Chronic pain: Medication decisions

Chronic pain can limit your quality of life and lead to additional, serious health problems. Finding effective treatment is important — as is balancing pain relief with your safety.

By Mayo Clinic Staff

Chronic pain is a serious health condition. Like any long-term health problem, the condition often leads to complications beyond your physical symptoms, such as new or worsened depression, anxiety, and difficulty sleeping. Chronic pain can make it more difficult to keep up at work, manage tasks at home and attend social gatherings, leading to problems in your relationships and financial instability. Some research suggests that the more severe your pain, the more serious these problems.

The serious consequences of chronic pain make finding effective treatment a critical goal. Unfortunately, this process is complex and uniquely personal. What works for one person’s chronic low back pain may not offer any relief for your osteoarthritis, for a number of reasons. Your diagnosis, biology and personal history all play a role, and finding pain therapies that bring you adequate relief can be a lengthy effort.

Working in partnership with your doctor, however, you can identify treatments that allow you to live an enjoyable, fulfilling life. The approach you choose should include more than just medication, but painkillers are likely to play a role. Learn about the risks and benefits of common pain medications so that you can make safe choices as you seek your solution.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs are most effective for mild to moderate pain that’s accompanied by swelling and inflammation. These drugs are commonly used for arthritis and pain resulting from muscle sprains, strains, back and neck injuries, or menstrual cramps.

  • Generic (brand) names. Ibuprofen (Advil, Motrin IB, others); naproxen sodium (Aleve); others
  • How they work. NSAIDs work by inhibiting certain enzymes in your body, called cyclooxygenase, that are released during tissue damage. By blocking the different types of cyclooxygenase (COX) — including COX-1 and COX-2 — NSAIDs can help reduce pain and inflammation that result from an injury.
  • Benefits and risks. When taken as directed, NSAIDs are generally safe. But if you take more than the recommended dosage — and sometimes even just the recommended dosage — NSAIDs may cause nausea, stomach pain, stomach bleeding or ulcers. Large doses of NSAIDs can also lead to kidney problems, fluid retention and high blood pressure. Risk of these conditions increases with age and in the presence of other health problems, including diabetes, a history of stomach ulcers or reflux, and kidney disease.
  • Bottom line. If you regularly take NSAIDs, talk to your doctor so that he or she can monitor you for possible side effects. Bear in mind that NSAIDs also have a ceiling effect — a limit as to how much pain they can control. This means that beyond a certain dosage, they don’t provide additional benefit. Exceeding the recommended dose may not relieve your pain and may increase your risk of serious side effects.

Acetaminophen

Acetaminophen is usually recommended as a first line treatment for mild to moderate pain, such as from a skin injury, headache or musculoskeletal condition. Acetaminophen is often prescribed to help manage osteoarthritis and back pain. It may also be combined with opioids to reduce the amount of opioid needed.

  • Generic (brand) names. Acetaminophen (Tylenol, others)
  • How it works. Doctors don’t know exactly how acetaminophen works. Some scientists believe there may be a third type of cyclooxygenase, COX-3, that acetaminophen blocks. Acetaminophen doesn’t affect the other two cyclooxygenase enzymes, and it doesn’t target inflammation — only pain. It may be less effective than NSAIDs.
  • Benefits and risks. Acetaminophen is generally considered safer than other nonopioid pain relievers because it doesn’t cause side effects such as stomach pain and bleeding. However, taking more than the recommended dose — or taking acetaminophen with alcohol — increases your risk of kidney damage and liver failure over time.
  • Bottom line. Acetaminophen is generally a safe option to try first for many types of pain, including chronic pain. Ask your doctor for guidance about other medications to avoid while taking acetaminophen. Acetaminophen is not as effective as NSAIDs for the treatment of knee and hip pain related to osteoarthritis.

COX-2 inhibitors

These medications were developed with the aim of reducing common side effects associated with traditional NSAIDs. COX-2 inhibitors are commonly used for arthritis and pain resulting from muscle sprains, strains, back and neck injuries, or menstrual cramps. They are as effective as NSAIDs and may be the right choice if you need long-term pain control without increased risk of stomach damage.

  • Generic (brand) names. Celecoxib (Celebrex, Consensi)
  • How they work. COX-2 inhibitors, another type of NSAID, work slightly differently from traditional NSAIDs. A COX-2 inhibitor blocks only the COX-2 enzyme — the one that’s more likely to cause pain and inflammation.
  • Benefits and risks. COX-1 enzymes help protect the lining of your stomach. NSAIDs, which block COX-1, can cause side effects such as stomach pain and bleeding. COX-2 inhibitors, on the other hand, help keep the stomach protected by acting only on COX-2 enzymes, allowing COX-1 to function normally.

    Although the risk of stomach bleeding is generally lower if you take a COX-2 inhibitor instead of an NSAID, bleeding can still occur, especially at higher doses. These medications may cause side effects, such as headaches and dizziness, and can lead to kidney problems, fluid retention and high blood pressure.

  • Bottom line. Older adults may be at higher risk of common COX-2 side effects compared with younger adults. If these medications help you manage chronic pain, aim to take the lowest effective dose for the shortest time possible, and follow up closely with your doctor.

Antidepressants and anti-seizure medications

Some medications commonly prescribed to manage depression and prevent epileptic seizures have also been found to help relieve chronic pain, including back pain, fibromyalgia and diabetes-related nerve pain (diabetic neuropathy). Because chronic pain often worsens depression, antidepressants may doubly benefit pain and mood symptoms.

  • Generic (brand) names. Tricyclic antidepressants used in the treatment of chronic pain include amitriptyline and nortriptyline (Pamelor).

    Serotonin and norepinephrine reuptake inhibitors (SNRIs) that may be prescribed to relieve chronic pain include duloxetine (Cymbalta), venlafaxine (Effexor XR, Pristiq) and milnacipran (Fetzima, Savella).

    Anti-seizure medications that are widely used for the treatment of chronic nerve pain, including postherpetic neuralgia and diabetic neuropathy, include gabapentin (Gralise, Neurontin, Horizant) and pregabalin (Lyrica).

  • How they work. These drugs may take several weeks before you notice the effects. Anti-seizure medications quiet pain signals from your nerve cells, and may be helpful primarily for stabbing or shooting pain resulting from nerve damage.
  • Benefits and risks. Side effects of these medications are generally mild, but may include nausea, dizziness or drowsiness. As a group, antidepressants and anti-seizure medications may, rarely, worsen depression or cause suicidal thoughts. If you notice changes in your thinking patterns or mood while taking these medications, talk with your doctor right away.
  • Bottom line. To reduce the risk of side effects, your doctor may start you out on a small amount of these medications and gradually increase the dose. Tricyclic antidepressants can make you drowsy, so your doctor likely will recommend that you take these medications before bedtime.

Opioids

Opioid medications are synthetic cousins of opium and the drugs derived from opium, such as heroin and morphine. These drugs are often prescribed for acute pain that stems from traumatic injury, such as surgery or a broken bone. Opioids currently cause the most prescription drug-related overdose deaths in the United States — and that rate is still rising. Because the risks are so great, opioids are used at the lowest dose possible, usually for just a few days.

  • Generic (brand) names. Hydrocodone (Hysingla ER, Zohydro ER); hydrocodone-acetaminophen (Norco, Anexsia 5/325, others); fentanyl (Actiq, Duragesic-100, others), oxycodone (OxyContin, Roxicodone, others); oxycodone-acetaminophen (Percocet, Roxicet, others); others
  • How they work. Opioids, just like real opium, mimic the natural pain-relieving chemicals — called endorphins — produced by your brain. These drugs “turn down the volume” on the pain signals your nervous system sends through your body. They also muffle other nerve cell functions, such as your breathing, heart rate and level of alertness.
  • Benefits and risks. Research shows that over time, your body adapts to these medications, and they bring less and less pain relief. This phenomenon, known as tolerance, means that you need more of the same medication to achieve the same degree of pain relief. Long-term use of opioids may lead to dependence on these medications and, eventually, addiction.

    The longer you use opioids, the greater your risk of becoming addicted. However, even using opioids to manage pain for more than a few days increases your risk. Researchers at Mayo Clinic have found that the odds you’ll still be on opioids a year after starting a short course increase after only five days on opioids.

  • Bottom line. Opioids are a last resort for chronic pain management. They may be the right choice for long-term pain related to cancer and its treatments or, in rare cases, noncancer pain that hasn’t responded to any other medications. Because the risks are so serious, you’ll need careful and frequent follow-ups with your doctor if you use opioids long term.

While there isn’t a cure for chronic pain, many effective pain medications are available to help you function effectively and enjoy your days. As you try different drugs, alone or in combination, work with your doctor to target the simplest long-term solution possible. Keep your medication risks to a minimum to improve your odds of many good days, for many years to come.

Pain medications at a glance

Medication type How they work First line option for Benefits Risks
NSAIDs Block COX-1 and COX-2 enzymes involved in pain and inflammation
  • Mild to moderate pain accompanied by swelling and inflammation
  • Arthritis pain and pain resulting from muscle sprains and strains, back and neck injuries, overuse injuries, and menstrual cramps
When taken as directed, generally safe for short- and long-term use
  • May cause nausea, stomach pain, stomach bleeding or ulcers
  • When taken in high doses, can lead to kidney problems, fluid retention and high blood pressure
  • Increased risk of side effects for older adults
Acetaminophen Unknown, but possibly blocks a COX-3 enzyme Mild to moderate pain Acetaminophen Unknown, but possibly blocks a COX-3 enzyme
COX-2 inhibitors Block COX-2 enzymes Rheumatoid arthritis, osteoarthritis, menstrual cramps and injury-related pain As effective as NSAIDs without damaging stomach lining at regular doses
  • Respiratory infection, headache and dizziness
  • When taken in high doses, can lead to stomach bleeding, kidney
    problems, fluid retention and high blood pressure
  • Increased risk of side effects for older adults
Antidepressants Interfere with certain chemical processes that cause you to feel pain
  • Neuropathic pain, chronic daily headaches, fibromyalgia
  • May be considered for chronic low back pain
  • Can be in doses much lower than what is currently used to treat depression
  • Side effects generally mild
  • Drowsiness possible with tricyclic antidepressants
  • Can take several weeks to produce desired effects
  • May worsen depression and cause suicidal thoughts in a small number of people
Anti-seizure medications Quiet pain signals from damaged nerves Postherpetic neuralgia, diabetic neuropathy, fibromyalgia Side effects generally mild
  • May cause dizziness, drowsiness, nausea, reduced coordination and weight changes
  • May worsen depression and cause suicidal thoughts in a small number of people
Opioids Activate feel-good neurotransmitters, called endorphins, that suppress pain and boost a sense of well-being
  • Acute pain, such as pain that follows surgery or a bone fracture
  • Typically prescribed for maximum of three days
Powerful relief during short periods of severe pain
  • Tolerance, dependence, misuse, addiction and overdose, which may begin to develop within one week of use
  • Responsible for the majority of accidental overdose deaths in the U.S.

Vivien Williams: 50 million. That’s how many people in the U.S. suffer from chronic pain. Many turn to opioid painkillers for relief.

Mike Hooten, M.D. (Anesthesiology, Mayo Clinic): The evidence is not all that clear about the efficacy of those drugs long-term for chronic pain.

Vivien Williams: Mayo Clinic pain management specialist Dr. Mike Hooten says what is clear about these painkillers is the risk associated with taking them.

Mike Hooten, M.D.: The problems of addiction, but a related problem of accidental overdose deaths.

Vivien Williams: Morphine, oxycodone and hydrocodone are commonly prescribed opioids. Dr. Hooten says they are very effective when used short-term for pain, for example, after a surgery. For long-term use …

Mike Hooten, M.D.: There are a small group of studies that may show some benefit in in certain highly select groups of patients.

Vivien Williams: But, for many cases of chronic pain, Dr. Hooten says non-opioid pain relievers combined with other therapies, such as stress management can help people manage pain and maintain a high quality of life. For the Mayo Clinic News Network, I’m Vivien Williams.

Vivien Williams: This can be a common scenario: raiding the medicine cabinet for leftover painkillers after a sprained ankle or toothache. There’s nothing wrong with popping an occasional opioid, right?

Mike Hooten, M.D. (Anesthesiology, Mayo Clinic): They are dangerous. They could have adverse effects that the individual doesn’t even know about.

Vivien Williams: Including addiction or accidental overdose. So, when is it appropriate to take opioids?

Mike Hooten, M.D.: After an operation, opioids are highly effective.

Vivien Williams: Dr. Mike Hooten is a pain management specialist at Mayo Clinic.

Mike Hooten, M.D: After trauma, for example, severe trauma, opioids would be appropriate.

Vivien Williams: Dr. Hooten says opioids are also beneficial during procedures, such as colonoscopies. Problems happen when people take them without a prescription or for too long.

Mike Hooten, M.D.: If they are predisposed to develop addiction, either neurobiologically or from a behavioral perspective, then all of a sudden we are selecting the individuals who may go on to have long-term problems.

Vivien Williams: If you have pain, talk to your health care provider. For the Mayo Clinic News Network, I’m Vivien Williams.