Cancer Patients Were Supposed to Be Exempt From CDC Opioid Guideline. They’re Not.

By Crystal Lindell

Cancer patients needing pain treatment were always meant to be exempt from the recommendations of the 2016 CDC opioid guideline, including the updated guideline released in 2022:

“This clinical practice guideline does not apply to patients undergoing cancer-related pain treatment, palliative care, or end-of-life care because… for many persons at the end of life, serious potential long-term opioid-related harms such as opioid use disorder might not be relevant.” 

A new study reveals that many older cancer patients were deprived of opioids anyway, even though they often require opioids as a first-line pain treatment.

The study looked at nearly 12,000 older adults on Medicare who were being treated for cancer from 2010 to 2020, including about 1,300 with advanced cancer or cancer pain.

Researchers found a significant 24% decline in opioid prescribing to cancer patients after the 2016 guideline was released. What did they get instead for pain relief?

There was a 7.5% increase in tramadol prescribing for cancer pain, while gabapentinoid prescribing for cancer patients rose by 25%. Even patients with advanced cancer were switched to tramadol or gabapentinoids, a class of nerve medication originally developed to treat seizures, not pain. 

“These findings suggest the 2016 guideline may have led to pain management shifts from first-line opioids to less-safe tramadol and less-effective gabapentinoids for older adults with cancer,” wrote lead author Rebecca Rodin, MD, Assistant Professor of Geriatrics and Palliative Medicine at the Icahn Mount School of Medicine at Mount Sinai.

It’s great to see the study authors call out tramadol and gabapentinoids as being “less safe” and “less effective.” Pain patients have long known that to be true, but the medical community still seems resistant to this information. 

While tramadol is technically an opioid, the DEA classifies it as a weaker Schedule IV drug, unlike oxycodone, hydrocodone and other opioids classified as Schedule II. The differentiation means doctors face less restrictions for prescribing it and less risk of going to prison. 

Gapabentin (Neurontin), pregabalin (Lyrica) and other gabapentinoids are prescribed off-label for cancer pain and chemotherapy-induced neuropathy —  even though they are medical conditions the drugs are not approved for. Gabapentinoids are not only ineffective analgesics for cancer pain, they can cause sedation and confusion, particularly in older adults.

Opioids, on the other hand, are very effective for moderate-to-severe cancer pain, with a response rate of 75% and a 50% average reduction in pain intensity.

Studies like this validate what the pain community has been trying to warn about for almost a decade: opioid-phobia has gone too far. It has reached a point where even cancer patients can’t get the pain relief they need.

Part of why this persists is that most people don’t think opioid restrictions are a problem until they or a loved one needs them. But if you wait until you’re dying from cancer to oppose opioid restrictions, it will be far, far too late. 

Of course, the other problem is, cancer is not the only thing that can cause debilitating pain. And people with other types of pain also deserve effective relief.

Another recent study by Dr. Rodin found that seriously ill patients in palliative and hospice care also have trouble getting opioids, due to inadequate supplies in pharmacies and insurance obstacles.

“The reality is that hundreds of thousands of seriously ill patients in the U.S. rely on opioids as a first-line treatment for pain. For people with advanced cancer, chronic organ failure, or other life-limiting conditions, opioids are often the only medications that can effectively control pain and allow them to function, Rodin wrote in a recent op/ed in STAT .  

Opioids have been used for centuries to treat pain for a reason: They work very well, and the risks of opioid addiction and.overdose are far less than what the public has been led to believe. 

Now we just need to convince doctors and the CDC of that. 

Discovery of Brain Protein Could Lead to New Chronic Pain Treatments

By Pat Anson, PNN Editor

Researchers have identified a protein in the brain that appears to play a prominent role in the maintenance of long-term pain -- a discovery that could lead to new treatments that stop short-term acute pain from progressing to chronic pain.

The protein RGS4 (Regulator of G protein signaling 4) is found in brain circuits that process pathological pain, mood and motivation.

"Our research reveals that RGS4 actions contribute to the transition from acute and sub-acute pain to pathological pain states and to the maintenance of pain," says Venetia Zachariou, PhD, a professor in The Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai in New York City.

"Because chronic pain states affect numerous neurochemical processes and single-target drugs are unlikely to work, it's exciting to have discovered a multifunctional protein that can be targeted to disrupt the maintenance of pain."

In studies on genetically modified mice, Zachariou and her colleagues found that genetic inactivation of RGS4 did not affect acute pain, but it promoted recovery from nerve injuries, chemotherapy-induced neuropathy and peripheral inflammation. Mice lacking RGS4 developed all the expected symptoms of a nerve injury, but recovered within 3 weeks and returned to physical activity.

The transition from acute to chronic pain is accompanied by numerous adaptations in immune, glial and neuronal cells, many of which are still not well understood. Chronic pain patients experience a number of debilitating symptoms besides pain, such as sensory deficits, depression and loss of motivation

Researchers believe future drugs that target RGS4 could prevent acute pain from transitioning to chronic pain. Currently available medications for chronic pain only treat the symptoms – not the underlying condition – and have major side effects.

Dr. Zachariou's laboratory is conducting further investigation into the actions of RGS4 in the spinal cord and mood-regulating areas of the brain to better understand the mechanism by which the protein affects sensory and pain symptoms.

Their findings are published online in The Journal of Neuroscience.