Abstract
Purpose :
Neuropathic ocular pain is a frequent occurrence in medium to severe dry eye syndrome (DES). Only palliative treatments, such as lubricants and anti-inflammatory drugs, are available to alleviate patients’ discomfort. Anesthetic drugs are not indicated, because they may interfere with the neural feedback between the cornea and the lacrimal gland, thus impairing tear production and lacrimation. Aim of this study has been to address the analgesic and not anesthetic activity of gabapentin (GBP), given as eye drops on the ocular surface, and to show that it does not decrease lacrimation.
Methods :
GBP (2%) or oxybuprocaine (BNX: 0.4%) eye drops were given to rabbits’ eyes. Sensibility was estimated by a Cochet-Bonnet esthesiometer and lacrimation measured by Schirmer strips. Pharmacokinetics (PK) was studied by HPLC/MS/MS in eye tissue extracts. Expression of neurotransmitters and aquaporin-5 (AQP5) was detected in lacrimal glands in vivo, and corneal epithelial cells in vitro.
Results :
Analgesic effects obtained by GBP instillation were distinct from anesthetic effects after BNX. PK analysis showed that the most part of GBT (97.7% at 30 minutes, and 96.7% at 2 hours) remains in the conjunctiva, and the cornea contains most of the remaining amount (2.1% at 30 minutes, and 2.5% at 2 hours). Schirmer test showed that BNX indeed decreased lacrimation in the first 30 minutes, whereas GBP – unexpectedly – even stimulated it, with an effect lasting 90 minutes. Correspondingly, the neuro-mediators Ach and Ne were decreased in the lacrimal glands after BNX treatment, while they were dramatically increased after GBP treatment. Similar findings were made for AQP5 expression. Notably, GBP also increased AQP5 expression in corneal epithelial cells in vitro.
Conclusions :
GBP appears to be endowed with anti-inflammatory (published), analgesic and secretagogue properties. Therefore, topic administration of GBP as eye drops could be the ideal treatment for neuropathic pain caused by severe dry eye.
This is a 2021 ARVO Annual Meeting abstract.