Combining agomelatine with gabapentin relieved nerve-injury pain in both facial and limb regions through noradrenaline-related signalling.
Male rats underwent constriction injury of either the sciatic nerve, affecting the hindpaw, or the infraorbital nerve, affecting the facial whisker-pad region. After pain hypersensitivity developed, researchers administered agomelatine and gabapentin alone or together, then tested whether drugs blocking melatonin, serotonin, or noradrenaline-related receptors altered the combination’s effects.
Agomelatine alone and low-dose gabapentin alone did not reduce mechanical pain hypersensitivity, whereas their combination produced strong pain-relieving effects, particularly in the facial nerve-injury model. Blocking serotonin receptor activity partly reproduced this benefit, while blocking noradrenaline-related alpha-two or beta-two receptors substantially reduced it, indicating that noradrenergic signalling is central to the combined treatment’s action.
