Dr. Sabrina Coninx from Ruhr-Universität Bochum and Dr. Peter Stilwell from McGill University, Canada, have investigated how philosophical approaches can be used to think in new ways about pain and its management. The researchers advocate not merely reducing chronic pain management to searching and treating underlying physical changes but instead adopting an approach that focuses on the person as a whole. Their work was published online in the journal “Synthese” on 15 April 2021.

It is not currently possible to treat chronic pain effectively in many cases. This has encouraged researchers from various disciplines to consider new approaches to pain and its management over recent years. “Pain research and clinical practice do not take place in a vacuum, but instead involve implicit assumptions regarding what pain is and how it can be treated,” says Sabrina Coninx, research assistant at the Bochum research training group Situated Cognition. “Our aim is to shed light on these assumptions and discover how we can think in new ways about pain and its management with the help of philosophical approaches.” In their work, the authors develop a holistic, integrative and action-oriented approach.

Viewing patients as a whole

In specific terms, they suggest three things: firstly, addressing pain should involve more than just looking for and treating underlying physiological changes. A holistic approach places the focus on patients as a whole and creates space for their experiences, concerns, expectations and narratives. The influence of socio-cultural practices in the generation of chronic pain should also be taken into account. For example, pain patients are often initially encouraged to protect themselves from injury and avoid activity, which may be helpful in the beginning but can contribute to chronification in the long run.

Secondly, according to the researchers, chronic pain should be understood as a dynamic process in which many different factors interact in a non-linear way. The initial cause of pain, for instance, is not necessarily the cause of its chronification and also does not need to be the most crucial factor in treatment. The complex interaction of subjective experience, expectations, learned behavioural patterns, neural reorganisation, stigmatisation and other factors therefore needs to be considered.

Focus on action possibilities

Thirdly, according to Coninx and Stilwell, patients should be encouraged to interact with their environment and identify possibilities for action. This is based on the assumption that chronic pain fundamentally changes the way in which patients perceive themselves and their relationship with their environment. Pain treatment could therefore involve helping the patient to increasingly notice positively associated and personally meaningful options for action and view themselves as capable of taking action again. There is then less focus on the body as an obstacle, and instead the patients pay more attention to how they can overcome limitations.

A study in cells and mice finds compound works with fewer side effects than opioids

Fentanyl, oxycodone, morphine–these substances are familiar to many as a source of both pain relief and the cause of a painful epidemic of addiction and death.

Scientists have attempted for years to balance the potent pain-relieving properties of opioids with their numerous negative side effects–with mostly mixed results.

Work by John Traynor, Ph.D., and Andrew Alt, Ph.D., and their team at the University of Michigan Edward F. Domino Research Center, funded by the National Institute on Drug Abuse, seeks to side-step these problems by harnessing the body’s own ability to block pain.

All opioid drugs–from poppy-derived opium to heroin–work on receptors that are naturally present in the brain and elsewhere in the body. One such receptor, the mu-opioid receptor, binds to natural pain-killers in the body called endogenous endorphins and enkephalins. Drugs acting on the mu-opioid receptor can cause addiction as well as unwanted side effects like drowsiness, problems with breathing, constipation and nausea.

“Normally, when you are in pain, you are releasing endogenous opioids, but they’re just not strong enough or long lasting enough,” says Traynor. The team had long hypothesized that substances called positive allosteric modulators could be used to enhance the body’s own endorphins and enkephalins. In a new paper published in PNAS, they demonstrate that a positive allosteric modulator known as BMS-986122 can boost enkephalins’ ability to activate the mu-opioid receptor.

What’s more, unlike opioid drugs, positive allosteric modulators only work in the presence of endorphins or enkephalins, meaning they would only kick in when needed for pain relief. They do not bind to the receptor in the way that opioids do instead binding in a different location that enhances its ability to respond to the body’s pain-relieving compounds.

“When you need enkephalins, you release them in a pulsatile fashion in specific regions of the body, then they are metabolized quickly,” explains Traynor. “In contrast, a drug like morphine floods the body and brain and sticks around for several hours.”

The team demonstrated the modulator’s ability to stimulate the mu-opioid receptor by isolating the purified receptor and measuring how it responds to enkephalins. “If you add the positive allosteric modulator, you need a lot less enkephalin to get the response.”

Additional electrophysiology and mouse experiments confirmed that the opioid receptor was more strongly activated by the body’s pain-relieving molecules leading to pain relief. In contrast the modulator showed much reduced side effects of depression of breathing, constipation and addiction liability.

Their next goal is to measure their ability to enhance activation of endogenous opioids under conditions of stress or chronic pain, explains Traynor, to ensure that they are effective but don’t lead to more dangerous responses like depression of breathing.

“While these molecules won’t solve the opioid crisis,” says Traynor, “they could slow it and prevent it from happening again because patients in pain could take this type of a drug instead of a traditional opioid drug.”