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Treatment of Pain
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
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 (due to ordinary injury of tissues) but are less effective for neuropathic pain (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, nondrug treatments are also important.
Analgesics fall into three categories:
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:
Severe sudden, relatively short-lived (acute) pain, as occurs after surgery or results from burns or broken bones
Chronic pain due to cancer and other chronic disorders that cause neuropathic pain (such as diabetes)
Opioids are preferred for these disorders because they are so effective in controlling pain. Opioids may be used to treat chronic pain not due to cancer when it is moderate or severe and persists despite other treatments. Doctors carefully evaluate people with this type of pain because opioids are sometimes misused or abused and can cause other problems in some people. For example, taking opioids can increase the risk of falling in older people because these drugs make people less alert. Opioids are not appropriate for everyone.
Doctors ask questions before prescribing these drugs for people to determine whether they are likely to
Doctors also explain what the risks and side effects of such treatment are and how to take and store the drug 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) 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.
Opioids are often most effective for chronic pain when combined with nonopioid analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) or adjuvant analgesics such as gabapentin (an anticonvulsant) or tricyclic antidepressants. 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 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.
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), dementia, or another brain disorder.
The following commonly occur when opioids are started:
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. In exceptional circumstances, people may be given a stimulant drug (such as methylphenidate or modafinil) to 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.
Constipation often develops, especially in older people. Stimulant laxatives, 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. 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 can result from taking opioids, especially in men with benign prostatic hyperplasia. 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.
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.
For most people, nausea and itching disappear or decrease within a few days. But constipation and retention of urine usually decrease much more slowly.
Serious side effects can occur when people take too much of an opioid. These side effects include a dangerous slowing of breathing and even coma. These effects can be reversed with naloxone, an antidote given intravenously. Nurses and family members should watch for these serious side effects of opioids.
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, 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, 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.
When possible, opioids are taken by mouth. 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. Opioids are given by injection when pain occurs suddenly or when people cannot take them by mouth or through a skin patch.
If people are helped by an opioid but cannot tolerate its side effects, an opioid can be injected directly into the space around the spinal cord through a pump. This method gets high concentrations of the drug to the brain. For long-term pain relief, a device that slowly releases an opioid can be implanted in the space around the spinal cord.
Morphine, the prototype of these drugs, can be taken by mouth (orally) 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 and is usually used to treat acute pain.
The controlled- and sustained-release forms provide relief for 8 to 24 hours. These forms are widely used to treat chronic pain when nonopioid analgesics do provide sufficient pain relief.
Rapid-acting opioids 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 are not swallowed. They provide relief very rapidly and are used only for specific types of pain due to cancer. Because they work rapidly, risk of side effects is greater.
In injected forms, 2 to 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).
Intravenously: Pain relief is almost immediate but does not last very long.
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.
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 have severe pain that occurs after surgery or that is due to a serious disorder such as cancer or a sickle cell crisis.
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.
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 are 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 suppository.
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 bleeding). 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 (such as omeprazole) or histamine-2 (H2) blockers (such as famotidine), which are used to treat peptic ulcers, can also help prevent stomach problems due to NSAIDs.
Bleeding problems: All NSAIDs except coxibs 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.
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).
Increased risk of heart and blood vessel disorders: Recent 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 NSAIDs are taken for a long time, certain tests are done regularly. They include blood pressure measurement, blood tests (such as a complete blood count and tests to check kidney and liver function), and tests for blood in stools (to check for bleeding in the digestive tract).
The risk of side effects may be increased for some groups of people, such as the following:
For older people, the risk of side effects due to NSAIDs, particularly indomethacin and ketorolac, is increased.
For people who drink alcoholic beverages regularly and take NSAIDs, the risk of digestive upset, ulcers, and liver damage may be increased.
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 (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 are 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 the particles that help blood clot (platelets) less likely 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. 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), 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.
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 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.
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.
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, 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 make blood clots more likely to form and thus may 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).
Nonsteroidal Anti-Inflammatory Drugs
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 suppository, 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.
Taking high doses for a long time, particularly when taken with NSAIDs or aspirin, may lead to kidney damage.
Adjuvant analgesics are drugs that are usually used to treat other problems and can be used to relieve pain.
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) and conditions such as fibromyalgia.
The adjuvant analgesics most commonly used for pain are
Antidepressants can potentially relieve pain in people who 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 and norepinephrine reuptake inhibitors (SSNRIs, including duloxetine) may have fewer side effects that limit how much of the drug can be taken. Duloxetine appears to be effective for neuropathic pain due to diabetes (called diabetic neuropathy), fibromyalgia, chronic low back pain, and nerve pain due to chemotherapy.
People may respond to one antidepressant and not to others.
Anticonvulsants may be used to relieve neuropathic pain. Gabapentin and pregabalin are used most often, but many others, including carbamazepine, clonazepam, lacosamide, lamotrigine, oxcarbazepine, phenytoin, tiagabine, topiramate, and zonisamide, may be tried.
Pregabalin can be used to relieve pain caused by fibromyalgia or nerve damage due to diabetes (diabetic neuropathy), a complication of shingles (postherpetic neuralgia), or a spinal cord injury. Anticonvulsants, such as topiramate, can prevent migraine headaches.
Mexiletine, used to treat abnormal heart rhythms, is sometimes used to treat neuropathic pain. It is similar to local anesthetics that are placed directly on or near a sore area to help reduce pain.
A local anesthetic, such as lidocaine, may be injected into the skin to control pain due to an injury or even due to neuropathic pain. Local anesthetics can also be injected in nerves to block pain—a procedure called a nerve block. For example, a sympathetic nerve block involves injecting a local anesthetic into 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.
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.
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.
Pamidronate (used to treat certain bone disorders) can help relieve neuropathic pain due to complex regional pain syndrome.
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.
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. The cream is most often used by people with localized pain due to arthritis. This cream must be applied several times a day.
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).
Spinal cord stimulation is commonly used to relieve neuropathic pain in people with nerve damage after back surgery or with complex regional pain syndrome. 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.
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.
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:
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)
Injecting the area around nearby collections of nerve cells called ganglia to help regulate the transmission of pain signals
Injecting a caustic substance (such as phenol) into a nerve to destroy it
Freezing the nerve (in cryotherapy)
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 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.
Mirror therapy may benefit people with phantom limb pain or neuropathic pain 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, 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 feeling) 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.
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