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【期刊论文】Decreased GDNF mRNA expression in dorsal spinal cord of unilateral arthritic rat
王韵, Ming Fang, Yun Wang, Hong-Xiang Liu, Xue-Song Liu and Ji-Sheng Han CA
Lippincott Williams & Wilkins Vol 11 No 4 20 March 2000,-0001,():
-1年11月30日
This work was supported by the National Natural Science Foundation of China (Grant Nos. 39770848, 39830160), and a grant from NIH (DA 03983), USA. It is now well established that nerve growth factor (NGF) plays a key role in inammation-induced hyperalgesia. It was also reported that brain derived neurotrophic factor (BDNF), another member of neurotrophins, contributed to the pain pathway as a neurotransmitter in the CNS. The present work demonstrated a down-regulation of glial cell line-derived neurotrophic factor (GDNF) mRNA expression in dorsal spinal cord in complete Freund's adjuvant-induced unilateral arthritic rats serving as a chronic pain model. The fast occurring and long lasting down-regulations suggest that GDNF might contribute to pain pathway in a way different from neurotrophins and might play a role in the maintenance of chronic pain status. NeuroReport 11:737-741
Arthritis, Chronic pain, GDNF, Neurotrophin, Rat, Spinal cord
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王韵, M. FANG, Y. WANG, Q. H. HE, Y. X. SUN, L. B. DENG, X. M. WANG AND J. S. HAN *
Neuroscience 117(2003)503-512,-0001,():
-1年11月30日
Neurotrophic factors, such as nerve growth factor and brain-derived neurotrophic factor, are members of the structurally related neurotrophin family that play important roles in pain modulation. Although there are also indications for the involvement of glial cell line-derived neurotrophic factor (GDNF), it is unclear whether and how GDNF is involved in inflammatory pain. In the present study, we studied the expression pattern of GDNF in dorsal root ganglia (DRG) and spinal cord, using confocal microscopy. We demonstrate that GDNF is well associated with nonpeptidergic pain pathway and that GDNF could possibly be anterogradely transported from DRG neurons to superficial spinal cord dorsal horn. We also studied the dynamic changes of GDNF expression in rats during chronic inflammation using injection of complete Freund's adjuvant as a model of chronic pain. We found that GDNF was down-regulated in both dorsal root ganglia and spinal cords 2 weeks after arthritis induction. To assess the impact of this down-regulation on pain transmission, we used a function-blocking antibody against GDNF delivered intrathecally in the same chronic-pain animal models. Injection of this antibody to GDNF produced no immediate effect, but decreased the delayed, bilateral hyperalgesia induced from a unilateral injection of complete Freund's adjuvant. The effect of this antibody coincided with the downregulation of GDNF immunoreactivity in response to inflammation, suggesting that GDNF supports biochemical changes that contribute to hyperalgesia.
GDNF,, pain pathway,, nociception,, arthritis,, IB4
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王韵, Cheng Huang a, Yun Wang a, *, Jaw-Kang Chang b, Ji-Sheng Han a
Neuroscience Letters 294(2000)159-162,-0001,():
-1年11月30日
This work was designed to examine whether brain endomorphins (EM1 and EM2), the endogenous m-opioid ligands, are involved in electroacupuncture (EA)-induced analgesia in the mice. C57BL/6J mice were given EA for 30min and the effect of EA-induced analgesia was assessed by radiant heat tail-ick latency (TFL). Intracerebroventricular (i.c.v.) injection of m-opioid receptor antagonist D-Phe-Cys-Tyr-D-Tyr-Orn-Thr-Pen-Thr-NH2 (CTOP), or antiserum against EM1 or EM2 was performed to see whether EA analgesia could be blocked. The results showed that: (1) i.c.v. injection of CTOP at 25
Endomorphin, m-Opioid receptor, Receptor antagonist, Analgesia, Antiserum, Electroacupuncture
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王韵, Rui-Qing Sun a, Yun Wang a, *, Cheng-Shui Zhao a, Jaw-Kang Chang b, Ji-Sheng Han a
Neuroscience Letters 311(2001)13-16,-0001,():
-1年11月30日
Orphanin FQ (OFQ) and endomorphins (EM) are newly characterized members of opioid peptide family. OFQ has been shown to antagonize morphine analgesia at supraspinal level, whereas endomorphins are highly selective endogenous ligands for mu receptor, showing analgesic effect at both spinal and supraspinal level. OFQ and EM-2 (EM2) immunoreactivity (ir) was measured by radioimmunoassay in nociception-related brain areas of rats subjected to L5/L6 spinal nerve ligation, using shamoperated rats as control. Itwasfound that: (1) the content of EM2-ir of spinal nerve ligated rats showed a significant increase (778%) in periaqueductal gray (PAG), and a significant decrease (43%) in striatum, compared with the control group. (2) a significant increase of the content of OFQ-ir was found in amygdala (1841%) and PAG (1459%), respectively in spinal nerve ligated rats. High pressure liquid chromatography showed that the EM2-ir and OFQ-ir were both heterogeneous with the major part eluting at the position of EM2 and OFQ standard, respectively. These results suggest that spinal nerve ligation induces significant changes in the content of EM2-ir and OFQ-ir in some discrete brain areas, which may play a role in nociceptive modulation.
Nociceptin/, Orphanin FQ, Endomorphins, Neuropathic pain, Radioimmunoassay
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王韵, Zi-Wei Chen, Kui Yang, Yun Wang*, Ji-Sheng Han
Neuroscience Letters 298(2001)199-202,-0001,():
-1年11月30日
Interactions between selective opioid agonists acting at m- and d-opioid receptors were evaluated by co-administering a low-effective dose of the selective m-opioid receptor agonist ohmefentanyl (OMF) with sequentially increasing doses of the selective d-opioid receptor agonist [D-Pen2, D-Pen5] enkephalin (DPDPE). Microphysiometer was used to measure the extracellular acidification rate (ECAR) of living cells in real-time, which re-ected the functional activity after agonistreceptor binding. The synergy (i.e. a more than additive effect) was observed with combinations of these two opioid agonists on differentiated SH-SY5Y cells functionally expressing both m- and d-opioid receptors. The demonstration of the synergy suggests that the agonists of the subtypes of opioid receptors can interact at cellular level.
Ohmefentanyl, [D-Pen2, D-Pen5] Enkephalin, Synergy, Microphysiometer, Extracellular acidification rate, SH-SY5Y cells
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