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The Journal of Neuroscience, January 15, 2003, 23(2):708-715

Absence of Thermal Hyperalgesia in Serotonin Transporter-Deficient Mice

Carola Vogel¹, Rainald Mössner², Manfred Gerlach², Thoralf Heinemann², Dennis L. Murphy³, Peter Riederer², Klaus-Peter Lesch², and Claudia Sommer¹

Departments of ¹ Neurology and ² Psychiatry and Psychotherapy, University of Würzburg, 97080 Würzburg, Germany, and ³ Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892

Antidepressants in the treatment of neuropathic pain are thought to partially exert their effect by inhibition of serotonin (5-HT) reuptake and thus activation of central antinociceptive pathways. Mice deficient for the 5-HT transporter (5-HTT/ mice) are regarded as a model of lifelong treatment with a serotonin reuptake inhibitor. Here we investigated 5-HTT/ mice and compared their pain-related behavior after a unilateral chronic constrictive sciatic nerve injury (CCI) with that of wild-type littermates. Wild-type mice reproducibly developed ipsilateral thermal hyperalgesia and mechanical allodynia after CCI. 5-HTT/ mice did not develop thermal hyperalgesia, but showed bilateral mechanical allodynia after the nerve injury. 5-HT levels as measured with HPLC increased after CCI in the injured nerve in both genotypes and decreased in the lumbar spinal cord in wild-type mice. 5-HTT/ mice had significantly lower 5-HT concentrations than wild-type mice in all tissues investigated. Thus, in 5-HTT/ mice, reduced 5-HT levels in the injured peripheral nerves correlate with diminished behavioral signs of thermal hyperalgesia, a pain-related symptom caused by peripheral sensitization. In contrast, bilateral mechanical allodynia, a centrally mediated phenomenon, was associated with decreased spinal 5-HT concentrations in 5-HTT/ mice and may possibly be caused by a lack of spinal inhibition.

Key words: serotonin; serotonin transporter-deficient mice; hyperalgesia; allodynia; neuropathy; chronic constriction injury

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Copyright © 2003 Society for Neuroscience  0270-6474/03/232708-08$05.00/0

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