Ocular inflammation induced by electroconvulsive treatment: contribution of nitric oxide and neuropeptides mobilized from C-fibres

Abstract

1. Electroconvulsive treatment (ECT) of rabbits produced ocular inflammation consisting of conjunctival hyperaemia, miosis and protein extravasation into the aqueous humour, reflected by the so-called aqueous flare response (AFR); the maximal reduction in pupil size was 3.8±0.1 mm (s.e. of mean, n=16) while the maximal AFR was 28.1±2.8 (arbitrary units).

2. ECT also caused release of substance P (SP), pituitary adenylate cyclase-activating peptide (PACAP)-27, -38 and calcitonin gene-related peptide (CGRP). The concentrations of SP and CGRP in the aqueous humour of normal, untreated eyes were 10.6±1.4 and 117.4±12.4 pmol l⁻¹, respectively, while the concentrations of PACAP-27 and -38 were below the detection limit. After ECT the concentrations of SP, PACAP-27, -38 and CGRP were 65.0±9.6, 46.9±8.4, 50.2±5.4 and 1109.9±133.1 pmol l⁻¹, respectively (s.e. of mean, n=12). Conceivably, ECT evoked an antidromic activation of sensory neurones in the trigeminal ganglion with the consequent release of neuropeptides from C-fibres in the uvea and the development of neurogenic inflammation.

3. Rabbits received the nitric oxide (NO) synthase inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME, 200 mg kg⁻¹, i.v.). This pretreatment inhibited the ECT-evoked conjunctival hyperaemia, miosis and AFR; under these circumstances the maximal reduction in pupil size was 1.9±0.1 mm while the maximal AFR was 2.7±0.9 (n=16). L-NAME also inhibited the ECT-evoked release of SP, PACAP-27, -38 and CGRP into the aqueous humour; the concentrations of SP and CGRP were 13.2±1.5 and 204.8±33.5 pmol l⁻¹, respectively, while PACAP-27 and -38 were below the detection limit (n=12).

4. The ECT-evoked miosis was also inhibited by pretreatment with the tachykinin receptor antagonist D-Pal⁹ spantide II (90 nmol, intravitreal injection); under these circumstances the maximal reduction in pupil size was only 0.7±0.03 mm, indicating an important role for SP in the miotic response. Pretreatment of the eye with capsaicin, which is known to cause functional ablation of C-fibres, inhibited the conjunctival hyperaemia, miosis and AFR by 4050%; the maximal reduction in pupil size being 2.2±0.2 mm and the maximal AFR 13.8±2.1 (arbitrary units) (n=8).

5. The results suggest (1) that ECT evokes ocular inflammation through antidromic C-fibre activation; (2) that SP contributes to the ECT-evoked miosis; and (3) that NO contributes to the antidromic C-fibre activation and possibly to the vascular responses mediated by the C-fibre transmitters.

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