SPINAL MODULATION OF THE INDUCTION OF CENTRAL SENSITIZATION

Peripheral tissue injury results in a change in the excitability of sp inal dorsal horn neurons, central sensitization, and the behavioral co rrelate, hyperalgesia. It is proposed here that a dynamic balance exis ts between excitatory and inhibitory synaptic input to the spinal dors al horn that functions to prevent central sensitization following brie f, mild, noxious stimulation, Following mon severe stimulation and inj ury, there is a loss of these inhibitory mechanisms that allow central sensitization to proceed. Single-unit recordings were made from L4-L5 deep dorsal horn neurons (wide dynamic range and nociceptive specific ) from barbiturate-anesthetized rats that were non-inflamed or had a c arrageenan-inflamed hindpaw. Baseline test responses to mechanical sti muli were obtained and normalized to 100%. An electrical conditioning stimulus (1 Hz, 20 s, C-fiber strength) was applied to the tibial nerv e or the neuronal receptive field. Five seconds later the test stimulu s was repeated and the magnitude of response compared to baseline. Dur ing the conditioning stimulus, 46% of the neurons from non-inflamed an d inflamed rats showed wind-up although the magnitude of wind-up was s ignificantly greater for inflamed rats. The remaining neurons showed n o change (36-46%) or wind-down (8-18%), Five seconds following the end of the conditioning stimulus 67% of the neurons from non-inflamed rat s had attenuated responses to mechanical stimuli (36% of baseline), Th e remaining neurons were either unaffected (30%) or facilitated (3%). Following inflammation significantly fewer neurons (28%) had attenuate d responses and the magnitude of attenuation was significantly less th an in non-inflamed rats (54% of baseline). The responses of the remain ing neurons were unaffected (54%) or facilitated (18%). During subsequ ent test stimuli, thr responses of 30% of the neurons from non-inflame d rats were facilitated to 140% of baseline, The responses of 46% of n eurons from inflamed rats were facilitated to 160% of baseline. In the se neurons there was significantly less initial attenuation following inflammation compared to non-inflamed rats. The response of the neuron during the electrical conditioning had no effect upon the response fo llowing conditioning. The conditioning stimulus given transcutaneously within the receptive field produced qualitatively similar results to tibial nerve stimulation. In non-inflamed rats, when the conditioning/ test-stimulus interval was increased from 5 s to 10-30 s. the response s of 20% of the neurons were attenuated (compared to 67%) and the mean magnitude of attenuation was 52% of baseline (compared to 36% of base line). However, the responses of only 33% of the neurons were ultimate ly facilitated (compared to 30%). The present study documents a short period following a low-frequency C-fiber input in which the response t o natural stimuli is suppressed, It is suggested that this attenuation , whether or not expressed, prevents a significant portion of deep dor sal horn neurons from becoming sensitized to C-fiber input. This funct ions to prevent central sensitization when the noxious stimulus does n ot produce inflammation and it is not beneficial to the animal to beco me hyperalgesic (i.e., to alter its behavior in order to protect an in jured limb and reduce painful sensations). Following injury-producing tissue damage and inflammation the mechanisms that produce the attenua tion are reduced, with a concomitant increase in excitation to electri cal and natural stimuli, suggesting that the attenuation is inhibitory modulation of nociceptive input and injury results in a disinhibition producing an increase in excitability and central sensitization. (C) 1997 Elsevier Science B.V.