Adjuvant analgesics are drugs that are usually used to treat other disorders, but can also relieve pain.
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...
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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...
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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:
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. |
Nonsteroidal Anti-Inflammatory Drugs
Type | Drug |
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Salicylates | Choline magnesium trisalicylate |
Coxibs | |
Others | Meclofenamate |
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.
Side effects of opioids
Opioids have many side effects. Side effects are more likely to occur in people with certain disorders: kidney failure, a liver disorder, chronic obstructive pulmonary disease (COPD), untreated sleep apnea, dementia, or another brain disorder.
The following commonly occur when opioids are used:
Drowsiness
Mental fuzziness or confusion
Nausea and vomiting
Constipation
Less common side effects of opioids include
Retention of urine
Involuntary contraction of muscles (called myoclonus)
Itching
A dangerous slowing of breathing
Death
Drowsiness
Confusion can also result from taking opioids, especially if people are older. Opioids increase the risk of falls in older people.
Nausea
The itching
Constipation often develops, especially in older people. Stimulant laxativesOsmotic agents
For most people, nausea and itching disappear or decrease within a few days. But constipation and retention of urine usually decrease much more slowly, if at all.
Serious side effects can occur when people take too much of an opioid. These side effects include a dangerous slowing of breathing (respiratory depression), coma, and even death. The following adds to the risk of developing respiratory depression and of dying from respiratory arrest:
Having certain conditions (such as liver, kidney, respiratory, or mental health disorders)
Having a substance use disorder
Taking other drugs that cause drowsiness (such as benzodiazepines)
Drinking alcohol
naloxone or spray it into the person's nose. Doctors or pharmacists usually teach the person taking the opioid and family members or caregivers how to administer naloxone.
Tolerance occurs in some people who take opioids repeatedly over time. They need higher doses because their body adapts to and thus responds less well to the drug. However, for most people, the same opioid dose remains effective for a long time. Often, the need for a higher dose means that the disorder is worsening, not that tolerance is developing.
Physical dependence usually develops in people who take opioids for a long time. That is, they experience withdrawal symptoms if the drug is stopped. Withdrawal symptoms include chills, abdominal cramping, diarrhea, trouble sleeping, and a jittery feeling. When opioids are stopped after long-term use, doctors reduce the dose gradually over a period of time to minimize the development of such symptoms.
Physical dependence is not the same as opioid use disorder (addiction). Dependence is characterized by a craving for the drug and compulsive, uncontrolled use of the drug despite the harm done to the user or other people. Most people who take opioids to control pain and have not previously had problems with drug abuse do not become addicted to opioids. Nonetheless, doctors regularly monitor people who are taking opioid analgesics for signs of addiction.
Administration of opioids
When possible, opioids are taken by mouth (orally). When opioids are taken by mouth, the dose and time they are taken can be adjusted more easily. When they need to be taken for a long time, they may be given by mouth or through a patch placed on the skin (transdermally). Opioids are given by injection (into a muscle or vein) when pain occurs suddenly or when people cannot take them by mouth or through a skin patch.
Some people who need to take opioids for a long time and are helped by an opioid taken by mouth cannot tolerate its side effects. For these people, an opioid can be injected directly into the space around the spinal cord through a pump (intrathecally).
Problems with use of opioids
Opioids are now the leading cause of accidental death and fatal drug overdose in the United States. Problems with using opioids include opioid misuse, diversion, and abuse.
Opioid misuse may be intentional or unintentional. It includes any use that differs from what is prescribed.
Diversion involves selling or giving a prescribed drug to others.
Abuse refers to recreational use of the drug. That is, the drugs are taken for the feelings of pleasure or sensations they produce, rather than to treat pain or another medical condition.
Up to one third of people taking opioids for a long time to treat chronic pain misuse them.
Opioid use disorder is the preferred term for what previously was called opioid addiction. It refers to compulsive use of opioids despite having problems caused by taking them. Also, people who have this disorder may require higher and higher doses to achieve the same effects and may experience withdrawal symptoms when they stop taking the opioid. They may try to stop taking opioids or reduce the amount they are taking but cannot. Taking high doses of opioids for a long time increases the risk of developing opioid use disorder.
Adjuvant Analgesics
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
Oral and topical local anesthetics
Antidepressants
norepinephrine
Tricyclic antidepressants are effective for neuropathic pain, headaches, fibromyalgia, and visceral (organ) hypersensitivity syndromes (such as chronic abdominal pain or pelvic pain). The doses of tricyclic antidepressants used to treat pain are usually too low to treat depression or anxiety. Thus, if tricyclic antidepressants are used to treat pain, additional drugs are usually needed to treat depression or anxiety if present.
diabetic neuropathy), fibromyalgia, chronic low back pain, chronic musculoskeletal pain, and nerve pain due to chemotherapy. The doses of duloxetine
People may respond to one antidepressant and not to others, so sometimes doctors try a few drugs until an effective one is found.
Antiseizure drugs
postherpetic neuralgia) and many other types of neuropathic pain.
fibromyalgia or nerve damage due to diabetes (diabetic neuropathy), postherpetic neuralgia, or neuropathic pain due to a problem in the brain or spinal cord.
Anesthetics
A local anesthetic,sympathetic nerve block involves injecting a local anesthetic around a group of nerves near the spine—in the neck for pain in the upper body or in the lower back for pain in the lower body. (A sympathetic nerve block can relieve pain caused by overactivity of the sympathetic nervous system, which prepares the body for stressful or emergency situations.)
Topical anesthetics,
used to treat abnormal heart rhythms, is sometimes used to treat neuropathic pain.
Other drugs
complex regional pain syndrome.
neuropathic pain or prevent migraines.
osteoarthritis. The cream is most often used by people with localized pain due to arthritis. This cream must be applied several times a day.
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
Mind-body techniques (such as meditation, yoga, and tai chi)
Manipulation and body-based therapies (such as chiropractic or osteopathic manipulation and massage therapy)
Energy-based therapies (such as therapeutic touch and Reiki)
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.
