Immunohistochemistry was applied to examine the correlation between neuropeptide Y (NPY) and the two calcium binding proteins (CaBPs) parvalbumin (PV) and calbindin D28k (CB) in the trigeminal ganglion following peripheral axotomy of the inferior alveolar nerve (IAN) in the rat. Five days following transection and application of FluoroGold (FG) to the cut end of the IAN, approximately 14.8% (80/539) and 18.6% (90/483) of FG-labeled IAN neurons in the trigeminal ganglion showed PV-like immunoreactivity (-LI) and CB-LI, respectively. The mean +/- S.D. area of FG-labeled PV-like immunoreactive (-IR) cells (FG/PV-IR cells) and FG/CB-IR cells were 835.9 +/- 303.1 mu m2 and 712.7 +/- 246.0 mu m2, respectively. FG/PV-IR cells were significantly larger than FG/CB-IR cells. Fourteen days following peripheral axotomy of the IAN, NPY-LI appeared in the medium- to large-sized cells. Double immunostaining revealed that approximately 3.3% (52/1569) of NPY-IR cells in the axotomized trigeminal ganglion displayed PV-LI, while approximately 26.7% (371/1392) of NPY-IR cells displayed CB-LI. The mean +/- S.D. cross-sectional areas of PV-IR and CB-IR trigeminal ganglion cells displaying NPY-LI were 819.5 +/- 265.6 mu m2 and 766.5 +/- 279.7 mu m2, respectively. There were no significant differences in the cross-sectional areas either between NPY/PV-IR cells and NPY/CB-IR cells, or between FG/PV-IR cells and NPY/PV-IR cells, or between FG/CB-IR cells and NPY/CB-IR cells. The present results indicate that injury-evoked medium- to large-sized NPY neurons were a different population from large-sized PV neurons, and NPY was partly co-localized with CB.