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4 Articles in this Series
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Treating Migraineurs With Allodynia Necessitates Careful Timing

Treating Migraineurs With Allodynia Necessitates Careful Timing

Presentation by Richard B. Lipton, MD, and commentary from Lawrence Robbins, MD

Allodynia appears to be a significant predictor of treatment response—once a migraineur develops allodynia, medication response appears muted, with triptans offering better relief for acute migraines,1,2 reported Richard B. Lipton, MD, professor and Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine, and director of the Montefiore Headache Center, in the Bronx, New York.

“Practitioners are aware that allodynia is the experience of ordinarily non-painful stimuli as painful, and that allodynia commonly occurs in people with migraine,” said Dr. Lipton, who presented the 2017 Howard G. Wolff Award Lecture1 during the American Headache Society 59th Annual Meeting in Boston, Massachusetts. The findings were published online in the journal Headache.2

In prior research, the prevalence of cutaneous allodynia arose with frequency of headaches, particularly among women.3-5 Over the course of a migraine attack, an estimated 66% of people will develop allodynia. The purpose of the current study was to determine what, if any, influence allodynia would have on response to treatment and would that influence depend upon which class of medication was used to treat a migraine, said Dr. Lipton.

Treating allodynia early during a migraine will provide the best long-term outcomes.

“We found that no matter what class of drug was taken by patients who had allodynia, they did not respond as well to acute treatment as those who do not have allodynia," Dr. Lipton told Practical Pain Management.1,2 "That was true for triptans, NSAIDS [nonsteroidal anti-inflammatory drugs], barbiturate combination products, and opioids." When comparing acute medications efficacy in patients without allodynia, "we found that triptans worked better than all the other classes of medications.

Despite that, all those drug classes worked less well after allodynia developed,” he said, “so the clinical message is that when treating a patient who has migraines with an acute medication, and if that patient has a tendency to experience allodynia, they will have better benefits if they are instructed to treat earlier—before the allodynia starts.”

Since it is known that as headache frequency increases, overuse of medication typically follows, the goal needs to be to treat early, but not too often. To resolve this dilemma, patients should be instructed to use preventive measures, such as behavioral strategies and pharmacological, to reduce headache frequency, Dr. Lipton told Practical Pain Management. “Patients should aim to take their medication about 30 minutes into a migraine, to keep the pain from worsening, and to prevent the allodynia from occurring,” he said.

Impact on Treatment Decisions

“While we have accepted that triptans are the best-in-class of the abortives, we still need further evidence, like the findings from this large study, to appreciate their effectiveness for most patients,” Lawrence Robbins, MD, a specialist in refractory headaches at the Robbins Headache Clinic, told Practical Pain Management. 

“These findings add to our knowledge of patients with migraines and allodynia, who likely will have a tendency to be more refractory and have less response to triptans and other medications,” said Dr. Robbins. “We don’t know why allodynia leads to excess brain stem firing, but we know that these patients probably have central sensitization with worsening response to treatment.”

“What is more interesting, is how to use these findings for clinical practice in someone who is difficult to treat,” he told Practical Pain Management. “It helps to have confirmation of a possible reason for a patient’s unresponsiveness to treatment, such as having allodynia.”

“As such, in patients with migraines who experience allodynia, we should try usual first-line management with a triptan, or other appropriate medication, and if the patient isn’t responsive, there are several good articles on managing refractory patients," Dr. Robbins said.6

Actively Inquire About Allodynia

“Allodynia typically presents within 1 to 2 hours after the first sign of pain," said Dr. Lipton. “While some patients may volunteer their specific experiences with allodynia to their physician, many more patients will not mention these out of fear of judgment.” After all, common complaints can seem outrageous to anyone who hasn’t experienced this hypersensitivity.

Common experiences reported by people with cutaneous allodynia4,5 include an inability to:

  • Bear having contact lenses in eyes
  • Brush their hair
  • Wear a hat, necklace, watch, ring, earrings
  • Keep hair tied in a ponytail
  • Wear a tie given the unbearable discomfort of a tight collar
  • Shave
  • Lay a head on the pillow
  • Shower

“As such, it is good practice to ask patients who present with migraines if they have ever experienced allodynia, to spare them from feeling crazy or sounding foolish.” Dr. Lipton said. Just acknowledging that these experiences as a usual occurrence in many people who have migraines will create a better setting for more optimal management going forward.

"Since allodynia is a risk for migraine progression, people who are prone to allodynia will get it unless they treat early," said Dr. Lipton. For example, patients who get a migraine once a week and take their medication, which works well so the allodynia doesn't develop, they may keep the pain from worsening and the allodynia from developing. "Then the allodynia won't be part of the attack," he said.

"Whereas patients who do not experience allodynia can afford to wait longer to treat, the hope is that by treating early, we may be effective in reducing the migraine from worsening over time and warding off the onset of the allodynia," Dr. Lipton told Practical Pain Management.

Background on the AAPP Study

Patients in the 2006 American Migraine Prevalence and Prevention (AMPP) Study,5 who were experiencing allodynia were known not to achieve 2-hour pain freedom (2hPF) and to suffer from inadequate 24-hour pain responsiveness (24hPR).

Relying on longitudinal data from the 2006 study, this trial aimed to assess 2hPF and 24hPR with triptans as compared with other acute medication treatments in order to gain a better understanding of their efficacy in the presence of allodynia in people with migraines.1,2

The 5,407 adult participants from the AAMP trial who were diagnosed with migraines completed the allodynia symptom checklist and the Mattering to Others Questionnaire and reported the use of a single acute medication, were included in the study. Of these patients, 83% were women with a mean age of 46 years.

Acute treatments for migraine pain were compared among 5 classes of treatment: triptans, NSAIDs, barbiturate combinations, opioids, and ergotamines.1,2

Among triptan users, the outcomes for 2hPF and 24hPR were significantly improved compared to the other agents (1.18 to 2.09, all significant with the exception of ergotamines; and 1.81 to 2.31, respectively).2

However, in migraine patients with allodynia, outcomes were significantly worse for both 2hPF and 2hhPR  (OR range: 1.42 to 1.56, and OR range: 130 to 1.34, respectively) across all medication classes.2

According to the study findings, triptans proved significantly better at lessening immediate pain (except for ergotamines for which the sample size was too small to draw any conclusion) as well as freedom from lingering pain, against the 4 typical classes of medications used to treat migraines.1,2 However, when cutaneous allodynia was reported, response to all medications was substantially diminished, increasing the likelihood of treatment failure.



  1. Lipton RB, Munjal S, Buse DC, et al. Allodynia is associated with initial and sustained response to acute migraine treatment: results from the American Migraine Prevalence and Prevention (AMPP) Study. The Howard G. Wolff Award Lecture. Presented at: American Headache Society 59th Annual Scientific Meeting; June 8-11, 2017; Boston, Massachusetts.
  2. Lipton RB, Munjal S, Buse DC, et al. Allodynia is associated with initial and sustained response to acute migraine treatment: results from the American Migraine Prevalence and Prevention (AMPP) Study. Headache. 2017 [Epub ahead of print]. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28603893.
  3. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF, on behalf of the AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68;343-349
  4. 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.  
  5. Lipton RB, Bigal ME, Ashina S, et al. Cutaneous allodynia in the migraine population. Ann Neurology. 2008;63(2):148-158.
  6. Robbins R. Refractory (difficult-to-treat) headache—outpatient strategies. In: Advanced Headache Therapy.  New York, NY: Springer Publishing Company; 2015:49-66.




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