Neurotensin (NT) has been reported to have antinociceptive effects at the spinal level. In situ hybridization, electrophysiology, immunohistochemistry, and electronmicroscopy were used to investigate the distribution of NT receptors, possible effects of NT on primary sensory neurons, and the effect of nerve injury on the expression of NT receptors and NT. NT receptor (R) mRNA was observed in more than 25% of the small dorsal root ganglion (DRG) neurons, which lacked neuropeptide Y NPY-R mRNA and essentially other neuropeptide mRNAs. Intracellular recording using voltage-clamp mode showed that NT evokes an outward current in NPY-insensitive small neurons, and NPY an outward current in NT-insensitive small neurons. Both peptides lacked effect on several small DRG neurons. In the superficial dorsal horn NT immunoreactive (IR) terminals directly contacted primary afferent terminals without synaptic specializations. This new category (> 25%) of the small DRG neurons expressing NT-R mRNA was complementary to the around 60% of small neurons expressing NPY-R mRNA (and also substance P and calcitonin gene-related peptide mRNAs) and to the rest exhibiting somatostatin mRNA expression. The electrophysiological results support this classification, showing that NT and NPY have inhibitory effects on separate subpopulations of small DRG neurons. After sciatic nerve transection, a marked decrease was observed in (1) the number of NT-R mRNA-positive neurons in DRGs, (2) NT mRNA-positive neurons in the dorsal horn, and (3) NT-IR cell bodies and fibers in laminae I-II. Thus, axotomy causes downregulation of several NT systems at the spinal level, suggesting that the possible effects of NT on primary sensory neurons is attenuated after peripheral axotomy.