Intractable Eye Pain: Indication for Triptans

Abstract

Management of pain is difficult in many eye diseases. Particularly in patients undergoing surgical procedures, postoperative intractable pain is a major concern and severely influences the patient's comfort. We present 13 patients (eight male, five female, mean age 36 years) in whom sumatriptan, a highly selective 5-HT_1B/1D agonist that is normally used as a specific anti-migraine drug, was used for the treatment of pain following photorefractive keratectomy (PRK). In two patients both eyes were operated on different days, resulting in a total of 15 operated eyes. A positive clinical response was achieved in all patients. In particular, in four patients, who received a second dose prophylactically 4 h following the first dose and before the recurrence of pain, we achieved excellent efficacy and stable control of pain. Further controlled studies are needed to investigate the usefulness of 5-HT_1B/1D agonists in painful eye conditions.

Introduction

The cornea has the highest concentrations of free nerve endings in the body and is therefore particularly sensitive to painful stimuli (1). Any ocular surgery, trauma or infection of the corneal epithelium may cause severe and persistent pain that is not well controlled by even strong analgesics. Furthermore, only a limited amount of local anaesthetic can be used without causing local toxicity and severe damage to the cornea (2). Therefore, in all forms of eye surgery, but also other painful conditions of the eye, adequate control of pain plays a major part in the care of the patient.

Sumatriptan is a highly selective agonist at the 5-hydroxytryptamine-1 (5-HT_1B/1D) receptor. It is an effective and well-tolerated treatment for acute migraine with and without aura (3). The exact mechanism of how 5-HT_1B/1D receptor agonists (triptans) relieve migraine pain is still unknown. Experimental findings suggest that 5-HT_1B/1D receptors have different effects on nociceptive processing in the trigeminal vs. spinal dorsal horns, providing a potential explanation for the lack of general analgesic effects of brain-penetrant 5-HT_1B/1D agonist anti-migraine drugs (4). If, however, triptans exclusively exert specific trigeminal but not spinal antinociceptive effects, the question arises, whether triptans also have direct effects on extracranial trigeminal sensation, i.e. eye pain, in addition to their efficacy against migraine headache pain.

Methods

We therefore tested this hypothesis, using a prospective and open pilot-study protocol, by treating 13 patients (eight male, five female, 25–57 years old, mean age 36 years) with intractable eye pain after excimer laser photorefractive keratectomy (PRK) with sumatriptan at a dose sufficient to relieve migraine pain. Pain following PRK was chosen as a model as these patients were operated routinely for treatment of myopia, providing a standardized corneal lesion that produces severe postoperative pain (5). In two patients both eyes were operated on different days, resulting in a total of 15 operated eyes. The study was approved by the local ethics committee. Following informed consent the patients were instructed to report the postoperative pain using a VAS scale (anchored at 0 = no pain and 10=worst pain). At VAS 5 patients were allowed to take a first dose of 100 mg sumatriptan orally.

Results

In 13 out of 15 operations (87%) the patients reported excellent and rapid relief of pain following the application of 100 mg sumatriptan. In two patients sumatriptan had no effect; these patients treated the pain with the standard medication of non-steroidal anti-inflammatory drugs (6), obtaining no effect on the pain either. Interestingly, most of the patients reported, whilst completely pain free, some residual non-painful, localized scratching sensation beneath the upper lid. This was interpreted as a foreign body sensation after corneal abrasion. Nine patients required a second dose, approximately 5 h following the first dose of sumatriptan, due to pain recurrence. In four patients a preventative second dose of sumatriptan (100 mg) was administered 4 h after the first dose, still at VAS = 0. All of these four patients stayed completely pain free for at least another 20 h.

Conclusion

Until now analgesic effects of sumatriptan have only been observed in patients with acute migraine and cluster headache. In these conditions it is questionable whether activation of peripheral nociceptors is present or whether the pain is central in origin. The present study provides the first clinical evidence that pain originating from nociceptor activation in the first trigeminal division can be relieved by sumatriptan. It is unknown whether this analgesic effect is specific to the first division of the trigeminal nerve or specific to the pathophysiology of corneal nociceptive fibres. The mechanism of action may involve hyperpolarization of peripheral trigeminal fibres (7) or inhibition of the central synapse in the nucleus caudalis (8). The latter would require an impairment of the blood brain barrier.

Further placebo-controlled studies are needed to investigate the usefulness of 5-HT_1B/1D agonists also in other painful ocular conditions, such as infection, ulceration, chemical irritation or trauma to the eye.