beta-endorphin and Diabetic-Neuropathies

To determine the possible role of endogenous opioid peptides in the action of imipramine and paroxetine in painful diabetic neuropathy, beta-endorphin concentrations in plasma were measured in 20 patients during a double-blind, placebo-controlled randomized three-way crossover trial. Despite a significant reduction in neuropathy symptoms during both imipramine and paroxetine treatment, the beta-endorphin level was unaltered throughout the study. The plasma concentration of beta-endorphin was not related to plasma drug concentrations. Thus, this study does not provide evidence of a role of endogenous opioid peptides in the mechanism of action of imipramine and paroxetine in painful diabetic neuropathy.

Topics: Adult; Aged; Antidepressive Agents; beta-Endorphin; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Imipramine; Male; Middle Aged; Paroxetine; Piperidines

The antinociceptive effects of the enantiomorphs of mexiletine (2-(2, 6-dimethylphenoxy)-1-methylethylamine monohydrochloride) and its main metabolite ((+/-)2-(2-hydroxymethyl-6-methylphenoxy)-1-methylethylamine oxalate: KOE2259) were studied in streptozotocin-induced diabetic mice using the tail-pinch and tail-flick test. Both (+)mexiletine and (-)mexiletine, at doses of 10 and 30 mg given i.p., produced dose-dependent inhibition of the tail-pinch response in diabetic, but not non-diabetic mice. On the other hand, KOE2259 had no significant effect on the tail-pinch response in both non-diabetic and diabetic mice. (+/-) Mexiletine given po also produced marked inhibition of the tail-pinch and tail-flick responses in both non-diabetic and diabetic mice. However, lidocaine, given either i.p. or po, had no significant effect on the tail-pinch response in both non-diabetic and diabetic mice. Intraperitoneal administration of mexiletine (30 mg/kg) significantly increased the serum beta-endorphin level in diabetic mice, but not in non-diabetic mice. These results indicate that both enantiomorphs of mexiletine produced an antinociceptive effect in diabetic mice. Furthermore, it is possible that the activation of the endogenous beta-endorphinergic system may be, at least in part, involved in the antinociceptive effect of mexiletine.

Topics: Animals; Anti-Arrhythmia Agents; beta-Endorphin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Dose-Response Relationship, Drug; Hyperalgesia; Male; Mexiletine; Mice; Mice, Inbred ICR; Stereoisomerism; Streptozocin

Intravenous infusion of lidocaine has a pain-relieving effect in patients with painful diabetic neuropathy. We measured plasma beta-endorphin (beta-EP), dynorphin immunoreactivity (DYN), and met-enkephalin (MET) before and after lidocaine infusion in 8 patients with painful diabetic neuropathy and in 10 controls. The pretreatment level of beta-EP and DYN was identical in the two groups. After lidocaine, beta-EP increased in diabetic patients from 3.4 to 5.5 pmol/L (median) (p less than 0.02) and in controls from 3.4 to 5.0 pmol/L (p less than 0.02). The concentration of DYN was stable, and MET was undetectable before and after lidocaine. Lidocaine reduced symptoms and pain score in diabetic patients was uncorrelated with the changes in beta-EP. Intravenous lidocaine increased plasma beta-EP and diminished complaints in patients with painful diabetic neuropathy.

Topics: Adult; beta-Endorphin; Diabetic Neuropathies; Dynorphins; Endorphins; Female; Humans; Lidocaine; Male; Middle Aged; Pain; Radioimmunoassay