Pain

Rebecca J Frey. The Gale Encyclopedia of Neurological Disorders. Editor: Stacey L Chamberlin & Brigham Narins. Gale, 2005.

Definition and Classification

Pain is a universal human experience. The International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.” Pain may be a symptom of an underlying disease or disorder, or a disorder in its own right.

At the same time that pain is a universal experience, however, it is also a complex one. While the physical sensations involved in pain may be constant throughout history, the ways in which humans express and treat pain are shaped by their respective cultures and societies. Since the 1980s, research in the neurobiology of pain has been accompanied by studies of the psychological and sociocultural factors that influence people’s experience of pain, their use of health care systems, and their compliance with various treatments for pain. As of 2003, the World Health Organization (WHO) emphasizes the importance of an interdisciplinary approach to pain treatment that takes this complexity into account.

Types of Pain

Pain can be classified as either acute or chronic. Acute pain is a direct biological response to disease, inflammation, or tissue damage, and usually lasts less than one month. It may be either continuous or recurrent (e.g., sickle cell disease). Acute pain serves the long-term wellbeing of humans and the higher animals by alerting them to an injury or condition that needs treatment. In humans, acute pain is often accompanied by anxiety and emotional distress; however, its cause can usually be successfully diagnosed and treated. Some researchers use the term “eudynia” to refer to acute pain.

In contrast, chronic pain has no useful biological function. It can be defined broadly as pain that lasts longer than a month following the healing of a tissue injury; pain that recurs or persists over a period of three months or longer; or pain related to a tissue injury that is expected to continue or get worse. Chronic pain may be either continuous or intermittent; in either case, however, it frequently leads to weight loss, sleep disturbances, fatigue, and other symptoms of depression. According to an article in the New York Times, chronic pain is the most common under-lying cause of suicide. Unlike acute pain, chronic pain is resistant to most medical treatments. It is sometimes called “maldynia,” and is considered a disorder in its own right.

Pain that is caused by organic diseases and disorders is known as somatogenic pain. Somatogenic pain in turn can be subdivided into nociceptive pain and neuropathic pain. Nociceptive pain occurs when pain-sensitive nerve endings called nociceptors are activated or stimulated. Most nociceptors in the human body are located in the skin, joints and muscles, and the walls of internal organs. There may be as many as 1,300 nociceptors in a square inch (6.4 square centimeter) of skin. However, there are fewer nociceptors in muscle tissue and the internal organs, as they are covered and protected by the skin. Nociceptors are specialized to detect different types of painful stimuli—some are sensitive to heat or cold, while others detect pressure, toxic substances, sharp blows, or inflammation caused by infection or overuse.

In contrast to nociceptive pain, neuropathic pain results from damage to or malfunctioning of the nervous system itself. It may involve the central nervous system (the brain and spinal cord); the peripheral nervous system (the nerve trunks leading away from the spine to the limbs, plus the 12 pairs of cranial nerves on the lower surface of the brain); or both. Neuropathic pain is usually associated with an identifiable disorder such as stroke, diabetes, or spinal cord injury, and is frequently described as having a “hot” or burning quality.

Psychogenic pain is distinguished from somatogenic pain by the influence of psychological factors on the intensity of the patient’s pain or degree of disability. The patient is genuinely experiencing pain—that is, he or she is not malingering—but the pain has either no organic explanation or else a weak one. Common psychogenic pain syndromes include chronic headache or low back pain; atypical facial pain; or pelvic pain of unknown origin.

Some cases of psychogenic pain belong to a group of mental disorders known as somatoform disorders. According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), somatoform disorders are defined by “the presence of physical symptoms that suggest a general medical condition,” but cannot be fully explained by such a condition, by the direct effects of a drug or other substance, or by another mental disorder. The somatoform disorders include somatization disorder, characterized by chronic complaints of unexplained physical symptoms, often involving multiple sites in the body; hypochondriasis is a preoccupation with illness that persists in spite of the doctor’s reassurance; and pain disorder, characterized by physical pain that is intensified by psychological factors, often becoming the focus of the patient’s life and impairing his or her family relationships and ability to work.

It is important to recognize that some pain syndromes may involve more than one type of pain. For example, a cancer patient may suffer from neuropathic pain as a side effect of cancer treatment as well as nociceptive pain associated with pressure from the tumor itself on nociceptors in a blood vessel or hollow organ. In addition to the somatogenic pain, the patient may experience psychogenic pain related to the loss of physical functioning or attractiveness, coupled with anxiety about the progression or recurrence of the cancer. Other pain syndromes do not fit neatly into either somatogenic or psychogenic categories. A case in point would be certain types of chronic headache that involve the stimulation of nociceptors in the tissues of the head and neck as well as psychogenic factors related to the patient’s handling of stress.

Description

How the Body Feels Pain

A person begins to feel pain when nociceptors in the skin, muscles, or internal organs detect pressure, inflammation, a toxic substance, or another harmful stimulus. The pain message travels along peripheral nerve fibers in the form of electrical impulses until it reaches the spinal cord. At this point, the pain message is filtered by specialized nerve cells that act as gatekeepers. Depending on the cause and severity of the pain, the nerve cells in the spinal cord may either activate motor nerves, which govern the ability to move away from the painful stimulus; block out the painful message; or release chemicals that increase or lower the strength of the original pain message on its way to the brain. The part of the spinal cord that receives and “processes” the pain messages from the peripheral nerves is known as the dorsal horn.

After the pain message reaches the brain, it is relayed to an egg-shaped central structure called the thalamus, which transmits the information to three specialized areas within the brain: the somatosensory cortex, which interprets physical sensations; the limbic system, which forms a border around the brain stem and governs emotional responses to physical stimuli; and the frontal cortex, which handles thinking. The activation of these three regions explains why human perception of pain is a complex combination of sensation, emotional arousal, and conscious thought.

In addition to receiving and interpreting pain signals, the brain responds to pain by activating parts of the nervous system that send additional blood to the injured part of the body or that release natural pain-relieving chemicals, including serotonin, endorphins, and enkephalins.

Factors that Affect Pain Perception

Location and severity of pain. Pain varies in intensity and quality. It may be mild, moderate, or severe. In terms of quality, it may vary from a dull ache to sharp, piercing, burning, pulsating, tingling, or throbbing sensations; for example, the pain from jabbing one’s finger on a needle feels different from the pain of touching a hot iron, even though both injuries involve the same part of the body. If the pain is severe, the nerve cells in the dorsal horn transmit the pain message rapidly; if the pain is relatively mild, the pain signals are transmitted along a different set of nerve fibers at a slower rate.

The location of the pain often affects a person’s emotional and cognitive response, in that pain related to the head or other vital organs is usually more disturbing than pain of equal severity in a toe or finger.

Gender. Recent research has shown that sex hormones in mammals affect the level of tolerance for pain. The male sex hormone, testosterone, appears to raise the pain threshold in experimental animals, while the female hormone, estrogen, appears to increase the animal’s recognition of pain. Humans, however, are influenced by their personal histories and cultures as well as by body chemistry. Studies of adult volunteers indicate that women tend to recover from pain more quickly than men, cope more effectively with it, and are less likely to allow pain to control their lives. One explanation of this difference comes from research with a group of analgesics known as kappa-opioids, which work better in women than in men. Some researchers think that female sex hormones may increase the effectiveness of some analgesic medications, while male sex hormones may make them less effective. In addition, women appear to be less sensitive to pain when their estrogen and progesterone levels are high, as happens during pregnancy and certain phases of the menstrual cycle. It has been noted, for example, that women with irritable bowel syndrome (IBS) often experience greater pain from the disorder during their periods.

Family. Another factor that influences pain perception in humans is family upbringing. Some parents comfort children who are hurting, while others ignore or even punish them for crying or expressing pain. Some families allow female members to express pain but expect males to “keep a stiff upper lip.” People who suffer from chronic pain as adults may be helped by recalling their family’s spoken and unspoken “messages” about pain, and working to consciously change those messages.

Culture and Ethnicity. In addition to the nuclear family, a person’s cultural or ethnic background can shape his or her perception of pain. People who have been exposed through their education to Western explanations of and treatments for pain may seek mainstream medical treatment more readily than those who have been taught to regard hospitals as places to die. On the other hand, Western medicine has been slower than Eastern and Native American systems of healing to recognize the importance of emotions and spirituality in treating pain. The recent upsurge of interest in alternative medicine in the United States is one reflection of dissatisfaction with a one-dimensional “scientific” approach to pain.

There are also differences among various ethnic groups within Western societies regarding ways of coping with pain. One study of African American, Irish, Italian, Jewish, and Puerto Rican patients being treated for chronic facial pain found differences among the groups in the intensity of emotional reactions to the pain and the extent to which the pain was allowed to interfere with daily functioning. However, much more work on larger patient samples is needed to understand the many ways in which culture and society affect people’s perception of and responses to pain.

Demographics

Acute pain, particularly in its milder forms, is a commonplace experience in the general population; most people can think of at least one occasion in the past week or month when they had a brief tension headache, felt a little muscle soreness, cut themselves while shaving, or had a similar minor injury. On the other hand, chronic pain is more widespread than is generally thought; the American Chronic Pain Association estimates that 86 million people in the United States suffer from and are partially disabled by chronic pain. Two Canadian researchers evaluating a set of 13 studies of chronic pain done in North America, Europe, and Australia reported that the prevalence of severe chronic pain in these parts of the world is about 8% in children and 11% in adults. In terms of the economic impact of chronic pain, various productivity audits of the American workforce have stated that such pain syndromes as arthritis, lower back pain, and headache cost the United States between $80 and $90 billion every year.

The demographics of chronic pain depend on the specific disorder, including:

  • Chronic pelvic pain (CPP) is more common in women than in men; it is thought to affect about 14% of adult women worldwide. In the United States, CPP is most common among women of reproductive age, particularly those between the ages of 26 and 30. It appears to be more common among African Americans than among Caucasians or Asian Americans. In addition, a history of sexual abuse before age 15 is a risk factor for CPP in adult life.
  • Lower back pain (LBP) is the most common chronic disability in persons younger than 45. One researcher estimates that 80% of people in the United States will experience an episode of LBP at some point in life. About 3-4% of adults are disabled temporarily each year by LBP, with another 1% of the working-age population disabled completely and permanently. While 95% of patients with LBP recover within six to 12 weeks, the back pain becomes a chronic syndrome in the remaining 5%.
  • Headaches in general are very common in the adult population in North America; about 95% of women and 90% of men in the United States and Canada have had at least one headache in the past twelve months. Most of these are tension headaches. Migraine headaches are less common than tension headaches, affecting about 11% of the population in the United States and 15% in Canada. Migraines occur most frequently in adults between the ages of 25 and 55; the gender ratio is about 3 F:1 M. Cluster headaches are the least common type of chronic headaches, affecting about 0.4% of adult males in the United States and 0.08% of adult females. The gender ratio is 7.5-5 M:1 F.
  • Atypical facial pain is a less-common chronic pain syndrome, affecting one or two persons per 100,000 population each year. It is almost entirely a disorder of adults. Atypical facial pain is thought to affect men and women equally, and to occur with equal frequency in all races and ethnic groups.

Evaluation of Pain

Patient Description and History

A doctor’s first step in evaluating a patient’s pain is obtaining a detailed description of the pain, including:

  • Severity
  • Timing (time of day; continuous or intermittent)
  • Location in the body
  • Quality (piercing, burning, aching, etc.)
  • Factors that relieve the pain or make it worse (temperature or humidity; body position or level of activity; foods or medications; emotional stress, etc.)
  • Its relationship to mood swings, anxiety, or depression

The doctor will then take the patient’s medical history, including past illnesses, injuries, and operations as well as a family history. In some cases, the doctor may need to ask about experiences of emotional, physical, or sexual abuse. The doctor will also make a list of all the medications that the patient takes on a regular basis. Other information that may help the doctor evaluate the pain includes the patient’s occupation and level of functioning at work; marriage and family relationships; social contacts and hobbies; and whether the patient is involved in a lawsuit for injury or seeking workers’ compensation. This information may be helpful in understanding what the patient means by “pain” as well as what may have caused the pain, particularly because many people find it easier to discuss physical pain than anxiety, anger, depression, or sexual problems.

Some doctors may give the patient a brief written pain questionnaire to fill out in the office. There are a number of different instruments of this type, some of which are designed to measure pain associated with cancer, arthritis, HIV infection, or other specific diseases. Most of these rating questionnaires ask the patient to mark their pain level on a scale from zero to 10 or zero to 100 with zero representing “no pain” and the higher number representing “worst pain imaginable” or “unbearable pain.” The patient then answers a few multiple-choice questions regarding the impact of the pain on his or her employment, relationships, and overall quality of life.

Physical Examination

A thorough physical examination is essential in identifying the specific disorders or injuries that are causing the pain. The most important part of pain management is removing the underlying cause(s) whenever possible, even when there is a psychological component to the pain.

Special Tests

Although there are no laboratory tests or imaging studies that can demonstrate the existence of pain as such or measure its intensity directly, the doctor may order special tests to help determine the cause(s) of the pain. These studies may include one or more of the following:

  • Imaging studies, usually x rays or magnetic resonance imagings (MRIs). These studies can detect abnormalities in the structure of bones or joints, and differentiate between healthy and diseased tissues.
  • Neurological tests. These tests evaluate the patient’s movement, gait, reflexes, coordination, balance, and sensory perception.
  • Electrodiagnostic tests. These tests include electromyography (EMG), nerve conduction studies, and evoked potential (EP) tests. In EMG, the doctor inserts thin needles in specific muscles and observes the electrical signals that are displayed on a screen. This test helps to pinpoint which muscles and nerves are affected by pain. Nerve conduction studies are done to determine whether specific nerves have been damaged. The doctor positions two sets of electrodes on the patient’s skin over the muscles in the affected area. One set of electrodes stimulates the nerves supplying that muscle by delivering a mild electrical shock; the other set records the nerve’s electrical signals on a machine. EP tests measure the speed of transmission of nerve impulses to the brain by using two electrodes, one attached to the patient’s arm or leg and the other to the scalp.
  • Thermography. This is an imaging technique that uses infrared scanning devices to convert changes in skin temperature into electrical impulses that can be displayed as different colors on a computer monitor. Pain related to inflammation, nerve damage, or abnormalities in skin blood flow can be effectively evaluated by thermography.
  • Psychological tests. Such instruments as the Minnesota Multiphasic Personality Inventory (MMPI) may be helpful in assessing hypochondriasis and other personality traits related to psychogenic pain.

Treatment

Treatment of either acute or chronic pain may involve several different approaches to therapy.

Medications

Medications to relieve pain are known as analgesics. Aspirin and other nonsteroidal anti-inflammatory drugs, or NSAIDs, are commonly used analgesics. NSAIDs include such medications as ibuprofen (Motrin, Advil), ketoprofen (Orudis), diclofenac (Voltaren, Cataflam), naproxen (Aleve, Naprosyn), and nabumetone (Relafen). These medications are effective in treating mild or moderate pain. A newer group of NSAIDs, which are sometimes called “superaspirins” because they can be given in higher doses than aspirin without causing stomach upset or bleeding, are known as COX-2 inhibitors. The COX-2 inhibitors include celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra).

For more severe pain, the doctor may prescribe an NSAID combined with an opioid, usually codeine or hydrocodone. Opioids, which are also called narcotics, are strong painkillers derived either from the opium poppy Papaver somniferum or from synthetic compounds that have similar effects. Opioids include such drugs as codeine, fentanyl (Duragesic), hydromorphone (Dilaudid), meperidine (Demerol), morphine, oxycodone (OxyContin), and propoxyphene (Darvon). They are defined as Schedule II controlled substances by the Controlled Substances Act of 1970, which means that they have a high potential for abuse in addition to legitimate medical uses. A doctor must have a special license in order to prescribe opioids. In addition to the risk of abuse, opioids cause potentially serious side effects in some patients, including cognitive impairment (more common in the elderly), disorientation, constipation, nausea, heavy sweating, and skin rashes.

If the patient’s pain is severe and persistent, the doctor will give separate dosages of opioids and NSAIDs in order to minimize the risk of side effects from high doses of aspirin or acetaminophen. In addition, the doctor may prescribe opioids that are stronger than codeine—usually morphine, fentanyl, or levorphanol.

The “WHO Ladder” for the treatment of cancer pain is based on the three levels of analgesic medication. Patients with mild pain from cancer are given nonopioid medications with or without an adjuvant (helping) medication. For example, the doctor may prescribe a tranquilizer to relieve the patient’s anxiety as well as the pain medication. Patients on the second “step” of the ladder are given a milder opioid and a nonopioid analgesic with or without an adjuvant drug. Patients with severe cancer pain are given stronger opioids at higher dosage levels with or without an adjuvant drug.

Acute pain following surgery is usually managed with opioid medications, most commonly morphine sulfate (Astromorph, Duramorph) or meperidine (Demerol). In some cases, NSAIDs that are available in injectable form (such as ketorolac) are also used. Patient-controlled analgesia, or PCA, allows patients to control the timing and amount of pain medication they receive. Although there are oral forms of PCA, the most common form of administration involves an infusion pump that delivers a small dose of medication through an intravenous line when the patient pushes a button. The PCA pump is pre-programmed to deliver no more than an hourly maximum amount of the drug.

Some types of chronic pain are treated by injections in specific areas of the body rather than by drugs administered by mouth or intravenously. There are three basic categories of injections for pain management:

  • Joint injections. Joint injections are given to treat chronic pain associated with arthritis. The most common medications used are corticosteroids, which suppress inflammation in arthritic joints, and hyaluronic acid, which is a compound found in the joint fluid of healthy joints.
  • Soft tissue injections. These are given to reduce pain in trigger points (areas of muscle that are hypersensitive to touch) and bursae, which are small pouches or sacs containing tissue fluid that cushions pressure points between tendons and bones. When a bursa becomes inflamed—a condition called bursitis—the person experiences pain in the nearby joint. Corticosteroids are the drugs most often used in soft tissue injections, although the doctor may also inject an anesthetic into a trigger point in order to relax the muscle.
  • Nerve blocks. Nerve blocks are injections of anesthetic around the fibers of a nerve to prevent pain messages relayed along the nerve from reaching the brain. They may be used to relieve pain in specific parts of the body for a short period; a common example of this type of nerve block is the lidocaine injections given by dentists before drilling or extracting a tooth. Some nerve blocks are injected in or near the spinal column to control pain that affects a larger area of the body; an example is the epidural injection given to women in labor or to patients with sciatica. A third type of nerve block is administered to block the sympathetic nervous system as part of pain management in patients with complex chronic pain syndromes.

Medications used to treat neuropathic pain include tricyclic antidepressants, anticonvulsant medications, selective serotonin reuptake inhibitors, topical creams containing capsaicin or 5% lidocaine, and diphenhydramine (Benadryl).

Surgery

Because surgery is itself a cause of pain, few surgical treatments to relieve pain were available prior to the discovery of safe general anesthetics in the mid-nineteenth century. For most of human history, doctors were limited to procedures that could be completed within two to three minutes because the patients could not bear the pain of the operation. Ancient Egyptian doctors gave their patients wine mixed with opium, while early European doctors made their patients drunk with brandy, tied them to the benches that served as operating tables, or put pressure on a nerve or artery to numb a specific part of the body.

Modern surgeons, however, can perform a variety of procedures to relieve either acute or chronic pain, depending on its cause. These procedures include:

  • Removal of diseased or dead tissue to prevent infection
  • Removal of cancerous tissue to prevent the spread of the cancer and relieve pressure on nearby healthy organs and tissues
  • Correction or reconstruction of malformed or damaged bones
  • Insertion of artificial joints or other body parts to replace damaged structures
  • Organ transplantation
  • Insertion of pacemakers and other electrical devices that improve the functioning of damaged organs or help to control pain directly
  • Cutting or destroying damaged nerves to control neuropathic pain

Psychotherapy. Psychotherapy may be helpful to patients with chronic pain syndromes by exploring the connections between anger, depression, or anxiety and physical pain sensations. One type of psychotherapy that has been shown to be effective is cognitive restructuring, an approach that teaches people to “reframe” the problems in their lives—that is, to change their conscious attitudes and responses to these stressors. Some psychotherapists teach relaxation techniques, biofeedback, or other approaches to stress management as well as cognitive restructuring.

Another type of psychotherapy that is effective in treating some patients with chronic pain is hypnosis. Although there is some disagreement among researchers as to whether hypnosis works by distracting the patient’s attention from painful sensations or whether it works by stimulating the release of endorphins (chemicals produced by the body that are released in response to stress or injury and act as natural analgesics), it has been approved by the American Medical Association since 1958 as a treatment for pain. Some therapists offer instruction in self-hypnosis to patients with chronic pain.

Complementary and alternative (cam) approaches cam therapies that are used in pain management include:

  • Acupuncture. Studies funded by the National Center for Complementary and Alternative Medicine (NCCAM) since 1998 have found that acupuncture is an effective treatment for chronic pain in many patients. It is thought that acupuncture works by stimulating the release of endorphins, the body’s natural painkillers.
  • Exercise. Physical exercise stimulates the body to produce endorphins.
  • Yoga. Practiced under a doctor’s supervision, yoga helps to maintain flexibility and range of motion in joints and muscles. The breathing exercises that are part of a yoga practice also relax the body.
  • Prayer and meditation. The act of prayer by itself helps many people to relax. In addition, prayer and meditation are ways to refocus one’s attention and keep pain from becoming the center of one’s life.
  • Naturopathy. Naturopaths include dietary advice and nutritional therapy in their treatment, which is effective for some patients suffering from chronic pain syndromes.
  • Hydrotherapy. Warm whirlpool baths ease muscular and joint pain.
  • Music therapy. Music therapy may involve listening to music, making music, or both. Some researchers think that music works to relieve pain by temporarily blocking the “gates” of pain in the dorsal horn of the spinal cord, while others believe that music stimulates the release of endorphins.

Pain Management

Pain management refers to a set of skills and techniques for coping with chronic pain. The goal of pain management is not complete elimination of pain; rather, the patient learns to keep the pain at a level that he or she can tolerate, and to make the most of life in spite of the pain. The American Chronic Pain Association (ACPA) lists seven coping skills that help in managing pain:

  • Not dwelling on physical pain symptoms
  • Emphasizing abilities rather than disabilities
  • Recognizing one’s feelings about the pain and discussing them freely
  • Using relaxation exercises to ease the emotional tension that makes pain worse.
  • Doing mild stretching exercises every day (with medical approval)
  • Setting realistic goals for improvement and evaluating them on a weekly basis
  • Affirming one’s basic rights: the right to make mistakes, the right to say no, and the right to ask questions

An important part of pain management is participation in a multidisciplinary pain program. Many hospitals and rehabilitation centers in the United States and Canada offer pain management programs. Ideally, the program will have its own unit apart from patient care areas. Good pain management programs offer comprehensive treatment that includes relaxation training and stress management techniques; group therapy, family therapy, personal counseling, and job retraining; physical therapy, including exercise and body mechanics; patient education regarding medications and other aspects of pain management; and aftercare or follow-up support.

The treatment team in a pain management program is usually headed by a neurologist, psychiatrist, or anesthesiologist with specialized training in pain management. Other members of the team include registered nurses, psychiatrists or psychologists, physical and occupational therapists, massage therapists, family therapists, and vocational counselors.

Clinical Trials

As of December 2003, the National Institutes of Health (NIH) was sponsoring 35 studies related to various chronic pain conditions and the effectiveness of such treatments as acupuncture, hypnosis, yoga, COX-2 inhibitors, and several experimental drugs.

Special Concerns

Pain Management in Special Populations

Pain management in the elderly and in children poses additional challenges. Although 20% of adults over 65 take an analgesic on a regular basis, older people are more vulnerable to the drug’s side effects, particularly the nausea and bleeding that sometimes results from long-term use of NSAIDs. Children require special attention because they do not have an adult’s ability to describe their pain. New tools have been developed since the mid-1990s to measure pain in children and to help doctors understand their nonverbal cues.

Addiction and Withdrawal

Doctors have debated the risk of opioid abuse for most of the past century. For many years, patients with severe chronic pain were not given enough of the drugs they needed to control their pain because of the fear that they would become addicted to the narcotics. In the mid-1980s, however, some experts in pain management argued that the risk of addiction was quite low, whether the patients suffered from cancer pain or from chronic pain unrelated to cancer. As a result, some synthetic narcotics—most notably oxycodone (OxyContin)—were widely prescribed and a growing number of patients became addicted to these drugs. As of 2003, researchers estimate that 3-14% of the population may have an underlying undiagnosed vulnerability to abuse these substances.

In addition to the risk of abuse, there is a risk of withdrawal symptoms and a temporary increase in pain (known as rebound pain) if opioid medications are dis-continued suddenly. Withdrawal symptoms include diarrhea, runny nose and watery eyes, restlessness, insomnia, anxiety, nausea, and abdominal cramps. These symptoms are usually treated with clonidine (Catapres), an antihypertensive drug, and NSAIDs or antihistamines. The various risks of long-term use of opioids in pain management are not yet fully understood.