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.

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Published in PLOS ONE, v. 11, no. 2, e0150164, p. 1-20.

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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This work was supported by grants from the Department of Veterans Affairs and the National Institutes of Health, including R01 NS 046406 to TJM and R01NS6236, R01NS45954, and R01DA37621 to BKT.

Related Content

Data used to generate the main findings of this paper are available from the Dryad database (doi:10.5061/dryad.qs626).

journal.pone.0150164.s001.EPS (345 kB)
S1 Fig. Effect of CCI on baseline escape latency.

journal.pone.0150164.s002.EPS (968 kB)
S2 Fig. Effect of drug administration on time on probes in naive rats.