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


BACKGROUND
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.


CONCLUSIONS
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.
Kato
Kinshi
K
Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima City, Japan. kinshi@fmu.ac.jp
Kikuchi
Shin-ichi
S
Konno
Shin-ichi
S
Sekiguchi
Miho
M
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000378:metabolism* / Q000601:surgery; D007405:Intervertebral Disc Displacement / Q000150:complications* / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000378:metabolism* / Q000601:surgery; D010147:Pain Measurement; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D012585:Sciatica / Q000209:etiology / Q000378:metabolism*; D012701:Serotonin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D013126:Spinal Nerve Roots / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid