Dexmedetomidine decreases hyperalgesia in neuropathic pain by increasing acetylcholine in the spinal cord

► Interaction between α2-adrenergic and acetylcholine in neuropathic pain was examined. ► Spinal α2-adrenoceptor activation suppressed hyperalgesia in rats with nerve injury. ► The anti-hyperalgesia was reversed by an intrathecal muscarinic receptor antagonist. ► Spinal α2-adrenoceptor activation increased acetylcholine in rats with nerve injury. ► Acetylcholine contributes to analgesia from spinal α2-adrenoceptor activation.