Differentiation between capsaicin-induced allodynia and hyperalgesia using a thermal operant assay

Investigations of new analgesic treatments ideally are coupled with the use of compassionate methods for pain testing in animals. Recently, we described a novel operant thermal testing device that can be used to quantify orofacial pain. The objective of the current study was to differentiate thermal allodynia from hyperalgesia using this operant thermal assay. Rats were trained to complete a task whereby they had a conflict between a positive reward and tolerance for thermal nociceptive stimulation. They were subjected to cool to hot temperatures (24-45 degrees C) and evaluated under naïve (untreated), capsaicin cream (0.075%), capsaicin/morphine, or morphine test conditions. The following outcome measures were evaluated: reward intake; licking contacts; facial contacts; time to complete 25, 50, and 75% of the events (licks and face contacts); facial contact duration; ratio of reward/stimulus contacts; and ratio of facial contact duration/event. Capsaicin produced an increase in mechanical sensitivity and a significant thermal allodynic effect at 42 degrees C and hyperalgesic effect at 45 degrees C. These effects were blocked with morphine pre-treatment. The temporal profile for completing the task was also significantly altered following capsaicin treatment. These data demonstrate that using the operant orofacial assay in conjunction with capsaicin cream can provide a reproducible, sensitive, minimally invasive, and powerful approach for quantifying and studying enhanced thermal pain within the trigeminal system. This technique provides an alternative to reflex tests of orofacial sensitivity, and it presents a pivotal link for translating basic pain research into clinic trial strategies.