Decrease in the descending inhibitory 5-HT system in rats with spinal nerve ligation.
The descending serotonergic (5-HT) system is shown to be plastically altered under pathological conditions such as inflammation or peripheral nerve lesion. Although much evidence indicates that the potentiation of descending facilitatory 5-HT pathways may contribute to the development of chronic pain, the inhibition of descending inhibitory 5-HT system may be functionally more important to the development of central sensitization and neuropathic pain. In the present study, we observed that the inhibitory effects of 5-HT and its receptor agonists including 1A, 1B, 3, 4, and probably 2C receptor agonists, on the C-fiber responses of dorsal horn wide dynamic range (WDR) neurons in the spinal cord decreased significantly following spinal nerve ligation (SNL). Furthermore, we found that the antagonistic effects of 5-HT 1B, 2C, 3, and 4 receptor antagonists on the 5-HT-induced inhibition of C-fiber responses of WDR neurons were also attenuated after SNL. In consistent with these observations, we also found an obvious decrease in the content of 5-HT and 5-HIAA, and a marked increase in the turnover rate of 5-HT (5-HIAA/5-HT) in the ipsilateral dorsal half of the lumbar spinal cord after SNL. These data indicate that a loss or decrease in the descending inhibitory 5-HT system upon the spinal processing of nociceptive information appears to occur following spinal nerve injury, and this kind of decrease in the descending inhibitory 5-HT system is proposed to be involved in the development of central sensitization and ultimately to the nerve injury-induced neuropathic pain.
Neuroscience Research Institute and Department of Neurobiology, Peking University, 38 Xue-Yuan Road, Beijing 100191, PR China.
Feng-Yu
FY
Liu
Xiao-Xiu
XX
Qu
Xu
X
Ding
Jie
J
Cai
Hong
H
Jiang
You
Y
Wan
Ji-Sheng
JS
Han
Guo-Gang
GG
Xing
D000200:Action Potentials; D000818:Animals; D007839:Functional Laterality; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008159:Lumbar Vertebrae; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D009437:Neuralgia / Q000209:etiology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013127:Spinal Nerves / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology*; D013997:Time Factors
D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid