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Reduced thermal hyperalgesia and enhanced peripheral nerve injury after hind paw inflammation in mice lacking the serotonin-transporter.
Eur J Pain. 2008 Aug; 12(6):790-7.EJ

Abstract

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 pain due to reduced tissue 5-HT levels and to greater peripheral nerve injury after inflammation. Human variants of the 5-HTT genotypes might be part of the factors determining the extent of nerve injury and hyperalgesia in inflammation.

Authors+Show Affiliations

Department of Neurology, University of Würzburg, Neurologische Klinik der Universität, D-97080 Würzburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18187350

Citation

Palm, Florian, et al. "Reduced Thermal Hyperalgesia and Enhanced Peripheral Nerve Injury After Hind Paw Inflammation in Mice Lacking the Serotonin-transporter." European Journal of Pain (London, England), vol. 12, no. 6, 2008, pp. 790-7.
Palm F, Mössner R, Chen Y, et al. Reduced thermal hyperalgesia and enhanced peripheral nerve injury after hind paw inflammation in mice lacking the serotonin-transporter. Eur J Pain. 2008;12(6):790-7.
Palm, F., Mössner, R., Chen, Y., He, L., Gerlach, M., Bischofs, S., Riederer, P., Lesch, K. P., & Sommer, C. (2008). Reduced thermal hyperalgesia and enhanced peripheral nerve injury after hind paw inflammation in mice lacking the serotonin-transporter. European Journal of Pain (London, England), 12(6), 790-7. https://doi.org/10.1016/j.ejpain.2007.11.009
Palm F, et al. Reduced Thermal Hyperalgesia and Enhanced Peripheral Nerve Injury After Hind Paw Inflammation in Mice Lacking the Serotonin-transporter. Eur J Pain. 2008;12(6):790-7. PubMed PMID: 18187350.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced thermal hyperalgesia and enhanced peripheral nerve injury after hind paw inflammation in mice lacking the serotonin-transporter. AU - Palm,Florian, AU - Mössner,Rainald, AU - Chen,Yong, AU - He,Lan, AU - Gerlach,Manfred, AU - Bischofs,Stefan, AU - Riederer,Peter, AU - Lesch,Klaus-Peter, AU - Sommer,Claudia, Y1 - 2008/01/09/ PY - 2007/08/27/received PY - 2007/11/02/revised PY - 2007/11/29/accepted PY - 2008/1/12/pubmed PY - 2008/8/21/medline PY - 2008/1/12/entrez SP - 790 EP - 7 JF - European journal of pain (London, England) JO - Eur J Pain VL - 12 IS - 6 N2 - 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 pain due to reduced tissue 5-HT levels and to greater peripheral nerve injury after inflammation. Human variants of the 5-HTT genotypes might be part of the factors determining the extent of nerve injury and hyperalgesia in inflammation. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/18187350/Reduced_thermal_hyperalgesia_and_enhanced_peripheral_nerve_injury_after_hind_paw_inflammation_in_mice_lacking_the_serotonin_transporter_ DB - PRIME DP - Unbound Medicine ER -