Chronic pain: Medication decisions

Chronic pain can limit quality of life and lead to serious health problems. Finding 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, it can lead to complications beyond physical symptoms such as depression, anxiety and trouble sleeping.

Chronic pain is pain that's long-lasting. It can lead to problems with relationships and finances. It makes it harder to keep up with work, tasks at home and social gatherings. Some research suggests that the more severe the pain, the more serious these problems.

For these reasons, finding effective treatment for chronic pain is important. But the process is complex and personal. What works for one person's chronic low back pain may not bring relief for another person's osteoarthritis.

There are a number of reasons for this. The cause of the chronic pain combined with a person's biology and history all play a role in pain management. And finding pain therapies that bring you relief can take time.

But by working with your health care providers, you can find treatments that allow you to function better and live a more enjoyable, fulfilling life. The approach you choose should include more than medication. But medications may likely play a role.

Learn about the risks and benefits of common pain medications so that you can make safe choices as you look for a solution to chronic pain.

Nonsteroidal anti-inflammatory drugs, known as NSAIDs

NSAIDs are most effective for mild to moderate pain that occurs with swelling and inflammation. These medications 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 stopping certain enzymes in your body from being released due to tissue damage. These enzymes are called cyclooxygenase (COX). NSAIDs block different types of COX, including COX-1 and COX-2. As a result, NSAIDs help reduce pain and swelling 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, NSAIDs may cause nausea, stomach pain, stomach bleeding or ulcers. Sometimes this can happen even when you take the recommended dosage.

    Large doses of NSAIDs also can lead to kidney problems, fluid retention and high blood pressure. Risks increase with age or if you have other health problems such as diabetes, a history of stomach ulcers or reflux, and kidney disease.

  • Bottom line. If you regularly take NSAIDs, talk to your health care provider. Your provider 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. Taking more than the recommended dose may not relieve the pain and may increase the risk of serious side effects.


Acetaminophen is usually recommended as a first line treatment for mild to moderate pain. It might be taken for pain due to a skin injury, headache, or conditions that affect the muscles and bones. Acetaminophen is often prescribed to help manage osteoarthritis and back pain. It also may be combined with opioids to reduce the amount of opioid needed.

  • Generic (brand) names. Acetaminophen (Tylenol, others).
  • How it works. Acetaminophen is thought to block the production of prostaglandins in the central nervous system. Prostaglandins are hormonelike substances that are involved in pain and inflammation. Unlike NSAIDs, acetaminophen doesn't target inflammation at the site of injury — only pain.
  • Benefits and risks. Acetaminophen is generally considered safer than other pain relievers. 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 the 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 health care provider 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

COX-2 inhibitors are another type of NSAID. These medications were developed with the aim of reducing the common side effects of 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 with less risk of stomach damage.

  • Generic (brand) names. Celecoxib (Celebrex).
  • How they work. COX-2 inhibitors work in a slightly different way than traditional NSAIDs. COX-2 inhibitors block only the COX-2 enzyme — the one that's more likely to cause pain and inflammation.
  • Benefits and risks. By acting only on COX-2 enzymes, they allow COX-1 enzymes to continue to function. COX-1 enzymes protect the lining of the stomach. NSAIDs, on the other hand, block COX-1 and can cause side effects such as thinning of the stomach lining. This can lead to ulcers and bleeding.

    The risk of stomach bleeding tends to be lower if you take a COX-2 inhibitor, but bleeding can still occur. This is true especially at higher doses. These medications also may cause headaches and dizziness. And they 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. Follow up closely with your health care provider.

Antidepressants and anti-seizure medications

Some medications commonly prescribed to manage depression and prevent epileptic seizures have been found to help relieve chronic pain. This is true especially for chronic nerve pain. They may help relieve back pain, fibromyalgia and diabetes-related nerve pain, known as diabetic neuropathy. Because chronic pain often worsens depression, antidepressants may offer the extra benefit of treating mood symptoms.

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

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

    Anti-seizure medications used to treat chronic nerve pain include gabapentin (Gralise, Neurontin, Horizant) and pregabalin (Lyrica). These medications treat the burning pain of shingles, known as postherpetic neuralgia. And they treat pain related to nerve damage in the legs and feet due to diabetes, known as diabetic neuropathy.

  • How they work. These medications may take several weeks before you notice the effects. Anti-seizure medications quiet pain signals from nerve cells. They may be helpful for stabbing or shooting pain 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 health care provider right away.
  • Bottom line. To reduce the risk of side effects, your provider may start you on a small amount of these medications and gradually increase the dose. When it's time to stop taking them, work with your health care provider to gradually wean off the medication. These type of medications can make you drowsy. Your health care provider likely will recommend that you take these medications before bedtime.


Opioid medications are synthetic cousins of opium and the drugs derived from opium such as heroin and morphine. These medications are typically prescribed for pain that's new, known as acute pain. Acute pain can stem from an injury, such as surgery or a broken bone.

Opioids currently cause the most prescription medication-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); hydrocodone-acetaminophen; fentanyl (Actiq, Fentora); oxycodone (OxyContin, Roxicodone, others); oxycodone-acetaminophen (Percocet); others.
  • How they work. Opioids, like real opium, mimic the natural pain-relieving chemicals produced by your brain. These chemicals are called endorphins. The medications turn down the volume on the pain signals your nervous system sends through your body. They also muffle other nerve cell functions, such as 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 is known as tolerance. It means that you need more of the medication to achieve the same degree of pain relief. Long-term use of opioids may lead to dependence on the medications and, eventually, addiction.

    The longer you use opioids, the greater the risk of becoming addicted. But even using opioids to manage pain for more than a few days increases your risk. Researchers have found that the odds of being on opioids a year after starting a short course increases after only five days on the medication.

  • 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. In rare cases, opioids may be used for 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 health care provider 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 medications, alone or in combination, work with your health care provider to find 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
  • Available without a prescription
  • 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 Thought to block prostaglandin production in the central nervous system Mild to moderate pain Available without a prescription When more than the recommended dose is taken or when taken with alcohol, increased risk of kidney damage and liver failure over time
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
  • Headache and dizziness
  • When taken in high doses, can lead to stomach bleeding, kidney problems, fluid retention, high blood pressure, heart attack and stroke
  • Increased risk of side effects for older adults
Antidepressants Interfere with certain chemical processes that cause you to feel pain
  • Neuropathic pain, chronic 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, depending on the type of antidepressant
  • 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
  • Blocks opioid receptors, which stop the release of chemicals that cause pain
  • Can stop the transmission of pain signals
  • Acute pain, such as pain that follows surgery or a bone fracture
  • Typically prescribed for a few days or less
Powerful relief during short periods of severe pain
  • Feeling drowsy, nausea, itchiness, constipation
  • 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.

Mayo Clinic Minute: Avoid opioids for chronic pain

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.

Mayo Clinic Minute: When are opioids OK to take?

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.

Feb. 08, 2023