Functional alteration of inhibitory influences on spinal motor output in painful diabetic neuropathy in rats

Diabetes is frequently accompanied by painful polyneuropathies that are mediated by enhanced neuronal excitability in the spinal cord, partly because of decrease in spinal intrinsic inhibitory influences. Changes in spinal excitatory-inhibitory balance may alter spinal segmental motor output. In the study presented here, the mono- and disynaptic (the fastest polysynaptic) reflexes (MSR and DSR, respectively) were recorded from L5 ventral roots in response to stimulation of the ipsilateral L5 dorsal root in spinalized streptozotocin (STZ)-induced diabetic rats with a reduced withdrawal threshold to mechanical stimuli. The diabetic rats generally exhibited larger spinal reflex amplitudes, the DSR being influenced in particular. We addressed whether recurrent and presynaptic inhibition of the spinal reflexes were altered in STZ-treated animals. The recurrent inhibition of the MSR and DSR elicited by preceding antidromic conditioning stimulation delivered to the recorded L5 ventral root was markedly suppressed in diabetic rats. By contrast, the presynaptic inhibition of the MSR and DSR elicited by preceding conditioning stimulation to the ipsilateral L4 dorsal root was not impaired. Thus, in diabetic painful neuropathy, reduced spinal intrinsic inhibition in the ventral horn contributes to an enhanced spinal segmental motor output.