Effect of acute topical application of (+)-pentazocine on the mechanical allodynia in diabetic mice

Mechanical allodynia is a major complication in diabetic mellitus. Peripheral σ1 receptors were shown to be involved in nociceptive perception. We therefore investigated the effect of σ1 receptor ligand (+)-pentazocine injected into the dorsal surface of the hindpaw on mechanical allodynia in streptozotocin-induced diabetic mice. Injection of (+)-pentazocine (30 μg) into the dorsal surface of the hindpaw did not affect the mechanical threshold and hindpaw NO contents in non-diabetic mice, whereas the mechanical allodynia and hindpaw contents of NO metabolites in diabetic mice were normalized by (+)-pentazocine. These effects of (+)-pentazocine in diabetic mice were inhibited by pretreatment with an σ receptor antagonist BD1047 into the same area, but not by systemic pretreatment with a κ-opioid receptor antagonist nor-binaltorphimine. These results suggest that (+)-pentazocine injected into the dorsal surface of the hindpaw increases the lowered mechanical threshold in diabetic mice through the activation of peripheral σ1 receptors. This attenuation may be, in part, due to the normalization of increased peripheral NO contents in the hindpaw of diabetic mice.