FORMALIN-EVOKED ACTIVITY IN IDENTIFIED PRIMARY AFFERENT-FIBERS - SYSTEMIC LIDOCAINE SUPPRESSES PHASE-2 ACTIVITY

Formalin injected subcutaneously into the paw is a frequently used pai n assay; it evokes an initial period of licking and flinching followed by a period of quiescence and last by a second period of intense and protracted licking and flinching. The prominent second phase is believ ed to reflect the development of a central (spinal cord) facilitation. This conclusion is based on the assumption that formalin evokes an in itial burst of activity in fine afferent fibers, followed by prolonged low levels of activity in C fibers. Detailed reports substantiating t his essential assumption have not been published, Thus, we recorded in situ from single sural nerve fibers, identified by their conduction v elocity and modality, in the barbiturate anesthetized rat, Following f ormalin (2.5%, 50 mu l) injection into their receptive fields, phase-1 activity was prominent in A beta and A delta fibers as well as in hig h-threshold C nociceptive afferent fibers, Phase-2 activity was observ ed in A delta fibers with receptive fields in hairy skin and in all me chanically sensitive C fibers. Mean phase-2 activity in these fibers w as 1/2-2/3 of the magnitude achieved in phase 1. Mechanically insensit ive fibers and A delta and C fibers with receptive field centers outsi de of the injection zone began firing 15 min or more post-injection an d would contribute to phase-2 but not phase-1, behavioral activity. In travenous infusion of low doses of lidocaine yielding plasma levels of 3.6-7.9 mu g/ml administered during phase 2 blocked formalin-evoked a ctivity in primary afferent fibers in a dose-related fashion without b locking either electrically or mechanically evoked activity. Effective plasma doses were comparable to those found to relieve neuropathic pa in. These data indicate that phase 2 in the formalin test is more clos ely related to ongoing afferent input than had previously been thought .