In normal rat lumbar 4 and 5 dorsal root ganglia (DRGs) a few large neurons expressed neurotensin-like immunoreactivity (LI). Twenty hours after crushing the lumbar 4 and 5 dorsal roots or the sciatic nerve, accumulations of neurotensin-LI were seen in many nerve fibers on the ganglionic side of both crushes, indicating a significant centrifugal transport of neurotensin under normal circumstances. A distinct increase in expression of neurotensin (peptide and mRNA) was observed in many large neuron profiles in the ipsilateral lumbar 4 and 5 DRGs two days after unilateral sciatic nerve transection. Two weeks after axotomy the number of neurotensin-positive neuron profiles was reduced and had almost reached normal levels. In the superficial dorsal horn of the lesion side the number of neurotensin immunoreactive fibers in laminae I-II was markedly reduced 7 days after peripheral axotomy. There was no detectable increase in neurotensin-L1 in laminae III-IV of spinal dorsal horn, in the dorsal column nuclei or in the peripheral neuroma (2-28 days after axotomy), suggesting that the amounts of neurotensin transported centrifugally from DRG neurons after axotomy are low. Neurotensin-LI only sometimes colocalized with neuropeptide Y-LI, another peptide known to be upregulated in large DRG neurons. These two peptides may therefore partly be localized in different populations of large DRG neurons. The present results show that, in contrast to the nerve injury-induced general downregulation of neurotensin systems in the superficial dorsal horn and of neurotensin receptor mRNA expression in DRGs as shown in previous studies, axotomy causes upregulation of expression of neurotensin peptide in some large DRG neurons.