Understanding Body Pathways Is Key To Future Pain Treatments

“Pain is a disease,” says pediatrician and anesthesiologist Elliot Krane, who works at Stanford University’s Packard Children’s Hospital. Krane’s take is different from the prevailing mindset that pain is instead a symptom of another underlying condition.

In fact, about 10% of patients with serious conditions, such as cancer, infections, or problems requiring operations, experience persistent pain even after the condition subsides, Krane says during a TED talk explaining his philosophy. TED is a non-profit that hosts discussions and disseminates videos designed to engage discussion and spread interesting ideas.

The pain that’s independent of a causing disorder can last for years, and at that point, Krane says, it takes on a new identity as a separate disease.

Chronic pain can take on a life of its own, independent from any primary condition, expert says. This influences how we develop pain treatments. 

Consider the case of Chandler, a 16-year-old fledgling ballerina who sprained her wrist during practice. Instead of healing as usual sprains do, Chandler developed a condition called allodynia. Her nerves stopped working properly so that every touch to the arm, even the lightest sensation, resulted in “excruciating, burning pain,” Krane recalls.

Chandler’s arm developed an abnormal look to it, as well. The arm was cold and purple, and its muscles were frozen.

Allodynia is frequently linked to headache sufferers, with up to 80% of people with migraines experiencing the condition during an attack, according to the American Headache Society. The painful condition may also accompany fibromyalgia, according to Everyday Health.

In patients with allodynia, the nervous system’s wiring goes very wrong.

Krane draws an analogy between the nervous system and a building’s electrical wiring. Just as flipping a light switch in a home sends signals firing through wires in the wall, ultimately producing light, nerves in the body communicate through the brain’s neurotransmitters and adjacent cells to process sensory signals and, if directed, produce pain sensations.

Krane says:

“It’s almost as if somebody came into your home and rewired your walls so that the next time you turned on the light switch, the toilet flushed three doors down, or your dishwasher went on, or your computer monitor turned off. That’s crazy, but that’s in fact, what happens with chronic pain.”

The complexity of the misfiring is what leads to the development of chronic pain, Krane adds. “The nervous system has plasticity. It changes, and it morphs in response to stimuli,” he says.

In chronic pain, the very foundations of the nervous system go awry, making it difficult to create pain treatments that work against the root cause.

Pain treatments for chronic conditions currently feature a mix of painkillers—essentially dulling the nervous system so it’s not quite so active—however, a regimen of pills isn’t very effective for disorders like allodynia, Krane says.

Physical and occupational therapy can help work at the level of the nerves in the body, retraining them so they don’t overreact and cause unnecessary pain, and a robust psychotherapy program helps to mitigate the emotional side effects of living with chronic pain—namely depression, stress, and feelings of hopelessness.

Krane says that future medications to heal chronic pain will work at a more fundamental level, fixing the nervous system instead of merely subduing it. Rewiring the house instead of tripping the circuit breakers. One target of future drugs could be the glial cells, which Krane says hold much blame for causing pain.

Glial cells are found in the brain, where they comprise about 90% of the structure, and also the spinal cord. These cells were once thought to operate as a kind of glue, keeping important biological components together. However, scientists now understand that glial cells play a key role in pain perception and can distort incoming sensory experiences.

When a person perceives pain, the glial cells activate, making proteins that signal neighboring nerves to release neurotransmitters, which then enliven more glial cells, creating what Krane calls a “positive feedback loop.”

Future pain treatments will be able to target renegade glial cells or the proteins gone wild to stop the cells’ over-firing, bring sensory perception back to normal, and alleviate chronic pain at its source.

Future chronic pain treatments could work at the cellular level to stop pain before it starts. 

Allodynia isn’t the only condition that could be helped by pain treatments of the future. Israeli researchers discovered a drug that works to stop the body from spreading pain signals related to neuropathic pain.

Neuropathy may result from conditions such as cancer, diabetes, and lupus, but it is difficult to treat with traditional pain medications. The drug, BL-7050, quieted extreme activity of neurons by using cells’ potassium pathways, which are implicated in neuropathic pain. The medication is still in the research phase and is not yet available in the U.S.

The development of future medications relies on a deepening understanding of cellular pathways and learning how biological components, such as glial cells and potassium pathways, contribute to chronic pain.

Researchers also must work to understand how the brain responds to pain, according to research from the University of Adelaide. Just as the nervous system is able to change its functioning with allodynia, the brain also has the ability to change in structure and function. Brain changes are known as neuroplasticity, and the phenomenon is critical to humans’ ability to learn new things and remember events.

Researchers hope that understanding changes in brain structure could lead to new pain treatments to reverse the changes.

Researchers found people with chronic pain had brains less able to change than those without chronic pain. In other words, they had less neuroplasticity. Understanding more about why this happens could lead to new clues in the search for more effective chronic pain medications, scientists say.

Researcher Dr. Ann-Maree Vallence says patients living with chronic pain find it difficult to carry on with normal activities. She adds:

“It is therefore imperative that we understand the causes of chronic pain, not just attempt to treat the symptoms with medication.”

Insights from the study could eventually be used in research to uncover targeted, truly effective chronic pain treatments, including chronic tension headaches, says Vallence.

Want to learn more? Watch Elliot Krane’s eight-minute “The Mystery of Chronic Pain” TED talk now! 

Image by albastrica mititica via Flickr