Everyone would like to walk through life pain-free. Instead, many people live with chronic pain conditions. Dr. Paul Durham, Missouri State University distinguished professor of biology and director of the Center for Biomedical and Life Sciences, researches factors that instigate chronic pain and tests products that might work to alleviate these pain states.

In his lab in the Jordan Valley Innovation Center, he employs several research assistants, as well as graduate and undergraduate students from Missouri State. He oversees the research they’re conducting on a nearly half million dollar National Institutes of Health grant he received, all of which correlates with his research interests in orofacial pain, the trigeminal nerve and inflammation promoted by calcitonin gene-related peptide (CGRP).

Relationship of CGRP and chronic pain

CGRP, which is made and released by trigeminal nerves, is known to promote inflammation and pain. Lauren Cornelison, a biology graduate student, is studying the effect of elevated levels of CGRP in the spinal cord on the development of pain. She utilizes a novel device developed in Durham’s lab that is now commercially available and von Frey filaments to study the effect of different types of inhibitors to decrease inflammation and pain caused by CGRP.

“What Lauren’s data is showing is that if you have elevated levels of CGRP in the spinal cord – which has been reported in migraine patients – it can act like a trigger to cause sensitization and activation of trigeminal nerves.  This type of bidirectional signaling has not been shown before but provides an explanation for why elevated levels of CGRP in the spinal cord leads to pain in the head and face during a migraine attack,” said Durham.

He, Cornelison and Jordan Hawkins, senior research scientist, shared this research at the Society for Neuroscience meeting held in Chicago Oct. 17-21.

Chronic jaw pain

Lindsey Koop, a biology graduate student, has been investigating the role of increased levels of the pro-inflammatory proteins CGRP and PKA in a model of TMD, or temporomandibular joint disorder. TMD is a common dental problem characterized by inflammation and pain in the jaw joint and muscles used for chewing.  Her research has shown that blocking the elevated levels of CGRP and PKA can inhibit the development of a more chronic pain condition.

Work in the Durham lab has shown that pain in one part of the head or face (like sinus pathology or TMD) can increase the risk of developing a more chronic pain condition in another area (migraine). Therefore, it is important to better understand how to block pain in one area so as to minimize the risk of other co-morbid pain.  For example, by blocking pain in the jaw joint, one can reduce the likelihood of developing chronic pain associated with migraine and possibly even lowering the risk of irritable bowel syndrome or IBS.

Prolonged jaw opening

“It’s amazing to me how many people actually have dental or orthodontic work that end up on long-term disability due to chronic pain,” said Durham. He’s not talking about just TMD but also other types of chronic pain in the head and face such as frequent headaches and migraine.

In this study, Cody Hyde, a junior biology major, is simulating prolonged jaw opening – like that in dental or orthodontic work – and correlating it to chronic pain. The Durham lab has found that keeping the mouth in a near maximum jaw opening position leads to inflammation and pain that is associated with TMD.

“Our prediction is that if someone comes in to a dental clinic and has a lot of stiffness or tension in their neck from stress, opening his or her mouth for a long period of time could do irreparable damage,” said Durham.

This line of research is just getting under way in their lab but is likely to provide evidence that having ongoing neck or shoulder muscle pain may be a significant risk factor for developing TMD symptoms if the jaw is held open too wide for a prolonged period of time.

Identifying the most vulnerable demographics

Through their testing, Durham and Hyde found that certain demographics were more susceptible to acquiring this pain: younger women. Durham explained that female jaws are smaller on average, and younger subjects have not only smaller jaws, but they also have more elasticity in the joint.

“The danger in that is that you can actually overextend it very easily. When the dentist needs to get in the back of your mouth and you can only open this far, they may force it farther,” added Durham.

Koop can attest to an enormous amount of orthodontia in her teenage years, which resulted in chronic migraines.

Cannabis without THC is effective

For years, medical marijuana has been a controversial topic, but cancer and HIV patients often use it to relieve pain. Durham, Hyde, Hawkins and Koop are studying whether cannabis can block pain pathways without THC (or tetrahydrocannabinol), the chemical responsible for most of marijuana’s psychological effects.

They recently conducted early basic studies and found it was actually working to block pain pathways similar to eating cacao. They presented their early findings at the American Academy of Neurology meeting in April.

“It’s (cannabis) actually going to be much more potent than aspirin,” said Durham. “The evidence suggests that if you go down this road, then you won’t need as strong a dose of narcotics like the morphine-based drugs to treat pain patients. We really need to minimize how much we’re using narcotics to treat pain patients.”

Looking to the future

From their expertise, Durham and his research team see a trend emerging for treating chronic pain: personalized medicine. Durham cited current studies of implantable devices that will administer anti-inflammatory agents directly into the body (without chance of overdose).

Durham is also working on a Department of Defense grant to develop biofuel cells that will generate electricity by glucose in an individual’s spinal cord.

“In other words, you don’t need a battery. Your glucose is the fuel for your own battery, and it generates enough voltage that runs this little pump,” said Durham. “It’s sci-fi but it’s definitely where we’re going.”

Durham’s lab was previously profiled in Mind’s Eye.

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