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. 2016 Jun 15;12:1744806916656635.
doi: 10.1177/1744806916656635. Print 2016.

EXPRESS: Voluntary and Evoked Behavioral Correlates in Neuropathic Pain States Under Different Housing Conditions

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Free PMC article

EXPRESS: Voluntary and Evoked Behavioral Correlates in Neuropathic Pain States Under Different Housing Conditions

Claudia Pitzer et al. Mol Pain. .
Free PMC article

Abstract

Background: There is an urgent need to develop and incorporate novel behavioral tests in classically used preclinical pain models. Most rodent studies are based upon stimulus-evoked hindpaw measurements even though chronic pain is usually a day and night experience. Chronic pain is indeed a debilitating condition that influences the sociability and the ability for voluntary tasks, but the relevant behavioral readouts for these aspects are mostly under-represented in the literature. Moreover, we lack standardization in most behavioral paradigms to guarantee reproducibility and ensure adequate discussion between different studies. This concerns not only the combination, application, and duration of particular behavioral tasks but also the effects of different housing conditions implicating social isolation.

Results: Our aim was to thoroughly characterize the classically used spared nerve injury model for 12 weeks following surgery. We used a portfolio of classical stimulus-evoked response measurements, detailed gait analysis with two different measuring systems (Dynamic weight bearing (DWB) system and CatWalk), as well as observer-independent voluntary wheel running and home cage monitoring (Laboras system). Additionally, we analyzed the effects of social isolation in all behavioral tasks. We found that evoked hypersensitivity temporally matched changes in static gait parameters, whereas some dynamic gait parameters were changed in a time-dependent manner. Interestingly, voluntary wheel running behavior was not affected in spared nerve injury mice but by social isolation. Besides a reduced climbing activity, spared nerve injury mice did not showed tremendous alterations in the home cage activity.

Conclusion: This is the first longitudinal study providing detailed insights into various voluntary behavioral parameters related to pain and highlights the importance of social environment on spontaneous non-evoked behaviors in a mouse model of chronic neuropathy. Our results provide fundamental considerations for future experimental planning and discussion of pain-related behavioral changes.

Figures

Figure 1.
Figure 1.
Analysis of nociceptive sensitivity and bodyweight in mice with spared nerve injury (SNI). All left column panels (a–c) show results from animals which were housed in groups (black circular symbols and black bars), all right column panels (d–f) show results from animals which were housed individually (red square symbols and red bars). (a, d) 40% response threshold toward the application of graded von Frey hair filaments. (b, e) response latency on a 2℃ coldplate. (c, f) Analysis of bodyweight changes over basal bodyweight up to 84 days following surgery. N = 6 mice/group, p < 0.05 indicated by * as compared to control group, † as compared to basal values within a group, two-way repeated measures ANOVA with post hoc Tukey test, except for the Coldplate test (b, e), where significant differences were calculated using a t test. All data points represent mean ± SEM.
Figure 2.
Figure 2.
Changes in static weight bearing following SNI. Grouped animals were analyzed using the Dynamic weight bearing system (Bioseb). The ratio of the left over the right hindpaw is shown for (a) paw weight and (b) paw print area. N = 6 mice/group, p < 0.05 indicated by * as compared to control group, † as compared to basal values within a group, two-way repeated measures ANOVA with post hoc Tukey test. All data points represent mean ± SEM.
Figure 3.
Figure 3.
Changes in static weight parameters following SNI in animals which were housed in groups (black circular symbols) (a, b) and animals which were housed individually (red square symbols) (c, d) using the CatWalk system (Noldus).The ratio of the left over the right hindpaw is shown for (a, c) paw intensity contact and (b, d) paw print area. N = 6 mice/group, p < 0.05 indicated by * as compared to control group, † as compared to basal values within a group, two-way repeated measures ANOVA with post hoc Tukey test. All data points represent mean ± SEM.
Figure 4.
Figure 4.
Changes in dynamic gait parameters following SNI in animals which were housed in groups (black circular symbols) (a–d) and animals which were housed individually (red square symbols) (e, f). The ratio of the left over the right hindpaw is shown for (a, e) stance duration, (b, f) swing phase (c, g) stride length, and (d, f) swing phase. N = 6 mice/group, p < 0.05 indicated by * as compared to control group, † as compared to basal values within a group, two-way repeated measures ANOVA with post hoc Tukey test. All data points represent mean ± SEM.
Figure 5.
Figure 5.
Consequence of neuropathic SNI on voluntary wheel running behavior. Mice were analyzed at each timepoint for their 24 h running behavior before (basal), at the day of surgery (OP) and up to 72 days following surgery. (a) Running distance (meter) of SNI and sham mice which were housed in groups except for the voluntary wheel running analysis. (b) Typical running profile of grouped mice at day 21. (c) Running distance (meter) of untrained SNI and sham mice which were housed in groups and only measured once at post-surgery day 28. (d) Running distance (meter) of SNI and sham mice which were housed individually. (e) Running distance (meter) of untrained SNI and sham mice which were housed individually and only measured once at post-surgery day 41. N = 6 mice/group, p < 0.05 indicated by * as compared to control group, † as compared to basal values within a group, two-way repeated measures ANOVA with post hoc Tukey test. All data points represent mean ± SEM.
Figure 6.
Figure 6.
Home cage behavior of mice following neuropathic SNI surgery. Mice were analyzed at each timepoint for their 24 h running behavior before (basal), at the day of surgery (OP) and up to 84 days following surgery. All left column panels (a–d) show results from SNI and sham animals which were housed in groups (black bars) except for the day of home cage monitoring, all right column panels (e–h) show results from SNI and sham animals which were housed individually (red bars). (a, e) Climbing frequency counts per 24-h time period. (b, f) Locomotion frequency counts per 24 h (c, g) Total immobility time (seconds) per 24 h intervals and (d, h) total moving distance (meters) per 24 h. N = 6 mice/group, p < 0.05 indicated by * as compared to control group, † as compared to basal values within a group, two-way repeated measures ANOVA with post hoc Tukey test. All data points represent mean ± SEM.
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