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. 2013 May 18;30(1):1–20. doi: 10.1007/s12264-013-1344-9

Spatial and temporal plasticity of synaptic organization in anterior cingulate cortex following peripheral inflammatory pain: multi-electrode array recordings in rats

Yun-Fei Lu 1,2, Yan Wang 1,2, Ying He 3, Fu-Kang Zhang 3, Ting He 1,2, Rui-Rui Wang 1,2,3, Xue-Feng Chen 1,2, Fei Yang 1,2, Ke-Rui Gong 3, Jun Chen 1,2,3,✉
PMCID: PMC5561851  PMID: 23686522

Abstract

To explore whether experiencing inflammatory pain has an impact upon intracortical synaptic organization, the planar multi-electrode array (MEA) technique and 2-dimensional current source density (2D-CSD) imaging were used in slice preparations of the anterior cingulate cortex (ACC) from rats. Synaptic activity across different layers of the ACC was evoked by deep layer stimulation through one electrode. The layer-localization of both local field potentials (LFPs) and the spread of current sink calculated by 2D-CSD analysis was characterized pharmacologically. Moreover, the induction of long-term potentiation (LTP) and changes in LTP magnitude were also evaluated. We found that under naïve conditions, the current sink was initially generated in layer VI, then spread to layer V and finally confined to layers II–III. This spatial pattern of current sink movement typically reflected changes in depolarized sites from deep layers (V–VI) to superficial layers (II–III) where intra- and extracortical inputs terminate. In the ACC slices from rats in an inflamed state (for 2 h) caused by intraplantar bee-venom injection, the spatial profile of intra-ACC synaptic organization was significantly changed, showing an enlarged current sink distribution and a leftward shift of the stimulus-response curves relative to the naïve and saline controls. The change was more distinct in the superficial layers (II–III) than in the deep site. In terms of temporal properties, the rate of LTP induction was significantly increased in layers II–III by inflammatory pain. However, the magnitude of LTP was not significantly enhanced by this treatment. Taken together, these results show that inflammatory pain results in distinct spatial and temporal plasticity of synaptic organization in the ACC, which may lead to altered synaptic transmission and modulation.

Keywords: anterior cingulate cortex, multi-electrode array, synaptic plasticity, intracortical synaptic organization, pain

Footnotes

These authors contributed equally to this work.

References

  • [1].Giamberardno NA, Jensen TS. Pain Comorbidities: Understanding and Treating the Complex Patient. Seattle: IASP Press; 2012. [Google Scholar]
  • [2].Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139:267–284. doi: 10.1016/j.cell.2009.09.028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [3].Fields HL. State-dependent opioid control of pain. Nat Rev Neurosci. 2004;5:565–575. doi: 10.1038/nrn1431. [DOI] [PubMed] [Google Scholar]
  • [4].Millan MJ. Descending control of pain. Prog Neurobiol. 2002;66:355–474. doi: 10.1016/S0301-0082(02)00009-6. [DOI] [PubMed] [Google Scholar]
  • [5].Porreca F, Ossipov M, Gebhart G. Chronic pain and medullary descending facilitation. Trends Neurosci. 2002;25:319–325. doi: 10.1016/S0166-2236(02)02157-4. [DOI] [PubMed] [Google Scholar]
  • [6].Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9:463–484. doi: 10.1016/j.ejpain.2004.11.001. [DOI] [PubMed] [Google Scholar]
  • [7].Apkarian AV, Hashmi JA, Baliki MN. Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain. 2011;152:S49–64. doi: 10.1016/j.pain.2010.11.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Chang C, Shyu BC. A fMRI study of brain activations during non-noxious and noxious electrical stimulation of the sciatic nerve of the rats. Brain Res. 2001;897:71–81. doi: 10.1016/S0006-8993(01)02094-7. [DOI] [PubMed] [Google Scholar]
  • [9].Shih YY, Chen YY, Chen CC, Chen JC, Chang C, Jaw FS. Whole-brain functional magnetic resonance imaging mapping of acute nociceptive responses induced by formalin in rats using atlas registration-based event-related analysis. J Neurosci Res. 2008;86:1801–1811. doi: 10.1002/jnr.21638. [DOI] [PubMed] [Google Scholar]
  • [10].Shih YY, Chiang YC, Chen JC, Huang CH, Chen YY, Liu RS, et al. Brain nociceptive imaging in rats using (18) f-fluorodeoxyglucose small-animal positron emission tomography. Neuroscience. 2008;155:1221–1226. doi: 10.1016/j.neuroscience.2008.07.013. [DOI] [PubMed] [Google Scholar]
  • [11].Chai SC, Kung JC, Shyu BC. Roles of the anterior cingulate cortex and medial thalamus in short-term and long-term aversive information processing. Mol Pain. 2010;6:42. doi: 10.1186/1744-8069-6-42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].Gao YJ, Ren WH, Zhang YQ, Zhao ZQ. Contributions of anterior cingulate cortex and amygdale to pain- and fearconditioned place avoidance in rats. Pain. 2004;110:343–353. doi: 10.1016/j.pain.2004.04.030. [DOI] [PubMed] [Google Scholar]
  • [13].Johansen JP, Fields HL, Manning BH. The affective component of pain in rodents: directive evidence for a contribution of the anterior cingulate cortex. Proc Natl Acad Sci U S A. 2001;98:8077–8082. doi: 10.1073/pnas.141218998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Lei LG, Sun S, Gao YJ, Zhao ZQ, Zhang YQ. NMDA receptors in the anterior cingulate cortex mediate pain-related aversion. Exp Neurol. 2004;189:413–421. doi: 10.1016/j.expneurol.2004.06.012. [DOI] [PubMed] [Google Scholar]
  • [15].Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science. 2000;288:1769–1772. doi: 10.1126/science.288.5472.1769. [DOI] [PubMed] [Google Scholar]
  • [16].Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science. 1997;277:968–971. doi: 10.1126/science.277.5328.968. [DOI] [PubMed] [Google Scholar]
  • [17].Thomas GJ, Slotnick BM. Impairment of avoidance responding by lesions in cingulate cortex in rats depends on food drive. J Comp Physiol Psychol. 1963;56:959–964. doi: 10.1037/h0048819. [DOI] [PubMed] [Google Scholar]
  • [18].Vogt BA. Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci. 2005;6:533–544. doi: 10.1038/nrn1704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Zhuo M. Neuronal mechanism for neuropathic pain. Mol Pain. 2007;3:14. doi: 10.1186/1744-8069-3-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Zhuo M. A synaptic model for pain: long-term potentiation in the anterior cingualte cortex. Mol Cells. 2007;23:259–271. [PubMed] [Google Scholar]
  • [21].Zhuo M. Cortical excitation and chronic pain. Trends Neurosci. 2008;31:199–207. doi: 10.1016/j.tins.2008.01.003. [DOI] [PubMed] [Google Scholar]
  • [22].Rainville P. Brain mechanisms of pain affect and pain modulation. Curr Opin Neurobiol. 2002;12:195–204. doi: 10.1016/S0959-4388(02)00313-6. [DOI] [PubMed] [Google Scholar]
  • [23].Donahue RR, LaGraize SC, Funchs PN. Electrical lesion of the anterior cingulate cortex decreases inflammatory, but not neuropathic nociceptive behavior in rats. Brain Res. 2001;897:131–138. doi: 10.1016/S0006-8993(01)02103-5. [DOI] [PubMed] [Google Scholar]
  • [24].LaGraize SC, Labuda CJ, Rutledge MA, Jackson RL, Fuchs PN. Differential effect of anterior cingulate cortex lesion on mechanical hypersensitivity and escape/avoidance behavior in an animal model of neuropathic pain. Exp Neurol. 2004;188:139–148. doi: 10.1016/j.expneurol.2004.04.003. [DOI] [PubMed] [Google Scholar]
  • [25].Pastoriza LN, Morrow TJ, Casey KL. Medial frontal cortex lesions selectively attenuate the hot plate response: possible nocifensive apraxia in the rat. Pain. 1996;64:11–17. doi: 10.1016/0304-3959(95)00070-4. [DOI] [PubMed] [Google Scholar]
  • [26].Ren LY, Lu ZM, Liu MG, Yu YQ, Li Z, Shang GW, et al. Distinct roles of the anterior cingulate cortex in spinal and supraspinal bee venom-induced pain behaviors. Neuroscience. 2008;153:268–278. doi: 10.1016/j.neuroscience.2008.01.067. [DOI] [PubMed] [Google Scholar]
  • [27].Vaccarino AL, Melzack R. Analgesia produced by injection of lidocaine into the anterior cingulum bundle of the rat. Pain. 1989;39:213–219. doi: 10.1016/0304-3959(89)90008-0. [DOI] [PubMed] [Google Scholar]
  • [28].Calejesan AA, Kim SJ, Zhuo M. Descending facilitatory modulation of a behavioral nociceptive response by stimulation in the adult rat anterior cingualte cortex. Eur J Pain. 2000;4:83–96. doi: 10.1053/eujp.1999.0158. [DOI] [PubMed] [Google Scholar]
  • [29].Koyama T, Tanaka YZ, Mikami A. Nociceptive neurons in the macaque anterior cingulate activate during anticipation of pain. Neuroreport. 1998;9:2663–2667. doi: 10.1097/00001756-199808030-00044. [DOI] [PubMed] [Google Scholar]
  • [30].Kung JC, Su NM, Fan RJ, Chai SC, Shyu BC. Contribution of the anterior cingulate cortex to laser-pain conditioning in rats. Brain Res. 2003;970:58–72. doi: 10.1016/S0006-8993(02)04276-2. [DOI] [PubMed] [Google Scholar]
  • [31].Lee CM, Chang WC, Chang KB, Shyu BC. Synaptic organization and input-specific short term plasticity in anterior cingulate cortical neurons with intact thalamic inputs. Eur J Neurosci. 2007;25:2847–2861. doi: 10.1111/j.1460-9568.2007.05485.x. [DOI] [PubMed] [Google Scholar]
  • [32].Shyu BC, Chen WF, Shih HC. Electrically and mechanically evoked nociceptive neuronal responses in the rat anterior cingulate cortex. Acta Neurochir Suppl. 2008;101:23–25. doi: 10.1007/978-3-211-78205-7_4. [DOI] [PubMed] [Google Scholar]
  • [33].Shyu BC, Sikes RW, Vogt LJ, Vogt BA. Nociceptive processing by anterior cingulate pyramidal neurons. J Neurophysiol. 2010;103:3287–3301. doi: 10.1152/jn.00024.2010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [34].Sikes RW, Vogt BA. Nociceptive neurons in area 24 of rabbit cingulate cortex. J Neurophysiol. 1992;68:1720–1732. doi: 10.1152/jn.1992.68.5.1720. [DOI] [PubMed] [Google Scholar]
  • [35].Wu JJ, Shih HC, Yen CT, Shyu BC. Network dynamics in nociceptive pathway assessed by the neuronal avalanche model. Mol Pain. 2012;8:33. doi: 10.1186/1744-8069-8-33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [36].Yamamura H, Iwata K, Tsuboi Y, Toda K, Kitajima K, Shimizu N, et al. Morphological and electrophysiological properties of ACCx nociceptive neurons in rats. Brain Res. 1996;735:83–92. doi: 10.1016/0006-8993(96)00561-6. [DOI] [PubMed] [Google Scholar]
  • [37].Hutchison WD, Davis KD, Lozano AM, Tasker RR, Dostrovsky JO. Pain-related neurons in the human cingulate cortex. Nat Neurosci. 1999;2:403–405. doi: 10.1038/8065. [DOI] [PubMed] [Google Scholar]
  • [38].Chen J, Lariviere R. The nociceptive and anti-nociceptive effects of bee venom injection and therapy: a double-edged sword. Prog Neurobiol. 2010;92:151–183. doi: 10.1016/j.pneurobio.2010.06.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [39].Gong KR, Cao FL, He Y, Gao CY, Wang DD, Li H, et al. Enhanced excitatory and reduced inhibitory synaptic transmission contribute to persistent pain-induced neuronal hyper-responsiveness in anterior cingulate cortex. Neuroscience. 2010;171:1314–1325. doi: 10.1016/j.neuroscience.2010.10.028. [DOI] [PubMed] [Google Scholar]
  • [40].Palomero-Gallagher N, Mohlberg H, Zilles K, Vogt BA. Cytology and receptor architecture of human anterior cingualte cortex. J Comp Neurol. 2009;508:906–926. doi: 10.1002/cne.21684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [41].Yang JW, Shih HC, Shyu BC. Introcortical circuits in rat anterior cingulate cortex are activated by nociceptive inputs mediated by medial thalamus. J Neurophysiol. 2006;96:3409–3422. doi: 10.1152/jn.00623.2006. [DOI] [PubMed] [Google Scholar]
  • [42].He Y, Liu MG, Gong KR, Chen J. Differential effects of long and short train theta burst stimulation on LTP induction in rat anterior cingulate cortex slices: multi-electrode array recordings. Neurosci Bull. 2009;25:309–318. doi: 10.1007/s12264-009-0831-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [43].Kang SJ, Liu MG, Chen T, Ko HG, Baek GC, Lee HR, et al. Plasticity of metabotropic glutamate receptor-dependent long-term depression in the anterior cingulate cortex after amputation. J Neurosci. 2012;32:11318–11329. doi: 10.1523/JNEUROSCI.0146-12.2012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [44].Lee CM, Sylantyev S, Shyu BC. Short-term synaptic plasticity in layer II III of the rat anterior cingulate cortex. Brain Res Bull. 2007;71:416–427. doi: 10.1016/j.brainresbull.2006.10.011. [DOI] [PubMed] [Google Scholar]
  • [45].Liu MG, Wang RR, Chen XF, Zhang FK, Cui XY, Chen J. Differential roles of ERK, JNK and p38 MAPK in pain-related spatial and temporal enhancement of synaptic responses in the hippocampal formation of rats: multi-electrode array recordings. Brain Res. 2011;1382:57–69. doi: 10.1016/j.brainres.2011.01.076. [DOI] [PubMed] [Google Scholar]
  • [46].Liu MG, Lu D, Wang Y, Chen XF, Li Z, Xu Y, et al. Counteracting roles of metabotropic glutamate receptor subtypes 1 and 5 in regulation of pain-related spatial and temporal synaptic plasticity in rat entorhinal-hippocampal pathways. Neurosci Lett. 2012;507:38–42. doi: 10.1016/j.neulet.2011.11.046. [DOI] [PubMed] [Google Scholar]
  • [47].Xu Y, Jin JH, Wang Y, Wang RR, Li Z, Chen J. Facilitation of synaptic transmission and connections of entorhinalhippocampal pathway by 5-HT2C receptor subtype: multielectrode array recordings. Acta Physiol Sin. 2012;64:259–268. [PubMed] [Google Scholar]
  • [48].Zhao XY, Liu MG, Yuan DL, Wang Y, He Y, Wang DD, et al. Nociception-induced spatial and temporal plasticity of synaptic connection and function in the hippocampal formation of rats: a multi-electrode recording. Mol Pain. 2009;5:55. doi: 10.1186/1744-8069-5-55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [49].Liu MG, Chen XF, He T, Li Z, Chen J. Use of multi-electrode array recordings in study of network synaptic plasticity in both time and space. Neurosci Bull. 2012;28:409–422. doi: 10.1007/s12264-012-1251-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [50].Wang DD, Li Z, Chang Y, Wang RR, Chen XF, Zhao ZY, et al. Neural circuits and temporal plasticity in hindlimb representation of rat primary somatosensory cortex: revisited by multi-electrode array on brain slices. Neurosci Bull. 2010;26:175–187. doi: 10.1007/s12264-010-0308-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [51].Zimmermann M. Ethical guidelines for investigation of experimental pain in conscious animals. Pain. 1983;16:109–110. doi: 10.1016/0304-3959(83)90201-4. [DOI] [PubMed] [Google Scholar]
  • [52].Chen J, Luo C, Li HL, Chen HS. Primary hyperalgesia to mechanical and heat stimuli following subcutaneous bee venom injection into the plantar surface of hindpaw in conscious rat: a comparative study with the formalin test. Pain. 1999;83:67–76. doi: 10.1016/S0304-3959(99)00075-5. [DOI] [PubMed] [Google Scholar]
  • [53].Lariviere WR, Melzack R. The bee venom test: a new tonic pain test. Pain. 1996;66:271–277. doi: 10.1016/0304-3959(96)03075-8. [DOI] [PubMed] [Google Scholar]
  • [54].Li KC, Chen J. Altered pain-related behaviors and spinal neuronal responses produced by s.c. injection of melittin in rats. Neuroscience. 2004;126:753–762. doi: 10.1016/j.neuroscience.2004.03.050. [DOI] [PubMed] [Google Scholar]
  • [55].Chen J, Luo C, Li HL. The contribution of spinal neuronal changes to development of prolonged, tonic nociceptive responses of the cat induced by subcutaneous bee venom injection. Eur J Pain. 1998;2:359–376. doi: 10.1016/S1090-3801(98)90034-9. [DOI] [PubMed] [Google Scholar]
  • [56].Chen J, Li HL, Luo C, Li Z, Zheng JH. Involvement of peripheral NMDA and non-NMDA receptors in development of persistent firing of spinal wide-dynamic-rang neurons induced by subcutaneous bee venom injection in the cat. Brain Res. 1999;844:98–105. doi: 10.1016/S0006-8993(99)01841-7. [DOI] [PubMed] [Google Scholar]
  • [57].Chen J, Chen HS. Pivotal role of capsaicin-sensitive primary afferents in development of both heat and mechanical hyperalgesia induced by intraplantar bee venom injection. Pain. 2001;91:367–376. doi: 10.1016/S0304-3959(00)00458-9. [DOI] [PubMed] [Google Scholar]
  • [58].Du YR, Xiao Y, Lu ZM, Ding J, Xie F, Fu H, et al. Melittin activates TRPV1 receptors in primary nociceptive sensory neurons via the phospholipase A2 cascade pathways. Biochem Biophys Res Commun. 2011;408:32–37. doi: 10.1016/j.bbrc.2011.03.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [59].Wang CM, Yang L, Lu D, Lu YF, Chen XF, Yu YQ, et al. Simultaneous multisite recordings of neural ensemble responses in the motor cortex of behaving rats to peripheral noxious heat and chemical stimuli. Behav Brain Res. 2011;223:192–202. doi: 10.1016/j.bbr.2011.04.032. [DOI] [PubMed] [Google Scholar]
  • [60].Chen HS, Chen J, Chen J, Guo WG, Zheng MH. Establishment of bee venom-induced contralateral heat hyperalgesia in the rat is dependent unpon central temporal summation of afferent input from the site of injury. Neurosci Lett. 2001;298:57–60. doi: 10.1016/S0304-3940(00)01728-6. [DOI] [PubMed] [Google Scholar]
  • [61].Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 5th ed. Amsterdam: Elsevier Academic Press; 2005. p. 367. [Google Scholar]
  • [62].Chang WC, Lee CM, Shyu BC. Temporal and spatial dynamics of thalamus-evoked activity in the anterior cingulate cortex. Neuroscience. 2012;222:302–315. doi: 10.1016/j.neuroscience.2012.07.014. [DOI] [PubMed] [Google Scholar]
  • [63].Shyu BC, Vogt BA. Short-term synaptic plasticity in the nociceptive thalamic-anterior cingulate pathway. Mol Pain. 2009;5:51. doi: 10.1186/1744-8069-5-51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [64].Raymond CR. LTP forms 1, 2 and 3: different mechanisms for the “long” in long-term potentiation. Trends Neurosci. 2007;30:167–175. doi: 10.1016/j.tins.2007.01.007. [DOI] [PubMed] [Google Scholar]
  • [65].Wang CC, Shyu BC. Differential projections from the mediodorsal and centrolateral thalamic nuclei to the frontal cortex in rats. Brain Res. 2004;995:226–235. doi: 10.1016/j.brainres.2003.10.006. [DOI] [PubMed] [Google Scholar]
  • [66].Narita M, Kuzumaki N, Narita M, Kaneko C, Hareyama N, Miyatake M, et al. Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical delta-opioid receptor dysfunction. J Neurochem. 2006;97:1369–1378. doi: 10.1111/j.1471-4159.2006.03824.x. [DOI] [PubMed] [Google Scholar]
  • [67].Schellinck HM, Stanford L, Darrah M. Repetitive acute pain in infancy increases anxiety but does not alter spatial learning ability in juvenile mice. Behav Brain Res. 2003;142:157–165. doi: 10.1016/S0166-4328(02)00406-0. [DOI] [PubMed] [Google Scholar]
  • [68].Suzuki T, Amata M, Sakaue G, Nishimura S, Inoue T, Shitaba M, et al. Experimental neuropathy in mice is associated with delayed behavioral changes related to anxiety and depression. Anesth Analg. 2007;104:1570–1577. doi: 10.1213/01.ane.0000261514.19946.66. [DOI] [PubMed] [Google Scholar]
  • [69].Wang J, Goffer Y, Xu D, Tukey DS, Shamir DB, Eberle SE, et al. A single subanesthetic dose of ketamine relieves depression-like behaviors induced by neuropathic pain in rats. Anesthesiology. 2011;115:812–821. doi: 10.1097/ALN.0b013e31822f16ae. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [70].Mochizuki H, Tashiro M, Kano M, Sakurada Y, Itoh M, Yanai K. Imaging of central itch modulation in the human brain using positron emission tomography. Pain. 2003;105:339–346. doi: 10.1016/S0304-3959(03)00249-5. [DOI] [PubMed] [Google Scholar]
  • [71].Mochizuki H, Sadato N, Saito DN, Toyoda H, Tashiro M, Okamura N, et al. Neural correlates of perceptual difference between itching and pain: a human fMRI study. Neuroimage. 2007;36:706–717. doi: 10.1016/j.neuroimage.2007.04.003. [DOI] [PubMed] [Google Scholar]
  • [72].Wei F, Li P, Zhuo M. Loss of synaptic depression in mammalian anterior cingulate cortex after amputation. J Neurosci. 1999;25:11107–11116. doi: 10.1523/JNEUROSCI.19-21-09346.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [73].Wu LJ, Zhao MG, Toyoda H, Ko SW, Zhuo M. Kainate receptor-mediated synaptic transmission in the adult anterior cingulate cortex. J Neurophysiol. 2005;94:1805–1813. doi: 10.1152/jn.00091.2005. [DOI] [PubMed] [Google Scholar]
  • [74].Nicoll RA, Kauer JA, Malenka RC. The current excitement in long-term potentiation. Neuron. 1988;1:97–103. doi: 10.1016/0896-6273(88)90193-6. [DOI] [PubMed] [Google Scholar]
  • [75].Sah P, Nicoll RA. Mechanisms underlying potentiation of synaptic transmission in rat anterior cingulate cortex in vitro. J Physiol. 1991;433:615–630. doi: 10.1113/jphysiol.1991.sp018446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [76].Wu LJ, Toyoda H, Zhao MG, Lee YS, Tang J, Ko SW, et al. Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. J Neurosci. 2005;25:11107–11116. doi: 10.1523/JNEUROSCI.1678-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [77].Xu H, Wu LJ, Wang H, Zhang X, Vadakkan KI, Kim SS, et al. Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex. J Neurosci. 2008;28:7445–7453. doi: 10.1523/JNEUROSCI.1812-08.2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [78].Zhao MG, Ko SW, Wu LJ, Toyoda H, Xu H, Quan J, et al. Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain. J Neurosci. 2006;26:8923–8930. doi: 10.1523/JNEUROSCI.2103-06.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [79].Wang H, Ren WH, Zhang YQ, Zhao ZQ. GABAergic disinhibiton facilitates polysynaptic excitatory transmission in rat anterior cingulate cortex. Biochem Biophys Res Commun. 2005;338:1634–1639. doi: 10.1016/j.bbrc.2005.10.132. [DOI] [PubMed] [Google Scholar]
  • [80].LaGraize SC, Fuchs PN. GABAA but not GABAB receptors in the rostral anterior cingulate cortex selectively modulate pain-induced escape/avoidance behavior. Exp Neurol. 2007;204:182–194. doi: 10.1016/j.expneurol.2006.10.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [81].Moriarty O, McGuire BE, Finn DP. The effects of pain on cognitive function: a review of clinical and preclinical research. Prog Neurobiol. 2011;93:385–404. doi: 10.1016/j.pneurobio.2011.01.002. [DOI] [PubMed] [Google Scholar]
  • [82].Byrne JH, Labar KS, Ledoux JE, Schafe GE, Sweatt JD, Thompson RF. Learning and memory: basic mechanisms. In: Byrne JH, Roberts JL, editors. From Molecules to Networks: An introduction to Cellular and Molecular Neuroscience. Amsterdam: Academic Press; 2009. pp. 539–608. [Google Scholar]
  • [83].Li XY, Ko HG, Chen T, Descalzi G, Koga K, Wang H, et al. Alleviating neuropathic pain hypersensitivity by inhibiting PKMzeta in the anterior cingulated cortex. Science. 2010;330:1400–1404. doi: 10.1126/science.1191792. [DOI] [PubMed] [Google Scholar]
  • [84].Liauw J, Wu LJ, Zhuo M. Calcium-stimulated adenylyl cyclases required for long-term potentiation in the anterior cingulated cortex. J Neurophysiol. 2005;94:878–882. doi: 10.1152/jn.01205.2004. [DOI] [PubMed] [Google Scholar]
  • [85].Toyoda H, Zhao MG, Ulzhofer B, Wu LJ, Xu H, Seeburg PH, et al. Roles of AMPA receptor subunit GluA1 but not GluA2 in synaptic potentiation and activation of ERK in the anterior cingulated cortex. Mol Pain. 2009;5:46. doi: 10.1186/1744-8069-5-46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [86].Wei F, Qiu CS, Kim SJ, Muglia L, Maas JW, Pineda VV, et al. Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases. Neuron. 2002;36:713–726. doi: 10.1016/S0896-6273(02)01019-X. [DOI] [PubMed] [Google Scholar]
  • [87].Zhao MG, Toyoda H, Lee YS, Wu LJ, Ko SW, Zhang XH, et al. Roles of NMDA NR2B subtype receptor in prefrontal longterm potentiation and contextual fear memory. Neuron. 2005;47:859–872. doi: 10.1016/j.neuron.2005.08.014. [DOI] [PubMed] [Google Scholar]
  • [88].You HJ, Chen J, Morch CD, Arendt-Nielsen L. Differential effect of peripheral glutamate (NMDA, non-NMDA) receptor antagonists on bee venom-induced spontaneous nociception and sensitization. Brain Res Bull. 2002;58:561–567. doi: 10.1016/S0361-9230(02)00806-7. [DOI] [PubMed] [Google Scholar]

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