Allodynia May Affect Treatment Response to Acute Migraine

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BOSTON — The understanding of the mechanisms of allodynia, a frequent migraine comorbidity, is essential to the treatment of both conditions as allodynia can be disabling and may affect the response to migraine treatment. This notion was highlighted during the Harold G. Wolff Award Lecture given by Richard Lipton, MD, director of the Montefiore Headache Center at Albert Einstein College of Medicine, New York, NY, at the American Headache Society (AHS) 59th Annual Scientific Meeting.¹ Dr Lipton presented results from a recently published article.²

As an introduction to his lecture, Dr Lipton sought to emphasize an essential aspect to the approach of headache care: “When patients tell us things, we should believe them, even if we don’t understand them,” he noted. Dr Lipton was referring to the fact that, when allodynia is described to clinicians by patients, the portrayal of their symptoms is oftentimes unclear and leaves them perplexed. Allodynia – most  commonly cutaneous – refers  to painful sensations in response to non-noxious skin stimulation. Up to two-thirds of patients with migraine experience comorbid allodynia.³

Taking allodynia into account in patients with migraine is essential, as it can provide clues regarding the pathophysiology of migraine and headache progression. In addition, there is evidence supporting the notion that allodynia may predict a patient’s response to migraine treatment. It is also important to understand allodynia to treat this disabling disorder itself. Allodynia is classified according to the nature or location of the stimulus. The nature of the stimulus that elicits allodynia may be classified as  mechanical static (eg, with head rested on pillow), as mechanical dynamic (eg, when brushing one’s hair), or as thermal. Allodynia location is classified as either cephalic or extracephalic.

The mechanisms underlying allodynia are thought to be associated with peripheral sensitization of meningeal nociceptors or with the activation of the trigeminal ganglion itself.^4,5 When the cutaneous areas affected by allodynia expand, central sensitization progresses. Extracephalic location of allodynia is usually associated with involvement of thalamic neurons.⁶

These findings were in part drawn  from the American Migraine Prevalence and Prevention (AMPP) database, a longitudinal study of the US population conducted by sending out questionnaires to American households to survey them on “headache occurrence, symptoms, medication use, and missed time from work because of headache,” among other questions between 2004 and 2009, and for which more than 100,000 responses were received.⁷

In the study, the authors assessed allodynia with a questionnaire, which included a symptom checklist of 12 questions. The investigators found that patients with chronic migraines had the highest rates of allodynia.⁸ These rates were present, but to a lesser extent, in patients with episodic migraine and tension-type headaches. They also found that as the rates of allodynia increased, so did headache disability, as measured by the Migraine Disability Assessment test.

The authors also found that cutaneous allodynia is a strong predictor of inadequate response to treatment with a number of abortives, including triptans, nonsteroidal anti-inflammatory drugs, opioids and barbiturates.⁹ The response did not differ significantly across medication types. The researchers also found that inadequate responses to medications are linked to progression from episodic to chronic migraine. Depression is also an effector of treatment response.

In conclusion, Dr Lipton noted “We need to understand the factors that drive headache in individual patients.”

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References

1. Lipton RB. Allodynia is associated with initial and sustained response to acute migraine treatment: results from the American Migraine Prevalence and Prevention. Presented at: the American Headache Society 59th Annual Meeting; June 8-11, 2017; Boston, Massachusetts.
2. Lipton RB, Munjal S, Buse DC, Fanning KM, Bennett A, Reed ML. Predicting Inadequate Response to Acute Migraine Medication: Results From the American Migraine Prevalence and Prevention (AMPP) Study. Headache. 2016;56(10):1635-1648.
3. Bigal ME, Ashina S, Burstein R, et al. Prevalence and characteristics of allodynia in headache sufferers: a population study. Neurology. 2008;70(17):1525-1533.
4. Levy D, Zhang XC, Jakubowski M, Burstein R. Sensitization of meningeal nociceptors: inhibition by naproxen. Eur J Neurosci. 2008;27(4):917-922.
5. Bernstein C, Burstein R. Sensitization of the trigeminovascular pathway: perspective and implications to migraine pathophysiology. J Clin Neurol. 2012;8(2):89-99.
6. Burstein R, Jakubowski M, Garcia-nicas E, et al. Thalamic sensitization transforms localized pain into widespread allodynia. Ann Neurol. 2010;68(1):81-91.
7. Bigal ME, Buse DC, Chen YT, et al. Rates and predictors of starting a triptan: results from the American Migraine Prevalence and Prevention Study. Headache. 2010;50(9):1440-1448.
8. Mathew PG, Cutrer FM, Garza I. A touchy subject: an assessment of cutaneous allodynia in a chronic migraine population. J Pain Res. 2016;9:10110-4.
9. Chu MK, Buse DC, Bigal ME, Serrano D, Lipton RB. Factors associated with triptan use in episodic migraine: results from the American Migraine Prevalence and Prevention Study. Headache. 2012;52(2):213-223.