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 (analgesics) may still be needed to quickly manage the pain.
(See also Overview of Pain Overview of Pain Pain is an unpleasant sensation signaling actual or possible injury. Pain is the most common reason people visit their doctor. Pain may be sharp or dull, intermittent or constant, or throbbing... read more .)
Doctors choose an analgesic based on the type and duration of pain and on the likely benefits and risks. Most analgesics are effective for nociceptive pain Nociceptive Pain Nociceptive pain is caused by an injury to body tissues. (See also Overview of Pain.) Most pain is nociceptive pain. It results from stimulation of pain receptors for tissue injury (nociceptors)... read more (due to ordinary injury of tissues) but are less effective for neuropathic pain Neuropathic Pain Neuropathic pain is caused by damage to or dysfunction of the nerves, spinal cord, or brain. (See also Overview of Pain.) Neuropathic pain may result from Compression of a nerve—for example... read more (due to damage or dysfunction of the nerves, spinal cord, or brain), which often requires different drugs. For some types of pain, especially chronic pain Chronic Pain Chronic pain is pain that lasts or recurs for months or years. Usually, pain is considered chronic if it does one of the following: Lasts for more than 3 months Lasts for more than 1 month after... read more , nondrug treatments Nondrug Pain Treatments 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.... read more are also important.
Analgesics fall into three categories:
Nonopioid Analgesics
A variety of nonopioid analgesics are available. They are often effective for mild to moderate pain. These drugs are often the preferred drugs for treating pain. People do not become physically dependent on these drugs or tolerant of their pain-relieving effects.
Aspirin and acetaminophen are available without a prescription (over-the-counter, or OTC). Several other nonopioid analgesics (such as ibuprofen, ketoprofen, and naproxen) are available OTC and by prescription, usually in higher-dose formulations, with more active ingredient per dose than OTC formulations.
OTC analgesics are reasonably safe to take for short periods of time, but their labels caution against taking them for more than 7 to 10 days to treat pain. A doctor should be consulted if symptoms worsen or do not go away.
Nonsteroidal Anti-Inflammatory Drugs
Most nonopioid analgesics are classified as nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are used to treat mild to moderate pain and may be combined with opioids to treat moderate to severe pain. NSAIDs not only relieve pain, but they may also reduce the inflammation that often accompanies and worsens pain. However, to reduce inflammation, NSAIDs usually need to be taken at high doses and for a relatively long time.
All NSAIDs can be taken by mouth. Two NSAIDs, ketorolac and diclofenac, can also be given by injection into a vein (intravenously) or muscle (intramuscularly). Indomethacin can be given by a suppository inserted in the rectum. Diclofenac is also available as a cream.
Although widely used, NSAIDs can have side effects, sometimes serious ones.
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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 Peptic Ulcer Disease A peptic ulcer is a round or oval sore where the lining of the stomach or duodenum has been eaten away by stomach acid and digestive juices. Peptic ulcers can result from Helicobacter pylori... read more
, and bleeding in the digestive tract (gastrointestinal bleeding Gastrointestinal Bleeding Bleeding may occur anywhere along the digestive (gastrointestinal [GI]) tract, from the mouth to the anus. Blood may be easily seen by the naked eye (overt), or blood may be present in amounts... read more 
). Coxibs (COX-2 inhibitors) are less likely to irritate the stomach and cause bleeding than other NSAIDs. However, if people take a coxib and aspirin, these problems are just as likely. Taking NSAIDs with food and using antacids may help prevent stomach irritation. The drug misoprostol can help prevent stomach irritation and ulcers, but it can cause other problems, including diarrhea. Proton pump inhibitors Proton pump inhibitors Stomach acid plays a role in a number of disorders of the stomach, including peptic ulcer, gastritis, and gastroesophageal reflux disease (GERD). Although the amount of acid present in the stomach... read more (such as omeprazole) or histamine-2 (H2) blockers Histamine-2 (H2) blockers Stomach acid plays a role in a number of disorders of the stomach, including peptic ulcer, gastritis, and gastroesophageal reflux disease (GERD). Although the amount of acid present in the stomach... read more (such as famotidine), which are used to treat peptic ulcers, can also help prevent stomach problems due to NSAIDs. -
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 also irritate the stomach’s lining. Coxibs are less likely to cause bleeding than other NSAIDs.
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Problems related to retaining fluids: 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).
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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.
Taking NSAIDs for a short time is unlikely to cause serious problems. If people take NSAIDs for a long time, problems are more likely to occur. 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.
The risk of side effects may be increased for some groups of people, such as the following:
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For older people, the risk of side effects due to NSAIDs, particularly indomethacin and ketorolac, is increased.
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For people who drink alcoholic beverages regularly and take NSAIDs, the risk of digestive upset, ulcers, and liver damage may be increased.
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For people with coronary artery disease, other heart and blood vessel (cardiovascular) disorders, or risk factors for these disorders, the risk of heart attacks and stroke may be higher.
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 these analgesics.
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 (acetylsalicylic acid) has been used for about 100 years. 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 (in a buffered product) to reduce this effect. The antacid creates an alkaline environment that helps aspirin dissolve and may reduce the time aspirin is in contact with the stomach lining. However, buffered aspirin can still irritate the stomach because aspirin also reduces the production of substances that help protect the stomach’s lining. These substances are a type of prostaglandin, which is similar to hormones.
Enteric-coated aspirin is designed to pass through the stomach intact and dissolve in the small intestine, thus minimizing direct irritation of the stomach. (Enteric refers to the small intestine.) However, enteric-coated aspirin may be absorbed erratically. If food and enteric-coated aspirin are ingested at about the same time, the aspirin is not absorbed as quickly because food delays the emptying of the stomach. Consequently, pain relief is delayed.
Aspirin increases the risk of bleeding throughout the body because it makes platelets—cell fragments in the blood that help blood clot—less able to do so. People who bruise easily may be especially vulnerable to this effect. Anyone who has ever had a bleeding disorder or uncontrolled high blood pressure should not take aspirin except under a doctor’s supervision. People who take aspirin and anticoagulants (such as warfarin) are closely monitored to avoid life-threatening bleeding. (Anticoagulants also interfere with blood clotting.) Usually, aspirin 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 Anaphylactic Reactions Anaphylactic reactions are sudden, widespread, potentially severe and life-threatening allergic reactions. Anaphylactic reactions often begin with a feeling of uneasiness, followed by tingling... read more ), leading to a rash, itching, severe breathing problems, or shock Shock Shock is a life-threatening condition in which blood flow to the organs is low, decreasing delivery of oxygen and thus causing organ damage and sometimes death. Blood pressure is usually low... read more . 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 Ear Ringing or Buzzing Ringing in the ears (tinnitus) is noise originating in the ear rather than in the environment. It is a symptom and not a specific disease. Tinnitus is very common—10 to 15% of people experience... read more ).
Most children and teenagers should not take aspirin because they could develop Reye syndrome Reye Syndrome Reye syndrome is a very rare but life-threatening disorder that causes inflammation and swelling of the brain and impairment and loss of function of the liver. The cause of Reye syndrome is... read more if they have or have just gotten over influenza or chickenpox. Although rare, Reye syndrome can have serious consequences, including death.
Topical NSAIDs
Some NSAIDs are available as creams or gels that are applied directly to the skin over the painful area. For example, diclofenac can be applied to a joint to relieve pain due to osteoarthritis Osteoarthritis (OA) Osteoarthritis is a chronic disorder that causes damage to the cartilage and surrounding tissues and is characterized by pain, stiffness, and loss of function. Arthritis due to damage of joint... read more 
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
NSAIDs such as ibuprofen, ketoprofen, and naproxen are generally believed to be gentler on the stomach than aspirin, although few studies have compared the drugs. Like aspirin, these drugs can cause digestive upset, ulcers, and gastrointestinal bleeding. They can make asthma worse and increase blood pressure. Taking one of these drugs probably slightly increases the risk of stroke, heart attack, and blood clots in the arteries of the legs. The risk may be lower with 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 does, people should not take these drugs with anticoagulants (such as warfarin) except under a doctor’s close supervision.
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)
Coxibs, such as celecoxib, differ from other NSAIDs. Other NSAIDs block the following two enzymes:
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:
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
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).
Acetaminophen
Acetaminophen is roughly comparable to aspirin in its potential to relieve pain and lower a fever.
But unlike NSAIDs, acetaminophen has the following characteristics:
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. 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 Analgesics
Opioid analgesics (sometimes called narcotics) are effective for many different types of pain. Usually, they are the strongest analgesics.
Opioids are chemically related to morphine, a natural substance extracted from poppies. Some opioids are extracted from other plants, and other opioids are produced in a laboratory.
Opioids are the mainstay for treatment of the following:
Opioids are preferred for these disorders because opioids are so effective in controlling pain.
Opioids may be underused in these situations because doctors
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Underestimate the dose needed to be effective
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Overestimate the risk of opioid side effects Side effects of opioids 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.... read more , such as an opioid use disorder Substance Use Disorders Substance use disorders generally involve behavior patterns in which people continue to use a substance despite having problems caused by its use. The substances involved tend to be members... read more (addiction Substance Use Disorders Substance use disorders generally involve behavior patterns in which people continue to use a substance despite having problems caused by its use. The substances involved tend to be members... read more )
However, in people with pain due to cancer or another terminal disorder or in hospice, concerns about side effects should not limit the use of opioids because side effects can usually be prevented or managed, and addiction is less of a concern.
If chronic pain is not due to cancer or a terminal disorder, opioids are usually not the first choice for treatment because the side effects of long-term opioid therapy can be serious. Opioid side effects include opioid use disorder Substance Use Disorders Substance use disorders generally involve behavior patterns in which people continue to use a substance despite having problems caused by its use. The substances involved tend to be members... read more (addiction), overdose, a dangerous slowing of breathing (respiratory depression), and death. Thus, when chronic pain is not due to cancer or a terminal disorder, other treatments, such as nonopioid drugs Nonopioid Analgesics 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.... read more and nondrug treatments Nondrug Pain Treatments 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.... read more , are used first. If these treatments are ineffective, doctors may consider using opioids but only when the need for pain relief and improved functioning outweighs the risks of opioids.
Opioids are not appropriate for everyone.
Doctors ask people questions before prescribing opioids for them. The questions are designed to determine whether people are likely to
Doctors also explain what the risks and side effects of opioids are and how to take and store opioids correctly.
The dose of an opioid is increased gradually, in stages, until the pain is relieved or the opioid’s side effects cannot be tolerated. Older people and newborns, who are more sensitive to the effects of opioids, are usually given lower doses.
Opioids are most effective when taken according to a schedule, before pain becomes severe.
If an opioid alone does not provide sufficient pain relief, the dose may be increased or another drug (such as an NSAID or an adjuvant analgesic Adjuvant Analgesics 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.... read more ) may be added, as in the following situations:
In people with chronic pain, increasing the dose of an opioid does not necessarily result in additional pain relief and may increase the risk of side effects.
For chronic pain, opioids are often used with nonopioid analgesics Nonopioid Analgesics 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.... read more , such as nonsteroidal anti-inflammatory drugs (NSAIDs), or adjuvant analgesics Adjuvant Analgesics 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.... read more , such as gabapentin (an antiseizure drug Drugs Used to Treat Seizures In seizure disorders, the brain's electrical activity is periodically disturbed, resulting in some degree of temporary brain dysfunction. Many people have unusual sensations just before a seizure... read more ) or tricyclic antidepressants Heterocyclic (including tricyclic) antidepressants Agomelatine, a new type of antidepressant, is a possible treatment for major depressive episodes. Several types of drugs can be used to treat depression: Selective serotonin reuptake inhibitors... read more . Nonopioid analgesics, such as acetaminophen, are sometimes combined with opioids in a single tablet.
Doctors usually monitor the response to opioids to determine whether opioids are effectively controlling the pain and/or people are having side effects. Based on this information, doctors determine whether continuing opioid therapy is appropriate. As the pain lessens, doctors reduce the dose of the opioid gradually, and when possible, they stop the opioid and switch to or continue to take a nonopioid analgesic.
Opioids provide long-term relief for only some people who are treated with them, and usually, they only partially relieve the pain. Some people decide to stop taking opioids because the pain relief is insufficient or because they cannot tolerate the side effects.
Side effects of opioids
Opioids have many side effects. Side effects are more likely to occur in people with certain disorders: kidney failure Overview of Kidney Failure This chapter includes a new section on COVID-19 and acute kidney injury (AKI). Kidney failure is the inability of the kidneys to adequately filter metabolic waste products from the blood. Kidney... read more , a liver disorder Overview of Liver Disease Liver disease can manifest in many different ways. Characteristic manifestations include Jaundice (a yellowish discoloration of the skin and whites of the eyes) Cholestasis (reduction or stoppage... read more , chronic obstructive pulmonary disease Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease is persistent narrowing (blocking, or obstruction) of the airways occurring with emphysema, chronic obstructive bronchitis, or both disorders. Cigarette... read more 
(COPD), untreated sleep apnea Sleep Apnea Sleep apnea is a serious disorder in which breathing repeatedly stops long enough to disrupt sleep and often temporarily decrease the amount of oxygen and increase the amount of carbon dioxide... read more 
, dementia Dementia Dementia is a slow, progressive decline in mental function including memory, thinking, judgment, and the ability to learn. Typically, symptoms include memory loss, problems using language and... read more , or another brain disorder.
The following commonly occur when opioids are used:
Less common side effects of opioids include
Drowsiness is a common side effect of opioids. For some people who take opioids, drowsiness disappears or decreases within a few days. If people continue to feel drowsy, a different opioid can be tried because the degree of drowsiness caused by different opioids varies. Before an important event that requires alertness, people may be given a stimulant drug (such as methylphenidate or modafinil) to offset the drowsiness. For some people, drinking a caffeinated beverage helps offset the drowsiness. When feeling drowsy after taking an opioid, people should avoid driving and take extra care to prevent falls and accidents.
Confusion can also result from taking opioids, especially if people are older. Opioids increase the risk of falls in older people.
Nausea sometimes occurs in people with pain, and opioids can increase the nausea. Antiemetic drugs taken by mouth, suppository, or injection help prevent or relieve nausea. Some commonly used antiemetic drugs are metoclopramide, hydroxyzine, and prochlorperazine.
The itching caused by taking opioids may be relieved by an antihistamine such as diphenhydramine, taken by mouth or given intravenously.
Constipation Constipation in Adults Constipation is difficult or infrequent bowel movements, hard stool, or a feeling that the rectum is not totally empty after a bowel movement (incomplete evacuation). (See also Constipation... read more often develops, especially in older people. Stimulant laxatives Laxatives Constipation is difficult or infrequent bowel movements, hard stool, or a feeling that the rectum is not totally empty after a bowel movement (incomplete evacuation). (See also Constipation... read more , such as senna, help prevent or relieve the constipation. Increasing the intake of fluids and the amount of fiber in the diet can also help. Osmotic agents Laxatives Constipation is difficult or infrequent bowel movements, hard stool, or a feeling that the rectum is not totally empty after a bowel movement (incomplete evacuation). (See also Constipation... read more such as polyethylene glycol can also be useful. These agents pull large amounts of water into the large intestine to stimulate bowel movements. Some people need enemas. When these measures are not effective, doctors may prescribe a drug (such as methylnaltrexone) that blocks only the effects of opioids in the stomach and intestine and does not lessen the pain relief.
Retention of urine Urinary Retention Urinary retention is inability to urinate or incomplete emptying of the bladder. People who have incomplete emptying of the bladder may have urinary frequency or urinary incontinence. If the... read more can result from taking opioids, especially in men with an enlarged prostate. Trying to urinate a second time after a brief pause (double voiding) or applying gentle pressure on the lowest part of the abdomen (the area over the bladder) during urination may help. Sometimes a drug that relaxes muscles of the bladder (such as tamsulosin) is used.
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:
Some of these side effects can be reversed with naloxone, an antidote usually given intravenously or sprayed into the nose.
For people who are at increased risk of opioid side effects (including respiratory depression), doctors may prescribe naloxone when they prescribe the opioid. Nurses and family members or caregivers should watch for serious side effects of opioids and, if such side effects occur, be ready to inject 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 Tolerance Tolerance is a person's diminished response to a drug, which occurs when the drug is used repeatedly and the body adapts to the continued presence of the drug. Resistance refers to the ability... read more 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 Long-term effects Opioids are a class of drugs derived from the opium poppy (including synthetic variations) that are pain relievers with a high potential for misuse. Opioids are used to relieve pain, but they... read more usually develops in people who take opioids Opioids Opioids are a class of drugs derived from the opium poppy (including synthetic variations) that are pain relievers with a high potential for misuse. Opioids are used to relieve pain, but they... read more for a long time. That is, they experience withdrawal symptoms if the drug is stopped. Withdrawal symptoms Withdrawal symptoms Opioids are a class of drugs derived from the opium poppy (including synthetic variations) that are pain relievers with a high potential for misuse. Opioids are used to relieve pain, but they... read more 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 addiction Substance Use Disorders Substance use disorders generally involve behavior patterns in which people continue to use a substance despite having problems caused by its use. The substances involved tend to be members... read more , which 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 Oral route Drugs are introduced into the body by several routes. They may be Taken by mouth (orally) Given by injection into a vein (intravenously, IV), into a muscle (intramuscularly, IM), into the space... read more 
). 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 Transdermal route Drugs are introduced into the body by several routes. They may be Taken by mouth (orally) Given by injection into a vein (intravenously, IV), into a muscle (intramuscularly, IM), into the space... read more ). Opioids are given by injection Injection routes Drugs are introduced into the body by several routes. They may be Taken by mouth (orally) Given by injection into a vein (intravenously, IV), into a muscle (intramuscularly, IM), into the space... read more (into a muscle or vein) when pain occurs suddenly or when people cannot take them by mouth or through a skin patch.
If people who need to take opioids for a long time and are helped by an opioid taken by mouth but cannot tolerate its side effects, an opioid can be injected directly into the space around the spinal cord through a pump (intrathecally Injection routes Drugs are introduced into the body by several routes. They may be Taken by mouth (orally) Given by injection into a vein (intravenously, IV), into a muscle (intramuscularly, IM), into the space... read more ). This method gets high concentrations of the drug to the brain.
Morphine, the prototype of these drugs, can be taken by mouth or by injection. Morphine comes in sustained-, controlled-, and immediate-release forms that are taken by mouth.
The immediate-release form of morphine provides short-lived relief (about 4 hours) and is usually used to treat acute pain.
The controlled- and sustained-release forms provide relief for 8 to 24 hours. These forms have been widely used to treat chronic pain when nonopioid analgesics do not provide sufficient pain relief. However, if pain is not related to cancer, experts recommend limiting the use of these long-acting (controlled- and sustained-release) opioids.
Rapid-acting opioids (lozenges or dissolvable tablets) are placed under the tongue (sublingual) or between the gums and cheek (buccal). There, they are allowed to dissolve and are absorbed through the mucous membrane that lines the cheek or that lies under the tongue. These forms should not be swallowed. They provide relief very rapidly. Because they work rapidly, risk of side effects may be greater. They are used for breakthrough pain in people with cancer. Breakthrough pain is a brief, often severe flare-up of pain that may occur when regularly scheduled treatment does not control pain.
In injected forms, 3 times less morphine is required than in the immediate-release oral form because when morphine is taken by mouth, much of the drug is chemically altered (metabolized) by the liver before it reaches the bloodstream. Usually, the route used does not change the drug’s effects, even though different routes use different amounts of morphine.
Pain relief with injected forms is quicker than that with oral forms, but relief does not last as long.
Morphine may be injected into a vein (intravenously), into a muscle (intramuscularly), or under the skin (subcutaneously).
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Intravenously: Pain relief is almost immediate but does not last very long.
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Intramuscularly: Pain relief is less rapid but lasts somewhat longer. Intramuscular injections are painful, and pain relief is less predictable, so this route is not used often.
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Subcutaneously: Pain relief is the least rapid but lasts the longest.
Injections can be given every few hours, but repeated injections can become annoying. Alternatively, a catheter can be inserted in a vein or under the skin and connected to a continuous-infusion pump, which supplies morphine continuously. The continuous infusion can be supplemented with extra doses when needed. Sometimes a device that enables a person to release the drug by pressing a button is used. However, the doctor determines how much of the drug is released and how often it can be released. This technique is called patient-controlled analgesia. Usually, continuous infusion is used for people who are hospitalized and who have severe pain that occurs after surgery or that is due to a serious disorder such as cancer or a sickle cell crisis.
Problems with use of opioids
Opioids Opioids Opioids are a class of drugs derived from the opium poppy (including synthetic variations) that are pain relievers with a high potential for misuse. Opioids are used to relieve pain, but they... read more 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 may misuse them.
Opioid use disorder Substance Use Disorders Substance use disorders generally involve behavior patterns in which people continue to use a substance despite having problems caused by its use. The substances involved tend to be members... read more 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.
Before prescribing opioids, doctors should evaluate people for risk factors for problems with taking opioids. Risk factors include
When the opioid is first prescribed, doctors explain the risks of opioids and the measures used to ensure that the drug is used safely. If problems occur, people are also told that they may be referred to a substance use specialist.
Doctors closely monitor all people who are treated with opioids to make sure opioid therapy is used safely. For example, they may test for other recreational drugs. Doctors also monitor interconnected state databases that track opioid prescriptions to check whether people are getting opioid prescriptions at more than one pharmacy. To prevent misuse, doctors typically restrict the person to a single pharmacy for filling opioid prescription.
To avoid misuse of their drug by others, people should keep opioids in a safe place and dispose of any unused drugs by returning them to the pharmacy.
Adjuvant Analgesics
Adjuvant analgesics are thought to work by changing the way the nerves process pain.
Increasingly, an adjuvant analgesic is the first and only drug used to treat pain due to nerve damage (neuropathic pain Neuropathic Pain Neuropathic pain is caused by damage to or dysfunction of the nerves, spinal cord, or brain. (See also Overview of Pain.) Neuropathic pain may result from Compression of a nerve—for example... read more ) and conditions such as fibromyalgia Fibromyalgia Fibromyalgia is characterized by poor sleep, fatigue, mental cloudiness, and widespread aching and stiffness in soft tissues, including muscles, tendons, and ligaments. Poor sleep, stress, strains... read more .
The adjuvant analgesics most commonly used for pain are
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Antidepressants Drug Treatment for Depression Agomelatine, a new type of antidepressant, is a possible treatment for major depressive episodes. Several types of drugs can be used to treat depression: Selective serotonin reuptake inhibitors... read more (such as amitriptyline, bupropion, desipramine, duloxetine, nortriptyline, and venlafaxine)
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Oral and topical local anesthetics
Antidepressants
Antidepressants can often relieve pain in people even when they do not have depression. Tricyclic antidepressants (such as amitriptyline, nortriptyline, and desipramine) may be more effective for this purpose than other antidepressants, but newer antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (SNRIs, including duloxetine, venlafaxine, and milnacipran) may have fewer of the side effects that limit how much of the drug can be taken.
Tricyclic antidepressants are effective for neuropathic pain Neuropathic Pain Neuropathic pain is caused by damage to or dysfunction of the nerves, spinal cord, or brain. (See also Overview of Pain.) Neuropathic pain may result from Compression of a nerve—for example... read more , headaches Overview of Headache A headache is pain in any part of the head, including the scalp, upper neck, face, and interior of the head. Headaches are one of the most common reasons people visit a doctor. Headaches interfere... read more , fibromyalgia Fibromyalgia Fibromyalgia is characterized by poor sleep, fatigue, mental cloudiness, and widespread aching and stiffness in soft tissues, including muscles, tendons, and ligaments. Poor sleep, stress, strains... read more , and visceral (organ) hypersensitivity syndromes (such as chronic abdominal 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.
Duloxetine appears to be effective for neuropathic pain due to diabetes (called diabetic neuropathy Nerve damage in diabetes People with diabetes mellitus have many serious long-term complications that affect many areas of the body, particularly the blood vessels, nerves, eyes, and kidneys. (See also Diabetes Mellitus... read more 
), fibromyalgia Fibromyalgia Fibromyalgia is characterized by poor sleep, fatigue, mental cloudiness, and widespread aching and stiffness in soft tissues, including muscles, tendons, and ligaments. Poor sleep, stress, strains... read more , chronic low back pain Low Back Pain Low back pain and neck pain are among the most common reasons for health care visits. The pain usually results from problems with the musculoskeletal system—most notably the spine, including... read more 
, chronic musculoskeletal pain, and nerve pain due to chemotherapy. The doses of duloxetine used to treat pain are also adequate to treat depression or anxiety if present. Venlafaxine has similar effects. Milnacipran is effective for fibromyalgia.
People may respond to one antidepressant and not to others.
Antiseizure drugs
Antiseizure drugs may be used to relieve neuropathic pain. Gabapentin and pregabalin are most commonly used, but many others, including carbamazepine, clonazepam, lacosamide, lamotrigine, oxcarbazepine, phenytoin, topiramate, and zonisamide, help relieve pain in some people.
Gabapentin can be used to treat the pain that can result from shingles (postherpetic neuralgia Postherpetic Neuralgia Postherpetic neuralgia is chronic pain in areas of skin supplied by nerves infected with herpes zoster (shingles). Shingles is a painful rash of fluid-filled blisters that is caused by reactivation... read more ) and many other types of neuropathic pain Neuropathic Pain Neuropathic pain is caused by damage to or dysfunction of the nerves, spinal cord, or brain. (See also Overview of Pain.) Neuropathic pain may result from Compression of a nerve—for example... read more .
Pregabalin can be used to relieve pain caused by 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, such as lidocaine, may be injected into the skin to control pain due to an injury or even neuropathic pain. Local anesthetics can also be injected around nerves to block pain—a procedure called a nerve block. For example, a 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.
Topical anesthetics, such as lidocaine applied as a lotion, an ointment, or a skin patch, can be used to control pain due to some conditions.
Mexiletine, used to treat abnormal heart rhythms, is sometimes used to treat neuropathic pain.
These anesthetics are usually used for a short period of time. For example, rinsing with small amounts of an anesthetic mouthwash a few times a day can relieve pain due to mouth sores. However, some people with chronic pain benefit from using topical anesthetics for a long time. For example, a lidocaine patch or gel can help relieve postherpetic neuralgia Postherpetic Neuralgia Postherpetic neuralgia is chronic pain in areas of skin supplied by nerves infected with herpes zoster (shingles). Shingles is a painful rash of fluid-filled blisters that is caused by reactivation... read more .
Other drugs
Corticosteroids, such as prednisone and dexamethasone, can be taken by mouth if severe pain is caused by inflammation (as occurs in gout).
Some evidence suggests that baclofen (a muscle relaxant) can help relieve neuropathic pain due to trigeminal neuralgia Trigeminal Neuralgia Trigeminal neuralgia is severe facial pain due to malfunction of the 5th cranial nerve (trigeminal nerve). This nerve carries sensory information from the face to the brain and controls the... read more .
Pamidronate (used to treat certain bone disorders) can help relieve neuropathic pain due to complex regional pain syndrome Complex Regional Pain Syndrome Complex regional pain syndrome is characterized by persistent burning or aching pain plus certain abnormalities that occur in the same area as the pain. Abnormalities include increased or decreased... read more .
Low doses of ketamine (an anesthetic) are sometimes given intravenously in a hospital to people who have complex regional pain syndrome when other treatments are ineffective.
Tizanidine (a muscle relaxant), taken by mouth, and clonidine (used to treat high blood pressure), taken by mouth or applied to the skin as a patch, can help relieve neuropathic pain or prevent migraines.
High-strength capsaicin (a substance found in hot peppers), given in a patch, helps relieve neuropathic pain due to postherpetic neuralgia. A low-strength capsaicin cream may also help reduce the pain caused by postherpetic neuralgia and by other disorders such as osteoarthritis Osteoarthritis (OA) Osteoarthritis is a chronic disorder that causes damage to the cartilage and surrounding tissues and is characterized by pain, stiffness, and loss of function. Arthritis due to damage of joint... read more . 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 Treatment of Pain and Inflammation Professional rehabilitation therapists treat pain and inflammation. Such treatment makes movement easier and enables people to participate more fully in rehabilitation. Techniques used include... read more ).
Transcutaneous electrical nerve stimulation (TENS) benefits some people. A gentle electric current is applied through electrodes placed on the skin’s surface. TENS produces a tingling sensation without increasing muscle tension. It can be applied continuously or several times a day for 20 minutes to several hours. The timing and length of stimulation vary because each person responds differently. Often, people are taught to use the TENS device, so that they can use it as needed.
Spinal cord stimulation is commonly used to relieve neuropathic pain Neuropathic Pain Neuropathic pain is caused by damage to or dysfunction of the nerves, spinal cord, or brain. (See also Overview of Pain.) Neuropathic pain may result from Compression of a nerve—for example... read more in people with nerve damage after back surgery or with complex regional pain syndrome Complex Regional Pain Syndrome Complex regional pain syndrome is characterized by persistent burning or aching pain plus certain abnormalities that occur in the same area as the pain. Abnormalities include increased or decreased... read more . This treatment involves implanting a spinal cord stimulator under the skin, usually in a buttock or abdomen. Like a heart pacemaker, this device generates electrical impulses. Small wires (leads) from the device are placed in the space around the spinal cord (epidural space). These leads transmit impulses to the spinal cord. The impulses change the way pain signals are sent to the brain and thus change how unpleasant symptoms are perceived.
A nerve block is frequently used to treat pain caused by damage to a specific large nerve. For this procedure, a nerve pathway that transmits pain signals is disrupted by doing one of the following:
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Injecting the area around the nerves with a local anesthetic to prevent the nerves from sending pain signals (doctors commonly use ultrasonography to help them locate the nerves to be treated)
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Injecting the area around nearby collections of nerve cells called ganglia to help regulate the transmission of pain signals
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Injecting a caustic substance (such as phenol) into a nerve to destroy it
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Freezing the nerve (in cryotherapy)
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Burning the nerve with a radiofrequency probe
Nerve blocks may also be used to treat severe cancer pain near the end of life and severe, persistent neuropathic pain when drugs cannot relieve the pain.
Acupuncture Acupuncture Acupuncture, a therapy within traditional Chinese medicine, is one of the most widely accepted CAM therapies in the Western world. Licensed practitioners do not necessarily have a medical degree... read more 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 Biofeedback Biofeedback, a type of mind-body medicine, is a method of bringing unconscious biologic processes under conscious control. In biofeedback, electronic devices are used to measure and report information... read more and other cognitive techniques Mind-Body Medicine Complementary or alternative medicine can be classified into five major categories of practice: Whole medical systems Mind-body techniques Biologically based practices Manipulative and body-based... read more (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.
Mirror therapy may benefit people with complex regional pain syndrome Complex Regional Pain Syndrome Complex regional pain syndrome is characterized by persistent burning or aching pain plus certain abnormalities that occur in the same area as the pain. Abnormalities include increased or decreased... read more , phantom limb pain, Phantom limb pain Neuropathic pain is caused by damage to or dysfunction of the nerves, spinal cord, or brain. (See also Overview of Pain.) Neuropathic pain may result from Compression of a nerve—for example... read more or neuropathic pain Neuropathic Pain Neuropathic pain is caused by damage to or dysfunction of the nerves, spinal cord, or brain. (See also Overview of Pain.) Neuropathic pain may result from Compression of a nerve—for example... read more after stroke. This therapy is taught by a health care practitioner. People sit with a large mirror facing their unaffected leg. The mirror reflects the image of the unaffected limb and hides the affected (painful or missing) limb, giving people the impression that they have two normal limbs. People are then instructed to move the unaffected limb while watching its reflected image. People feel as if they are moving two normal limbs. If people who do this exercise for 30 minutes a day for 4 weeks, pain is usually substantially reduced. This therapy changes the pathways in the brain that control perception (or sensation) in the body.
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
| Generic Name | Select Brand Names |
|---|---|
Choline magnesium trisalicylate |
No US brand name |
prochlorperazine |
COMPRO |
methylphenidate |
CONCERTA, RITALIN |
Mefenamic acid |
PONSTEL |
metoclopramide |
REGLAN |
carbamazepine |
TEGRETOL |
Buprenorphine |
BUPRENEX |
acetaminophen |
TYLENOL |
nortriptyline |
AVENTYL |
dexamethasone |
OZURDEX |
oxcarbazepine |
TRILEPTAL |
Hydromorphone |
DILAUDID |
Indomethacin |
INDOCIN |
Flurbiprofen |
ANSAID, OCUFEN |
hydroxyzine |
VISTARIL |
Pamidronate |
AREDIA |
milnacipran |
SAVELLA |
misoprostol |
CYTOTEC |
Pentazocine |
TALWIN |
desipramine |
NORPRAMIN |
venlafaxine |
EFFEXOR XR |
lamotrigine |
LAMICTAL |
duloxetine |
CYMBALTA |
pregabalin |
LYRICA |
Tizanidine |
ZANAFLEX |
lacosamide |
VIMPAT |
diclofenac |
CATAFLAM, VOLTAREN |
ketoprofen |
NEXCEDE |
Fenoprofen |
NALFON |
topiramate |
TOPAMAX |
zonisamide |
ZONEGRAN |
omeprazole |
PRILOSEC |
tamsulosin |
FLOMAX |
clonazepam |
KLONOPIN |
famotidine |
PEPCID |
gabapentin |
NEURONTIN |
Meperidine |
DEMEROL |
prednisone |
RAYOS |
clonidine |
CATAPRES |
ibuprofen |
ADVIL, MOTRIN IB |
capsaicin |
QUTENZA |
Methadone |
DOLOPHINE |
Meloxicam |
MOBIC |
Oxycodone |
OXYCONTIN |
phenytoin |
DILANTIN |
lidocaine |
XYLOCAINE |
Oxaprozin |
DAYPRO |
bupropion |
WELLBUTRIN, ZYBAN |
celecoxib |
CELEBREX |
modafinil |
PROVIGIL |
Piroxicam |
FELDENE |
ketorolac |
SPRIX |
ketamine |
KETALAR |
naproxen |
ALEVE, NAPROSYN |
morphine |
DURAMORPH PF, MS CONTIN |
baclofen |
LIORESAL |
warfarin |
COUMADIN |
Fentanyl |
ACTIQ, DURAGESIC, SUBLIMAZE |
Sulindac |
CLINORIL |
naloxone |
EVZIO |
Tramadol |
ULTRAM |
