This study was to examine the effects of microinjection of human recombinant interleukin 2 (IL-2) into locus coeruleus (tc) on spinal nociception. Following application of IL-2 (0.1 mul, 10 pM) into LC, the percentage of inhibition of nociceptive C responses of reflex at 3, 9, 15, 21 and 27 min after injection were 88.2 +/- 9.4%, 84.0 +/- 11.8%, 89.7 +/- 10.5%, 57.1 +/- 8.7% and 26.3 +/- 12.2%, respectively. Also, the expression of Fos protein in superficial dorsal horn was reduced by 73.01 +/- 13.58% of control (P<0.0001). Naloxone (10 <mu>g, i.p.) completely blocked the IL-2-induced inhibition of C responses. The results clearly show that IL-2 receptors present in LC mediate descending inhibition of the spinal nociception, which may couple with the activation of opioid receptors on LC neurons. (C) 2000 Harcourt Publishers Ltd.