Sustained graded pain and hyperalgesia from harmless experimental tissue acidosis in human skin

The present study was performed to decide whether tissue acidosis can induce sustained pain and, by that, possibly contribute to the pain in inflammation or ischaemia. A motorized syringe pump was used to infuse an isotonic phosphate buffer solution (pH 5.2) via sterile filter and cannula into the palmar forearm skin of human subjects (n = 6). This resulted in a localized burning pain sensation (edema and flare response) that was sustained as long as a constant flow was maintained. Flow rates between 1.2 and 12 ml/h were needed to reach individual pain ratings around 20% of a visual analogue scale (VAS). Increasing the flow in multiples of this basic rate led to approximately log-linear increases in individual pain ratings with reasonable congruence of the slopes. Stopping the pump or cooling the skin close to the cannula caused an abrupt pain relief. Prolonged infusion at flow rates producing pain ratings around 20% VAS led to localized changes in mechanical sensitivity: The touch threshold increased--as it did with control infusion of phosphate buffer at pH 7.4. However, the punctate force producing a threshold sensation of pain dropped from 64 to 5.7 mN (median values); the final level was usually reached within 15 min. In conclusion, experimental tissue acidosis provides a controllable and harmless method to produce sustained, graded and spatially restricted pain and hyperalgesia to mechanical stimulation.