In another important discussion, Amynah Pradhan, PhD, of the University of Illinois at Chicago, laid out the reasoning behind why long-term opioid use is a problem in pain conditions in her talk titled “Opioids in General in Migraine.”  Of the 4 opioid receptor subtypes, the mu receptor is the one most often occupied in an effort to relieve pain since it is a good analgesic. In addition to opioids, it can be activated with food as well as sexual activity. With chronic stimulation or overstimulation, the patient develops a type of euphoria, thought to be the reason behind the development of addiction, Dr Pradhan explained.  The most common opiates that act on the mu receptor are morphine, hydromorphone, and oxycodone. When used for the treatment of migraine, opioid treatments lead to more frequent and severe migraine. Studies have found that the greater number of opioid-use days, the more likely someone is to develop more frequent headaches.

Dr Pradhan’s lab conducted a study to determine why activation of the mu receptor leads to medication overuse headaches or rebound headaches. They used a known migraine trigger, nitroglycerin, to develop a chronic migraine model in mice.  They found the effect of nitroglycerin to be dose-dependent. They also found that mice that had headaches induced by nitroglycerin and treated with morphine developed an increased basal hypersensitivity.

Continue Reading

Alternately, Dr Pradhan discussed the targeting of the delta receptor, which may have a lower risk of side effects from medication overuse or rebound. The delta receptor, which is mainly active in chronic pain states, has a low potential for addiction and has an overall antidepressant and anxioytic effect. These receptors are mainly in the cortex and forebrain, as well as amygdala and hippocampus – areas that have been implicated in pain awareness and emotional processing. Molecules that are delta agonists reduce pain when activated by acute nitroglycerin but do not increase basal hypersensitivity, suggesting that they could be a potential target for pain control.

Additional highlights included the Seymour Solomon Lecture Award, which was given to Dawn Buse, PhD, who proceeded to give a very relevant talk about the relationship between stress and headache. She also warned about the dangers of physician burnout and ways to reduce stress for the practitioner as well as the patient – a topic that is top-of-mind among many clinicians.

Overall, the American Headache Society put on another educational, informative, and enjoyable meeting for all attendees, both seasoned and new to the profession.

For more coverage of AHS 2016, go here.


  1. Cameron C, Kelly S, Hsieh SC, et al. Triptans in the Acute Treatment of Migraine: A Systematic Review and Network Meta-Analysis. Headache. 2015;55 Suppl 4:221-35.