Beneficial effects of galanin system on diabetic peripheral neuropathic pain and its complications

Diabetic peripheral neuropathic pain (DPNP) is a distal spontaneous pain, caused by lesion of sensory neurons and accompanied by depression and anxiety frequently, which reduce life quality of patients and increase society expenditure. To date, antidepressants, serotonin-noradrenaline reuptake inhibitors and anticonvulsants are addressed as first-line therapy to DPNP, alone or jointly. It is urgently necessary to develop novel agents to treat DPNP and its complications. Evidences indicate that neuropeptide galanin can regulate multiple physiologic and pathophysiological processes. Pain, depression and anxiety may upregulate galanin expression. In return, galanin can modulate depression, anxiety, pain threshold and pain behaviors. This article provides a new insight into regulative effects of galanin and its subtype receptors on antidepressant, antianxiety and against DPNP. Through activating GALR1, galanin reinforces depression-like and anxiogenic-like behaviors, but exerts antinociceptive roles. While via activating GALR2, galanin is referred to as anti-depressive and anti-anxiotropic compounds, and at low and high concentration facilitates and inhibits nociceptor activity, respectively. The mechanism of the galanin roles is relative to increase in K⁺ currents and decrease in Ca²⁺ currents, as well as neurotrophic and neuroprotective roles. These data are helpful to develop novel drugs to treat DPNP and its complications.