Authorship note: MRS and JKN contributed equally to this work. Conflict of interest:MJI is an inventor on US patent US 8338457 B2, "Selective ablation of pain-sensing neurons by administration of a vanilloid receptor agonist, " issued to the NIH, and is on the scientific advisory board of Ark Animal Health. JDH has received research support through a cooperative research and development agreement with Sorrento Therapeutics. JKN, ELR, and RMC are employees of Velocity Laboratories, a company that provides fee-for-service behavioral testing using operant pain assays.

Background Detecting behaviors related to orofacial pain in rodent models often relies on subjective investigator grades or methods that place the animal in a stressful environment. In this study, an operant-based behavioral assay is presented for the assessment of orofacial tactile sensitivity in the rat. New Methods In the testing chamber, rats are provided access to a sweetened condensed milk bottle; however, a 360° array of stainless steel wire loops impedes access. To receive the reward, an animal must engage the wires across the orofacial region. Contact with the bottle triggers a motor, requiring the animal to accept increasing pressure on the face during the test. To evaluate this approach, tolerated bottle distance was measured for 10 hairless Sprague-Dawley rats at baseline and 30 minutes after application of capsaicin cream (0.1%) to the face. The experiment was repeated to evaluate the ability of morphine to reverse this effect. Results The application of capsaicin cream reduced tolerated bottle distance measures relative to baseline (p<0.05). As long as morphine did not cause reduced participation due to sedation, subcutaneous morphine dosing reduced the effects of capsaicin (p<0.001). Comparison with Existing Method For behavioral tests, experimenters often make subjective decisions of an animal’s response. Operant methods can reduce these effects by measuring an animal’s selection in a reward-conflict decision. Herein, a method to measure orofacial sensitivity is presented using an operant system. Conclusions This operant device allows for consistent measurement of heightened tactile sensitivity in the orofacial regions of the rat.

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Structured Abstract Objectives To investigate and discuss the effects of cocoa on orofacial pain. Setting and Sample Population The Department of Orthodontics at the University of Florida (UF). Male and female hairless rats (N=20/group) were tested. Materials and Methods Rats were tested using the Orofacial Pain Assessment Device (OPAD) before and after changing their food from the standard chow to a cocoa-enriched or control-equivalent diet. Results Male rats fed the cocoa diet had a significantly higher operant pain index when tested at 37°C as compared to control diet-fed animals. Female rats on the cocoa diet had a significantly higher pain index when tested at 18°C and 44°C, as compared to animals fed the control diet. Capsaicin-induced pain was inhibited, with cocoa-diet male rats having a significantly higher pain index than control-diet male rats and cocoa-diet female rats at both 37°C and 44°C. Cocoa-diet female rats had a significantly higher pain index at 44°C than control-diet females. Mechanical sensitivity was affected following capsaicin cream, with a significantly decreased tolerated bottle distance in both cocoa- and control-diet animals, but there was no difference between cocoa- and control-diet groups. Conclusion Using the OPAD operant system, we demonstrated that a diet rich in cocoa was effective in inhibiting neurogenic inflammatory pain in rats. This has implications for the use of novel alternative therapies such as diet modification for pain control.