Bilateral chronic constriction of the sciatic nerve: a model of long-term cold hyperalgesia

Effects of chronic constriction injury (CCI) and sham surgery of both sciatic nerves were evaluated for reflex lick/guard (L/G) and operant escape responses to thermal stimulation of rats. Experiment 1 compared L/G and escape responses to 0.3 degrees C, 43 degrees C, and 47 degrees C stimulation during a period of 60 days after CCI. Experiment 2 evaluated escape from 44 degrees C, 47 degrees C, and 10 degrees C for 100 days after CCI. The rats escaped from heat or cold stimulation of the paws in a dark compartment by climbing on a thermally neutral platform in a brightly lit compartment. For reflex testing, a single compartment provided no escape option. There was no significant effect of bilateral CCI on reflex or escape responses to nociceptive heat. However, there were long-term increases in the duration of L/G responding during trials of 0.3 degrees C stimulation and in the duration of escape responding to 10 degrees C. Hyperalgesia for cold was confirmed by a preference test, with a 2-compartment shuttle box with one floor heated (45 degrees C) and the other floor cooled (10 degrees C). Occupancy of the heated compartment was significantly increased by CCI (indicating a relative aversion for cold).

For preclinical testing of treatments for allodynia/hyperalgesia after nerve injury, it is crucial to use methods of testing that are sensitive to effects on nociception throughout the neuraxis. Operant escape testing satisfies this criterion and is sensitive to bilateral CCI of rats, which avoids asymmetric postural/motor influences of unilateral CCI.