, buprenorphine induced analgesia in short term period, suggesting a possible use in the management of patients with DN-associated neuropathic pain. Effect was particularly evident for allodynia, one of the most discomforting symptom in patients with DPN. This work is in part supported by unrestricted research grant from “Grunenthal Italia”