Skip to main content
Top
Published in: Molecular Pain 1/2009

Open Access 01-12-2009 | Research

A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain

Authors: Jing Hu, Zhe Wang, Yan-Yan Guo, Xiao-Nan Zhang, Zhao-Hui Xu, Shui-Bing Liu, Hong-Ju Guo, Qi Yang, Fu-Xing Zhang, Xiao-Li Sun, Ming-Gao Zhao

Published in: Molecular Pain | Issue 1/2009

Login to get access

Abstract

The midbrain periaqueductal grey (PAG) is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA) caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp), one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.
Appendix
Available only for authorised users
Literature
1.
go back to reference Vaccarino AL, Clemmons HR, Mader GJ Jr, Magnusson JE: A role of periaqueductal grey NMDA receptors in mediating formalin-induced pain in the rat. Neurosci Lett 1997, 236: 117–119. 10.1016/S0304-3940(97)00770-2PubMedCrossRef Vaccarino AL, Clemmons HR, Mader GJ Jr, Magnusson JE: A role of periaqueductal grey NMDA receptors in mediating formalin-induced pain in the rat. Neurosci Lett 1997, 236: 117–119. 10.1016/S0304-3940(97)00770-2PubMedCrossRef
2.
go back to reference Guo W, Robbins MT, Wei F, Zou S, Dubner R, Ren K: Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for descending pain facilitation. J Neurosci 2006, 26: 126–137. 10.1523/JNEUROSCI.3686-05.2006PubMedCrossRef Guo W, Robbins MT, Wei F, Zou S, Dubner R, Ren K: Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for descending pain facilitation. J Neurosci 2006, 26: 126–137. 10.1523/JNEUROSCI.3686-05.2006PubMedCrossRef
3.
go back to reference Ji RR, Kohno T, Moore KA, Woolf CJ: Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 2003, 26: 696–705. 10.1016/j.tins.2003.09.017PubMedCrossRef Ji RR, Kohno T, Moore KA, Woolf CJ: Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 2003, 26: 696–705. 10.1016/j.tins.2003.09.017PubMedCrossRef
4.
go back to reference Zhuo M: Glutamate receptors and persistent pain: targeting forebrain NR2B subunits. Drug Discov Today 2002, 7: 259–267. 10.1016/S1359-6446(01)02138-9PubMedCrossRef Zhuo M: Glutamate receptors and persistent pain: targeting forebrain NR2B subunits. Drug Discov Today 2002, 7: 259–267. 10.1016/S1359-6446(01)02138-9PubMedCrossRef
6.
go back to reference Vanegas H, Schaible HG: Descending control of persistent pain: inhibitory or facilitatory? Brain Res Brain Res Rev 2004, 46: 295–309. 10.1016/j.brainresrev.2004.07.004PubMedCrossRef Vanegas H, Schaible HG: Descending control of persistent pain: inhibitory or facilitatory? Brain Res Brain Res Rev 2004, 46: 295–309. 10.1016/j.brainresrev.2004.07.004PubMedCrossRef
7.
go back to reference Bee LA, Dickenson AH: Descending facilitation from the brainstem determines behavioural and neuronal hypersensitivity following nerve injury and efficacy of pregabalin. Pain 2008, 140: 209–223. 10.1016/j.pain.2008.08.008PubMedCrossRef Bee LA, Dickenson AH: Descending facilitation from the brainstem determines behavioural and neuronal hypersensitivity following nerve injury and efficacy of pregabalin. Pain 2008, 140: 209–223. 10.1016/j.pain.2008.08.008PubMedCrossRef
8.
go back to reference Leith JL, Wilson AW, Donaldson LF, Lumb BM: Cyclooxygenase-1-derived prostaglandins in the periaqueductal gray differentially control C- versus A-fiber-evoked spinal nociception. J Neurosci 2007, 27: 11296–11305. 10.1523/JNEUROSCI.2586-07.2007PubMedCrossRef Leith JL, Wilson AW, Donaldson LF, Lumb BM: Cyclooxygenase-1-derived prostaglandins in the periaqueductal gray differentially control C- versus A-fiber-evoked spinal nociception. J Neurosci 2007, 27: 11296–11305. 10.1523/JNEUROSCI.2586-07.2007PubMedCrossRef
9.
go back to reference Behbehani MM: Functional characteristics of the midbrain periaqueductal gray. Prog Neurobiol 1995, 46: 575–605. 10.1016/0301-0082(95)00009-KPubMedCrossRef Behbehani MM: Functional characteristics of the midbrain periaqueductal gray. Prog Neurobiol 1995, 46: 575–605. 10.1016/0301-0082(95)00009-KPubMedCrossRef
10.
go back to reference Porreca F, Ossipov MH, Gebhart GF: Chronic pain and medullary descending facilitation. Trends Neurosci 2002, 25: 319–325. 10.1016/S0166-2236(02)02157-4PubMedCrossRef Porreca F, Ossipov MH, Gebhart GF: Chronic pain and medullary descending facilitation. Trends Neurosci 2002, 25: 319–325. 10.1016/S0166-2236(02)02157-4PubMedCrossRef
11.
go back to reference Fields HL, Malick A, Burstein R: Dorsal horn projection targets of ON and OFF cells in the rostral ventromedial medulla. J Neurophysiol 1995, 74: 1742–1759.PubMed Fields HL, Malick A, Burstein R: Dorsal horn projection targets of ON and OFF cells in the rostral ventromedial medulla. J Neurophysiol 1995, 74: 1742–1759.PubMed
12.
go back to reference Starowicz K, Maione S, Cristino L, Palazzo E, Marabese I, Rossi F, de Novellis V, Di Marzo V: Tonic endovanilloid facilitation of glutamate release in brainstem descending antinociceptive pathways. J Neurosci 2007, 27: 13739–13749. 10.1523/JNEUROSCI.3258-07.2007PubMedCrossRef Starowicz K, Maione S, Cristino L, Palazzo E, Marabese I, Rossi F, de Novellis V, Di Marzo V: Tonic endovanilloid facilitation of glutamate release in brainstem descending antinociceptive pathways. J Neurosci 2007, 27: 13739–13749. 10.1523/JNEUROSCI.3258-07.2007PubMedCrossRef
13.
go back to reference Renno WM: Prolonged noxious stimulation increases periaqueductal gray NMDA mRNA expression: a hybridization study using two different rat models for nociception. Ir J Med Sci 1998, 167: 181–192. 10.1007/BF02937933PubMedCrossRef Renno WM: Prolonged noxious stimulation increases periaqueductal gray NMDA mRNA expression: a hybridization study using two different rat models for nociception. Ir J Med Sci 1998, 167: 181–192. 10.1007/BF02937933PubMedCrossRef
14.
go back to reference Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH: Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 1994, 12: 529–540. 10.1016/0896-6273(94)90210-0PubMedCrossRef Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH: Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 1994, 12: 529–540. 10.1016/0896-6273(94)90210-0PubMedCrossRef
15.
go back to reference Munoz A, Woods TM, Jones EG: Laminar and cellular distribution of AMPA, kainate, and NMDA receptor subunits in monkey sensory-motor cortex. J Comp Neurol 1999, 407: 472–490. 10.1002/(SICI)1096-9861(19990517)407:4<472::AID-CNE2>3.0.CO;2-2PubMedCrossRef Munoz A, Woods TM, Jones EG: Laminar and cellular distribution of AMPA, kainate, and NMDA receptor subunits in monkey sensory-motor cortex. J Comp Neurol 1999, 407: 472–490. 10.1002/(SICI)1096-9861(19990517)407:4<472::AID-CNE2>3.0.CO;2-2PubMedCrossRef
16.
go back to reference Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY: Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 1994, 368: 144–147. 10.1038/368144a0PubMedCrossRef Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY: Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 1994, 368: 144–147. 10.1038/368144a0PubMedCrossRef
17.
go back to reference Wu LJ, Toyoda H, Zhao MG, Lee YS, Tang J, Ko SW, Jia YH, Shum FW, Zerbinatti CV, Bu G, Wei F, Xu TL, Muglia LJ, Chen ZF, Auberson YP, Kaang BK, Zhuo M: Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. J Neurosci 2005, 25: 11107–11116. 10.1523/JNEUROSCI.1678-05.2005PubMedCrossRef Wu LJ, Toyoda H, Zhao MG, Lee YS, Tang J, Ko SW, Jia YH, Shum FW, Zerbinatti CV, Bu G, Wei F, Xu TL, Muglia LJ, Chen ZF, Auberson YP, Kaang BK, Zhuo M: Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. J Neurosci 2005, 25: 11107–11116. 10.1523/JNEUROSCI.1678-05.2005PubMedCrossRef
19.
go back to reference Zhao MG, Ko SW, Wu LJ, Toyoda H, Xu H, Quan J, Li J, Jia Y, Ren M, Xu ZC, Zhuo M: Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain. J Neurosci 2006, 26: 8923–8930. 10.1523/JNEUROSCI.2103-06.2006PubMedCrossRef Zhao MG, Ko SW, Wu LJ, Toyoda H, Xu H, Quan J, Li J, Jia Y, Ren M, Xu ZC, Zhuo M: Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain. J Neurosci 2006, 26: 8923–8930. 10.1523/JNEUROSCI.2103-06.2006PubMedCrossRef
20.
go back to reference Ghelardini C, Galeotti N, Vivoli E, Norcini M, Zhu W, Stefano GB, Guarna M, Bianchi E: Molecular interaction in the mouse PAG between NMDA and opioid receptors in morphine-induced acute thermal nociception. J Neurochem 2008, 105: 91–100. 10.1111/j.1471-4159.2007.05117.xPubMedCrossRef Ghelardini C, Galeotti N, Vivoli E, Norcini M, Zhu W, Stefano GB, Guarna M, Bianchi E: Molecular interaction in the mouse PAG between NMDA and opioid receptors in morphine-induced acute thermal nociception. J Neurochem 2008, 105: 91–100. 10.1111/j.1471-4159.2007.05117.xPubMedCrossRef
21.
go back to reference Berrino L, Oliva P, Rossi F, Palazzo E, Nobili B, Maione S: Interaction between metabotropic and NMDA glutamate receptors in the periaqueductal grey pain modulatory system. Naunyn Schmiedebergs Arch Pharmacol 2001, 364: 437–443. 10.1007/s002100100477PubMedCrossRef Berrino L, Oliva P, Rossi F, Palazzo E, Nobili B, Maione S: Interaction between metabotropic and NMDA glutamate receptors in the periaqueductal grey pain modulatory system. Naunyn Schmiedebergs Arch Pharmacol 2001, 364: 437–443. 10.1007/s002100100477PubMedCrossRef
22.
go back to reference Rylski M, Duriasz-Rowinska H, Rewerski W: The analgesic action of some flavonoids in the hot plate test. Acta Physiol Pol 1979, 30: 385–388.PubMed Rylski M, Duriasz-Rowinska H, Rewerski W: The analgesic action of some flavonoids in the hot plate test. Acta Physiol Pol 1979, 30: 385–388.PubMed
23.
go back to reference Wei F, Wang GD, Kerchner GA, Kim SJ, Xu HM, Chen ZF, Zhuo M: Genetic enhancement of inflammatory pain by forebrain NR2B overexpression. Nat Neurosci 2001, 4: 164–169. 10.1038/83993PubMedCrossRef Wei F, Wang GD, Kerchner GA, Kim SJ, Xu HM, Chen ZF, Zhuo M: Genetic enhancement of inflammatory pain by forebrain NR2B overexpression. Nat Neurosci 2001, 4: 164–169. 10.1038/83993PubMedCrossRef
24.
go back to reference Jia D, Gao GD, Liu Y, He SM, Zhang XN, Zhang YF, Zhao MG: TNF-alpha involves in altered prefrontal synaptic transmission in mice with persistent inflammatory pain. Neurosci Lett 2007, 415: 1–5. 10.1016/j.neulet.2006.12.032PubMedCrossRef Jia D, Gao GD, Liu Y, He SM, Zhang XN, Zhang YF, Zhao MG: TNF-alpha involves in altered prefrontal synaptic transmission in mice with persistent inflammatory pain. Neurosci Lett 2007, 415: 1–5. 10.1016/j.neulet.2006.12.032PubMedCrossRef
25.
go back to reference Robinson D, Calejesan AA, Zhuo M: Long-lasting changes in rostral ventral medulla neuronal activity after inflammation. J Pain 2002, 3: 292–300. 10.1054/jpai.2002.125183PubMedCrossRef Robinson D, Calejesan AA, Zhuo M: Long-lasting changes in rostral ventral medulla neuronal activity after inflammation. J Pain 2002, 3: 292–300. 10.1054/jpai.2002.125183PubMedCrossRef
26.
go back to reference Zhuo M, Gebhart GF: Modulation of noxious and non-noxious spinal mechanical transmission from the rostral medial medulla in the rat. J Neurophysiol 2002, 88: 2928–2941. 10.1152/jn.00005.2002PubMedCrossRef Zhuo M, Gebhart GF: Modulation of noxious and non-noxious spinal mechanical transmission from the rostral medial medulla in the rat. J Neurophysiol 2002, 88: 2928–2941. 10.1152/jn.00005.2002PubMedCrossRef
27.
go back to reference Zhuo M, Gebhart GF: Effects of neonatal capsaicin treatment on descending modulation of spinal nociception from the rostral, medial medulla in adult rat. Brain Res 1994, 645: 164–178. 10.1016/0006-8993(94)91650-0PubMedCrossRef Zhuo M, Gebhart GF: Effects of neonatal capsaicin treatment on descending modulation of spinal nociception from the rostral, medial medulla in adult rat. Brain Res 1994, 645: 164–178. 10.1016/0006-8993(94)91650-0PubMedCrossRef
28.
go back to reference Ren K, Dubner R: Descending modulation in persistent pain: an update. Pain 2002, 100: 1–6. 10.1016/S0304-3959(02)00368-8PubMedCrossRef Ren K, Dubner R: Descending modulation in persistent pain: an update. Pain 2002, 100: 1–6. 10.1016/S0304-3959(02)00368-8PubMedCrossRef
29.
go back to reference Fields HL, Bry J, Hentall I, Zorman G: The activity of neurons in the rostral medulla of the rat during withdrawal from noxious heat. J Neurosci 1983, 3: 2545–2552.PubMed Fields HL, Bry J, Hentall I, Zorman G: The activity of neurons in the rostral medulla of the rat during withdrawal from noxious heat. J Neurosci 1983, 3: 2545–2552.PubMed
30.
go back to reference Calejesan AA, Kim SJ, Zhuo M: Descending facilitatory modulation of a behavioral nociceptive response by stimulation in the adult rat anterior cingulate cortex. Eur J Pain 2000, 4: 83–96. 10.1053/eujp.1999.0158PubMedCrossRef Calejesan AA, Kim SJ, Zhuo M: Descending facilitatory modulation of a behavioral nociceptive response by stimulation in the adult rat anterior cingulate cortex. Eur J Pain 2000, 4: 83–96. 10.1053/eujp.1999.0158PubMedCrossRef
31.
go back to reference Zhuo M: Cortical excitation and chronic pain. Trends Neurosci 2008, 31: 199–207. 10.1016/j.tins.2008.01.003PubMedCrossRef Zhuo M: Cortical excitation and chronic pain. Trends Neurosci 2008, 31: 199–207. 10.1016/j.tins.2008.01.003PubMedCrossRef
33.
go back to reference Toyoda H, Zhao MG, Zhuo M: Enhanced quantal release of excitatory transmitter in anterior cingulate cortex of adult mice with chronic pain. Mol Pain 2009, 5: 4. 10.1186/1744-8069-5-4PubMedCentralPubMedCrossRef Toyoda H, Zhao MG, Zhuo M: Enhanced quantal release of excitatory transmitter in anterior cingulate cortex of adult mice with chronic pain. Mol Pain 2009, 5: 4. 10.1186/1744-8069-5-4PubMedCentralPubMedCrossRef
34.
go back to reference Xu H, Wu LJ, Wang H, Zhang X, Vadakkan KI, Kim SS, Steenland HW, Zhuo M: Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex. J Neurosci 2008, 28: 7445–7453. 10.1523/JNEUROSCI.1812-08.2008PubMedCentralPubMedCrossRef Xu H, Wu LJ, Wang H, Zhang X, Vadakkan KI, Kim SS, Steenland HW, Zhuo M: Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex. J Neurosci 2008, 28: 7445–7453. 10.1523/JNEUROSCI.1812-08.2008PubMedCentralPubMedCrossRef
35.
go back to reference Urban MO, Coutinho SV, Gebhart GF: Involvement of excitatory amino acid receptors and nitric oxide in the rostral ventromedial medulla in modulating secondary hyperalgesia produced by mustard oil. Pain 1999, 81: 45–55. 10.1016/S0304-3959(98)00265-6PubMedCrossRef Urban MO, Coutinho SV, Gebhart GF: Involvement of excitatory amino acid receptors and nitric oxide in the rostral ventromedial medulla in modulating secondary hyperalgesia produced by mustard oil. Pain 1999, 81: 45–55. 10.1016/S0304-3959(98)00265-6PubMedCrossRef
36.
go back to reference Javanmardi K, Parviz M, Sadr SS, Keshavarz M, Minaii B, Dehpour AR: Involvement of N-methyl-D-aspartate receptors and nitric oxide in the rostral ventromedial medulla in modulating morphine pain-inhibitory signals from the periaqueductal grey matter in rats. Clin Exp Pharmacol Physiol 2005, 32: 585–589. 10.1111/j.1440-1681.2005.04234.xPubMedCrossRef Javanmardi K, Parviz M, Sadr SS, Keshavarz M, Minaii B, Dehpour AR: Involvement of N-methyl-D-aspartate receptors and nitric oxide in the rostral ventromedial medulla in modulating morphine pain-inhibitory signals from the periaqueductal grey matter in rats. Clin Exp Pharmacol Physiol 2005, 32: 585–589. 10.1111/j.1440-1681.2005.04234.xPubMedCrossRef
37.
go back to reference Kim HW, Kwon YB, Roh DH, Yoon SY, Han HJ, Kim KW, Beitz AJ, Lee JH: Intrathecal treatment with sigma1 receptor antagonists reduces formalin-induced phosphorylation of NMDA receptor subunit 1 and the second phase of formalin test in mice. Br J Pharmacol 2006, 148: 490–498. 10.1038/sj.bjp.0706764PubMedCentralPubMedCrossRef Kim HW, Kwon YB, Roh DH, Yoon SY, Han HJ, Kim KW, Beitz AJ, Lee JH: Intrathecal treatment with sigma1 receptor antagonists reduces formalin-induced phosphorylation of NMDA receptor subunit 1 and the second phase of formalin test in mice. Br J Pharmacol 2006, 148: 490–498. 10.1038/sj.bjp.0706764PubMedCentralPubMedCrossRef
38.
go back to reference Zou X, Lin Q, Willis WD: Role of protein kinase A in phosphorylation of NMDA receptor 1 subunits in dorsal horn and spinothalamic tract neurons after intradermal injection of capsaicin in rats. Neuroscience 2002, 115: 775–786. 10.1016/S0306-4522(02)00490-6PubMedCrossRef Zou X, Lin Q, Willis WD: Role of protein kinase A in phosphorylation of NMDA receptor 1 subunits in dorsal horn and spinothalamic tract neurons after intradermal injection of capsaicin in rats. Neuroscience 2002, 115: 775–786. 10.1016/S0306-4522(02)00490-6PubMedCrossRef
39.
go back to reference Caudle RM, Perez FM, Del Valle-Pinero AY, Iadarola MJ: Spinal cord NR1 serine phosphorylation and NR2B subunit suppression following peripheral inflammation. Mol Pain 2005, 1: 25. 10.1186/1744-8069-1-25PubMedCentralPubMedCrossRef Caudle RM, Perez FM, Del Valle-Pinero AY, Iadarola MJ: Spinal cord NR1 serine phosphorylation and NR2B subunit suppression following peripheral inflammation. Mol Pain 2005, 1: 25. 10.1186/1744-8069-1-25PubMedCentralPubMedCrossRef
40.
go back to reference Ren K, Dubner R: Enhanced descending modulation of nociception in rats with persistent hindpaw inflammation. J Neurophysiol 1996, 76: 3025–3037.PubMed Ren K, Dubner R: Enhanced descending modulation of nociception in rats with persistent hindpaw inflammation. J Neurophysiol 1996, 76: 3025–3037.PubMed
41.
go back to reference Hargreaves K, Dubner R, Brown F, Flores C, Joris J: A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988, 32: 77–88. 10.1016/0304-3959(88)90026-7PubMedCrossRef Hargreaves K, Dubner R, Brown F, Flores C, Joris J: A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988, 32: 77–88. 10.1016/0304-3959(88)90026-7PubMedCrossRef
42.
go back to reference Cheppudira BP: Characterization of hind paw licking and lifting to noxious radiant heat in the rat with and without chronic inflammation. J Neurosci Methods 2006, 155: 122–125. 10.1016/j.jneumeth.2006.01.001PubMedCrossRef Cheppudira BP: Characterization of hind paw licking and lifting to noxious radiant heat in the rat with and without chronic inflammation. J Neurosci Methods 2006, 155: 122–125. 10.1016/j.jneumeth.2006.01.001PubMedCrossRef
43.
go back to reference Miguel TT, Nunes-de-Souza RL: Defensive-like behaviors and antinociception induced by NMDA injection into the periaqueductal gray of mice depend on nitric oxide synthesis. Brain Res 2006, 1076: 42–48. 10.1016/j.brainres.2005.12.095PubMedCrossRef Miguel TT, Nunes-de-Souza RL: Defensive-like behaviors and antinociception induced by NMDA injection into the periaqueductal gray of mice depend on nitric oxide synthesis. Brain Res 2006, 1076: 42–48. 10.1016/j.brainres.2005.12.095PubMedCrossRef
44.
go back to reference D'Amico M, Berrino L, Maione S, Filippelli A, de Novellis V, Rossi F: Endothelin-1 in periaqueductal gray area of mice induces analgesia via glutamatergic receptors. Pain 1996, 65: 205–209. 10.1016/0304-3959(95)00178-6PubMedCrossRef D'Amico M, Berrino L, Maione S, Filippelli A, de Novellis V, Rossi F: Endothelin-1 in periaqueductal gray area of mice induces analgesia via glutamatergic receptors. Pain 1996, 65: 205–209. 10.1016/0304-3959(95)00178-6PubMedCrossRef
45.
go back to reference Toyoda H, Zhao MG, Ulzhofer B, Wu LJ, Xu H, Seeburg PH, Sprengel R, Kuner R, Zhuo M: Roles of the AMPA receptor subunit GluA1 but not GluA2 in synaptic potentiation and activation of ERK in the anterior cingulate cortex. Mol Pain 2009, 5: 46. 10.1186/1744-8069-5-46PubMedCentralPubMedCrossRef Toyoda H, Zhao MG, Ulzhofer B, Wu LJ, Xu H, Seeburg PH, Sprengel R, Kuner R, Zhuo M: Roles of the AMPA receptor subunit GluA1 but not GluA2 in synaptic potentiation and activation of ERK in the anterior cingulate cortex. Mol Pain 2009, 5: 46. 10.1186/1744-8069-5-46PubMedCentralPubMedCrossRef
46.
go back to reference Hayashi Y, Shi SH, Esteban JA, Piccini A, Poncer JC, Malinow R: Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Science 2000, 287: 2262–2267. 10.1126/science.287.5461.2262PubMedCrossRef Hayashi Y, Shi SH, Esteban JA, Piccini A, Poncer JC, Malinow R: Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Science 2000, 287: 2262–2267. 10.1126/science.287.5461.2262PubMedCrossRef
47.
go back to reference Park JS, Yaster M, Guan X, Xu JT, Shih MH, Guan Y, Raja SN, Tao YX: Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain. Mol Pain 2008, 4: 67. 10.1186/1744-8069-4-67PubMedCentralPubMedCrossRef Park JS, Yaster M, Guan X, Xu JT, Shih MH, Guan Y, Raja SN, Tao YX: Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain. Mol Pain 2008, 4: 67. 10.1186/1744-8069-4-67PubMedCentralPubMedCrossRef
48.
go back to reference Wei F, Vadakkan KI, Toyoda H, Wu LJ, Zhao MG, Xu H, Shum FW, Jia YH, Zhuo M: Calcium calmodulin-stimulated adenylyl cyclases contribute to activation of extracellular signal-regulated kinase in spinal dorsal horn neurons in adult rats and mice. J Neurosci 2006, 26: 851–861. 10.1523/JNEUROSCI.3292-05.2006PubMedCrossRef Wei F, Vadakkan KI, Toyoda H, Wu LJ, Zhao MG, Xu H, Shum FW, Jia YH, Zhuo M: Calcium calmodulin-stimulated adenylyl cyclases contribute to activation of extracellular signal-regulated kinase in spinal dorsal horn neurons in adult rats and mice. J Neurosci 2006, 26: 851–861. 10.1523/JNEUROSCI.3292-05.2006PubMedCrossRef
49.
go back to reference Liu H, Chandler S, Beitz AJ, Shipley MT, Behbehani MM: Characterization of the effect of cholecystokinin (CCK) on neurons in the periaqueductal gray of the rat: immunocytochemical and in vivo and in vitro electrophysiological studies. Brain Res 1994, 642: 83–94. 10.1016/0006-8993(94)90908-3PubMedCrossRef Liu H, Chandler S, Beitz AJ, Shipley MT, Behbehani MM: Characterization of the effect of cholecystokinin (CCK) on neurons in the periaqueductal gray of the rat: immunocytochemical and in vivo and in vitro electrophysiological studies. Brain Res 1994, 642: 83–94. 10.1016/0006-8993(94)90908-3PubMedCrossRef
50.
go back to reference Zhao MG, Hulsmann S, Winter SM, Dutschmann M, Richter DW: Calcium-regulated potassium currents secure respiratory rhythm generation after loss of glycinergic inhibition. Eur J Neurosci 2006, 24: 145–154. 10.1111/j.1460-9568.2006.04877.xPubMedCrossRef Zhao MG, Hulsmann S, Winter SM, Dutschmann M, Richter DW: Calcium-regulated potassium currents secure respiratory rhythm generation after loss of glycinergic inhibition. Eur J Neurosci 2006, 24: 145–154. 10.1111/j.1460-9568.2006.04877.xPubMedCrossRef
Metadata
Title
A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain
Authors
Jing Hu
Zhe Wang
Yan-Yan Guo
Xiao-Nan Zhang
Zhao-Hui Xu
Shui-Bing Liu
Hong-Ju Guo
Qi Yang
Fu-Xing Zhang
Xiao-Li Sun
Ming-Gao Zhao
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2009
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/1744-8069-5-71

Other articles of this Issue 1/2009

Molecular Pain 1/2009 Go to the issue