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Participation of 5-hydroxytryptamine in pain-related behavior induced by nucleus pulposus applied on the nerve root in rats.

AbstractSTUDY DESIGN: The role of 5-hydroxytryptamine (5-HT) in sciatica in lumbar disc herniation (LDH) in rats was investigated. OBJECTIVE: We evaluated the effects of exogenous 5-HT applied on the nerve root on pain-related behavior, the release of endogenous 5-HT in plasma, and the expression of 5-HT2A receptors in dorsal root ganglion (DRG) in a rat LDH model. SUMMARY OF BACKGROUND DATA: In previous studies, 5-HT2A receptor antagonists improved sciatica in patients with LDH and attenuated pain-related behavior induced by nucleus pulposus applied to the nerve root in rats. METHODS: Adult female Sprague-Dawley rats were divided into four experimental groups [control group; low-dose (10 microg) 5-HT-group; high-dose (30 microg) 5-HT-group; and autologous nucleus pulposus (NP) and saline group] and each drug was applied to the L5 nerve root. Von Frey tests were used for pain-behavior testing. To assess levels of endogenous 5-HT released in capillaries surrounding inflamed nerve roots, we measured 5-hydroxyindole acetic acid (5-HIAA), a metabolite of 5-HT. Expression of 5-HT2A receptors in the left L5 DRG was examined by immunohistochemical and immunoblotting analyses in the control and NP groups. RESULTS: Mechanical withdrawal thresholds of the high-dose 5-HT and the NP groups were significantly decreased after surgery compared with the control group and recovered after 14 days in the high-dose 5-HT group. 5-HIAA in plasma was increased by nucleus pulposus applied on the nerve root for 7 days after surgery. The expression of 5-HT2A receptors was enhanced in a time-dependent manner by nucleus pulposus. CONCLUSION: Exogenous 5-HT to the nerve root induced pain-related behavior with short-lasting effects compared with the nucleus pulposus application. 5-HIAA content in plasma and expression of 5-HT2A receptors in DRG neurons increased early time points after the nucleus pulposus application. These results suggest that 5-HT plays a role in the early phase of the chemical pathogenesis of sciatica in LDH in rats.
AuthorsKinshi Kato, Shin-ichi Kikuchi, Shin-ichi Konno, Miho Sekiguchi (Affiliation: Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima City, Japan. kinshi at fmu.ac.jp)
JournalSpine (Spine) Vol. 33 Issue 12 Pg. 1330-6 (May 20 2008) ISSN: 1528-1159 United States
PMID18496345 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Receptor, Serotonin, 5-HT2A
  • Serotonin
  • Hydroxyindoleacetic Acid
Topics
  • Animals
  • Behavior, Animal
  • Blotting, Western
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Female
  • Ganglia, Spinal (metabolism)
  • Hydroxyindoleacetic Acid (blood)
  • Immunohistochemistry
  • Intervertebral Disk (metabolism, surgery)
  • Intervertebral Disk Displacement (complications, metabolism)
  • Lumbar Vertebrae (metabolism, surgery)
  • Pain Measurement
  • Pain Threshold
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A (metabolism)
  • Sciatica (etiology, metabolism)
  • Serotonin (administration & dosage, blood, metabolism)
  • Spinal Nerve Roots (metabolism)
  • Time Factors
  • Up-Regulation