Sensitization of spinal neurons by non-noxious stimuli in the awake but not anesthetized state

The observation that peripheral trauma causes enhanced spinal neuronal excitability has provided the scientific rationale for the concept of "pre-emptive analgesia." The premise has been that only noxious stimuli cause sensitization in sensory pathways, but this premise has not been tested in the conscious state.

Responses of single spinal neurons were recorded in instrumented sheep that were untrained and free from drugs or recent surgery, in either fully conscious or halothane-anesthetized states. Receptive field (RF) size was measured before and after non-noxious mechanical conditioning stimulation.

Noxious conditioning stimuli in anesthetized sheep caused enlargement of RF areas, as expected. Conditioning with nonpainful scratching or other stimuli was without effect in anesthetized animals; in marked contrast, it caused enlargement of RF size in conscious animals, in which 29 of 33 wide dynamic range units but only 1 of 12 low-threshold mechanoreceptive neurons were affected.

Sensitization of spinal sensory neurons evidently is a process that is not restricted to pathologic pain states but rather that occurs under normal physiologic conditions independent of painful stimuli. The significance of such sensitization processes therefore needs reevaluation. The sensitization triggered by non-nociceptive afferents is likely to be opioid-resistant and therefore may contribute to the rather disappointing results seen in several clinical trials of "pre-emptive analgesia."