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Metabolic relationship between periaqueductal gray and rostral ventromedial medulla reflects chronic neuropathic pain

  • P1-323
  • Geehoon Chung:1 Chang-Eop Kim:2 Jun Kim:2 Sang Jeong Kim:1,2 
  • 1:Department of Brain&Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea 2:Department of Physiology, College of Medicine, Seoul National University, Seoul, Korea 

Ventrolateral Periaqueductal gray (VL-PAG) integrates pain modulation signals from various brain areas and sends signal to rostral ventromedial medulla (RVM), thus modulates pain signals from spinal cord. In this study, we investigated the change of the PAG property following chronic neuropathic pain. Brain glucose metabolism was measured with 18F-Fluorodeoxyglucose (FDG) - Positron Emission Tomography (PET) scan from neuropathic pain animals and control animals. Analysis of brain images revealed that glucose metabolism of VL-PAG and RVM were negatively correlated to each other in neuropathic pain group but not in control group. This negative correlation may reflect altered property of PAG-RVM function which is responsible for modulation of endogenous analgesic system. As PAG contains GABAergic inhibitory neurons which give tonic inhibition to all pathways in the PAG, we hypothesized that the inhibitory influences on PAG neurons are increased during pain state and increased inhibitory influence disrupts activation of analgesic function. To verify this issue, PAG neurons projecting to RVM were labelled by retrograde tracing technique and inhibitory inputs they receive were measured from acute slice. Indeed, frequency and amplitude of spontaneous inhibitory postsynaptic current were increased in pain animals compared to control animals. To provoke endogenous analgesic function, VL-PAG neurons were activated by in-vivo administration of metabotropic glutamate receptor agonist. Activation of the VL-PAG neurons induced powerful analgesic effect sufficient to cancel out neuropathic mechanical allodynia. During this analgesic state, another FDG-PET scan was performed and result showed that the neuropathic pain-induced negative correlation between PAG-RVM was reversed to positive correlation. Interestingly, metabolic response to this interference was different between neuropathic pain group and control group, suggesting altered capability of the glutamate receptors in PAG region during chronic neuropathic pain state.

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