IMMUNOMODULATION OF AFFERENT NEURONS IN GUINEA-PIG ISOLATED AIRWAY

1. The trachea, larynx and main bronchi with the right vagus nerve and nodose ganglion were isolated from guinea-pigs passively immunized 24 h previously with serum containing anti-ovalbumin antibody 2. The air ways were placed in one compartment of a Perspex chamber for recording of isometric tension while the nodose ganglion and attached vagus ner ve were pulled into another compartment. Action potentials arriving fr om single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in the ganglion. Mechanosensitivity of the nerve endings was quantified u sing calibrated von Frey filaments immediately before and after exposu re to antigen (10 mu g ml(-1) ovalbumin). 3. Ten endings responded to the force exerted by the lowest filament (0.078 mN) and were not furth er investigated. In airway from thirteen immunized guinea-pigs, the me chanical sensitivity of A delta afferent fibres (conduction velocity = 4.3 +/- 0.6 m s(-1)) was enhanced 4.1 +/- 0.9-fold following airway e xposure to antigen (P < 0.005). Mechanical sensitivities of afferent f ibres (conduction velocity = 4.3 +/- 0.6 m s(-1)) from non-immunized c ontrol guineapig airways were unaffected by antigen (n = 13). 4. Antig en did not overtly cause action potential generation except in one ins tance when the receptive field was located over the smooth muscle. Thi s ending also responded to methacholine suggesting that spatial change s in the receptive field, induced by muscle contraction, were responsi ble for the activation. 5. The mediators responsible for these effects are unknown, although histamine, prostaglandins, leukotrienes and tac hykinins do not appear to be essential. The increase in mechanical res ponsiveness was not associated with the smooth muscle contraction sinc e leukotriene C4, histamine and tachykinins, which all caused a simila r contraction to anti gen, did not affect mechanical thresholds. Moreo ver, the antigen-induced increases in excitability persisted beyond th e duration of the smooth muscle contraction. 6. These results demonstr ate that antigen-antibody-mediated inflammatory processes may enhance the excitability of vagal afferent nerve terminals projecting from the airway and thus map contribute to the pathophysiology of allergic air way diseases.