Mechanical Conflict System: A Novel Operant Method for the Assessment of Nociceptive Behavior

• Published in: PloS one 2016-02, Vol.11 (2), p.e0150164
• Main Authors: Harte, Steven E, Meyers, Jessica B, Donahue, Renee R, Taylor, Bradley K, Morrow, Thomas J
• Format: Article
• Language: English
• Subjects: Analgesics; Analgesics - administration & dosage; Analgesics - therapeutic use; Animal research models; Animals; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - therapeutic use; Avoidance Learning - physiology; Behavior; Biology and Life Sciences; Choice Behavior; Conditioning, Operant - physiology; Conflict, Psychological; Darkness; Diabetes; Diabetic neuropathy; Dose-Response Relationship, Drug; Escape behavior; Escape Reaction - physiology; Ethology - instrumentation; Fear; Foot Injuries - physiopathology; Foot Injuries - psychology; Hyperalgesia - etiology; Hyperalgesia - physiopathology; Hyperalgesia - psychology; Injections, Intraperitoneal; Isoindoles - administration & dosage; Isoindoles - therapeutic use; Laboratory animals; Latency; Ligation; Light; Light - adverse effects; Male; Medicine and Health Sciences; Morphine; Morphine - administration & dosage; Morphine - therapeutic use; Neuralgia; Neuralgia - drug therapy; Neuralgia - etiology; Neuralgia - physiopathology; Neurokinin-1 Receptor Antagonists - administration & dosage; Neurokinin-1 Receptor Antagonists - therapeutic use; Neurology; Neuropathy; Nociceptive Pain - drug therapy; Nociceptive Pain - physiopathology; Nociceptive Pain - psychology; Operant conditioning; Pain; Pain perception; Pharmacology; Physiology; Pregabalin - administration & dosage; Pregabalin - therapeutic use; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Research and Analysis Methods; Rodents; Sciatic Nerve - injuries; Sciatic Nerve - physiopathology; Tachykinin; Tachykinin receptors; Veterans
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0150164

A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor) in rats with neuropathic pain induced by constriction nerve injury (CCI) and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg), morphine (2.5 and 5 mg/kg), and the tachykinin NK1 receptor antagonist, RP 67580 (1 and 10 mg/kg). Results indicate that escape latency increased as a function of probe height in both naive and CCI rats. Pregabalin (10 and 30 mg/kg) and morphine (5 mg/kg), but not RP 67580, decreased latency to escape in CCI rats suggesting an antinociceptive effect. In contrast, morphine (10 mg/kg) but not pregabalin (30 mg/kg) increased escape latency in naive rats suggesting a possible anxiolytic action of morphine in response to light-induced fear. No order effects following multiple test sessions were observed. We conclude that the MCS is a valid method to assess behavioral signs of affective pain in rodents.