Evaluation of dynamic weight bearing for measuring nonevoked inflammatory hyperalgesia in mice.

Abstract

Animal models in pain research have suggested that inclusion of both evoked and nonevoked behavioral measures is needed to better reflect the human pain experience. Individuals with chronic pain are known to experience spontaneous pain, in addition to pain after exposure to an external stimulus. Recently, the dynamic weight bearing (DWB) apparatus was developed to assess for nonevoked hyperalgesia by capturing weight bearing and surface distribution in the paws of mice after acute inflammation. The aim of this study was to evaluate the DWB test as a measure of nonevoked hyperalgesia. The experimental group received an intraplantar injection in the left hind paw of the inflammatory agent--complete Freund's adjuvant (CFA)--whereas the vehicle control group received a saline injection and the naive control group had no treatment. Calipers and a plethysmometer were used to verify inflammation and the hot-plate test was used as a measure for stimulus-evoked hyperalgesia. Data were collected at baseline; 3 hours; and 1, 3, and 7 days after injection. Mice injected with CFA showed a statistically significant higher mean paw thickness and volume displacement compared with the vehicle and naive control groups. In the hot-plate testing, CFA-treated mice showed lower response temperature at 7 days compared with the other groups. On the DWB test, CFA-treated mice showed a reduction in the ipsilateral paw load and surface area compared with the contralateral paw load at Days 1, 3, and 7. Mice with inflammation showed alterations in weight bearing as well as increased thermal hyperalgesia in comparison with control groups. These findings support the use of the DWB test as a tool for measuring nonevoked inflammatory hyperalgesia in a mouse model.