The use of the Fos technique to investigate the physiology and pharmacology of trigeminovascular sensation
Migraine is a disabling condition which affects approximately 10% of the population. The burden of migraine is recognised by the W.H.O., which lists it among the top 20 causes of disability. The underlying cause is largely unknown, but what is known is that the trigeminal nerve plays a central role in relaying nociceptive information from the &quot pain-sensitive&quot intracranial/extracerebral blood vessels to the central nervous system (CNS). This pathway is referred to as the &quot trigeminovascular system&quot . In the CNS, second order neurones are located in the dorsal horn of the caudal medulla (CM) and upper cervical spinal cord (C1 and C2). A better understanding of these cells, their anatomical location, the physiological factors that activate them and the drugs that may act to inhibit them will advance our current understanding of migraine. This thesis aims to extend knowledge of second order cells in the trigeminovascular system by using the immunohistochemical detection of the nuclear proto-oncogene cfos as a marker of neurons activated by noxious stimuli. The specific aims were:- 1. To delineate the population of cells in the brainstem and spinal cord which are involved in processing trigeminovascular nociception in the cat (Felis catus) and monkey (Macaca nemestrina), following either electrical or mechanical stimulation of the superior sagittal sinus or middle meningeal artery. 2. To develop and evaluate a model that may be useful to screen drugs of potential benefit in the treatment of migraine. The following findings were made: 1. In cat and monkey, lamina I and lamina II outer (IIo) of CM, C1 and C2, and the caudal nucleus tractus solitarius (cNTS) of CM and lamina X of C1 and C2 are two anatomically- and functionally-continuous nuclei which receive sensory input from dural structures and which are activated following stimulation of these structures. 2. Fos expression in lamina I/IIo can be attenuated by pretreatment with drugs that are effective in the treatment of migraine, but not by drugs which are ineffective in the treatment of migraine. This work suggests that monitoring Fos expression in these neurones is an effective method for the preclinical evaluation of antimigraine drugs.
Trigeminovascular system, Migraine, Fos technique, Central nervous system (CNS), Caudal nucleus tractus solitarius (cNTS), Intracranial/extracerebral blood vessels, Caudal medulla (CM), Upper cervical spinal cord (C1 and C2), Brainstem, Spinal cord, Superior sagittal sinus, Middle meningeal artery, Lamina I and lamina II outer (IIo)
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