Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia?

To study the role of protons in ischemic muscle pain we employed the "submaximal effort tourniquet technique' and, in a second attempt, an intramuscular pressure infusion of acid phosphate buffer. The pH measured in the forearm skin covering the muscles at work during the tourniquet test continuously dropped to a mean value of pH 7.00 +/- 0.26, starting 1 min after the contractions, while the pain increased in direct correlation with the hydrogen ion concentration (r = 0.96). After restoring the blood supply, the intradermal proton concentration decreased more slowly than the muscular pain. The same subjective quality of deep muscular pain was achieved with pressure infusion of acid phosphate buffer (pH 5.2) into the forearm muscles. Constant flow rates evoked constant, apparently non-adapting magnitudes of pain with a log-linear stimulus-response relationship (r = 0.93). Changes in flow rate were followed by changes in pain ratings with a certain phase lag. We conclude that muscular pain induced by infusion of acidic phosphate buffer and pain from ischemic contractions are generated through the same mechanisms based on the algogenic action of protons.

Pain due to experimental acidosis in human skin: evidence for non-adapting nociceptor excitation.

The mechanisms of acid pain induction by superfusion of a human blister base and by intradermal infusion of acid phosphate buffer are compared in this study. Superfusion of a freshly opened blister base with CO2-saturated 'synthetic interstitial fluid' (pH 6.1) led to pain that linearly faded away during 15 min. In contrast, the protein content of the blister effluate approached a very low basal level within the first 5 min of superfusion, irrespective of the pH applied, which suggests a progressive sealing of the blister base impeding macromolecular permeation first, and invasion of protons and CO2 later. In contrast, pressure infusion of an acidic buffer into the skin induced constant pain for as long as a flow rate was maintained. The time course and distribution of the intracutaneous pH changes induced were monitored at different distances to the infusion point using a pH-sensitive needle electrode. The continuous infusion produced a restricted area of cutaneous tissue acidosis where pH values were sufficiently low presumably to excite nociceptors. This area had relatively sharp borders, and in the border zone a steady-state of the local pH was reached within about 20 min (at an infusion rate of 40 ml/h) suggesting a balance between acidifying and neutralizing forces. The acid pain increased during the first minutes of infusion closely in parallel to the pH near the infusion point, remained constant at constant pH and flow rate and declined more rapidly than the pH was able to recover after discontinuation of the infusion. In conclusion, the results suggest that the pain from the experimental tissue acidosis is due to non-adapting excitation of a relatively constant population of nociceptors terminating in a spatially restricted volume of tissue.