Treatment of Pain

ByJames C. Watson, MD, Mayo Clinic College of Medicine and Science
Reviewed/Revised Jun 2022 | Modified Aug 2023
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Pain relievers (analgesics) are the main drugs used to treat pain. Doctors choose a pain reliever based on the type and duration of pain and on the drug's likely benefits and risks. Most pain relievers are effective for nociceptive pain (due to injury) but are less effective for neuropathic pain (due to damage or dysfunction of the nerves, spinal cord, or brain). For many types of pain, especially chronic pain, nondrug treatments are also important.

In some cases, treating the underlying disorder eliminates or minimizes the pain. For example, setting a broken bone in a cast or giving antibiotics for an infected joint helps reduce pain. However, even if the underlying disorder can be treated, pain relievers may still be needed to quickly manage the pain.

(See also Overview of Pain.)

Did You Know...

  • Pain is often treated with a combination of drugs and nondrug treatments.

Drugs used to relieve pain fall into three categories:

  • Nonopioid

  • Opioid (narcotic)

  • Adjuvant (drugs that are usually used to treat other problems such as seizures or depression but that can also relieve pain)

Nonopioid Pain Relievers

A variety of nonopioid pain relievers are available. They are often effective for mild to moderate pain and sometimes for severe pain. These drugs are often preferred for treating pain. People do not become physically dependent on these drugs or tolerant of their pain-relieving effects.

OTC pain relievers are reasonably safe to take for short periods of time. People should follow the instructions on the label for the maximum dose, frequency, and length of time the drug should be taken. A doctor should be consulted if symptoms worsen or do not go away.

Nonsteroidal Anti-Inflammatory Drugs

Diclofenac is also available as a cream.

Although widely used, NSAIDs can have side effects, sometimes serious ones.

  • Problems in the digestive tract: All NSAIDs tend to irritate the stomach’s lining and cause digestive upset (such as heartburn, indigestion, nausea, bloating, diarrhea, and stomach pain), peptic ulcers, and bleeding in the digestive tract (gastrointestinal bleedingProton pump inhibitorshistamine-2 (H2) blockers

  • Bleeding problems: All NSAIDs interfere with the clotting tendency of platelets (cell-like particles in the blood that help stop bleeding when blood vessels are injured). Consequently, NSAIDs increase the risk of bleeding, especially in the digestive tract if they irritate the stomach’s lining. Coxibs are less likely to cause bleeding than other NSAIDs.

  • Fluid retention or kidney problems: NSAIDs sometimes cause fluid retention and swelling. Regular use of NSAIDs may also increase the risk of developing a kidney disorder, sometimes resulting in kidney failure (a disorder called analgesic nephropathy).

  • Increased risk of heart and blood vessel disorders: Studies suggest that with all NSAIDs except aspirin, the risk of heart attack, stroke, and blood clots in the legs may be increased. The risk appears to be higher with higher doses and longer use of the drug. The risk is also higher with some NSAIDs than with others. These problems may be related directly to the drug’s effect on clotting or indirectly to a small but persistent increase in blood pressure caused by the drug.

People who take NSAIDs for a long time are more likely to have these problems. Such people need to have regular appointments with their doctor to check for high blood pressure, kidney failure, and ulcers or bleeding in the digestive tract and to evaluate their risk of heart disease and stroke. Taking NSAIDs for a short time is unlikely to cause serious problems.

The risk of side effects may be increased for some groups of people, such as the following:

  • Older people

  • People who drink alcoholic beverages regularly

  • People with coronary artery disease, other heart and blood vessel (cardiovascular) disorders, or risk factors for these disorders

Older people and people who have heart failure, high blood pressure, or a kidney or liver disorder require a doctor’s supervision when they take NSAIDs. Some prescription heart and blood pressure drugs may not work as well when taken with NSAIDs.

Did You Know...

  • If taken for a long time, NSAIDs, including those available without a prescription, can have serious side effects.

NSAIDs vary in how quickly they work and how long they relieve pain. Although NSAIDs are about equally effective, people respond to them differently. One person may find a particular drug to be more effective or to have fewer side effects than another.

Aspirin

Aspirin is taken by mouth and provides 4 to 6 hours of moderate pain relief.

Because aspirin can irritate the stomach, it may be combined with an antacid (called buffered) or coated so that it passes quickly through the stomach and dissolves when it reaches the small intestine (called enteric coated). These products are intended to reduce stomach irritation. However, buffered or enteric-coated aspirin can still irritate the stomach because aspirin also reduces the production of substances that help protect the stomach’s lining. These substances are called prostaglandins.

Aspirin increases the risk of bleeding throughout the body because it makes platelets less able to function. Platelets are cell fragments in the blood that help blood clot. Anyone who has an increased tendency to bleed (a bleeding disorder such as hemophilia) or uncontrolled high blood pressure should not take aspirin except under a doctor’s supervision. People who take aspirinaspirin should not be taken in the week before scheduled surgery.

Aspirin can aggravate asthma. People with nasal polyps are likely to develop wheezing if they take aspirin. A few people, who are sensitive (allergic) to aspirin, may have a severe allergic reaction (anaphylaxis), leading to a rash, itching, severe breathing problems, or shock. Such a reaction requires immediate medical attention.

In very high doses, aspirin can have serious side effects such as abnormal breathing, fever, or confusion. One of the first signs of an overdose may be noise in the ears (tinnitus).

Most children and teenagers should not take aspirin because they could develop Reye syndrome if they have or have just gotten over influenza or chickenpox. Although rare, Reye syndrome can have serious consequences, including death.

Topical NSAIDs

osteoarthritis and help improve movement. Diclofenac is also available as a patch, which can be used to relieve acute pain due to minor sprains, strains, and bruises.

Ibuprofen, ketoprofen, and naproxen

naproxen than with other NSAIDs. Thus, naproxen may be a better choice when people with a high risk of these disorders require NSAIDs.

Although ibuprofen, ketoprofen, and naproxen generally interfere with blood clotting less than aspirin

People who are allergic to aspirin may also be allergic to ibuprofen, ketoprofen, and naproxen. If a rash, itching, breathing problems, or shock develops, medical attention is required immediately.

Coxibs (COX-2 inhibitors)

  • COX-1, which is involved in the production of prostaglandins that protect the stomach and play a crucial role in blood clotting

  • COX-2, which is involved in the production of prostaglandins that promote inflammation

Coxibs tend to block mainly COX-2 enzymes. Thus, coxibs are as effective as other NSAIDs in the treatment of pain and inflammation. But coxibs are less likely to damage the stomach and to cause nausea, bloating, heartburn, bleeding, and peptic ulcers. They are also less likely to interfere with clotting than are other NSAIDs.

Because of these differences, coxibs may be useful for people who cannot tolerate other NSAIDs and for people who are at high risk of certain complications (such as gastrointestinal bleeding) from use of other NSAIDs. Such people include the following:

  • Older people

  • People taking anticoagulants

  • People with a history of ulcers

  • People taking an analgesic for a long time

However, coxibs, like other NSAIDs, appear to increase the risk of heart attack, stroke, and blood clots in the legs. As a result, before people with certain conditions are given a coxib, they are told about the risk and the need to be closely monitored. These conditions include

  • Cardiovascular disorders (such as coronary artery disease)

  • Strokes

  • Risk factors for these disorders

Coxibs, like other NSAIDs, are not appropriate for people who have heart failure or who are at increased risk of heart failure (such as those who have had a heart attack).

How Nonsteroidal Anti-Inflammatory Drugs Work

Nonsteroidal anti-inflammatory drugs (NSAIDs) work in two ways:

  • They reduce the sensation of pain.

  • At higher doses, they reduce the inflammation that often accompanies and worsens pain.

NSAIDs have these effects because they reduce the production of hormone-like substances called prostaglandins. Different prostaglandins have different functions, such as making nerve cells more likely to respond to pain signals and causing blood vessels to widen (dilate).

Most NSAIDs reduce prostaglandin production by blocking both cyclooxygenase (COX) enzymes (COX-1 and COX-2), which are crucial to the formation of prostaglandins. One type of NSAID, the coxibs (COX-2 inhibitors), tend to block mainly COX-2 enzymes.

Only COX-2 enzymes are involved in the production of prostaglandins that promote inflammation and the resulting pain. These prostaglandins are released in response to an injury—burn, break, sprain, strain, or invasion by a microorganism. The result is inflammation, which is a protective response: The blood supply to the injured area increases, bringing in fluids and white blood cells to wall off the damaged tissue and remove any invading microorganisms.

Prostaglandins that are formed through the action of COX-1 enzymes help protect the digestive tract from stomach acid and play a crucial role in blood clotting. Because most NSAIDs block COX-1 enzymes and thus reduce the production of these prostaglandins, they may irritate the stomach’s lining. Such irritation can cause digestive upset, peptic ulcers, and bleeding in the digestive tract.

Because coxibs block mainly COX-2 enzymes, they are less likely to cause problems due to stomach irritation. However, coxibs block some COX-1 enzymes, so even coxibs may slightly increase the risk of these problems.

Table

Acetaminophen

But unlike NSAIDs, acetaminophen has the following characteristics:

  • Has virtually no useful anti-inflammatory activity

  • Does not affect the blood’s ability to clot

  • Has almost no adverse effects on the stomach

How acetaminophen works is not clearly understood.

Acetaminophen is taken by mouth or a suppository inserted into the rectum, and its effects generally last 4 to 6 hours.

Acetaminophen appears to be a very safe drug. However, high doses can lead to liver damage, which may be irreversible (see ). People with a liver disorder should use lower doses than those usually prescribed. Whether lower doses taken for a long time can harm the liver is less certain. People who regularly consume large amounts of alcohol are probably at highest risk of liver damage from overuse of acetaminophen. People who are taking acetaminophen and stop eating because of a bad cold, influenza, or another reason may be more vulnerable to liver damage.

Opioid Pain Relievers

Opioid pain relievers (analgesics)—sometimes called narcotics—are effective for many different types of pain. Usually, they are the strongest pain relievers.

Opioids are often prescribed for a few days to treat severe pain that is likely to lessen quickly (such as pain due to injury or after surgery). Doctors usually switch people to nonopioid pain relievers as soon as possible because opioids may have side effects and there is a risk of misuse or addiction. Opioids are not usually recommended to treat people with chronic pain.

Doctors sometimes prescribe opioids for longer periods of time for people who have severe pain due to cancer or a terminal illness, especially as part of care at the end of life, including hospice care. In these situations, side effects can usually be prevented or managed, and misuse or addiction is less of a concern.

Before prescribing opioids for any type of chronic pain, doctors consider

  • What the usual treatment approach is

  • Whether other treatments could be used

  • Whether the person has a high risk of side effects from an opioid

  • Whether the person is at risk of misuse or abuse of an opioid drug or is likely to use the drugs for other purposes (for example, to sell them)

Doctors may refer people to a pain specialist or a mental health care practitioner who has expertise in substance misuse if the risk of having a problem is high. For example, people who have had an addiction usually need such a referral.

When opioids are prescribed for chronic pain, doctors explain the nature of the person's disorder (if known) and the risks and benefits of other possible treatments, including nonopioid drugs and no treatment. Doctors ask people about their goals and expectations. They usually give the person written information that describes the risks of taking opioids. After people discuss this information with their doctor and understand it, they are asked to sign an informed consent document.

When doctors prescribe an opioid for chronic pain, they explain the risks and side effects of opioids. People are advised

  • Not to drink alcohol or take antianxiety drugs or sleep aids when taking the opioid

  • To take the recommended dose at the recommended times and not to change the dose

  • To store the opioid in a safe, secure place

  • Not to share the opioid with anyone

  • To contact their doctor if the drug makes them drowsy or they have any other side effects (such as confusion, constipation, or nausea)

  • To dispose of unused pills as directed

If an opioid is prescribed, doctors have usual practices to ensure the person's safety. Doctors typically ask the person to get opioid prescriptions only from one doctor and fill prescriptions at the same pharmacy every time. They see the person frequently for follow-up visits and monitor the use of the drug to make sure it is safe and effective. For example, doctors may periodically test the person's urine to determine whether the drug is being taken correctly. They also ask the person to sign an agreement that specifies conditions required for opioid use, including any monitoring that may be needed. To avoid misuse by others, the person should keep opioids in a safe place and dispose of any unused drugs by returning them to the pharmacy.

Adjuvant Analgesics

Adjuvant analgesics are drugs that are usually used to treat other disorders, but can also relieve pain.

Adjuvant analgesics are thought to work by changing the way nerves process pain.

An adjuvant analgesic is the first and only drug used to treat pain due to nerve damage (neuropathic pain) and conditions such as fibromyalgia.

The adjuvant analgesics most commonly used for pain are

Nondrug Pain Treatments

In addition to drugs, many other treatments can help relieve pain.

Applying cold or warm compresses directly to a painful area often helps (see Treatment of Pain and Inflammation).

Neuromodulation methods use electric stimulation to change how nerves process pain. Techniques include the following:

  • Transcutaneous electrical nerve stimulation (TENS)

  • Spinal cord stimulation

  • Peripheral nerve stimulation

Physical or occupational therapy may be used to relieve chronic pain and help people function better. Sometimes doing exercises or increasing activity level helps. For example, walking regularly can help relieve lower back pain more effectively than resting in bed.

Complementary and integrative medicine may be used to treat chronic pain. For example, doctors may suggest one or more of the following:

Acupuncture involves inserting tiny needles into specific areas of the body. How acupuncture works is poorly understood, and some experts still doubt the technique’s effectiveness. Some people find substantial relief with acupuncture, at least for a time.

Biofeedback and other cognitive techniques (such as relaxation training, hypnosis, and distraction techniques) can help people control, reduce, or cope with pain by changing the way they focus their attention. In one distraction technique, people may learn to visualize themselves in a calm, comforting place (such as in a hammock or on a beach) when they feel pain.

Cognitive behavioral therapy may reduce pain and pain-related disability and help people cope. This type of therapy includes counseling to help people focus on coping with the pain, rather than on its effects and limitations. It may include counseling to help people and their family work together to manage pain.

The importance of psychologic support for people in pain should not be underestimated. Friends and family members should be aware that people in pain suffer, need support, and may develop depression and anxiety, which may require psychologic counseling.

Drugs Mentioned In This Article
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