Investigating the role of CeA-PAG descending antinociceptive circuitry in inflammatory chronic pain

• Main Authors: Yi Chen Liao, 廖怡甄
• Other Authors: H. L. Wang
• Format: Others
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/32507373570535623844

碩士 === 長庚大學 === 生物醫學研究所 === 100 === Electrical or chemical stimulation of central amygdala nucleus (CeA) inhibits spinal pain transmission and produces an analgesic effect. CeA sends a dense ipsilateral excitatory projection to midbrain periaqueductal gray (PAG) and activates PAG-rostral ventromedial medulla (RVM) descending anti-nociceptive neuronal circuitry. Recently, several lines of evidence suggest that chronic inflammatory pain is due to long-term neuroplastic changes in brain regions, which control pain transmission in the spinal dorsal horn through descending modulatory pathways. Recent studies also suggest that activation of glial cells and a subsequent release of gliotransmitters or proinflammatory cytokines, which modulate neuronal activity and synaptic strength, contribute to the development of pain hypersensitivity after nerve injury or peripheral inflammation. Thus, it is very likely that during chronic inflammatory pain, activation of glial cells in CeA could induce hyperalgesia by causing synaptic plasticity of CeA-PAG projection neurons and attenuate the activity of CeA-PAG-RVM descending antinociceptive circuitry. Intraplantar injection of Complete Freund's adjuvant (CFA) resulted in erythema and edema at the site of injection. Mechanical allodynia was observed in CFA-injected rats within 24 hours after CFA injection and lasted about 7 days. Four days after microinjecting yellow-green fluorescent microspheres into the lateral and ventrolateral PAG of 3 to 4 weeks-old saline or CFA-injected rats, fluorescently labeled CeA-PAG projection neurons were mainly found in the medial division of central amygdala nucleus (CeAM). CFA administration decreased the frequency of spontaneous miniature EPSCs (mEPSCs) in CeAM-PAG projection neuron from CFA-treated rats in the absence of change in the mean amplitude of mEPSCs. CFA injection also increased the frequency of spontaneous IPSCs in CeAM-PAG projection neurons without significantly affecting the mean amplitude of mIPSCs. CFA injection induced the hypertropy and an increase in the number of GFAP-positive astrocytes in the CeAM region. Furthermore, microinjection of fluorocitrate, a metabolic inhibitor of astrocytes, into CeAM area significantly attenuated astrocyte activation and CFA-induced mechanical allodynia. Fluorocitrate also attenuated CFA-induced impairment of excitatory glutamatergic transmission and CFA-induced enhancement of inhibitory GABAergic transmission in CeAM-PAG projection neurons. Our results strongly suggest that astroglial activation is involved in peripheral inflammation-induced synaptic plasticity of CeAM-PAG projection neurons, which impairs the activity of CeAM-PAG descending antinociceptive pathway and causes resulting mechanical allodynia.