The Interaction Mechanism Of Neurogenic Inflammation Between Nose And Eyes In Allergic Rhinoconjunctivitis

Aim:When allergic conjunctivitis?AC?and allergic rhinitis?AR?coexist,it is called allergic rhinoconjunctivitis?ARC?.ARC is a hypersensitive immune response to allergens together in the conjunctivae and nasal mucosa.At present,the pathogenesis of ARC has been verified in many aspects,such as epidemiology,clinical research and experimental observation,but the precise mechanisms remain incompletely understood.A large number of studies confirmed that neurogenic inflammation plays a very important role in the pathophysiology involved in allergic rhinitis,and nasal mucosa and conjunctivae have a common embryonic origin and innervations.Therefore,based on the research of neurogenic inflammation response,this study investigated the contribution of neurogenic inflammation to ocular allergy after nasal allergen provocation.Methods:1.Sixty SD Rats of SPF level were randomly divided into 3 groups,including the non capsaicin group?NC?,the capsaicin group?C?and the normal control group?N?.2.Rats in the non capsaicin group were sensitized by intraperitoneal?i.p.?injection of ovalbumin and Al?OH?₃ gel:a total of 7 times every other day,and intranasally challenged via administration of ovalbumin?OVA?:a total of 7 times once a day,and were given saline instead of capsaicin e.n.on day 10.Rats in the normal control group were repeatedly sensitized and challenged with saline at the same dose.3.Half of the rats in each group were killed by cervical dislocation 1 h after the last challenge,and the other half were killed after 24 h.Therefore,there were 6 groups in all,namely NC1?killed at 1 hour after the last challenge in non capsaicin group?,NC24?killed at 24 hours after the last challenge in non capsaicin group?,C1?killed at1 hour after the last challenge in capsaicin group?,C24?killed at 24 hours after the last challenge in capsaicin group?,N1?part of the N group sacrificed 1 hour after the last challenge?,N24?part of the N group sacrificed 24 hours after the last challenge?.4.Bilateral nasal mucosa and conjunctiva were isolated microscopically,and the tissues were taken for immunohistochemistry,western blotting and real-time polymerase chain reaction.The slide was observed under light microscopy and analyzed with image analysis system.Nerve growth factor?NGF?,substance P?SP?and vasoactive intestinal peptide?VIP?were detected.Results:1.Immunohistochemical stainings showed those proteins localized in cytoplasm of the glandular epithelial cells and the pseudostratified ciliated columnar epithelial cells,distributed in both nasal mucosa and conjunctivae tissues.2.The levels of SP,VIP and NGF were increased in both nasal mucosa and conjunctivae at 1 hour and 24 hours after OVA application?p<0.05?.Higher levels of SP,VIP and NGF expression were found in the nasal mucosa and conjunctivae at 24hours after OVA application?p<0.05?.3.After the destruction of sensory nerves in the nose by capsaicin,the protein levels and mRNA expressions of SP,VIP and NGF were inhibited in the nasal mucosa tissue and conjunctivae of OVA-sensitized rats.Conclusions:1.Nasal challenge with OVA can activate the sensory nerve fibers in the nasal cavity releasing the neuropeptide SP.At the same time,the sensory nerve fibers in nasal mucosa and conjunctivae can also be antidromically stimulated,leading to the local release of neuropeptide SP through axonal reflex.It is indicated that the eyes and nose can interact through the sensory nerve pathway.2.On the other hand,nasal sensory nerves as for afferent nerve will spread the impulse to central,leading to nasal and conjunctival efferent parasympathetic response that release VIP.It is indicated that the eyes and nose can interact through the parasympathetic pathway.3.NGF can regulate neuronal development,enhance the production of neuropeptides,and participate in the immune response between the eyes and nose.4.Neurogenic inflammation may be responsible for naso-ocular relationship in ARC.