The current study investigated the roles of various subtypes of opioid receptors expressed in the thalamic nucleus submedius (Sm) in inhibition of mirror-image allodynia induced by L5/L6 spinal nerve ligation in rats. Morphine was microinjected into the Sm, which produced a dose-dependent inhibition of mirror-image allodynia; this effect was antagonized by pretreatment with non-selective opioid receptor antagonist naloxone. Microinjections of endomorphin-1 (mu-receptor agonist), or [D-Ala(2), D-Leu(5)]-enkephalin (DADLE, delta-/mu-receptor agonist), also inhibited mirror-image allodynia, and these effects were blocked by the selective mu-receptor antagonist, beta-funaltrexamine hydrochloride. The DADLE-induced inhibition, however, was not influenced by the delta-receptor antagonist naltrindole. The kappa-receptor agonist, spiradoline mesylate salt, failed to alter the mirror-image allodynia. These results suggest that Sm opioid receptor signaling is involved in inhibition of mirror-image allodynia; this effect is mediated by mu- (but not delta- and kappa-) opioid receptors in the rat model of neuropathic pain.