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 but are less effective for neuropathic pain, which often requires different drugs. For some types of pain, especially chronic pain, nondrug treatments are also important.
Analgesics fall into three categories: opioid (narcotic) analgesics, nonopioid analgesics, and adjuvant analgesics (drugs that are usually given for reasons other than pain but that sometimes relieve pain).
Opioid Analgesics
Opioid analgesics (narcotics), the most powerful analgesics, are the mainstay for treatment of severe acute pain and chronic pain due to cancer and other serious disorders. Opioids are preferred because they are so effective in controlling pain. The use of opioids to treat chronic pain not due to cancer is becoming more acceptable but is still relatively uncommon. Opioids are not appropriate for everyone.
Opioids are all chemically related to morphine, a natural substance extracted from poppies, although some opioids are extracted from other plants and other opioids are produced in a laboratory.
Opioids have many side effects. People who take opioids for acute pain often become drowsy. For some people, this drowsiness is welcome, but for others, it is not. Most people who take opioids become tolerant of this effect and do not continue to feel drowsy. Some people who continue to feel drowsy are given stimulant drugs, such as methylphenidate, to keep them awake and alert. Opioids may also cause confusion, especially in older people.
Opioids often cause constipation and retention of urine, especially in older people. Stimulant laxatives (see Section 9, Chapter 129), such as senna, help prevent or relieve the constipation. Increasing intake of fluids can also help.
Sometimes people with pain feel nauseated, 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.
Taking too much of an opioid can have serious side effects, including 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 side effects of opioids.
Doctors carefully weigh the benefits and side effects when they consider these drugs for the treatment of chronic pain. With repeated use of opioids over time, some people need higher doses because the body adapts to and thus responds less well to the drug; this phenomenon is called tolerance. For other people, the same dose remains effective for a long time.
People who take opioids for a long time usually become dependent on them; that is, they experience withdrawal symptoms if the drug is stopped. When opioids are stopped after long-term use, the dose must be gradually tapered to minimize the development of such symptoms. Dependence is not the same as addiction, which is the disruptive behavior or activity associated with obtaining and using the drug. Although addiction is possible, it appears to be rare among people who take opioids to control pain. Too often, exaggerated concern about the addiction potential of opioids (see Section 7, Chapter 108) leads to undertreatment of pain and needless suffering. People with severe pain should not avoid opioids, and adequate doses should be taken as needed.
When possible, opioids are taken by mouth. Opioids are given by injection when people cannot take them by mouth. For people who are helped by an opioid but cannot tolerate its side effects, an opioid can be administered directly into the space around the spinal cord through a pump, thus providing high concentrations of the drug to the brain. One opioid, fentanyl, is available as a skin patch. It provides pain relief for up to 72 hours.
Different opioid analgesics have different advantages and disadvantages. Morphine, the prototype of these drugs, can be taken by mouth (orally) or by injection. There are two oral forms: sustained-release and immediate-release. Different sustained-release forms provide relief for 8 to 24 hours. These drugs are widely used to treat chronic pain. The immediate-release form provides short-lived relief, usually for less than 3 hours. In injected forms, 2 to 6 times less morphine is required than in oral forms, 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 difference in the amount needed for the different routes does not change the effects of the drug. 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). With the intravenous form of morphine, pain relief is almost immediate but does not last very long. With the intramuscular form, pain relief is less rapid but lasts somewhat longer. With the subcutaneous form, 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 control release of the drug by pressing a button is used. This technique is called patient-controlled analgesia. Usually, continuous infusion is used for people who have severe pain due to a serious disorder.
Opioids are essential to the management of acute pain. For example, opioid analgesics are usually prescribed after surgery. They are most effective when taken every few hours, before pain becomes severe. The dose may be increased, or another drug (such as a nonsteroidal anti-inflammatory drug) may be added if the pain temporarily worsens, if the person needs to exercise (movement can be more painful), or if the wound dressing is about to be changed. When the pain eases, doctors reduce the dose and prescribe nonopioid analgesics, such as acetaminophen.
 See the drug table Opioid Analgesics.
Nonopioid Analgesics
A variety of nonopioid analgesics are available. Several (such as aspirin, ibuprofen, ketoprofen, naproxen, and acetaminophen) are available in prescription and nonprescription (over-the-counter, or OTC) strengths (see Section 2, Chapter 18). Prescription-strength formulations contain 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 also reduce the inflammation that often accompanies and worsens pain.
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. Coxibs (COX-2 inhibitors), a new type of NSAIDs, are less likely to irritate the stomach and cause bleeding than other NSAIDs.
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.
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.
NSAIDs cause fluid retention and swelling in 1 to 2% of people. Regular use of NSAIDs may also increase the risk of developing a kidney disorder, sometimes resulting in renal failure (a disorder called analgesic nephropathy).
For older people, the risk of side effects due to NSAIDs is increased. For people who drink alcoholic beverages regularly and take NSAIDs, the risk of digestive upset, ulcers, and liver damage may be increased. People with heart failure, high blood pressure, or kidney or liver disorders 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).
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 also increases the risk of bleeding throughout the body because it reduces the clotting tendency of platelets. 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 (see Section 3, Chapter 24). Such a reaction requires immediate medical attention.
In very high doses, aspirin can cause serious side effects such as abnormal breathing. One of the first signs of an overdose is noise in the ears (tinnitus).
Children and teenagers who have or may have influenza or chickenpox must not take aspirin because they could develop Reye's syndrome. Although rare, Reye's syndrome can have serious consequences, including death.
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 bleeding in the digestive tract.
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, rofecoxib, and valdecoxib, are a new type of NSAID. Other NSAIDs block two enzymes: COX-1, which is involved in the production of the prostaglandins that protect the stomach and play a crucial role in blood clotting; and COX-2, which is involved in the production of the prostaglandins that promote inflammation. Coxibs tend to block only 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; to cause nausea, bloating, heartburn, bleeding, and peptic ulcers; and to interfere with clotting than are other NSAIDs.
Because of these differences, coxibs are useful for people who cannot tolerate other NSAIDs and for people who are at high risk of complications from use of other NSAIDs. Such people include older people, people who are taking anticoagulants, those who have a history of ulcers, and those who must take an analgesic for a long time.
 See the sidebar How Nonsteroidal Anti-Inflammatory Drugs Work.
 See the table Nonsteroidal Anti-Inflammatory Drugs.
Acetaminophen
This drug is roughly comparable to aspirin in its potential to relieve pain and lower a fever. But unlike NSAIDs, acetaminophen has virtually no useful anti-inflammatory activity, does not affect the blood's ability to clot, and has almost no adverse effects on the stomach. How acetaminophen works is not clearly understood.
Acetaminophen is taken by mouth or suppository, and its effects generally last 4 to 6 hours. High doses can lead to liver damage, which may be irreversible. People with a liver disorder should use lower doses than usually taken. Whether lower doses taken for a long time can harm the liver is less certain. People who 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 may lead to kidney damage.
Adjuvant Analgesics
Adjuvant analgesics are drugs that are not usually used for pain relief but may relieve pain in certain circumstances and that, when used to relieve pain, are usually used with other analgesics or nondrug pain treatments.
The adjuvant analgesics most commonly used for pain are antidepressants (such as amitriptyline and desipramine) (see Section 7, Chapter 101), anticonvulsants (such as gabapentin, carbamazepine, and phenytoin) (see Section 6, Chapter 85), and oral and topical local anesthetics.
Antidepressants can potentially relieve pain in people who do not have depression. There is some evidence that tricyclic antidepressants are more effective for this purpose than other antidepressants, but selective serotonin reuptake inhibitor (SSRI) antidepressants (such as fluoxetine) are tolerated better. People may respond to one antidepressant and not others.
Anticonvulsants may be used to relieve neuropathic pain. Gabapentin is used most often, but many others, including phenytoin, carbamazepine, clonazepam, divalproex, lamotrigine, topiramate, and oxcarbazepine, may be tried. Anticonvulsants, such as divalproex, can also prevent migraine headaches.
Mexiletine, a local anesthetic taken by mouth to treat abnormal heart rhythms, is sometimes used to treat neuropathic pain. Local anesthetics are more commonly placed directly on or near a sore area to help reduce pain. For example, doctors may inject a local anesthetic, such as lidocaine, into the skin to control pain due to an injury or even due to neuropathic pain syndromes. Local anesthetics are also used in nerve blocks. 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.
Occasionally, pain related to nerve injury can be treated by injecting a caustic substance, such as phenol, into a nerve to destroy it, by freezing the nerve (in cryotherapy), or by burning the nerve with a radiofrequency probe. These techniques may be used to treat facial pain due to trigeminal neuralgia.
Topical anesthetics, such as lidocaine applied as a lotion, ointment, or 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, an anesthetic mouthwash can be used to relieve a sore throat. However, some people with chronic pain benefit from using topical anesthetics for a long time. For example, a lidocaine patch can be used to relieve postherpetic neuralgia.
A cream containing capsaicin, a substance found in hot peppers, sometimes helps reduce the pain caused by such disorders as herpes zoster and osteoarthritis. It 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 Section 1, Chapter 7). Ultrasonography that provides deep heat (diathermy) may relieve the pain of osteoarthritis and muscle strain.
Some people benefit from transcutaneous electrical nerve stimulation (TENS). 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. TENS may be useful for chronic pain.
Acupuncture involves inserting tiny needles into specific areas of the body (see Section 25, Chapter 306). The mechanisms by which acupuncture works are 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.
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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