A non-reflexive method based on the variability of temperature and bioimpedance in measuring inflammatory hyperalgesia and analgesia in mice
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Background: Preclinical studies measure withdrawal responses to evoking thermal and mechanical stimuli instead of the more clinically important spontaneous pain. New method: Therefore, we studied the effect of peripheral inflammation induced by intraplantar administration of complete Freund’s adjuvant (CFA) in mice on the variability of temperature and bioimpedance as an index of pain produced by inflammation. To this end, we initially determined mathematical scores based on changes in temperature and bioimpedance (STB) for animals with an inflamed paw and compared these scores with commonly used measures of inflammatory pain. We then pharmacologically validated the tool using dexamethasone. Results: The STB analysis resembled the response found in the von Frey Hair (vFH) test. The CFA-induced increase in STB and vFH tests were reversed by intraperitoneal administration of dexamethasone. The correlation between the STB and vFH measurements showed a high correlation coefficient (R2=0.911, p < 0.001). Comparison with existing method: Our results also demonstrated that CFA paw injection induced mechanical hyperalgesia in mice and remained virtually unaltered during all time-points tested for 5 days, as measured with vFHs. The administration of CFA into the paw induced a large increase in paw volume that was apparent 1 and 5 days after the injection. The CFA injection resulted in a significant (p<0.05) decrease in the response latency to the heat stimulus, as evaluated on day 4 post-CFA injection. Conclusions: The data presented here suggest that STB may provide a novel non-invasive approach for inflammatory pain detection.
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