Interaction of 5-hydroxytryptamine and tumor necrosis factor-α to pain-related behavior by nucleus pulposus applied on the nerve root in rats.
METHODS
The effects of exogenous 5-hydroxytryptamine (5-HT), tumor necrosis factor(TNF)-α, 5-HT + TNF in combination, and autologous nucleus pulposus (NP) at dorsal root ganglion (DRG) were examined using rat models.


OBJECTIVE
To examine the interaction of 5-HT with TNF for pain-related behavior in a rat lumbar disc herniation (LDH) model.


BACKGROUND
5-HT and TNF have been shown to play roles in sciatica in lumbar disc herniation as chemical factors.


METHODS
Adult female Sprague-Dawley rats were divided into six groups: 5-HT group, TNF group, 5-HT + TNF (combination) group, NP group, control group, and naive group. Von Frey tests were used for pain-related behavior testing. Expressions of activating transcription factor 3 and calcitonin gene-related peptide (CGRP) were evaluated immunohistochemically. Expressions of TNF, TNF receptor 1 (TNFR1), and 5-HT2A receptors in the left L5 DRG were examined using western blotting. Plasma levels of 5-hydroxyindole acetic acid, a metabolite of 5-HT, were measured.


RESULTS
Mechanical withdrawal thresholds were significantly decreased in the 5-HT, TNF, combination, and NP groups compared with controls. Thresholds recovered after 14 days in the 5-HT and TNF groups, and after 28 days in the combination group. Exogenous 5-HT and TNF to the nerve root induced pain-related behavior and lasted for a shorter period compared with combination and NP groups. Activating transcription factor 3- and calcitonin gene-related peptide-immunoreactive DRG neurons were significantly increased only in the early phase in 5-HT, TNF, combination, and NP groups. TNF induced 5-HT2A receptor expressions in the DRG, while 5-HT induced TNF and TNF receptor 1 expressions.


CONCLUSIONS
The present findings suggest that both 5-HT and TNF induce pain-related behavior and interact with each other to prolong pain-related behavior in a rat LDH model.
Department of Orthopedic Surgery, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan. hkhk0105@yahoo.co.jp
Hiroshi
H
Kobayashi
Shin-ichi
S
Kikuchi
Shin-ichi
S
Konno
Kinshi
K
Kato
Miho
M
Sekiguchi
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D007405:Intervertebral Disc Displacement / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000378:metabolism* / Q000633:toxicity; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000633:toxicity
D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin