Mouse preferential incising force orientation changes during jaw closing muscle hyperalgesia and is sex dependent

Abstract

Introduction Mouse incising is controlled by a central pattern generator and this activity can change in the presence of pain. The incising frequency and maximum force generation decreases with pain. In this study, we used repetitive acidic injections in the left masseter muscle of male and female mice to determine differences between baseline and jaw muscle pain conditions and the effect of sex on preferential incising direction. Methods A within subject design was used to evaluate data previously acquired using multi-axis force data (X, Y and Z) from the 4th baseline recording day and day 7 post-injection (day of maximal pain response) for each mouse of each sex. A total of 34 female and male (age 3–9 months) CD-1 mice were evaluated. After mathematically rotating the X and Y axes to align the Y axis to be parallel to the wire struts of the cage top, data were analyzed to determine incising direction preference during baseline (non-pain) and pain (day 7) conditions and between sex. Radar plots of X–Y, X–Z and Y–Z axes depicted the average direction of incising preference between baseline and pain conditions for each sex. Statistical differences among groups were tested using a mixed model ANOVA. Results Similar to previous findings, female mice had a more robust difference in incising direction preference when comparing male and female pain conditions and this was most evident in the X–Z axes. The incising frequencies most commonly affected were 5.3, 6.2 and 7.6 Hz. Male mice varied little in their incising direction preference between the baseline and pain conditions. In addition, statistical comparison of ratios of the percent of time spent incising in the Z versus X axes for each incising frequency found that the incising preference was not different when comparing 5.3 and 7.6 Hz frequencies. Finally, female mice used a novel approach to minimize pain while incising by rotating their head and body nearly 180 degrees while males did not use this strategy as frequently. Conclusions The preferred incising direction changes in a jaw muscle pain condition and this information can be used to further characterize functional pain in the masticatory muscle system. The changes were dependent on the incising frequency generated by the central pattern generator for incising.

Mouse incising central pattern generator: Characteristics and modulation by pain

“…Our findings provide for an inhibitory effect of pain on central pattern generator neurons and are based on the finding that the median peak amplitude is decreased in the pain condition compared to the non-pain condition when comparing peak amplitudes at each incising frequency and similar force direction. No statistically significant differences were detected when median peak amplitudes in non-pain and pain conditions were compared without consideration of incising frequency and force direction in our previous study [40]. Median tolerance values observed in the multiple regression analyses for both non-pain and pain conditions were > 0.8 which supports the conclusion that inter-peak intervals and force load duration are equally affected by pain.…”

“…The correlation between inter-peak intervals and force load duration was not found to change in the pain condition. It has previously been shown by us and others that pain increased the inter-peak intervals (or lowered the incising/fictive rhythmic jaw movement frequency) in both male and female mice [40] and male rabbits [37, 38]. In addition, the force peak amplitude of rhythmic bursts was also reduced.…”

Voluntary biting behavior as a functional measure of orofacial pain in mice

“…Some human studies also did not see sex difference in bite force [5,33]. Female mice seem trickier in incising activity [34]. These results suggest that factors such as level of habituation to the test, motivation, physical status and sex may offset the effect of body weight on biting behavior.…”

“…We also noted that the TL mice, particularly females, could alternate the healthy side to incise, which would compensate for the tenderness on the site of tendon injury. Female mice are able to develop a novel incising strategy to accommodate pain, while males do not do so as frequently [34]. There was also a significant difference in preferential incising direction between male and female mice [34].…”

“…Female mice are able to develop a novel incising strategy to accommodate pain, while males do not do so as frequently [34]. There was also a significant difference in preferential incising direction between male and female mice [34]. Repetitive acidic saline injections into the masseter muscle induce decreased incising frequencies and this effect lasts significantly longer in female compared to male mice [52].…”