EFFECT OF CHRONIC SCIATIC-NERVE LESION ON THE NEUROGENIC INFLAMMATORYRESPONSE IN INTACT AND ACUTELY INJURED DENERVATED RAT SKIN

A supersensitivity to the neuropeptide substance P (SP) has been shown to develop in post-terminal membranes of many denervated tissues. Thi s study examined changes in the sensitivity of post-terminal vascular receptors to SP and calcitonin gene-related peptide (CGRP) in rat skin microvasculature following sciatic nerve section. In anaesthetised ra ts, 0.5 cm of sciatic nerve in the right mid-thigh region was removed, Two weeks later, SP (100 mu M) and sodium nitroprusside (SNP, 1 mM), a direct smooth muscle vasodilator, were introduced into denervated in tact footpad skin. via the electrophoresis technique, Laser doppler fl owmeter was used to record changes in relative blood flow in the rat h ind footpad. The results showed a significant increase in SP response over controls and slight increase in smooth muscle reactivity as deter mined by an increase in the vascular response to SNP. In another set o f experiments, the sensitivity of post-terminal receptors vias examine d over a 4 weeks period in an acutely injured footpad skin of sciatic nerve lesioned rats. A vacuum-induced blister was raised on the hind f ootpad and SP, CGRP (each at 1 mu M) or SNP (100 mu M) were superfused over the blister base. In nerve lesioned rats, using the acutely inju red footpad skin model, the results showed a reduction in the vascular responses to SP, CGRP and SNP. The response to SP continued to decrea se over time reaching 22% of control values by 4 weeks. Responses to S NP and CGRP were reduced to 53% and 45% respectively by 2 weeks and th en improved to 75% of control values by 4 weeks. Possible contribution s of sympathetic efferents and the saphenous nerve to these reduced re sponses in acutely injured skin of nerve lesioned rats were examined u sing guanethidine (50 mg/kg i.p.) or sectioned saphenous nerve respect ively. These procedures did not significantly modify the reduced vascu lar responses in the blister base of lesioned rats, Possible activatio n of endogenous opioids and/or the release of endothelin due to bliste r induction in nerve lesioned rats was examined using naloxone and the endothelin receptor antagonist, BQ-123, respectively. Treatment with naloxone increased SP response in lesioned rats to 41% of control valu e with no change in smooth muscle reactivity. BQ-123 significantly inc reased the responses to SP and SNP to 51% and 100% of their own contro l values respectively, It is concluded that supersensitivity of post-t erminal vascular receptors develops in intact skin following chronic n erve lesion. On the other hand, acute injury of the denervated skin ar ea induces activation of endogenous inhibitory modulatory mechanisms t hat masks this supersensitivity.