Thermal hyperalgesia in rat evoked by intrathecal substance P at multiple stimulus intensities reflects an increase in the gain of nociceptive processing.

Substance P (SP) is associated with primary afferent depolarization after a noxious or tissue-damaging peripheral stimulus and is proposed to be a "pain transmitter'. However, current work has shown that activation of spinal neurokinin receptors evokes few signs of "pain behavior', but rather decreases nociceptive thresholds, suggesting a modulatory role through additive or multiplicative mechanisms. The current study addressed this question by examining the change in nociceptive threshold under three different radiant thermal stimuli after intrathecal SP administration in unanesthetized rats. With increasing stimulus intensity, the numerical change in withdrawal latency after intrathecal SP decreased, but the fractional change from baseline latency did not change, suggesting that SP increases the gain of spinal nociceptive processing.