Dear Editor,

Klein and colleagues show a significant correlation between blood pressure – both systolic and diastolic – and intraocular pressure (IOP).[1] Law et al. recently showed that blood pressure lowering drugs prevent a significant proportion of headaches; however, the causal relation between hypertension and headache – whether migrainous or non- migrainous -- remains ambiguous.[2] In the absence of a clear link between headache and hypertension, hypertensive headache has also been regarded as a myth or “socio-psychological” disorder[3] despite a typical circadian pattern and throbbing character.[2]

A statistically significant inverse relation between blood pressure – both systolic and diastolic -- and non-migrainous headache in a large cross-sectional study[4] indicates that there is a third, critical, idiosyncratic perfusion-related variable between hypertension and headache. Migraine is not a pan-trigeminal disorder.[5,6] In humans, pain and temperature fibers from only the ophthalmic area descend to the lower limit of the first cervical spinal segment; this long held view is supported by sectional studies at and below the obex for severe trigeminal neuralgia. Nuchal pain in migraine or hypertensive headache likely involves ophthalmic nerve fibres.[6] Additionally, photophobia of migraine is a reflex involving the ophthalmic nerve. Third, ipsilateral migraine aura or headache has never been reported following enucleation or evisceration of the eye.[5,6] Dental extraction (upper or lower jaw) is only rarely associated with migrainous headache.[7] Headache, migrainous or non-migrainous, primarily involves the ophthalmic division of the trigeminal nerve.[5,6]

A nexus between migraine, autonomic dysfunction, and IOP has been recently proposed.[6] Autonomic hypofunction prevails in migraine patients and can underlie sudden ocular choroidal congestion in diverse stressful clinical circumstances; mechanical deformation of the corneo-scleral envelope might generate both the scintillating scotoma as well the headache of migraine.[5,6] Remarkably, a higher blood pressure is correlated with a higher IOP.[1] Tamponade function of IOP maintains ocular integrity; a higher IOP limits ocular choroidal hyperperfusion and possibly prevents the development of headache at relatively higher levels of blood pressure. Every physiological function has an upper threshold; the tamponde effect of rising IOP is probably overwhelmed in severe or malignant hypertension, hypertensive encephalopathy, and pheochromocytoma- related surges of blood pressure.[8]

The common action by which migraine prophylactic agents prevent attacks likely involves a lowering of the IOP; propranolol, atenolol, metoprolol, nadolol, clonidine, flunarizine, verapamil, diuretics and angiotensin converting enzyme inhibitors lower IOP.[1,5,6] Intriguingly, the prophylactic effect of migraine preventing agents is not predictable or dose-dependent, a feature that might reflect the ceiling effect in lowering IOP. Also, lowering IOP beyond a certain critical threshold – that varies for every individual – can aggravate the tendency to develop ocular choroidal congestion and mechanical deformation of the pressure-sensitive ophthalmic nerve fibers of the iris and the chamber angle. Vasodilating anti-hypertensive agents like nifedipine, hydralazine, and enalapril commonly induce headache possibly by a combination of lowering the IOP and inducing choroidal congestion.

Rather than being a simple function of blood pressure, headache in hypertension patients appears to be the outcome of a complex interaction between autonomic function, choroidal perfusion and IOP, the many trait- and state-dependent factors that determine the mechanical properties of the corneo-scleral envelope, and the endogenous pain control mechanism.[8] Hypertension-associated headache – migrainous or non-migrainous, spontaneous or antihypertensive drug-induced -- is not “all in the mind”; a clear link with variations of the IOP appears to be emerging.

References

1. Klein BEK, Klein R, Knudtson MD. Intraocular pressure and systemic blood pressure: longitudinal perspective: The Beaver Dam Eye Study. Br J Ophthalmol 2005;89:284-7.

2. Law M, Morris JK, Jordan R, Wald N. Headaches and the treatment of blood pressure. Results from a meta-analysis of 94 randomized placebo- controlled trials with 24 000 participants. Circulation 2005;112:2301-6.

3. Friedman D. Headache and hypertension: refuting the myth. J Neurol Neurosurg Psychiatry 2002;72:431.

4. Hagen K, Stovner LJ, Vatten L, Holmen J, Zwart J-A, Bovim G. Blood pressure and risk of headache: a prospective study of 22 685 adults in Norway. J Neurol Neurosurg Psychiatry. 2002;72:463-466.

5. Gupta VK. Lamotrigine, migraine aura and headache: tightening the Gordian knot of primary headache? J Neurol Neurosurg Psychiatry. (28 November 2005). Available at: http://jnnp.bmjjournals.com/cgi/eletters/76/12/1730#764

6. Gupta VK. Migrainous scintillating scotoma and headache is ocular in origin: a new hypothesis. Med Hypotheses. 2005 (In press). Available online 13 December 2005.

7. Strauss RA, Eschenroeder TA. Hemiplegic migraine following third molar extractions under intravenous sedation. J Oral Maxillofac Surg 1989;47:184-6.

8. Gupta VK. Does the mysterious link between hypertension and headache lie at the level of the eye? Circulation (In press).