Comparison of operant escape and reflex tests of nociceptive sensitivity

• Stimulus–response functions for reflexes and operant escape are compared.
• Assessment of neuropathic pain is compared for reflexes and operant escape.
• Sex, age and stress effects on reflex and escape responding are compared.
• Reflex and escape effects of morphine and cholinergic denervation are compared.
• Control procedures for reflex and escape effects are discussed.

Testing of reflexes such as flexion/withdrawal or licking/guarding is well established as the standard for evaluating nociceptive sensitivity and its modulation in preclinical investigations of laboratory animals. Concerns about this approach have been dismissed for practical reasons – reflex testing requires no training of the animals; it is simple to instrument; and responses are characterized by observers as latencies or thresholds for evocation. In order to evaluate this method, the present review summarizes a series of experiments in which reflex and operant escape responding are compared in normal animals and following surgical models of neuropathic pain or pharmacological intervention for pain. Particular attention is paid to relationships between reflex and escape responding and information on the pain sensitivity of normal human subjects or patients with pain. Numerous disparities between results for reflex and operant escape measures are described, but the results of operant testing are consistent with evidence from humans. Objective reasons are given for experimenters to choose between these and other methods of evaluating the nociceptive sensitivity of laboratory animals.