Home > Encyclopedia of Drugs, Alcohol, and Addictive Behavior > Pain, Drugs Used For

Pain is a sensation unique to an individual. Its perception depends on the injury involved and the situation or context. A bruise obtained in a football game may not be appreciated at the time of the injury, yet in other circumstances the pain from a minor injury, such as stubbing a toe, may be overwhelming. The extent of the injury does not predict the amount of pain experienced; it is this wide variability that makes the treatment of pain difficult.

Within the brain, there are two systems that can appreciate the sensation of pain. One deals with the objective component and tells the exact location of the injury and what type of injury it is. The other is more diffuse and comprises the "hurt." Many people have experienced both types of pain. Touching a hot object or stubbing a toe is quickly followed by the appreciation that an injury has occurred, followed an instant later by the pain. It is this second pain that contains the "suffering," the "hurt," and the elimination of this second pain is the goal of ANALGESIC therapy.

Physicians have divided pains into three general categories. The first, and most common, is termed somatic pain. This results from tissue injury, such as a broken leg, metastases in the bone from cancer, muscle pulls, or ligament sprains. The second is termed visceral pain, which results from activation of pain fibers in internal organs, typically in the abdomen or chest. This category includes discomfort associated with gall bladder disease, peptic ulcers, or pancreatitis, to name a few. Unlike somatic pain, visceral pain is poorly localized. The most difficult pain to understand and to treat is deafferentation, or neuropathic pain, which is a consequence of injury to nerves. It is difficult for patients to describe these sensations, but they often use terms such as "burning," "shooting," or "electriclike." This type of pain is commonly seen in cancer patients where tumors invade nerve bundles. It also is seen with mild damage to nerves. The most common class of injury is the peripheral neuropathies. This collection of disorders results from a wide variety of causes; it affects nerves as they course through the body. The longest nerves are most sensitive to injury, which explains why this type of pain is most likely to develop in the feet. Diabetes is one of the most common causes. A special type of pain also falling in this classification is postherpetic neuralgia, a burning and/or shooting pain associated with Herpes zoster, known as shingles.

When considering pain, it is important to classify it as either acute (short-term) or chronic (long-term). The duration of many kinds of pain can be anticipated. The acute pain associated with surgery is usually limited in duration and, over the period of several days, decreases markedly. In contrast, the chronic pain associated with disseminated cancer can often be severe and persistent, actually increasing over time. Acute pain is associated with a number of very specific symptoms that are usually recognized by others—making it relatively easy to be believed. Patients may be pale and sweaty, the heart may be beating rapidly, and they may be grimacing. Chronic pain is different; it is usually defined as pain that persists for six months or longer. Many of the signs we see acutely wear off during this time, despite the continued pain, leading some observers to conclude that the pain is minimal or even absent; this conclusion is incorrect and often leads to undertreatment and therefore unnecessary suffering. Despite the sophistication of modern medicine, the most accurate estimate of pain remains simply to ask the patient. Chronic pain may seem to have no cause, at times, may be difficult to evaluate or treat, and often requires specialists. Special pain clinics exist for such cases.

Pain medicines (analgesics) are often broken into three major groups. The first group comprises the most commonly used drugs—aspirin, acetaminophen, and related compounds; these drugs are effective for mild to moderate pain. The second group include the OPIOIDS (OPIATES). Some opioids are used for moderate pain while others are typically employed for more severe pain. Thirdly, there are a number of drugs used either for specific pain syndromes or in conjunction with the first two groups. The agents in this last group are termed adjuvant drugs.

The choice of analgesic is based on both the type of pain and its intensity. Most pain is treated in a standardized fashion. Initial therapy often utilizes aspirin, ibuprofen, or acetaminophen. These agents are available without prescription and can be very effective for mild to moderate types of pain. They have a number of properties that make them excellent analgesics. Their effectiveness against a wide variety of different types of pain and their oral dosage greatly enhance their utility. Unfortunately, these agents exhibit relatively low ceiling effects. This means that the maximal degree of analgesia that can be obtained by a drug can be limited, regardless of the dose. These drugs also reduce fevers and help with the muscle aches commonly associated with viral diseases, such as colds and influenza.

Typically, these agents act at the site of injury, leading to their classification as peripherally acting drugs as opposed to centrally acting drugs, such as the opiates, which work within the brain and spinal cord. These nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin work directly on the mechanisms of inflammation, which explains their effectiveness against arthritis. Ibuprofen became the first nonsteroidal drug approved for sale without a prescription, based on its long use and excellent safety record. Over the years, a number of additional drugs have been developed, many with analgesic potencies approaching those of morphine (Table 1). All of these require prescriptions and carry risks greater than the drugs available over the counter. Side effects include a tendency to irritate the stomach and to interfere with the actions of platelets, a blood cell important in clotting; therefore, aspirin and the nonsteroidal anti-inflammatory drugs should be avoided in patients with ulcer disease, since the drugs can cause bleeding. Acetaminophen does not irritate the stomach and does not interfere with platelets—however, it has its own potential problems. Although it is one of the safest drugs available when used as directed, overdoses with acetaminophen can be very dangerous. Overdoses are associated with major damage to the liver, which can be life-threatening. Care must be taken to use only the recommended doses of acetaminophen.

As an alternative to NSAIDs, a new class of drugs, COX-2 (cyclooxygenase-2) inhibitors, are being used to treat and manage arthritis pain and inflammation. Three COX-2 inhibitors have been developed: celecoxib (brand name Celebrex), rofecoxib (brand name Vioxx), and meloxicam (brand name Mobic). Meloxicam is the most recent of the three, having been approved by the Food and Drug Administration (FDA) in April 2000, while Celebrex, the first to be marketed, became the fastest-selling drug in history.

COX-2 inhibitors, when compared to NSAIDs, are better for the intestinal and stomach linings (Kubetin, 2000). On the other hand, like NSAIDs, they have been found to cause renal (kidney) side-effects, such as reductions in filter rates (McCarthy, 2000).

Opioids work within the brain and spinal cord to relieve the second pain—the hurt—described above. In this regard, they are amazing, since they take away pain without interfering with other sensations, unlike local anesthetics. It is this ability to selectively act on the hurt that makes them so valuable. A number of opioids are used for moderate pain (see Table 1). Of these, CODEINE is the most widely used, both alone and in combination with the nonopioids described above, followed by OXYCODONE. Both are usually used in combination with either aspirin or acetaminophen. The peripheral and central analgesics's work complement each other. If they work well together, they also bring with them the side effects of all the ingredients. Thus, both codeine and oxycodone produce constipation and sedation, along with occasional nausea, while the aspirin or acetaminophen have the problems noted above. Propoxyphene is another opioid used for mild to moderate pain. Like the others, it is most often used in combination with aspirin or acetaminophen. Standard doses are not much more effective than aspirin or acetaminophen alone, but at sufficiently high doses propoxyphene is an effective painkiller.

Pentazocine is a relatively unusual analgesic. It is an opioid indicated for moderate pain, but unlike morphine and codeine, which act primarily through mu receptors, pentazocine works in part through kappa receptors. Caution must be used when taking this agent along with other opioids, since it is a mixed AGONIST / ANTAGONIST and can precipitate WITHDRAWAL symptoms in dependent people. Many opioid addicts report an "allergy" to pentazocine when being treated by physicians, to avoid the possibility of withdrawal.

For more severe pain, a number of highly potent opioids are available (see Table 1). They include MORPHINE, hydromorphone, levorphanol, MEPERIDINE, and METHADONE. All are available orally. Morphine is now available in special slow-release formulations, which permit dosing as infrequently as every twelve hours. This is much more convenient for patients, particularly at night, when they no longer have to awaken to take their medicines. Special care must be taken when using these long-acting analgesics. Slow-release morphine, like methadone, may take days to reach stable levels in the blood. Thus, it can be difficult to adjust dosages without "overshooting"—which, if severe, can lead to OVERDOSES that may be life-threatening.

In hospitals, many patients receive opiates by injection or intravenously. Doses need to be adjusted to compensate for differing distributions and metabolism, but these changes are relatively straightforward for physicians working in the area of pain. Special devices are also available that permit patients to dose themselves, as needed, within specified guidelines. This approach is termed patient controlled analgesia (PCA). Even more sophisticated routes of administration are available. Some medications can be injected deep in the back, adjacent to the spinal canal (epidurally) where they can act primarily on the spinal cord. Localizing the medication to the spinal cord can minimize the side effects produced in the brain, such as nausea and respiratory depression.

The chronic use of opioids leads to a lessening of potency, which is termed tolerance. To overcome this, it may be necessary to increase the dose to maintain a constant effect. Furthermore, all patients taking sufficient quantities of drug for an extended time will become physically dependent—that is, they will experience some withdrawal if the drug is stopped. Very few patients taking opioids for medicinal purposes will ever become addicted, as the term is now used by psychiatrists. This distinction between the standard physiological responses of TOLERANCE / DEPENDENCE and ADDICTION is important, because fear of addiction should not interfere with the appropriate medical therapy of pain.