Our knowledge of the basic mechanisms responsible for headache leaves much to be desired, although the contributions of Wolff and his collaborators have added materially to our information. They have established that vasomotor states are responsible for certain types of headache, but since either widening or narrowing of extra- and intracranial arteries may produce headache, the matter remains complicated and in some ways seemingly contradictory. Patients with migraine clearly have impaired autoregulation of normal vasomotor mechanisms (Simard and Paulson, 1973; Sakai and Meyer, 1978; Oleson et al., 1981; Lauritzen et al., 1983b). In migraine, the prodromes are usually accompanied by diminution of cerebral blood flow (O'Brien, 1971; Skinhoj, 1973; Simard and Paulson, 1973; Hachinski et al., 1978; Henry et al., 1978; Sakai and Meyer, 1978; Lauritzen et al., 1983, a and b), although whether the primary event is cortical ischemia or whether blood flow diminishes as a consequence of depressed cortical function is uncertain. It is possible that migraine headaches, with their periodicity and varied neurologic and systemic manifestations are the result of a neuronal trigger mechanism residing in the pons, in the trigeminovascular nucleus as described by Moskowitz (See discussion of pathophysiology in my chapter on Migraine).

The headache of migraine is usually associated with increased cerebral and extracranial blood flow, but this is not invariably the case (Olesen et al., 1981). Since the studies of Graham and Wolff (1938), it has been assumed that the pain of migraine headache is caused by distention of large vessels, chiefly the extracranial arteries, with release of a sensitizing bradykinin-like substance around the affected vessels. The mechanism certainly appears to involve sensitization of vascular walls and their surrounding structures to distention and does not depend upon cerebral blood flow, since the headache may be relieved by injection of ergotamine tartrate or codeine while cerebral perfusion is still increased (Norris et al., 1975; Hachinski et al., 1978; Sakai and Meyer, 1978). However, the extracranial vascular concept of migraine has been criticized by Blau (1978) and by Drummond and Lance (1983). Drummond and Lance assessed the extracranial circulation of 66 migrainous patients during unilateral headache by recording the pulse amplitude of the superficial temporal artery and its main frontal branch, by facial thermography, and by changes in the intensity of headache when temporal or carotid arteries were compressed. These investigators concluded that dilation of the superficial temporal artery and its branches contributes substantially to migraine headache in only a minority of patients.

As knowledge of the neurogenic control of the circulation, particularly the cortical microcirculation, has increased, the number of chemical transmitter agents known to be involved has expanded to include acetyl-choline (Burnstock, 1980), norepinephrine (Raichle et al., 1975; Bates et al., 1977), serotonin (Reinhard et al., 1979), substance P (Chan-Palay, 1977), neurotensin (Chan-Palay, 1977), vasoactive intestinal polypeptide (Larsson et al., 1976), and adenosine and its triphosphate (ATP) (Burnstock, 1980). Thus, almost any theory that links central neurotransmission, humoral changes, and vascular reactivity to the mechanism of migraine has become tenable.

There is also evidence of platelet aggregation (Deshmukh and Meyer, 1977) and a platelet release reaction (Gawal et al., 1979) in patients having a migraine attack. Anthony et al. (1968) first reported that a serotonin releasing factor was present in the blood during migraine headache, an observation that has been confirmed by others (Dvilansky et al., 1976; Mück-Seler et al., 1979). Platelet serotonin content increases before a migrainous headache and then falls during the headache phase in most patients. It is possible that the released serotonin is adsorbed to vessel walls since the combination of serotonin and bradykinin is known to produce vascular pain (Sicuteri et al., 1965). Since the inhibition of transmission in pain pathways by enkephalins is known to be regulated by serotonergic neurons originating in the brainstem raphe nuclei, the mechanism of migraine appears to involve changes in mono-amine transmission in the central nervous system, associated with or followed by a platelet release reaction. The resulting neural and humoral changes are accompanied by depression of cortical function and diminished regional cerebral blood flow.

Although the mechanism responsible for migraine headache may be increasingly understood, mechanisms of other types of headaches remain obscure. Headaches may be associated with high blood pressure as well as low blood pressure. Headaches are usually associated with increased intracranial pressure, but intractable headache sometimes follows lumbar puncture when the intracranial pressure is lowered.

Wolff and his associates have confirmed that although the pia arachnoid, ependymal lining of the ventricles, and choroid plexuses are insensitive to pain, other cranial structures are quite pain sensitive. These structures include the dura, the intracranial and dural arteries, the great venous sinuses and their tributaries, and the fifth, ninth, and tenth cranial--and upper three cervical--nerves. Ray and Wolff (1940) concluded that headaches may result from: (1) traction on the veins with displacement of the great venous sinuses; (2) traction on the middle meningeal artery; (3) traction on large arteries at the base of the brain; (4) distention and dilation of intra- and extracranial arteries; (5) inflammation in or about any of the pain-sensitive structures of the head; and (6) direct pressure by tumors on the cranial and cervical nerves that contain pain-afferent fibers from the head.
 

 

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