Assessment of Postoperative Analgesic Efficacy and Animal Well-Being Using a Novel Triaxial Accelerometer Device, the Rodent Fitbit-Like Telemetry Device
Accurate postoperative pain management is crucial for good animal welfare and science. We sought to evaluate mouse postoperative pain management efficacy by measuring activity using a novel triaxial acceleration device—the Rodent Fitbit-like telemetry device (RFB)—to monitor home cage activity. To determine if analgesics impacted activity levels, we evaluated activity in C57BL/6 male and female mice (n = 6) that were attached with the RFB and administered EthiqaXR (XR; 3.25 mg/kg), meloxicam sustained release (MSR; 6 mg/kg), combined XR/MSR, or bupivacaine (5 mg/mL) compared with control mice provided sterile saline (5 mL/kg) subcutaneously. Activity in XR/MSR and XR-treated mice was significantly increased on night 0 (N0) but only trended downward from N2 to N4 compared with baseline. No significant changes in activity were detected after administration of MSR, bupivacaine, and saline. We examined the effective analgesic period of XR, MSR, XR/MSR, and bupivacaine based on electric von Frey and the RFB using a hind paw incision pain model in C57BL/6 male (n = 8) and female mice (n = 7) attached with the RFB. Preoperative XR and XR/MSR mice had reduced pain based on von Frey with no reduction in activity based on the RFB compared with other treatment groups. Only mice provided saline demonstrated a significant decrease in activity on N0, suggesting limited duration of spontaneous pain elicited from the minor pain model. In summary, activity was an effective and sensitive indicator for detecting pain using a paw incision pain model in C57BL/6 mice within the first 24 h postsurgery. Additional studies using a major operative procedure should be performed to determine the effectiveness of activity as a pain detection indicator.
Experimental diagram outlining (A) part I, aim 1; (B) part I, aim 2; and (C) part II, aim 1 and aim 2. VF, electronic von Frey.
The Rodent Fitbit-like telemetry device contains (A) an outer case, (B) the internal sleeve, and (C) the RFB accelerometer device with a T&E 3-V CR1025 lithium battery. (D) Device was sutured externally along the nape of mice. The device dimensions are 9 mm × 7 mm × 3 mm.
Part I, aim 1: impact of RFB device on activity levels in control (nonattached) and RFB-attached B6 mice. No statistically significant difference was demonstrated between control and RFB mice nor between male and female mice. *Distance traveled relative to time was found to be statistically significant compared with initial starting activity (10 min) by 2-way repeated measure ANOVA (P < 0.05).
Part I, aim 2: locomotor activity measurement (normalized acceleration of gravity; mean ± SEM) without surgical manipulation in B6 mice. Arrow indicates the day of analgesic administration. *Acceleration of gravity (activity) was significantly higher (P < 0.05) from baseline in 2 treatment groups based on 2-way repeated measure ANOVA.
Part II, aim 1: mechanical hypersensitivity (force; mean ± SEM) with B6 mice provided saline, bupivacaine, MSR, XR, or XR and MSR on the (A) ipsilateral (surgical) and (B) contralateral (naïve) paw. Arrow indicates the day of surgery. *Hypersensitivity was significantly lower (P < 0.05) from baseline in some treatment groups on some nights based on 2-way repeated measure ANOVA.
Part II, aim 2: locomotor activity measurement (normalized acceleration of gravity; mean ± SEM) with surgical manipulation of right hind paw in B6 mice. Arrow indicates the day of surgery. *Acceleration of gravity (activity) was significantly different (P < 0.05) from baseline for 2 treatment groups at N0 based on 2-way repeated measure ANOVA.
Part II, aim 3: plasma concentration (ng/mL; mean ± SEM) in male and female B6 mice treated with either (A) MSR or (B) XR assessed at each time point over 96 h (n = 3/group/time point). The horizontal dashed line represents the purported therapeutic plasma concentrations for MSR and XR, which have been reported at 911 and 1 ng/mL, respectively.
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