An in vitro study of the properties of single vagal afferents innervating guinea-pig airways

Abstract

1. A novel preparation of the trachea and main bronchi with attached vagus nerve from the guinea-pig maintained in vitro was used to study the properties of single vagal afferent nerve fibres with identified receptive fields. 2. Recordings were made from twenty-eight C fibres with a mean conduction velocity of 0.9 +/- 0.1 m s-1 and twenty-four A delta fibres with a mean conduction velocity of 8.4 +/- 1.3 m s-1. Receptive fields for C and A delta fibres were of small diameter, distributed throughout the trachea and right bronchus and possessed very low mechanical thresholds of 2.2 +/- 0.4 and 1.1 +/- 0.3 mN respectively. 3. The chemosensitivity of isolated afferents was studied by applying drugs directly onto identified receptive fields. A delta fibres were insensitive to capsaicin (up to 3 microM), bradykinin (3 microM), histamine (10 microM) and 5-hydroxytryptamine (5-HT; 10 microM) applied for up to 1 min. Histamine (10 microM), 5-HT (10 microM) and m-chlorophenylbiguanide (10 microM) were also ineffective in exciting C fibres. 4. Capsaicin, at concentrations ranging from 30 nM to 3 microM, evoked a sustained firing of all C fibres tested when applied for a period of 30 s directly onto receptive fields. Bradykinin (0.1-1 microM) also potently excited C fibres in a concentration-related manner. The effect of bradykinin appeared to be mediated by a B2 receptor since it was not mimicked by the selective B1 receptor agonist [des-Arg9]-bradykinin (3 microM) and was abolished by prior application of the selective B2 receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (HOE 140; 0.1 microM). HOE 140 was without effect against capsaicin-evoked discharge of C fibres. 5. Capsaicin- and bradykinin-evoked discharge of C fibres was present to a similar degree in preparations pretreated with ibuprofen (1 microM), indicating that it was not dependent on, or influenced by, endogenous prostaglandin production. 6. These data demonstrate that single vagal afferents may be studied in vitro and provide the first examination of the properties of sensory fibres innervating guinea-pig airways. C and A delta fibres both exhibit low threshold mechanical sensitivity but show marked differences in terms of their chemosensitivity.