Neurotensin (NT) is a tridecapeptide and plays an analgesic effect in the CNS.But the effect of NT on nociception in the spinal dorsal born still need to be further investigated.Thus, we found that both NT-immunoreactive (IR) and neurotensin receptor 2 (NTR2)-IR neuronal cell bodies and fibers as well as terminals were located in the superficial layers of the spinal dorsal horn.The asymmetrical synapses between NT-IR terminals and GABA-IR neurons were observed.Some GABA-IR neurons contained NTR2 mRNA.In lamina Ⅱ, NT (2μM) induced an inward current in only a small part of the neurons (14%) and had no effect on sEPSCs.While in some (54%) of the recorded neurons, NT increased the frequency of GABAergic sIPSCs with no effect on its amplitude.In the presence of tetradotoxin (TTX), the facilitaory effect of NT on sIPSCs was blocked.SR 142948A, an antagonist of both NTR1 and NTR2, but not SR 48692, an antagonist of NTR 1, antagonized the facilitatory effect of NT on sIPSCs.Behavioral test showed that, 5 min after NT intrathecal injection, the heat responding latency of the hind paw was lengthened.This effect was antagonized by SR 142948A instead of SR 48692.In the formalin test, 5 min before formalin (5%) subcutaneous injection to the hind paw, NT was intrathecaly injected.NT significantly reduced the number of flinches during both the first phase (0-10 min) and the second phase (15-60 min) of formalin test.In the first phase, both SR 48692 and SR 142948A antagonized the effect of NT, while in the second phase, SR 142948A but not SR 48692 antagonized the effect of NT.These results suggesi that NT might binds to NTR2 expressed by GABAergic neurons and causes activation of GABAergic neurons, which in turn enhancing GABA release, results in the inhibition of nociceptive transmission in the spinal dorsal horn.