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
Analgesia
Analgesia
Analgesia is the loss of pain without the loss of consciousness.
Techniques for controlling and relieving pain include acupuncture , anesthesia , hypnosis, biofeedback , and the use of 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 in surgery , and to cure disease . In Western medicine the discovery of ether was a landmark in the development of anesthesia. 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.
Presently, efforts are underway to develop powerful nonaddictive pain-relieving drugs. In order to improve the effectiveness and minimize the harm of analgesic drugs, pharmacological research has focused on the mechanism of how analgesics accomplish the task of pain relief. Mechanism in this context means the way the drug works in the body to accomplish its results.
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, further 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 antifever 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-thecounter 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, 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. The blocking of prostaglandin production throughout the body, not just at the site of the pain, is the major theory that is currently accepted among medical scientists, although there are other theories to explain how these drugs work. 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
The treatment of severe pain, like pain that 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 has 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 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. These chemicals are 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 does provide pain relief by occupying receptor sites that block pain signals to the brain. The new group of agonist-antagonist medications show improved performance over morphine for providing pain relief, with fewer side effects and less chance of addiction.
The present challenge for medical science is to find medicines that are as effective as the opiates and morphine for relieving pain but do not have their side effects. Recent research on the brain has uncovered how endorphins and other related brain chemicals work, and provides hope for improved analgesic drugs.
See also Novocain.
Resources
books
Berkow, Robert and Andrew J. Fletcher. The Merck Manual ofDiagnosis and Therapy. Rahway: Merck Research Laboratories, 1992.
Gold, Mark S., and Michael Boyett. Wonder Drugs: How TheyWork. New York: Simon & Schuster, 1987.
Kehrer, James P., and Daniel M. Kehrer. Pills and Potions. New York: Arco, 1984.
McCaffery, Margo, and Alexandra Beebe. Pain: Clinical Manual for Nursing Practice. St. Louis: Mosby, 1989.
McKenry, Leda M., and Evelyn Salerno. Mosby's Pharmacology in Nursing. St. Louis: Mosby, 1989.
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.
Jordan P. Richman
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.
analgesia
The anatomical approach implies the relief of pain by surgery or by injection. Nerve compression, which may occur at several sites, most commonly the sciatica that results from disc protrusion in the spinal canal, or the carpal tunnel syndrome at the wrist, can be cured by operation; and, rarely, severe intractable pain, such as trigeminal neuralgia, which affects the face, may, as a last resort, be treated by division or destruction of the appropriate nerve. Analgesia may also be produced by the injection of a local anaesthetic, generally into the epidural space around the spinal cord, for the relief of pain in childbirth, or when analgesia is required for some days after an operation, or after a major injury which involves fractures of the ribs.
Two recent advances in the understanding of the physiological mechanisms of pain and its suppression have suggested new approaches to pain relief, and have explained the efficacy of some very old methods. The gate control theory of pain, first proposed in 1965 by Patrick Wall (physiologist at University College, London) and Ronald Melzack, has given rise to the use of transcutaneous electrical nerve stimulation (TENS) by means of a small battery-operated apparatus, to produce analgesia. This involves the electrical stimulation of nerves at or adjacent to the painful region, which enter the spinal cord at about the same level. It has been used with some effect for the treatment of chronic pain, and to produce relief during childbirth. The gate control theory also offers a physiological explanation for the efficacy of such psychology-laden folk remedies as rubbing the offending part; the application of cold or of counterirritants such as camphor; cupping; and moxibustion (the burning of small piles of moxa, the common mugwort, on the skin, to produce a blister).
The discovery in 1973 of opiate receptors in the central nervous system led to the search for, and discovery of, endogenous analgesic substances, the endorphins a year later, the assumption of the scientists having been that the receptors must be there for a physiological purpose. The release of these hormones at times of stress explains the phenomenon that pain may not be felt until some considerable time after the injury — the legendary footballer who continues to play with a broken leg, for example. This observation of delayed pain in the wounded, described by the Harvard anesthesiologist Henry Beecher (1907–76) during the 1943 North Africa campaign, was already well-known to earlier army surgeons. Richard Wiseman (1622–76), caring for the injured during the English Civil War, advised that wounds should be cleaned and dressed as soon as possible, before pain began to be felt. The discovery of endorphins has given rise to hopes that analgesics with more specific sites of action than opiates, and without their undesirable side-effects such as constipation, respiratory depression, and addiction, might be synthesized. Both the gate control theory and endorphin release have been invoked in attempts to give physiological respectability to acupuncture for the relief of pain.
The greatest part of pain relief, however, is dependent on pharmacological agents. The relief of acute, intermittent pain, such as during childbirth or dentistry, can be achieved rapidly and effectively by the intermittent inhalation of an analgesic gas or vapour: nitrous oxide, or until recently, when it was judged too expensive to manufacture in pure form, trichlorethylene (trilene). Otherwise pain relief involves the administration, either by mouth or by injection, of analgesic drugs. These come in gradations of effectiveness, and with different mechanisms of action, which make them more appropriate either for acute or chronic requirements. The basis of the most potent analgesics is still the opiates. Opium, the dried juice of the poppy seed capsule, is one of the oldest drugs known. It was mentioned by Homer, and by Aristotle, but until 1805, when the German apothecary Friedrich Wilhelm Sertürner (1783–1841) prepared pure crystals of the active principle — to which the French scientist Gay-Lussac gave the name morphine — it was available only as a crude, unstandardized preparation. Sertürner's researches opened the door to the isolation of many alkaloids, and eventually to the synthesis of morphine derivatives such as diamorphine (heroin), and codeine.
During the 1980s two methods of administration developed which made the patient less dependent on the attention of others; the battery operated syringe pump and electronic, fail-safe, patient-controlled systems. The first may be used when there is the need to provide continuous analgesia in advanced cancer, and the second to relieve pain postoperatively.
Of the milder analgesics, salicylic acid was isolated from willow bark, and its acetyl derivative, better known as aspirin, was prepared in 1897, and was hailed as a wonder drug for its analgesic and antipyretic (fever-controlling) properties. During the first half of the twentieth century it was used for the control of both acute pain and chronic inflammatory conditions such as rheumatic fever. For acute use it has largely been replaced by paracetamol, which came on the market in 1953 and has generally proved a safer analgesic, certainly in children.
Drugs used for the control of long-standing pain include the non-steroidal anti-inflammatory drugs (NSAIDS). The first of these, ibuprofen, resulted from the screening of more than one thousand compounds in the laboratories of Boots of Nottingham, and was patented in 1964. Since then a number of non-steroidals effective in chronic conditions, such as rheumatoid arthritis, have been synthesized, and have been found effective also in relieving postoperative pain. They, and also acetylsalicylic acid, act by preventing the synthesis of prostaglandins, which are to a large extent the cause of the pain, swelling, redness, and fever characteristic of inflammation.
States of ‘altered consciousness’, hypnosis, autohypnosis, euphoria, and psychosomatic conditions such as hysteria, may be accompanied by insensitivity to pain. Hypnosis has been used successfully for obstetric pain relief, and has even been able to produce the profound analgesia necessary for surgical operations, but it is a very time-consuming process. However, even such a simple measure as relieving anxiety can be effective in reducing the severity of pain. Who has not experienced the relief which comes from just making an appointment with the doctor or dentist? In recent years an attempt has been made to relieve psychologically certain — mercifully rare — states of chronic pain that are not susceptible to relief by any of the conventional methods. Often no anatomical or pathological cause can be found, and the condition becomes all-absorbing and is characterized by a state of alienation from ordinary everyday life. Attempts to produce relief have invoked research into medical anthropology — into, for example, the trance-like state which may be entered into to relieve the pain of certain initiation rites. Another approach has been to attempt to dissociate the physical pain from the sufferer's response to it, involving an attempt to rebuild a life around the pain. While much abstruse philosophy has been written about the theory behind this movement, essentially it involves listening to the sufferer, taking his symptoms seriously, and finding some means of taking his mind off them.
David Zuck
Bibliography
Melzack, R. and and Wall, P. (1992). The challenge of pain. Penguin Books, Harmondsworth.
Rey, R. (1998). The history of pain. Harvard University Press, Cambridge, MA.
Sneader, W. (1985). Drug discovery — the evolution of modern medicines. Wiley, Chichester.
See also opiates and opoid drugs; pain.
analgesia
an·al·ge·si·a / ˌanlˈjēzēə; -zhə/ • n. Med. the inability to feel pain.