buprenorphine and Diabetic-Neuropathies

To evaluate the efficacy and safety of transdermal buprenorphine in patients with diabetic peripheral neuropathic pain (DPNP).. This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial enrolled patients with type 1 or type 2 diabetes and stable glycemic control who had been experiencing moderate to severe DPNP for at least 6 months on maximal tolerated conventional therapy. Patients were randomly assigned to receive buprenorphine (5 μg/h) or placebo patches. The dose was titrated to effect to a maximum of 40 μg/h. Paracetamol was available as rescue analgesia. The severity of pain and other symptoms of DPNP were assessed daily in a patient diary and at clinic visits.. One hundred eight-six patients were enrolled, with 93 randomized to either buprenorphine or placebo. A high proportion of patients did not complete the study (buprenorphine 37 of 93, placebo 24 of 93). The main reason for premature withdrawal in the buprenorphine group was adverse events commonly due to untreated nausea and/or vomiting. Among the per-protocol population, more patients in the buprenorphine group (86.3%) experienced a 30% reduction in average versus baseline pain at week 12 than those in the placebo group (56.6%, P < 0.001). A nonsignificant trend favored the buprenorphine group within the intention-to-treat analysis of the same end point (51.7% vs. 41.3%, P = 0.175).. Transdermal buprenorphine, when tolerated, is an effective therapy for DPNP and provides another option to manage this challenging painful condition. Nausea and constipation need to be managed proactively to optimize treatment outcomes.

Topics: Acetaminophen; Administration, Cutaneous; Adult; Aged; Analgesics, Non-Narcotic; Analgesics, Opioid; Buprenorphine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Nausea; Neuralgia; Treatment Outcome; Vomiting; Withholding Treatment

Diabetic peripheral neuropathy (DPN) can induce loss of nociception as well as mechanical hyperalgesia and tactile allodynia. Pharmacological and clinical studies have shown that buprenorphine, a low-molecular-weight, lipophilic, opioid analgesic available as a transdermal matrix patch formulation, acts on neuropathic pain. To assess the role of buprenorphine in the treatment of DPN-associated neuropathic pain, we used a well-established experimental rat model of DPN in which buprenorphine at doses of 1.2 and 2.4 microg/kg/h was administered by implantable Alzet osmotic pumps for 3 weeks. 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 reversed the diabetes-induced allodynia up to day 7 of treatment. Buprenorphine did not alter either thermal perception or NCV.. This study evaluated, through a multimodal approach, the analgesic effect of buprenorphine in an experimental rat model of painful DPN. Our results suggest a possible role for buprenorphine in the management of DPN-associated neuropathic pain.

Topics: Action Potentials; Analgesics, Opioid; Animals; Buprenorphine; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrodiagnosis; Hyperalgesia; Infusion Pumps, Implantable; Male; Neural Conduction; Peripheral Nervous System; Rats; Rats, Sprague-Dawley; Treatment Outcome

Streptozotocin-induced hyperglycemia accompanied by a chronic decrease in the nociceptive threshold is considered a useful model of experimental hyperalgesia. We examined (1) the effect of the opioid receptor agonists and (2) the effect of the magnesium ions (Mg(2+)) on the antinociceptive action of opioid agonists in a diabetic neuropathic pain model. When administered alone, opioid agonists like morphine (5 mg/kg i.p.) and fentanyl (0.0625 mg/kg i.p.), as well as the partial agonist buprenorphine (0.075 mg/kg) had only little effect on streptozotocin-induced hyperalgesia. However, pretreatment with Mg(2+) at a dose of 40 mg magnesium sulfate/kg i.p. markedly enhanced the analgesic activity of all three investigated opioids. Practical aspects of co-administration of magnesium and opioids in diabetic neuropathy are discussed.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Drug Synergism; Drug Therapy, Combination; Fentanyl; Hyperalgesia; Injections, Intraperitoneal; Magnesium Sulfate; Male; Morphine; Pain Measurement; Pain Threshold; Rats; Rats, Wistar; Streptozocin