Pain research in 2015 has been ground-breaking and full of promise. From a newly-discovered “pain switch” to treating pain with light instead of opioids, here are our top six most fascinating new treatments and discoveries of 2015.

1. Off switch for pain

In what is arguably one of the most promising discoveries this year, Saint Louis University researcher Daniela Salvemini, Ph.D. and colleagues within SLU, the National Institutes of Health (NIH) and other academic institutions have discovered a way to block the pathway of pain for chronic neuropathic pain in animal subjects. This includes pain caused by chemotherapy and bone cancer.

Activating the A3 receptor in the brain and spinal cord – either naturally with the chemical adenosine or with a simulated chemical developed by NIH – helped prevent or reverse pain caused by neuropathic damage.

Dr. Salvemini believes this may be a breakthrough in the research that can lead to non-pharmaceutical pain relief:

“It has long been appreciated that harnessing the potent pain-killing effects of adenosine could provide a breakthrough step towards an effective treatment for chronic pain. Our findings suggest that this goal may be achieved by focusing future work on the A3AR pathway, in particular, as its activation provides robust pain reduction across several types of pain.”

2. Light as a pain reliever

Scientists at Washington University in St. Louis have also focused their research on non-pharmaceutical treatments for the most severe chronic pain. This has resulted in the discovery of a way to activate the opioid receptors in the brain – without opioids. By attaching the light-sensing protein rhodopsin to key opioid receptors in the brain, researchers were able to offer pain relief in laboratory mice without providing drugs.

This is the first step in the research. The next step is to focus on finding efficient and effective ways of activating this pathway. Opioid receptors in the brain provide multiple functions, including working with the gastrointestinal and respiratory systems. Still, this is a promising start.

First author Edward R. Siuda, a graduate student in the laboratory of Michael R. Bruchas, PhD, an assistant professor of anesthesiology and of neurobiology, believes that this discovery could help combat the epidemic of opioid prescription while still offering relief to chronic pain patients:

“It’s conceivable that with much more research we could develop ways to use light to relieve pain without a patient needing to take a pain-killing drug with side effects.”

3. Optogenetic stimulation to relieve pain

In another study that utilizes light as a way to control pain, the physics team at the University of Texas at Arlington, in collaboration with bioengineering and psychology researchers, found that a specific frequency of light applied to the region of the brain called the anterior cingulate cortex (ACC) could control pain in laboratory mice. While this type of stimulation has been attempted before, this specific frequency is the first to inhibit pain-sensing activity (rather than inhibit and increase, as in previous experiments).

Samarendra Mohanty, an assistant professor of physics and leader of the biophysics and physiology lab in the UT Arlington college of science, noted the specific differences between this breakthrough and previous studies:

“Our results clearly demonstrate, for the first time, that optogenetic stimulation of inhibitory neurons in ACC leads to decreased neuronal activity and a dramatic reduction of pain behavior. Moreover, we confirmed optical modulation of specific electrophysiological responses from different neuronal units in the thalamus part of the brain, in response to particular types of pain-stimuli.”

4. Spinal cord neurons as gatekeepers

Pain signals are sent up the spine to be interpreted by the brain, but researchers at the University of Zurich have identified certain spinal cord neurons that act as gatekeepers, determining which signals get through to the brain and which do not.

Disabling glycine-releasing neurons lead to an increased sensitivity to pain and signs of spontaneous pain in laboratory mice, while activating it lead to a decreased sensitivity. The researchers caution that treatments based on this discovery are a long way off, but believe that this confirmation of the Gate Control Theory of pain should be further investigated.

5. New delivery method for pain relief

Common over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) used for pain relief can lead to serious side effects that include gastrointestinal bleeding and ulcers.

MChem undergraduate student Edward Howe, working in Professor David Smith’s research team in the department of chemistry at the University of York, developed a slightly more alkaline gel that interacts with NSAIDs like naproxen to enable higher doses of NSAIDs to be delivered more safely. The alkaline pH mimics the pH of the intestine rather than the acidic pH of the stomach, resulting in less potential damage or side effects. Professor Smith noted that this is not the first time a gel has been proposed, but this gel is different:

“Although researchers have used gels before to try and improve the formulation of naproxen, this is the first time that a self-assembling system has been used for the job, with the advantages of directed interactions between the nanoscale delivery scaffold and the drug. As such, this is the first time that such precise control has been achieved.”

6. Pain-sensing gene discovered

Another discovery from researchers at the University of Cambridge has the potential to lead to new developments in more effective pharmaceutical pain treatment.

Studying the genetic map of 11 families across Europe and Asia with members who had the inherited condition known as congenital insensitivity to pain (CIP), professor Geoff Woods from the Cambridge Institute for Medical Research at the University of Cambridge and his team identified the gene PRDM12 as responsible for pain sensing. One of two variants of this gene were blocking pain-sensing neurons in patients with CIP.

Dr. Ya-Chun Chen from the University of Cambridge, the study’s first author, had this to say about the possibilities this discovery could unfold:

“We are very hopeful that this new gene could be an excellent candidate for drug development, particularly given recent successes with drugs targeting chromatin regulators in human disease. This could potentially benefit those who are at danger from lack of pain perception and help in the development of new treatments for pain relief.”

On top of these six discoveries, researchers have also developed an implantable ion pump to control pain at the source, discovered a potentially longer-lasting painkiller, searched for alternatives to medical marijuana, and focused on bridging the gap between laboratory experiments and human clinical trials.

Which discovery in pain treatments are you most excited about?

Image by Steve Sliker at



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