Opioid painkillers may only temporarily ease the discomfort of arthritis


Opioid painkillers may temporarily ease the discomfort of arthritis, but they have no clear lasting benefit, a research review finds.

In an analysis of 23 clinical trials, researchers found that, on average, opioid medications were somewhat effective at easing pain in patients with osteoarthritis.

That’s the common form of arthritis in which cartilage cushioning the joints gradually wears down, leading to swelling, stiffness and pain.

But the trials found no evidence that opioids improved patients’ quality of life or helped with their depression.

And any benefits for pain seemed to wane with time.

“We found that the magnitude of these effects is small and continues to decrease over time,” said lead researcher Dr. Raveendhara Bannuru.

He is director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center, in Boston.

Treatment guidelines for chronic pain, other than cancer-related pain, already say opioids should be a last resort.

With osteoarthritis, Bannuru said, the drugs are only recommended if a patient has not gotten relief from other medical therapies, and if surgery – like knee or hip replacement – is not an option.

Instead, patients should try to exercise regularly and maintain a healthy lifestyle.

As for medications, Bannuru said, topical versions of nonsteroidal anti-inflammatory drugs (NSAIDs) – like ibuprofen and naproxen – are a “first choice.”

These creams or ointments help people avoid the side effects that can come with prolonged used of oral NSAIDs (such as Motrin, Advil, Aleve), Bannuru noted.

Injections of hyaluronic acid, a substance in joint fluids, are another option, he said.

In addition, aerobic activity, like walking, and exercises that strengthen the muscles around the arthritic joint can be helpful, according to Dr. Steven Eyanson, a rheumatologist who was not involved in the study.

And if a patient is overweight, shedding some pounds can help ease pain and improve joint function, said Eyanson, a retired adjunct assistant professor at the University of Iowa in Iowa City.

“In the case of osteoarthritis, the benefits of therapy by opioid pain relief are very limited,” Eyanson said.

Bannuru was scheduled to present the findings Saturday at the American College of Rheumatology’s annual meeting, in Atlanta.

Research presented meetings is generally considered preliminary until it is published in a peer-reviewed journal.

For the study, the researchers pooled the results of 23 previously published clinical trials that involved more than 11,400 osteoarthritis patients.

Overall, the investigators found, opioid treatment had a modest effect on people’s pain over two to 12 weeks. At higher doses, the drugs were actually less effective, and carried a higher risk of side effects, such as nausea, constipation and diarrhea.

“In light of dependency concerns and the discomfort that many patients feel while taking the drugs, it would appear that there is no optimal therapeutic window for the use of oral opioids in osteoarthritis,” Bannuru said.

The results come during a national crisis of opioid addiction that, according to government figures, is killing 130 Americans each day.

After years of skyrocketing, prescriptions for opioids – like OxyContin, Vicodin and Percocet – have been declining since 2012, according to the U.S. Centers for Disease Control and Prevention.

In recent years, illegal opioids – like heroin and illicitly manufactured fentanyl – have become the biggest concern.

Still, prescription opioids were involved in 36% of opioid overdose deaths in 2017, the CDC says.

“We hope the results of our study will empower osteoarthritis patients to have informed discussions with their health care providers about the safest and most effective treatment options for their pain,” Bannuru said.

Eyanson said that, to him, “the take-home messages are that opioids have limited benefit in osteoarthritis pain control, and have significant potential for risk.”

Most osteoarthritis patients will benefit from a “more holistic approach”—including medication and non-drug therapies, and in some cases, surgery, he added.

Black sage, Salvia mellifera, is a traditional medicine of the Chumash Indians of California [1,2]. It is used as a sun tea made from the stems and leaves of the plant to treat pain. S. mellifera sun tea is also traditionally used to cure chronic pain.

The authors have used this and other Chumash medicines to treat many pain patients. Black sage contains 54 monoterpenoids and several diterpenoids such as carnosol (41%), carnosic acid (22%), salvicanol (15%) and rosmanol (9%) [3,4].

The monoterpenoids are 1.8-cineole (39.8%), camphor (12.2%), α-pinene (9.2%), limonene (2.2%), myrcene (2%), γ-terpinene (2%), terpene-4-ol (2%) and many less abundant monoterpenoids.

Currently in the US, chronic pain affects 60%, or more, of people over the age of 65 [5]. Chronic pain is pain that continues long after the initial cause of the pain is gone, such as back injuries, car accidents, surgery, nerve damage and infections.

Unfortunately, there is no cure for chronic pain—only partial short-term therapies are available—but chronic postsurgical pain can sometimes be prevented [6].

The causes of chronic pain are only now being understood and may involve chemokines. It has been proposed that peripheral and central sensitization mechanisms perpetuate chronic pain [6,7] but none of these mechanisms adequately explain how to cure chronic pain. Opioids and other drugs are used to manage pain and chronic pain [6].

Patients seek these drugs that cause 100,000 or more deaths every year [8]. In the US, there is an opioid crisis and a non-steroidal anti-inflammatory drugs (NSAIDs) crisis due to excessive use of these dangerous oral drugs. Many patients believe that pain comes from the brain. Therefore, pain must be treated with drugs that penetrate into the brain.

Pain is felt in the skin due to the abundance of pain receptors in the skin, such as transient receptor potential cation (TRP) channels, prostaglandin receptors, histamine receptors, muscarinic receptors and many more [9,10].

The safest and most effective treatment for pain is to apply a medicine to the skin [9,10]. Topical medicines are safer than oral medicines and could save the lives of thousands of pain patients. The dilemma with topical pain medicines is to find potent medicines that can treat even severe pain, yet do not have toxicity problems.

Sagebrush liniment contains cineole, which is more powerful than morphine [11] and is used by topical application to treat broken bones, gunshot wounds, cancer pain and other severe pain [11,12]. Sagebrush liniment can also provide long-term relief from chronic pain. Several topical pain medicines are commercially available with more under development [13].

Chronic pain may be caused by a pain chemokine cycle that involves the release of chemokines in the skin by damaged or stressed cells [8,14].

Chemokines attract macrophages to the skin and induce cyclooxygenase-2 (COX-2) in macrophages, which release prostaglandins.

Prostaglandins cause pain by binding to prostaglandin receptors and prolong pain by inducing the phosphorylation of TRP channels [11]. This activates TRP channels and makes them more sensitive to stimuli. Phosphorylation of Na+ channels is also induced by prostaglandins [15], which may make them more sensitive to stimuli. Both TRP and Na+ channels, as well as many other skin receptors, are important in pain [10].

Prostaglandins also enhance the release of chemokines in the skin. Chemokines cause the activation of TRP channels to increase and prolong pain. Macrophages secrete IL-23 and IL-1β that induce the synthesis of IL-17 by skin resident T cells. IL-17 induces chemokine release in the skin.

Chemokines stimulate the release of IL-17. This establishes a self-perpetuating pain chemokine cycle in which prostaglandins, chemokines and IL-17 cause, enhance and prolong pain. The skin produces pain during chronic pain. Curing chronic pain involves inhibiting TRP channels, chemokine production, IL-17 production, COX-2 expression and perhaps other mechanisms [8,16].

The brain may be involved in the pain chemokine cycle (Figure 1). The activation of afferent sensory neurons in the skin leads to chemokine release in the brain [17]. Chemokines in the brain modulate the actions of other neurons, including descending and peripheral neurons, which may result in chemokine release in the skin [17]. These chemokines can be released in sites distant from the site of application of medicine to the skin.

The Medicine

Black sage sun tea is made by collecting fresh branches and leaves of S. mellifera, black sage. This plant material, 115 g, is put into 2 L of fresh or sea water.

This is put under the sun for 6–8 h to make a sun tea.

The plant material is removed from the preparation prior to use. A patient soaks both feet in the sun tea for 20 min.

The sun tea is then stored in a refrigerator until the next day. The patient uses the same sun tea as a foot soak for 20 min.

This is repeated daily for a total of about seven treatments. Patients were also advised to perform 20 min or so of mild exercise daily, such as walking. All patients were asked to read and sign an informed consent form that guarantees the privacy of their information. The sagebrush liniment is described in other publications [11,12].

None of the preparations described in this work are commercially available. The name of the ethics committee: University of Southern California Institutional Review Board, ethical approval code: Application HS-19-00042.

More information: The Arthritis Foundation has more on treating osteoarthritis.


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