Measuring Behavior 2005: Negus

Preclinical assessment of analgesic drugs in assays of acute pain

S.S. Negus

Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, Belmont, MA, USA

Pain is a pervasive public health problem, and analgesic drugs play a central role in its treatment. Currently, the most widely used analgesics include mu opioid agonists such as morphine and non-steroidal anti-inflammatory drugs (NSAIDS) such aspirin. Although these drugs are useful across a wide range of conditions, they are not uniformly ef.cacious, and undesirable side-effects often limit their use. Consequently, one long-standing focus of drug discovery has been the search for novel analgesics. Meaningful research on pain and analgesia depends on the development of validated procedures for identifying the presence of pain and quantifying its magnitude. Pain has been defined as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.’ As such, pain is essentially a subjective experience, and its existence in humans is typically assessed using some sort of verbal report. Verbal reports are obviously not suitable for measuring pain in animals, and this presents a challenge to preclinical assessment of candidate analgesics. How does one tell if an animal is in pain, and how does one tell if a putative analgesic is effective in reducing that pain? Historically, the most widely used assays for assessment of pain and analgesia in animals have involved three components:

Acute delivery of a thermal, mechanical, chemical or electrical noxious stimulus, which is defined as a stimulus capable of producing tissue damage.
Measurement of a noxious stimulus-evoked behavior, such as tail withdrawal following immersion of the tail in hot water, or abdominal constrictions/writhing after intraperitoneal administration of dilute acetic acid.
Assessment of the ability of drugs to decrease the rate, frequency or intensity of the noxious stimulus-evoked behavior.

In this approach the occurrence of noxious stimulus-evoked behaviors are interpreted as evidence of ‘nociception’, and nociception in animal is thought to be related to pain in humans. Drug-induced decreases in nociception are interpreted as evidence of ‘antinociception’, and antinociception in animals is thought to be related to analgesia in humans. Advantages and disadvantages of this type of assay will be reviewed.

Paper presented at Measuring Behavior 2005 , 5^th International Conference on Methods and Techniques in Behavioral Research, 30 August - 2 September 2005, Wageningen, The Netherlands.