Several lines of evidence have shown that stimulation or inactivation of lateral hypothalamus (LH) produces antinociception. In this study, we assessed the role of nucleus locus coeruleus (LC) in antinociceptive response induced by LH stimulation or inactivation in the rat. The cholinergic agonist carbachol (125 nmol/0.5 μl saline) or lidocaine (2%; 0.5 μl) was unilaterally microinjected into the LH with the LC inactivation concurrently. Antinociceptive responses were obtained by tail-flick test and represented as maximal possible effect (MPE) at 5, 10, 15, 20, 30 and 60 min after drug administration. The results showed that microinjection of carbachol into the LH significantly induced antinociception at 5 and 10 min (p < 0.001). This effect was significantly blocked by microinjection of lidocaine into the LC. On the other hand, microinjection of lidocaine into LH-induced antinociception at 5 (p < 0.01) and 10 (p < 0.05) min after administration. However, inactivation of the LC following the LH inactivation increased MPE at 5 min after injection. These findings support the conclusion that antinociception produced by LH stimulation or inactivation involves two separate mechanisms. It seems that analgesic response induced by LH stimulation is mediated in part by the subsequent activation of spinally projecting noradrenergic neurons in the LC cell group.