Algesics excite axotomised afferent nerve fibres within the first hours following nerve transection in rats.

The direct consequences of a peripheral nerve injury at the lesion site itself are often twofold: axons of afferent (and efferent) nerve fibres are transected and the tissue surrounding the nerve injury site is inflamed. Recent studies have shown that a few hours after nerve transection, 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 the ectopic excitability of axotomised cutaneous A and C fibres by chemical 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 E2 (PGE2), a solution with increased proton concentration (pH 6.0) or a combination of inflammatory mediators ('inflammatory soup', containing histamine, 5-HT, BK and PGE2 (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 capsaicin, painful irritants, excited 8.3% and 5.0% of the C fibres, respectively. Among the axotomised A fibres tested, between 0.8% and 1.7% were excited by BK, PGE2, inflammatory soup (IS) or HS. Capsaicin and acid pH did not excite cut A fibres. In total, the number of chemically excited C fibres (50/547) significantly exceeded the number of activated 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, respectively). 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 stimulation. This evoked activity is preferentially found in unmyelinated fibres, many of which have nociceptive functions. Chemically evoked discharges as described in the present study may therefore contribute to the induction of pain and paraesthesias in patients with peripheral nerve lesion when the injury site is inflamed.