Interaction of 5-Hydroxytryptamine and Tumor Necrosis Factor-α to Pain-Related Behavior by Nucleus Pulposus Applied on the Nerve Root in Rats

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.To examine the interaction of 5-HT with TNF for pain-related behavior in a rat lumbar disc herniation (LDH) model.5-HT and TNF have been shown to play roles in sciatica in lumbar disc herniation as chemical factors.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.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.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.