ALGESICS EXCITE AXOTOMISED AFFERENT NERVE-FIBERS WITHIN THE FIRST HOURS FOLLOWING NERVE TRANSECTION IN RATS

The direct consequences of a peripheral nerve injury at the lesion sit e itself are often twofold: axons of afferent (and efferent) nerve fib res are transected and the tissue surrounding the nerve injury site is inflamed. Recent studies have shown that a few hours after nerve tran section, axotomised myelinated (A) and unmyelinated (C) afferents may respond to mechanical and thermal stimuli applied to the cut nerve end . Here, 5-24 h after sural nerve ligation and transection we studied t he ectopic excitability of axotomised cutaneous A and C fibres by chem ical agents, most of which excite afferent terminals in skin. Topical application of bradykinin (BK; 10(-4) M) to the nerve stump excited 7. 3% of all C fibres tested. Application of prostaglandin E-2 (PGE(2)), a solution with increased proton concentration (pH 6.0) or a combinati on of inflammatory mediators ('inflammatory soup', containing histamin e, 5-HT, BK and PGE(2) (all 10(-5) M) at a pH of 7.0) activated 2.7-4. 3% of all C fibres tested. Hypertonic saline solution (HS; 4.5%) and c apsaicin, painful irritants, excited 8.3% and 5.0% of the C fibres, re spectively. Among the axotomised A fibres tested, between 0.8% and 1.7 % were excited by BK, PGE(2), inflammatory soup (IS) or HS. Capsaicin and acid pH did not excite cut A fibres. In total, the number of chemi cally excited C fibres (50/547) significantly exceeded the number of a ctivated A fibres (10/469). Local norepinephrine application (0.5-2.4. 10(-3) M) did not activate A or C fibres (234 and 224 fibres tested, r espectively). The results indicate that already during the first hours after transection of a peripheral skin nerve a significant proportion of axotomised afferents can be excited by topical chemical stimulatio n. This evoked activity is preferentially found in unmyelinated fibres , many of which have nociceptive functions. Chemically evoked discharg es as described in the present study may therefore contribute to the i nduction of pain and paraesthesias in patients with peripheral nerve l esion when the injury site is inflamed. (C) 1997 International Associa tion for the Study of Pain. Published by Elsevier Science B.V.