EFFECTS OF CLASSICAL ALGOGENS

The classical mediators have hitherto been demonstrated to be prone to profound tachyphylaxis (as seen with BK and serotonin); HIS and PGE2 do not prevent this loss of excitatory action on nociceptors. Hyperosmolarity and transiently increased potassium levels in inflamed tissue also cannot explain significant ongoing discharge. Specific excitatory effects of acidic pH, however; can facilitate responses to inflammatory mediators and vice versa. In addition, recruitment of unmyelinated afferents and sustained non-adapting activity occur when moderately low pH (pH 6.1) and inflammatory mediators (10(-6) M) combine to mimick the inflammatory exudate. This maintains a primary afferent input from inflamed tissue to the central nervous system.