To clarify the differential effects on spinal circuitry caused by physical vs functional disconnection from the periphery, we compared changes produced by 3-, 7- or 14-day unilateral sciatic axotomy or tetrodotoxin (TTX) nerve blockade on the abundance or activity of NADPH diaphorase (NDP), cytochrome oxidase (CO) and acid phosphatase (AP) in the spinal cord. Following axotomy, AP and NDP were decreased in the dorsal horn and increased in large cells in the dorsolateral motor nuclei while CO was decreased in ventral horn neuropil. TTX induced a decrease of CO in the ventral horn and NDP in the dorsal horn. This suggests that physical vs functional disconnection causes modulation of distinct intracellular pathways in sensory afferents, dorsal horn neurons and motoneurons.