The effects of galanin on neuropathic pain in streptozotocin-induced diabetic rats

Diabetic neuropathy is a common complication associated with diabetes and is frequently painful. However, mechanisms responsible for diabetic neuropathic pain are still unclear. Experimental evidence has shown that the galanin and its receptor are involved in pain sensitization. The objective of the present study was to investigate the role of galanin and its receptor antagonist or agonist on neuropathic pain in streptozotocin-induced diabetic rats. The expression of galanin, galanin receptors 1 and 2 in dorsal root ganglion (DRG) and spinal dorsal horn (SDH) in diabetic rats were detected by Western blot assay. The effects of galanin, galanin receptor antagonist M35, galanin receptor 1 agonist M617, and galanin receptor 2 agonist AR-M1896 on neuropathic pain were evaluated by mechanical stimuli. The results showed that (1) the diabetic rats showed a significant mechanical hyperalgesia between 4 and 12 weeks; (2) galanin receptor 1 expression decreased in SDH in diabetic rats; (3) galanin receptor 2 expression decreased in DRG and SDH in diabetic rats; (4) intrathecal administration of exogenous galanin attenuated diabetic neuropathic pain, this effect could be blocked by pre-treatment with galanin receptor antagonist M35; and (5) intrathecal administration of galanin receptor 1 agonist M617, but not galanin receptor 2 agonist AR-M1896, attenuated diabetic neuropathic pain. These results imply that galanin acts through receptor 1, but not galanin receptor 2, to exert analgesic effect in diabetic neuropathic pain and is one of the potential therapeutic targets on diabetic neuropathic pain sensitization.