Guinea pigs were passively sensitized by sera containing antidinitrophenyl reaginic antibody and specifically challenged by dinitrophenyl-bovine serum albumin injected through the stylomastoid foramen. Nystagmus, head deviation, negative summating potentials on electrocochleography, and an increase of threshold and wave I peak latency on auditory brain stem response testing were observed after local challenge. These physiologic changes were reversible and resolved within several days. We also used Tranilast before the specific challenge. It is a blocking agent of chemical mediator release from mast cells. Negative summating potentials and head deviation were not observed after the use of this agent. In the animals that showed physiologic changes, we observed endolymphatic hydrops, mast cell degranulation, and eosinophil infiltration histologically in the challenged side of the inner ear. These results suggest that the physiologic and histologic changes provoked in the inner ear of the sensitized animals may have been induced by type I allergy.

To investigate patients with Menière's disease and the association of cholinergic hyperreactivity, we performed muscarinic acetylcholine receptor assay using peripheral blood lymphocytes from patients with Menière's disease and non-dizzy, non-allergic control subjects. Cholinergic receptor maximal bindings (Bmax) and dissociation constants (Kd) were compared between the two groups, indicating the number and the affinities of the receptors, respectively. The receptor Bmax value in Meniére's patients during the remission state (108.6 +/- 51.2 fmol/l x 10(6) lymphocytes) was higher than that in normal controls (45.8 +/- 9.2 fmol/l x 10(6) lymphocytes) (p < 0.01). Furthermore, during an exacerbated state, Bmax was increased significantly (223.7 +/- 90.2 fmol/l x 10(6) lymphocytes) compared to the remission state (p < 0.01). In contrast, Kd values for the receptor did not differ between the two groups. These results suggest that patients with Menière's disease have cholinergic hyperreactivity, which may be further upregulated during a state of exacerbation due to an increase in the number of cholinergic receptors.

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Although many studies have suggested a relation between allergy and Ménière’s disease, the pathophysiology of this condition remains controversial. The aim of this study was to clarify whether an anaphylactic reaction in the inner ear can disturb hearing and equilibrium, and whether such disturbances recur in response to repeated anaphylactic reactions. Increases in audiological threshold, nystagmus, and endolymphatic hydrops were observed in response to a single exposure to antigen administered to actively sensitized guinea pigs. The increase in audiological threshold was maximal 10 h after antigen challenge (p < 0.005) and returned to the baseline level after 7 days. Nystagmus and the increase in audiological threshold induced by antigen exposure were inhibited by prior administration of pemirolast potassium (p < 0.05), an inhibitor of chemical mediator release from mast cells. A second challenge with antigen 7 days after the first also induced an increase in audiological threshold (p < 0.05) and nystagmus. These results suggest that studies of repeated antigen challenge in actively sensitized animal models may increase our understanding of the pathophysiology of Ménière’s disease.

Time course studies of electrocochleography and the auditory brain stem response were performed in guinea pigs that were passively sensitized by sera containing antidinitrophenyl reaginic antibody and specifically challenged by dinitrophenyl-bovine serum albumin injected through the stylomastoid foramen. A negative summating potential on electrocochleography was observed from 12 to 48 hours, but not at 72 hours, after the specific challenge. A threshold increase on the auditory brain stem response was observed 15 minutes after the specific challenge; the threshold recovered to the prechallenge level within 7 days. Further, we used Tranilast, a blocking agent of chemical mediator release from mast cells, before the specific challenge. A negative summating potential and head deviation were not observed after the use of this agent. These results suggest that the auditory change provoked in the inner ear of the sensitized guinea pig may have been induced by type I allergy.