Dr Frank Porreca Talks Through the Challenges of Measuring Migraine Pain

Pain is a subjective response with multiple features and components, said Frank Porreca, PhD, professor of pharmacology and anesthesiology at the University of Arizona and a member of the Department of Collaborative Research at Mayo Clinic in Arizona.

Transcript:

The American Journal of Managed Care® (AJMC®): Can you elaborate on your research into understanding pain-induced motivational behavior and reward circuits as a basis for discovering new migraine therapies with a high likelihood of translation?

Dr. Porreca: One of the problems that we've always had is to measure pain. Pain is a subjective response, and so it has multiple components. It has a sensory component. We can sort of know where the pain is, we can discriminate the location of the pain: it's in my finger, it's in my shoulder, whatever it is. But it also has other features that are a little bit different from other sensory responses. Pain has an affective component and a motivational component. So pain is a sensation, but unlike other sensations that are sort of affectively neutral, pain is unpleasant. Pain is always unpleasant. It's unpleasant at threshold. It's the unpleasantness of pain that produces motivation. We have pain, we have strong motivation to escape and to seek relief from that pain condition.

The reason for describing that, is how do we measure pain? Well, measuring pain, even in humans is difficult. The way that we measure pain in humans is we ask humans about their pain. We say, 'how much pain do you have?' We use rating scales, numerical rating scales, visual analog scales, something like that, and the humans tell us. Now it's okay to do that and we believe humans when they tell us their pain is an 8 out of 10, or 7 out of 10, or 5 out of 10. But what we would prefer to do is we'd like to have an objective measure of pain, sort of like a blood test. What is your cholesterol level, you know? You get a number. We don't have that in humans, because pain, again, is fundamentally subjective.

Now, if you take that, and you translate it to the preclinical laboratory, and you say, how do we measure pain in a non-verbal animal? Well, that becomes particularly challenging, because we can't ask the animal about their pain, and yet, we'd like to know if our treatment produced relief of pain, like in migraine. So one of the things that we have done is we focused on the motivational qualities of pain. Pain is aversive, it produces motivation to escape and to seek relief. What we find is that if we have relief of an aversive state, then that is actually rewarding. The way that you can think about it is if it's a very, very hot day, for example, and you jump in the swimming pool, well, that makes you feel better. Relief of an aversive state is rewarding, and it activates the classical mesolimbic dopaminergic reward pathway. And it produces motivation. That's what we've done. If we have ongoing pain, we produce relief of ongoing pain that animals will seek; a context that there is a learning paradigm where they can seek a context that's associated with relief of that aversive state. That gives us insight into whether the pain is there and secondly, whether the treatment that we've given, is effective in producing relief of pain by removing the motivation on the part of the animal to seek a context that's associated with with relief of an aversive state.