Intractable eye pain: indication for triptans

A May1, MA Gamulescu2, U Bogdahn1 & CP Lohmann2

1Department of Neurology and 2Department of Ophthalmology, University of Regensburg, Regensburg, Germany

May A, Gamulescu MA, Bogdahn U & Lohmann CP. Intractable eye pain: indication

for triptans. Cephalalgia 2002; 22:195–196. London. ISSN 0333-1024

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-HT1B/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-HT1B/1D

agonists in painful eye conditions. uEye pain, photorefractive keratectomy, sumatriptan

Arne May, Department of Neurology, University of Regensburg, Universitatsstraße 84,

D-93053 Regensburg, Germany. Tel.+49 (0) 941 941 3001, fax+49 (0) 941 941 3005,

e-mail arne.may@klinik.uni-regensburg.de Received 14 December 2001, accepted 2 January 2002

Introduction

The cornea has the highest concentrations of free nerve

endings in the body and is therefore particularly sensi-

tive 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-HT1B/1D) receptor. It is an

effective and well-tolerated treatment for acute migraine

with and without aura (3). The exact mechanism of

how 5-HT1B/1D receptor agonists (triptans) relieve

migraine pain is still unknown. Experimental findings

suggest that 5-HT1B/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-HT1B/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.

# Blackwell Science Ltd Cephalalgia, 2002, 22, 195–196 195

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 sumatrip-

tan, due to pain recurrence. In four patients a pre-

ventative 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-HT1B/1D agonists also

in other painful ocular conditions, such as infection,

ulceration, chemical irritation or trauma to the eye.

Acknowledgements

The authors wish to thank Holger Kaube for his very helpfuladvice on the manuscript.

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