Abstract

Mechanical allodynia is a major complication in diabetic mellitus. Peripheral σ 1 receptors were shown to be involved in nociceptive perception. We therefore investigated the effect of σ 1 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 σ 1 receptors. This attenuation may be, in part, due to the normalization of increased peripheral NO contents in the hindpaw of diabetic mice.

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