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The contribution of GABAA and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord

作者:Lucia G. Sivilotti, C. J. Woolf · 发表于:Journal of Neurophysiology · 年份:1994 · DOI:10.1152/jn.1994.72.1.169 · 被引用次数:471 · 研究领域:Pain Mechanisms and Treatments、Botulinum Toxin and Related Neurological Disorders、Transcranial Magnetic Stimulation Studies

1. Pain hypersensitivity is characterized by an increase in the response to noxious stimuli (hyperalgesia) and a reduction in threshold such that innocuous stimuli begin to elicit pain (allodynia). These sensitivity changes can be produced by an increase in excitability of dorsal horn neurons; the phenomenon of central sensitization. We have now examined whether a reduction in local segmental inhibitory mechanisms produces similar changes. The model system used for studying touch-evoked allodynia has been the recruitment of a low-threshold mechanoreceptor input to the nociceptive flexion withdrawal reflex in the decerebrate-spinal rat. 2. Hamstring flexor alpha motoneurons are characterized by high-threshold cutaneous receptive fields. Mechanical stimuli (pinch or firm pressure) evoke a brisk firing response in these cells, whereas low-intensity stimuli (light touch or brush) produce little or no effect, as expected for the output neurons of the nociceptive flexion withdrawal reflex. 3. Primary afferent C fiber conditioning inputs have previously been shown to produce prolonged increases in the excitability of the flexion reflex, as measured by the augmentation of the response to high-intensity peripheral stimuli. We have now examined whether these conditioning inputs and segmental disinhibition modify the responsiveness of the reflex to low-threshold inputs. 4. Brief (20 s), low-frequency (1 Hz), C fiber conditioning stimuli to the sural nerve increased the response of the h...