Analgesics as reinforcers with chronic pain: Evidence from operant studies

• Rats with nerve injury self-administer opioids for relief of spontaneous pain.
• Neuropathic pain alters supraspinal mechanisms of opioid self-administration.
• Intrathecal clonidine is self-administered selectively by rats with neuropathic pain.
• Acute but not chronic pain reduces reinforcement from electrical brain stimulation.
• Neuropathic pain reduces opioid stimulation of dopaminergic reward areas.

Previously preclinical pain research has focused on simple behavioral endpoints to assess the efficacy of analgesics in acute and chronic pain models, primarily reflexive withdrawal from an applied mechanical or thermal stimulus. However recent research has been aimed at investigating other behavioral states in the presence of pain, including spontaneous, non-elicited pain. One approach is to investigate the reinforcing effects of analgesics in animals with experimental pain, which should serve as reinforcers by virtue of their ability to alleviate the relevant subjective states induced by pain. The gold standard for assessing drug reinforcement is generally accepted to be drug self-administration, and this review highlights the ability of drugs to serve as reinforcers in animals with experimental neuropathic pain, and the extent to which this behavior is altered in chronic pain states. Additionally, intracranial self-stimulation is an operant procedure that has been used extensively to study drug reinforcement mechanisms and the manner in which neuropathic pain alters the ability of drugs to serve as reinforcers in this paradigm will also be discussed. Drug self-administration and intracranial self-stimulation have promise as tools to investigate behavioral effects of analgesics in animals with chronic pain, particularly regarding the mechanisms through which these drugs motivate consumption in a chronic pain state.