Evaluation of TRPV1 on Thermal Operant Orofacial Pain Behaviors

Objective: A large body of evidence exists supporting a role for the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1) in noxious-mediated responses. The goal of this study was to investigate the role of TRPV1 on orofacial pain. Methods: We used a mouse operant thermal pain testing system to assess orofacial pain. TRPV1 knock-out (k.o.) and wild-type (w.t.) CB57BL6 mice (20-30g, age- and sex-matched) were fasted overnight and placed in the operant testing chamber that was equipped with a reward sipper tube (sweetened milk) and a thermode stimulus (range: 37-55°C). In order to obtain this reward, mice would choose to make facial contacts with the thermode to complete the task. An event was recorded with each thermode and reward bottle contact. Depending on the stimulus temperature, the mice made a decision to continue or cease receiving the reward. We evaluated the number of reward licks as our outcome measure using Labview/Excel (custom routines generously provided by Dr. Charles Widmer). Results: There was a significant temperature effect on reward licking for both CB57BL6 (F_2,32=13.37,P<0.001) and TRPV1 k.o. (F_2,32=28.86,P<0.001) mice. For the w.t. mice, there was a significant decrease (P<0.05) in licks at 48°C (694±123) and 55°C (166±36) as compared to baseline 37°C (1104±135). For TRPV1 k.o. mice, there was a significant decrease in licking at 55°C (274±55) as compared to 48°C (1246±79) and 37°C (1419±114). TRPV1 k.o. mice had significantly higher licks at 48°C (P<0.05), but similar licks at 37°C and 55°C, as compared to the w.t. mice. Conclusion: Our data indicates that TRPV1 modulates thermal sensitivity in the face at noxious hot (48°C), but not ultrahot (55°C) temperatures. This study validates the use of this operant system in mice and has implications for completing further mechanistic studies relating to TRPV1 and trigeminally-mediated pain. Support: NIH-NIDCR grant T32DE007200.