Analgesia
Analgesia
Mechanism of nonaddictive analgesics
Mechanism of addictive analgesics
Analgesia is the loss of pain without the loss of consciousness.
Techniques for controlling and relieving pain include acupuncture, anesthesia, hypnosis, biofeedback, and analgesic drugs. Acupuncture is the ancient Chinese practice of inserting fine needles along certain pathways of the body and is used to relieve pain, especially during surgery, and to cure disease. In Western medicine the discovery of ether was a landmark in the development of anesthesia (causing loss of sensation and, usually, consciousness during medical procedures). Other techniques for pain control include electrical stimulation of the skin, massage, and stress-management therapy.
Analgesia is of primary importance for the treatment of injury or illness. The main agents for accomplishing analgesia in medical practice are analgesic drugs. These fall into two main categories: addictive and nonaddictive. Nonaddictive analgesics are generally used for treating moderate to severe pain and can be purchased without a prescription as over-the-counter drugs. More powerful analgesics have the potential for addiction and other undesirable side effects. They are usually used in hospitals or prescribed for relief from severe pain. Pharmacological research has focused on the development of powerful nonaddictive pain-relieving drugs by focusing on how analgesics relieve pain.
Nonaddictive analgesics
While sold under many different brand names, the three main nonaddictive analgesics are aspirin, acetaminophen, and ibuprofen.
Aspirin was first synthesized in 1853 from vinegar and salicylic acid (acetylsalicylic acid). It is a member of the salicin family, which is a bitter white chemical found in willow bark and leaves. The analgesic qualities of willow bark were known to the ancient Greeks and others throughout the ages. In 1898 a German company, Bayer, developed and marketed acetylsalicylic acid from industrial dyes and one year later named it aspirin. It soon became enormously popular as a pain reliever and anti-fever medicine. Its use as an anti-inflammatory for the treatment of arthritis and rheumatism made it the gold standard for readily available pain relief.
One of the major drawbacks of aspirin, however, is its effect on the stomach. It acts as an irritant and can cause bleeding ulcers in persons who take it over a long period of time. Recent research shows that aspirin’s effectiveness not only as an analgesic but also as an anticoagulant makes it useful in the treatment of heart attacks and stroke, as well as in preventive medicine for other diseases.
Acetaminophen, introduced in 1955, is an over-the-counter drug that has become a very popular alternative to aspirin, since it relieves moderate pain without irritating the stomach. For the treatment of arthritis and rheumatism, acetaminophen does not have aspirin’s anti-inflammatory effect, but as a pain and fever reliever it is just as effective as aspirin.
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) first introduced as a prescription drug in 1974. The Food and Drug Administration allowed it to be marketed as an over-the-counter drug in 1984. As an analgesic for minor pain and fever, it has about the same performance as aspirin and acetaminophen. Unlike acetaminophen, however, it can be irritating to the stomach.
Mechanism of nonaddictive analgesics
Pain that is caused by trauma (injury) in the body sets off the creation of a chemical called prostaglandin. The initial pain is caused by the nerve impulse that relays the injury message to the brain. According to the prostaglandin theory, the pain that is felt afterward is due to the prostaglandin at the site of the injury sending pain messages to the spinal cord, which then transmits these messages to the brain.
In 1971, a Nobel prize–winning pharmacologist, Sir John R. Vane (1927–2004), theorized that by blocking the formation of certain prostaglandins, aspirin was able to relieve the inflammation and pain that accompanies the trauma of damaged cells. Even though analgesics like aspirin had been used for centuries, Vane’s discovery was the first real breakthrough in understanding how they work, and interest in prostaglandin research grew rapidly.
How over-the-counter medicines like aspirin, acetaminophen, and ibuprofen are able to temporarily relieve mild to moderate pain and even some severe pain is not completely understood. Although there are multiple theories to explain how these drugs work, the major theory is that they block prostaglandin production throughout the body, not just at the site of the pain. Recent research suggests that aspirin has the ability to shut off communication of pain-transmitting nerves in the spinal cord.
The effectiveness of over-the-counter pain medicine depends on the kind of pain being experienced. Some pain originates in the skin and mucous areas of the body, while other pain comes from the smooth muscles and organs within the body. This latter type of pain is often difficult to pinpoint; it may feel like a generalized dull ache or throb, or may be referred pain, meaning pain that is felt in a part of the body away from its actual source.
Addictive analgesics
Treating severe pain, like that which accompanies heart attack, kidney stones, gallstones, or terminal cancer, requires the use of prescription medicines that are far more potent than nonprescription drugs. Morphine, a drug derived from opium, has a long history of effective relief of severe pain, but it also is addictive and can have dangerous side effects. Morphine and other drugs like it are called opiates.
Unlike nonaddictive drugs, increasing dosages of opiates also increases their analgesic effects. Thus, when they are self-administered, as pain increases, there is a danger of an overdose. Morphine is both a
KEY TERMS
Addictive analgesics— Opiate drugs, like morphine, that provide relief from severe pain.
Agonist-antagonist analgesics— Drugs that provide pain relief in addition to blocking the effects of narcotics; these may be more effective and safer than opiates.
Antagonists— Drugs that block the effects of narcotics.
Endorphins— Biochemicals produced by the brain that act as opiates and reduce pain.
Nonaddictive analgesics— Drugs that relieve minor to moderate and, in some cases, severe pain.
Prostaglandins— Hormone-like substances found throughout the body, some of which are responsible for the pain and inflammation of an injury or illness.
Referred pain— Pain that is felt away from the part of the body in which it originates.
depressant and a stimulant. As a stimulant, it may cause nausea and vomiting, constriction of the pupils of the eye, and stimulation of the vagus nerve, which regulates heartbeat. This stimulation of the vagus nerve interferes with the treatment of pain in coronary thrombosis. Its main side effects—addictive potential, tolerance (dosages must be increased to get the same effect), constipation, and a marked depression of the respiratory system—restrict morphine’s use as an analgesic.
Mechanism of addictive analgesics
The first line of defense against pain in the body is the endorphins, peptides (compounds of amino acids) found in the brain and parts of the central nervous system. Like opiates, they produce a sense of well being (euphoria) and relieve pain. Endorphins are released from a transmitting nerve cell and then bind to the receptor sites of a receiving cell. After an endorphin sends the message to block pain signals to the receptor site, it is annihilated, thus allowing other endorphins to be produced.
Morphine molecules flow through the spaces (synapses) between these sending and receiving cells and position themselves on the receptor sites, locking out endorphins. The morphine molecule sends the same message as the endorphin to block the pain signal. With long-term use of morphine, the endorphins decline in number and so do the receptor sites, leading to the twin problems of addiction and drug tolerance.
Development of new analgesics
The first phase in the development of new analgesics came with the development of narcotic blockers used to help drug addicts who overdose on a narcotic. Since these drugs have the ability to block the effects of morphine, they are called antagonists. They do not, however, provide any pain relief.
A second generation of narcotic antagonists are called agonist-antagonist analgesics. An agonist drug relieves pain by occupying receptor sites that block pain signals to the brain. The new group of agonist-antagonist medications was more effective than morphine for providing pain relief, with fewer side effects and less chance of addiction.
The present challenge for medical science is to find drugs that are as effective as opiates and morphine for relieving pain but without their side effects. Recent brain research has uncovered how endorphins and other related brain chemicals work, providing hope for improved analgesic drugs.
See also Novocain.
Resources
BOOKS
Berkow, Robert, and Andrew J. Fletcher. The Merck Manual of Diagnosis and Therapy. Rahway: Merck Research Laboratories, 1992.
Kehrer, James P., and Daniel M. Kehrer. Pills and Potions. New York: Arco, 1984.
O’Neil, Maryadele J. Merck Index: An Encyclopedia of Chemicals, Drugs, & Biologicals. 13th ed. Whitehouse Station, NJ: Merck & Co., 2001.
Physicians Desk Reference 2003 with Physicians Desk Reference Family Guide. Montvale, NJ: Medical Economics, 2002.
PERIODICALS
Kiefer, D. M. “Chemistry Chronicles: Miracle Medicines.” Today’s Chemist 10, no. 6 (June 2001): 59-60.
OTHER
“Analgesics and Anti-Inflammatory Drugs” Merck. (accessed October 14, 2006) <http://www.merck.com/mmhe/sec02/ch018/ch018d.html>.
“Anesthesia and Analgesia” University of Virginia Health System. <http://www.healthsystem.virginia.edu/internet/ccm/Anesth/aneshome.cfm> (accessed October 14, 2006).
Jordan P. Richman