Extended allergen exposure in asthmatic monkeys induces neuroplasticity innucleus tractus solitarius

Background: Extended exposure to allergen exacerbates asthma symptoms, in p art via complex interactions between inflammatory cells and mediators. One consequence of these interactions is the triggering of local and central ne rvous system (CNS) neuronal activity that might further exacerbate the asth malike symptoms by causing bronchoconstriction, mucous secretion, increased microvascular leak, and cough. One CNS region that might be particularly i mportant is the caudomedial nucleus tractus solitarius (NTS). NTS neurons n ot only integrate primary afferent inputs from lung sensory nerve fibers bu t also have direct exposure to inhaled allergens and allergen-induced Wood- borne inflammatory mediators via a deficient blood-brain barrier. Given the capacity of CNS neurons to undergo plasticity, allergen-induced changes in NTS neuronal properties could contribute to the exaggerated respiratory re sponses to extended allergen exposure. Objective: In a recently developed rhesus monkey model of allergic asthma, we tested the hypothesis that extended exposure to allergen increases the i ntrinsic excitability of NTS neurons. Methods: Three adult monkeys were sensitized and then repeatedly exposed to aerosols of house dust mite allergen; 4 monkeys served as controls. Whole- cell current-clamp recordings were made to measure 3 indices of excitabilit y: resting membrane potential, input resistance, and number of action poten tials evoked by current injections. Results: Extended allergen exposure depolarized the resting membrane potent ial by 14% and increased the number of action potentials evoked by current injections (5-fold). Conclusion: The finding that NTS neurons in a primate model of allergic ast hma undergo intrinsic increases in excitability suggests that CNS mechanism s might contribute to the exaggerated symptoms in asthmatic individuals exp osed to allergen.