Conference Coverage

Treatment Challenges When Headache Has Central and Peripheral Involvement

Diagnosis and treatment can be complicated when the headache history includes evidence of central and peripheral causes of pain.


ASHEVILLE, NC—Although neurologists tend to classify disorders as problems of either the CNS or the peripheral nervous system, patients with headache may have symptoms that indicate the involvement of both systems, according to an overview provided at the Eighth Annual Scientific Meeting of the Southern Headache Society. Research has revealed anatomic connections between extracranial and intracranial spaces that could contribute to the generation of headaches. Thus, the central and peripheral nervous systems “do not have to be two separate spaces and two separate pathologies,” said Pamela Blake, MD, Director of the Headache Center of Greater Heights in Houston.

Problems With Prevention and Acute Treatment

One patient presented to Dr. Blake with an eight-year history of throbbing headaches and constant pain and tightness in the neck and occiput. The pain radiated to her temples and forehead two to four times per week with accompanying photophobia, phonophobia, and nausea. The patient also had mild allodynia. The frontal pain and accompanying symptoms were consistent with episodic migraine, but the allodynia and pain in the neck and occiput were not, said Dr. Blake. A possible diagnosis was episodic migraine without aura with chronic tension-type headaches and neck pain, she added.

Pamela Blake, MD

A 2017 study published in the Journal of Headache and Pain suggested that this headache type is problematic. Among 148 migraineurs, the researchers identified 100 patients who also had tension-type headache and chronic neck pain. Compared with healthy controls, these patients had less physical activity, less psychologic well-being, more perceived stress, and poorer self-rated health. Pain reduced these patients’ ability to perform physical activity, which could make treatment more difficult, according to the authors.

Patients with these symptoms have trigeminal and occipital pain. “These symptoms do not appear to be solely, or even primarily, central,” said Dr. Blake. The frontal pain responds to triptans, but the occipital pain, which is the more constant pain, does not. “Preventive medications do not work well in this population, and that’s why they have chronic headaches,” said Dr. Blake.

Physiologic and Pathophysiologic Mechanisms

Research by Schueler and colleagues suggested a potential physiologic explanation for combined central and peripheral involvement in headache. They applied a fluorescent tracer to proximally cut meningeal nerves in rat skulls and to distal branches of the spinosus nerve in human calvaria that was lined with dura mater. They observed that branches of the spinosus nerve travel “along the middle meningeal artery, supplying the dura, entering the cranial bone, and running through the calvarium,” said Dr. Blake. Branches of the spinosus nerve also “entered the tenderness junctions of the pericranial muscles, including in the neck.”

This work indicates a connection between intracranial and extracranial areas but does not shed light on the pathophysiology of a headache with central and peripheral symptoms, said Dr. Blake. In 2016, she and her colleagues took perivascular biopsies from healthy controls and subjects with chronic migraine and predominantly occipital headache. They found a significant increase in the expression of proinflammatory genes and a decrease in the expression of anti-inflammatory genes among migraineurs, compared with controls. “This was the first evidence of localized extracranial pathophysiology in chronic migraine,” said Dr. Blake.

This inflammation could result from compression of the occipital nerves. A 2013 study by Schmid et al found that progressive nerve compression results in chronic local and remote immune-mediated inflammation. Stress also can cause inflammation. “Many patients who present with occipital nerve compression headaches had the onset of their pain during a time of intense stress,” said Dr. Blake.

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