Importance of Sensory Innervation in the Leptin Induced Protection of Oral Mucosa in the Experimental Model Znaczenie unerwienia czuciowego w ochronie błony śluzowej jamy ustnej indukowanej przez leptynę w modelu doświadczalnym

Background. Ulcerations of an oral mucosa are a common clinical problem. It is reported that in the oral cavity biologically active leptin receptor OB−R is present on the sensory fibres, known for their protective role in the mucosa of the GI tract. Objectives. To evaluate the role of exogenous leptin in to establish healing of ulcerations of the oral mucosa and mechanisms underlying this action. Material and Methods. 64 Wistar rats were used. Animals were anesthetized. Oral mucosa ulcerations were pro− duced (70% acetic acid). After 7 days of healing, ulcer area (UA) was determined and examined histologically. Microcirculatory blood flow (LDBF) in the ulcer margin was measured. Eight experimental groups were estab− lished: I – placebo (0.9% saline). II – control (leptin 25 µg/kg s.c.). III – leptin after sensory denervation (capsaicin). IV – leptin + nitric oxide synthase blocker (L−NNA). V – leptin + L−NNA + nitric oxide donor (SNAP). VI – lep− tin + CGRP. VII – leptin + CGRP1 receptor blocker (CGRP 8–37). VIII – leptin + L−NNA + CGRP. Results. Leptin administration markedly decreased UA by 35%, and increased LDBF by 29% in comparison to placebo group. In sensory denervated animals and after CGRP1 receptor blockade neither protective effects of lep− tin nor increase in LDBF were observed (UA were markedly increased with concomitant decrease of LDBF in com− parison to control). Similar effect was observed after blockade of NO synthase, NO donor administration abolished this effect. After administration of leptin with CGRP significant reduction of UA by 37% was observed with increase of LDBF by 45% in comparison to the control group. This effect were abolished by administration of NO synthase blocker. Conclusions. Leptin accelerates healing of experimentally induced ulcerations of the oral mucosa. This effect depends on CGRP released from sensory capsaicin sensitive fibres. Observed protective effects are at least in part due to increased microcirculatory blood flow in the ulcer healing zone what is evoked by NO derived vasorelax− ation (Dent. Med. Probl. 2007, 44, 3, 314–322).