With Cancer Treatment Comes Pain

With Cancer—and Treatment—Comes Pain – RELIEF: PAIN RESEARCH NEWS, INSIGHTS AND IDEAS

Cancer remains a devastating disease, to be sure. But while many people still lose their lives to cancer, many more survive than at any other time in history, thanks to advances in the understanding and treatment of cancer.

With increased survival rates, though, patients are spending many more years living with the symptoms of cancer—including pain.

Since all opioid guidelines exclude limits on treating cancer pain, when do cancer patients convert from cancer patients to chronic pain patients?  

After how long are cancer patients expected to transition from unlimited opioids to virtually none?  

Historically, very little research was done to investigate cancer-related pain—in part because outcomes were dire, and patients with severe pain often did not live long. But today, as people recover and live longer, researchers have realized the tremendous need for better treatments for pain associated with cancer—and with cancer therapies.  

How does cancer cause pain?

At its core, cancer pain arises like all pain: when a potentially damaging stimulus activates pain-sensing nerves that spread throughout the skin, muscles, organs and bones, they send signals to the brain that culminate in the experience of pain

Cancer can invade different tissues of the body; once established, cancerous tumors transform the cellular environment.

“Our primary hypothesis is that cancer cells produce molecular mediators to activate and sensitize nerves that come into contact with the cancer,” Schmidt says. Nerve activation causes transmission of a pain signal, and nerve sensitization makes nerves more likely to fire, which can lead to spontaneous nerve activity and pain.

In addition to nociceptive pain, once the immune system detects cancer, immune cells flock to the site of a tumor, making conditions ripe for inflammatory pain too.

Immune cells release chemicals that activate pain-sensing neurons. In addition, when cancer cells invade bone, they promote growth of cells called osteoclasts that break down bone by releasing acid; this also promotes pain signaling.

Cancer also causes neuropathic pain, particularly at later stages of the disease; when tumors become very large, they compress organs and nerves and break bones.

Neuropathic pain can also arise from nerve damage caused by surgery, radiation or chemotherapy.

The pain that stems from cancer and its treatment can take many forms, depending on the type, severity, and location of cancer, as well as the course of treatment. To complicate matters, not everyone experiences these conditions the same way.

Around twenty percent of oral cancer patients don’t have pain, while others suffer excruciating pain. “Part of that equation is patient susceptibility to pain,”

Is cancer pain different from non-cancer pain?

The emotional component of pain—the suffering—depends on widespread activity throughout the brain, and the circumstances associated with pain have a tremendous impact on the experience.

“We know that most pain is exacerbated by catastrophizing, by thinking about it,” and fearing the worst, Mantyh says.

Cancer may be unique among chronic pain conditions in that the threat is very real. “It’s difficult to have cancer and not wonder whether every new pain isn’t some tumor cell infiltrating your joints or bone or lung,”

“A very important part of cancer pain is the suffering,” says Eija Kalso, a pain researcher at the University of Helsinki, Finland. “What the pain means to a patient has a significant impact on the emotional experience. If it is a terminal case of cancer, the patient may be in crisis.”

Fear of death, worrying about what will happen to one’s children, concerns about finances—all these sources of anxiety lead to enhanced pain.

So, opioids are given to cancer patients to reduce the suffering caused by the fear of death, not the actual pain that all humans suffer?

How do researchers study cancer pain?
Researchers are investigating cancer pain in animal models to better understand the cellular and molecular mechanisms at play. But as with all animal models of disease, researchers struggle to create conditions that mimic the human situation.

In one of the most commonly used models of cancer pain, mice receive an injection of tumor cells directly into their bones—something that does not occur in humans. In most studies, mice are injected with sarcoma cells, which form primary bone tumors, a type of cancer that accounts for only three percent of human cancer cases,

Moreover, the tumors contain rodent cancer cells, not human cancer cells. “There are big differences in the expression signatures of genes in rodent and human cancers,” he says, meaning that the cells turn on and off different genes and produce different proteins

Once the researchers introduced human cancer cells to mice with compromised immune systems—leaving them unable to fight off the invasion—the mice developed metastatic bone tumors. By genetically labeling the cancer cells with a glowing protein derived from fireflies, the researchers were able to visualize the site of tumor growth by imaging the animals’ entire bodies in a machine that detects bioluminescence.

How do cancer treatments causes harm?

Paradoxically, the very treatments that may save a cancer patient’s life can also cause chronic pain.

Nerve damage from surgery or radiation therapy can lead to neuropathic pain, and chemotherapy can cause a condition called chemotherapy-induced peripheral neuropathy (CIPN).

As many as three-quarters of patients receiving chemotherapy may develop CIPN, and about a third of patients still experience CIPN six months after stopping treatment. Much like other pain conditions, physicians cannot yet predict who will develop CIPN, but risk factors include smoking and previous neuropathic pain

Just in the past few years, researchers have determined that chemotherapeutic drugs damage nerves by causing dysfunction in mitochondria, the energy-generating machines within cells. “We hypothesize that, as a consequence of that dysfunction, nerves develop abnormal, spontaneous [electrical] discharge,” Salvemini says.

What tools are available to treat cancer pain?

As researchers continue to investigate new treatments for cancer-related pain, what medications are currently available? Unfortunately, just as is the case for chronic pain in the general population, when it comes to tools for treating cancer pain, Schmidt says, “there are not many, and they are not good—they are blunt tools.”

And just as patients differ in their experience of pain, so do they in their responses to pain medications. However, a better understanding of the specific type of pain patients suffer from can help physicians choose the best tools available to treat it.

Some patients receive “nerve blocks,” in which local anesthetics are delivered to nerves in an affected area. “If we can anesthetize the nerves innervating [i.e., supplying] the cancer, the patient can get relief,” Schmidt says.

Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen can help combat inflammatory pain, and a class of drugs called bisphosphonates can help neutralize the acidic environment that contributes to the bone pain often seen in cancer patients.

And neuropathic pain from cancer or chemotherapy can sometimes be eased with anti-depressant or anti-seizure medications prescribed for other neuropathic pain conditions. Those drugs are thought to enhance pain-dampening signals from the brain to the spinal cord.

Opioid drugs such as morphine, which mimic the brain’s own natural pain-killing molecules, are the most powerful drugs available for severe pain, including cancer-related pain, but “not everyone responds to them,” Schmidt says, “and they are associated with significant side effects.”

Kalso said that the acceptance of higher risks from opioids in terminal cancer patients contributed to rampant overuse of opioids in chronic pain management.

In 1986, the World Health Organization (WHO) published what came to be known as the “analgesic stepladder,” a document that advised stepping up the dose of opioid drugs to very high doses to control pain.

The guidelines, intended for patients with terminal cancer, were meant to reduce the stigma associated with prescribing and taking opioid drugs and to prevent people from dying in severe untreated pain.

But the recommendations have been widely applied to patients with non-terminal cancers and other chronic pain conditions.

There needs to be a division between terminal and non-terminal cancer pain treatment, because the goals are so different,” Kalso emphasizes.

“Pain treatment in a cancer survivor shouldn’t be any different from other chronic pain patients,” who should not receive chronic opioids in ever-increasing doses, she added.

This callous and cruel doctor assumes all chronic pain requires “ever-increasing doses”, which is not usually the case. Many chronic pain patients stabilize on a dosage for years and even decades, but she ignorantly denies this reality.

This is the first time I’ve seen the distinction made between pain from terminal versus non-terminal cancer, and I find it outrageous and insulting to cancer patients.

Perhaps it hints at the real attitude toward opioids: they only want to give opioids if we’re about to die (and thus be mercifully relieved of pain). 

Such a macabre attitude is offensive and extremely damaging to those of us who must continue living in pain.

The article makes clear that cancer pain is as variable as any other, yet there seems to be compassion only for those who are close to death, and none for those of us who have much, much longer to live with the same level of pain.

Focusing on the whole person

How important is pain management for patients with cancer? “It’s enormous,” says Mantyh.

Today, people may live for decades with cancer-related pain.

“In order to allow them to live the life they want to live, we have got to control the pain,” he stresses.

This statement applies to anyone with chronic pain, not just if it results from cancer, and is exactly what we’ve been trying to communicate all along.

To do that, Mantyh suggests patients advocate for pain relief as part of their course of treatment. “Treating the cancer is the foremost concern, but pain management should be built into any treatment strategy.”   

I still don’t understand how chronic cancer-treatment pain or any other chronic pain differs from cancer pain and why the treatment should be so different.
Even some doctors agree that the distinction seems arbitrary and artificial, and the information in this article still doesn’t explain it.

I believe the difference between terminal cancer versus non-terminal cancer and all other chronic pain exists only in a doctor’s mind.

ALLl severe chronic pain is equally disabling.

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