Reduced thermal hyperalgesia and enhanced peripheral nerve injury after hind paw inflammation in mice lacking the serotonin‐transporter

作者：Florian Palm, Rainald Mößner, Yong Chen, Lan He, Manfred Gerlach, Stefan Bischofs, Peter Riederer, Klaus‐Peter Lesch, Claudia Sommer · 发表于：European Journal of Pain · 年份：2008 · DOI：10.1016/j.ejpain.2007.11.009 · 被引用次数：29 · 研究领域：Pain Mechanisms and Treatments、Neuropeptides and Animal Physiology、Neuroscience and Neuropharmacology Research

Mice lacking the serotonin-transporter (5-HTT-/- mice) develop reduced thermal hyperalgesia after nerve injury, concomitant with reduced serotonin (5-HT) levels in nervous tissue. Here we investigated pain behaviour in 5-HTT-/- mice compared to their wild type littermates after hind paw inflammation induced by complete Freund's adjuvant (CFA). We used standard tests for pain behaviour, high performance liquid chromatography for measurement of 5-HT, and immunohistochemistry of hind paw skin tissue and L5 dorsal root ganglia (DRG) to measure local inflammation and nerve injury. After intraplantar CFA injection, hyperalgesia to heat was attenuated in 5-HTT-/- mice compared to wild type mice. Their 5-HT levels in nervous and adrenal tissue were reduced. An intraplantar injection of 5-HT four days after CFA transiently brought withdrawal latencies of 5-HTT-/- mice down to the level of wild type mice, thus rescuing the phenotype and supporting the role of 5-HT in the development of CFA-induced thermal hyperalgesia. The density of intraepidermal nerve fibres in plantar skin after CFA injection was reduced to a higher degree in 5-HTT-/- mice than in wild type mice, suggesting greater peripheral nerve injury in the knock-out mice during hind paw inflammation. Accordingly, a higher number of injured DRG neurons was identified by activating transcription factor 3 (ATF3) staining in 5-HTT-/- mice after CFA. We conclude that the phenotype of 5-HTT-/- mice leads to reduced inflammatory pai...