Pain: Behavioral Methods For Measuring Analgesic Effects Of Drugs

Pain is a sensation produced by potentially harmful stimuli, such as intense heat, stretching, cutting, or chemical irritation. The ways in which information about these stimuli is carried to the brain and the interpretation that results are very complex. Pain sometimes occurs in the absence of a harmful stimulus, such as in phantom-limb pain (where the limb has long been missing). In other instances, pain is not even felt, although harmful stimuli are present. Thus pain is both a sensation and a response to that sensation. The response to pain can vary depending on the individual and the circumstances. Given this complexity, it is not surprising that pain can be modified in many ways—by a variety of drugs, by hypnosis, and by stimulation such as acupuncture.

PAIN TRANSMISSION

The transmission of pain involves two systems—an ascending and a descending neural system. Ascending neural systems carry information about potentially harmful stimuli from peripheral nerves to the spinal cord and from there to the brain, where information about the emotional and psychological aspects of painful stimuli is incorporated. In addition, the perception of painful stimuli is altered by descending neural systems, which send information from the brain back to the spinal cord. Pain transmission can be altered at any point in this loop. Drugs such as aspirin (an analgesic) relieve pain by reducing pain sensitivity in the periphery. Local anesthetics such as lidocaine (Xylocaine) and procaine (Novocaine) relieve pain by blocking nerve conduction in specific areas. Morphine and other opioids (narcotics) alter pain transmission by interfering with the processing of painful stimuli in the spinal cord and the brain.

MORPHINE AND OTHER OPIOIDS IN HUMAN PATIENTS

Among all the drugs that relieve pain, opium and its derivative morphine, are certainly the best known. When morphine is given to patients who are experiencing severe pain, they often say the pain is less intense or that it no longer exists. Other patients say the pain is still present, but it just does not bother them. Thus, morphine affects both the sensation of pain and the patient's response to the painful stimulus. It is generally believed that morphine acts in both the spinal cord and the brain. In the spinal cord, morphine inhibits the flow of information about painful stimuli from the spinal cord to the brain. In the brain, morphine alters pain perception by modifying activity in the descending pain-control system. In addition to relieving pain, morphine-like drugs produce a sense of pleasure (or euphoria) in some patients. Morphine and other opioids are the most effective drugs known for the relief of pain. Although their usefulness is sometimes limited by the fact that they can produce DEPENDENCE, this is generally not a problem in clinical settings.

NONOPIOID ANALGESICS

Although the opioids are considered the most effective drugs for the treatment of pain, THC (delta9-TETRAHYDROCANNABINOL), the active constituent of MARIJUANA, has some pain-relieving properties, but it is not as effective as morphine in this respect. Very large doses of drugs such as ALCOHOL and the BARBITURATES also appear to relieve pain; however, these effects do not represent true analgesia, since they only occur at doses of alcohol and the barbiturates that produce a loss of consciousness. Thus, the organism's lack of response to painful stimuli is simply an inability to respond.

STUDIES IN LABORATORY ANIMALS

To determine whether a newly-developed compound has pain-relieving properties, scientists use behavioral procedures developed in laboratory animals. In general, these procedures measure the time it takes an organism to respond to a painful stimulus, first when no drug is present and then after a drug is given. Morphine and other opioids consistently alter this and other measures of pain perception. For example, morphine increases the time it takes an animal to remove its tail from a warm water bath, as illustrated in Figure 1. It takes about 2 seconds for the monkey to remove its tail from a warm water bath if morphine is not given. A small amount of morphine increases tail-removal time to about 8 seconds; larger amounts of morphine increase the time to as much as 20 seconds. Modification of pain perception also depends on the intensity of the painful stimulus. If the water in the bath is very hot, only very large amounts of morphine will increase the time it takes animals to withdraw their tail, whereas a lesser amount of morphine will increase response time at lower temperatures. Similarly, some drugs such as BUPRENORPHINE are most effective in relieving pain when the pain is mild. Since buprenorphine also produces less dependence than morphine, it may be a very useful drug for treating mild forms of pain. By combining data about the pain-relieving effects of a drug with data about its likelihood to produce dependence, information is obtained about the usefulness of a new drug in a clinical setting.

(SEE ALSO: Addiction: Concepts and Definitions; Pain: Drugs Used for; Opiates/Opioids)

BIBLIOGRAPHY

BEECHER, H. K. (1959). Measurement of subjective responses. New York: Oxford University Press.

WASACZ, J. (1981). Natural and synthetic narcotic drugs. American Scientist, 69, 318-324.

LINDA DYKSTRA