This study investigates Ca(2+)/calmodulin kinase IIalpha (CaMKIIalpha) in primary sensory neurons. Immunohistochemical staining with a CaMKIIalpha antibody demonstrates 28% of dorsal root ganglion (DRG) cells are positively stained and have a diameter of 27 +/- 2.4 microm (mean +/- S.D.). Placement of tight ligatures around the sciatic nerve demonstrates a build up of immunoreaction product proximal to the ligatures indicating that CaMKIIalpha is transported into the peripheral processes of DRG cells. Immunostaining of lumbar dorsal roots at the electron microscopic level demonstrates reaction product in 15.4 +/- 2.1% of unmyelinated and 2.4 +/- 1.0% of myelinated axons, indicating that CaMKIIalpha is transported into the central processes of DRG cells. Electron microscopic analysis of normal digital nerves demonstrates CaMKIIalpha labeling in 3.3 +/- 0.3% of unmyelinated and 2.0 +/- 1.1% of myelinated cutaneous axons. These percentages increase significantly to 14.1 +/- 2.3% for unmyelinated and 5.1 +/- 1.4% for myelinated axons 48 h after complete Freund's adjuvant-induced inflammation of the hindpaw. The data indicate that CaMKIIalpha is present in small diameter primary sensory neurons, that it is transported into the peripheral and central processes of these cells and may play a role in processing noxious input, particularly in the inflamed state.