Effects of Topical Gabapentin on Ocular Pain and Tear Secretion

Abstract

Neuropathic ocular pain is a frequent occurrence in medium to severe dry eye disease (DED). 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, impairing tear production and lacrimation. Gabapentin (GBT) is a structural analog of gamma-amino butyric acid that has been used by systemic administration to provide pain relief in glaucomatous patients. We have already shown in a rabbit model system that its topic administration as eye drops has anti-inflammatory properties. We now present data on rabbits’ eyes showing that indeed GBT given topically as eye drops has analgesic but not anesthetic effects. Therefore, opposite to an anesthetic drug such as oxybuprocaine, GBT does not decrease lacrimation, but–unexpectedly–even stimulates it, apparently through the upregulation of acetylcholine and norepinephrine, and by induction of aquaporin 5 (AQP5) expression in the lacrimal gland. Moreover, data obtained in vitro on a primary human corneal epithelial cell line also show direct induction of AQP5 by GBT. This suggests that corneal cells might also contribute to the lacrimal stimulation promoted by GBT and participate with lacrimal glands in the restoration of the tear film, thus reducing friction on the ocular surface, which is a known trigger of ocular pain. In conclusion, GBT is endowed with analgesic, anti-inflammatory and secretagogue properties, all useful to treat neuropathic pain of the ocular surface, especially in case of DED.

Potential Therapeutic Role of Pituitary Adenylate Cyclase-Activating Polypeptide for Dry Eye Disease

“…Gabapentin (GBT) is a structural analog of gamma-amino butyric acid that is used as an antiepileptic drug as well as to provide pain relief in glaucomatous patients [ 88 ]. GBT also has analgesic and anti-inflammatory properties, so it may be useful as a DED medication [ 89 ].…”

Unveiling the Power of Gabapentin-Loaded Nanoceria with Multiple Therapeutic Capabilities for the Treatment of Dry Eye Disease

“…73 Second, GBT's antianxiety and sedative effects may indirectly influence the activity of the lacrimal glands, thereby affecting tear secretion. 65 The topography of the cornea in different groups was evaluated to understand the responses of the various materials used to treat DE (Figure 5i). The uniform green color map denotes healthy corneas without any aberration, while the color varies from orange to red with increasing aberration.…”

Aquaporins and Neuropathic Pain

“…In a study of rats and mice, the expression of AQP5 was up-regulated after crushed sciatic nerve injury, and neuropathic pain is one of the main symptoms of sciatic nerve injury, suggesting that AQP5 may be related to neuropathic pain [40]. In addition, topical administration of gabapentin was found to alleviate neuropathic ocular pain by inducing AQP5 expression in the lacrimal gland, and resveratrol was found to mitigate neuropathic pain by inhibiting AQP5 activation caused by chronic contractile injury [16,135]. Moreover, studies have indicated that AQP5 colocalizes with AQP2 in the kidney, and AQP5 can also regulate AQP2 expression, which is associated with neuropathic pain [15,41,136].…”