Intravenous galanin (1–16) and a GalR1 agonist attenuate allodynia in rats with spared nerve injury

Abstract Introduction: Chronic pain is a major unmet medical need, with current treatments often providing limited relief. The neuropeptide galanin, acting through GalR1-3 receptors, has been implicated in pain modulation. Although galanin analogues are typically administered intrathecally, emerging evidence suggests that peptides can cross the blood–brain barrier. We hypothesized that systemic administration of the biologically active fragment galanin (1–16) could attenuate neuropathic pain. Objectives: To evaluate whether intravenous galanin (1–16) reduces pain-like behaviors in a rat model of neuropathic pain and to compare its effects when using a selective GalR1 agonist. Methods: Male Sprague–Dawley rats underwent spared nerve injury. Animals received intravenous galanin (1–16), M617 (selective GalR1), or vehicle. Mechanical and cold allodynia were assessed using von Frey filaments and acetone testing, respectively. Open-field tests evaluated locomotor activity to exclude more general behavioral effects. Data were analyzed using blinded protocols and appropriate statistical tests. Results: Galanin (1–16) and M617 significantly reversed mechanical allodynia compared with vehicle, with effects evident at 0.5 hours, peaking at 2 hours, still present after 4 hours, and absent by 6 hours ( P < 0.0001). No significant differences were observed between galanin (1–16) and M617. By contrast, neither compound significantly affected cold allodynia. Locomotor activity, total distance travelled, or center time were not affected by galanin (1–16). Conclusion: Intravenous administration of galanin (1–16) produces robust but transient antiallodynic effects in neuropathic rats, likely mediated through GalR1 activation, without impairing locomotion. These findings highlight the therapeutic potential of systemically administered galanin or galanin analogues targeting GalR1 for neuropathic pain management.