Central nervous system hyperexcitability

Laser-evoked potentials (LEPs) are among the reliable neurophysiological tools to investigate patients with neuropathic pain, as they can provide an objective account of the functional status of thermo nociceptive pathways. The goal of a case-control study of a single medical center in Belgium was to explore the functioning of the nociceptive afferent pathways by examining LEPs in patients with chronic whiplash-associated disorders (cWAD), patients with chronic fatigue syndrome (CFS), and healthy controls (HCs).

The LEPs of 21 patients with cWAD, 19 patients with CFS, and 18 HCs were analyzed in this study.

All participants received brief nociceptive CO2 laser stimuli applied to the dorsum of the left hand and left foot while brain activity was recorded with a 32-channel electroencephalogram (EEG). LEP signals and transient power modulations were compared between patient groups and HCs.

No between-group differences were found for stimulus intensity, which was supraliminal for Aδ fibers. The amplitudes and latencies of LEP wave components N1, N2, and P2 in patients with cWAD and CFS were statistically similar to those of HCs. There were no significant differences between the time-frequency maps of EEG oscillation amplitude between HCs and both patient populations.

EEG responses of heat-sensitive Aδ fibers in patients with cWAD and CFS revealed no significant differences from the responses of HCs. These findings thus do not support a state of generalized central nervous system hyperexcitability in those patients 1).


2: Hanlon LA, Raghupathi R, Huh JW. Depletion of microglia immediately following traumatic brain injury in the pediatric rat: Implications for cellular and behavioral pathology. Exp Neurol. 2019 Jun;316:39-51. doi: 10.1016/j.expneurol.2019.04.004. Epub 2019 Apr 10. PubMed PMID: 30980832; PubMed Central PMCID: PMC6544393.

3: Khedr EM, Al Fawal B, Abdelwarith AM, Saber M, Tony AAH, El-Bassiony A, Rothwell JC. Changes in recruitment of motor cortex excitation and inhibition in patients with drug-induced tardive syndromes. Neurophysiol Clin. 2019 Feb;49(1):33-40. doi: 10.1016/j.neucli.2018.10.001. Epub 2018 Oct 23. PubMed PMID: 30366858.

4: Hanoglu L, Yildiz S, Cakir T, Hanoglu T, Yulug B. FDG-PET Scanning Shows Distributed Changes in Cortical Activity Associated with Visual Hallucinations in Eye Disease. Endocr Metab Immune Disord Drug Targets. 2019;19(1):84-89. doi: 10.2174/1871530318666180830112709. PubMed PMID: 30160221.

5: Agarwal S, Koch G, Hillis AE, Huynh W, Ward NS, Vucic S, Kiernan MC. Interrogating cortical function with transcranial magnetic stimulation: insights from neurodegenerative disease and stroke. J Neurol Neurosurg Psychiatry. 2019 Jan;90(1):47-57. doi: 10.1136/jnnp-2017-317371. Epub 2018 Jun 4. Review. PubMed PMID: 29866706.

6: Falowski SM. An Observational Case Series of Spinal Cord Stimulation Waveforms Visualized on Intraoperative Neuromonitoring. Neuromodulation. 2019 Feb;22(2):219-228. doi: 10.1111/ner.12781. Epub 2018 Apr 29. PubMed PMID: 29707900.

7: Zhou L, Zhou L, Su LD, Cao SL, Xie YJ, Wang N, Shao CY, Wang YN, Zhou JH, Cowell JK, Shen Y. Celecoxib Ameliorates Seizure Susceptibility in Autosomal Dominant Lateral Temporal Epilepsy. J Neurosci. 2018 Mar 28;38(13):3346-3357. doi: 10.1523/JNEUROSCI.3245-17.2018. Epub 2018 Feb 28. PubMed PMID: 29491011; PubMed Central PMCID: PMC5884462.

8: Hadamitzky M, Herring A, Kirchhof J, Bendix I, Haight MJ, Keyvani K, Lückemann L, Unteroberdörster M, Schedlowski M. Repeated Systemic Treatment with Rapamycin Affects Behavior and Amygdala Protein Expression in Rats. Int J Neuropsychopharmacol. 2018 Jun 1;21(6):592-602. doi: 10.1093/ijnp/pyy017. PubMed PMID: 29462337; PubMed Central PMCID: PMC6007742.

9: Wang T, Hurwitz O, Shimada SG, Tian D, Dai F, Zhou J, Ma C, LaMotte RH. Anti-nociceptive effects of bupivacaine-encapsulated PLGA nanoparticles applied to the compressed dorsal root ganglion in mice. Neurosci Lett. 2018 Mar 6;668:154-158. doi: 10.1016/j.neulet.2018.01.031. Epub 2018 Feb 3. PubMed PMID: 29355697; PubMed Central PMCID: PMC5829013.

10: Kim W, Chung Y, Choi S, Min BI, Kim SK. Duloxetine Protects against Oxaliplatin-Induced Neuropathic Pain and Spinal Neuron Hyperexcitability in Rodents. Int J Mol Sci. 2017 Dec 5;18(12). pii: E2626. doi: 10.3390/ijms18122626. PubMed PMID: 29206213; PubMed Central PMCID: PMC5751229.

11: Cordeiro Matos S, Zamfir M, Longo G, Ribeiro-da-Silva A, Séguéla P. Noradrenergic fiber sprouting and altered transduction in neuropathic prefrontal cortex. Brain Struct Funct. 2018 Apr;223(3):1149-1164. doi: 10.1007/s00429-017-1543-7. Epub 2017 Nov 1. PubMed PMID: 29094305.

12: Nagendran T, Larsen RS, Bigler RL, Frost SB, Philpot BD, Nudo RJ, Taylor AM. Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling. Nat Commun. 2017 Sep 20;8(1):625. doi: 10.1038/s41467-017-00652-y. PubMed PMID: 28931811; PubMed Central PMCID: PMC5607003.

13: Kopach O, Medvediev V, Krotov V, Borisyuk A, Tsymbaliuk V, Voitenko N. Opposite, bidirectional shifts in excitation and inhibition in specific types of dorsal horn interneurons are associated with spasticity and pain post-SCI. Sci Rep. 2017 Jul 19;7(1):5884. doi: 10.1038/s41598-017-06049-7. PubMed PMID: 28724992; PubMed Central PMCID: PMC5517549.

14: Weisshaar CL, Kras JV, Pall PS, Kartha S, Winkelstein BA. Ablation of IB4 non-peptidergic afferents in the rat facet joint prevents injury-induced pain and thalamic hyperexcitability via supraspinal glutamate transporters. Neurosci Lett. 2017 Aug 10;655:82-89. doi: 10.1016/j.neulet.2017.07.006. Epub 2017 Jul 6. PubMed PMID: 28689926; PubMed Central PMCID: PMC5572830.

15: Lam AD, Deck G, Goldman A, Eskandar EN, Noebels J, Cole AJ. Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease. Nat Med. 2017 Jun;23(6):678-680. doi: 10.1038/nm.4330. Epub 2017 May 1. PubMed PMID: 28459436; PubMed Central PMCID: PMC5461182.

16: Vaudano AE, Ruggieri A, Avanzini P, Gessaroli G, Cantalupo G, Coppola A, Sisodiya SM, Meletti S. Photosensitive epilepsy is associated with reduced inhibition of alpha rhythm generating networks. Brain. 2017 Apr 1;140(4):981-997. doi: 10.1093/brain/awx009. PubMed PMID: 28334965; PubMed Central PMCID: PMC5837657.

17: Wolf JA, Johnson BN, Johnson VE, Putt ME, Browne KD, Mietus CJ, Brown DP, Wofford KL, Smith DH, Grady MS, Cohen AS, Cullen DK. Concussion Induces Hippocampal Circuitry Disruption in Swine. J Neurotrauma. 2017 Jul 15;34(14):2303-2314. doi: 10.1089/neu.2016.4848. Epub 2017 May 4. PubMed PMID: 28298170; PubMed Central PMCID: PMC5510797.

18: Stern S, Santos R, Marchetto MC, Mendes APD, Rouleau GA, Biesmans S, Wang QW, Yao J, Charnay P, Bang AG, Alda M, Gage FH. Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium. Mol Psychiatry. 2018 Jun;23(6):1453-1465. doi: 10.1038/mp.2016.260. Epub 2017 Feb 28. PubMed PMID: 28242870; PubMed Central PMCID: PMC5573640.

19: Li Y, Tatsui CE, Rhines LD, North RY, Harrison DS, Cassidy RM, Johansson CA, Kosturakis AK, Edwards DD, Zhang H, Dougherty PM. Dorsal root ganglion neurons become hyperexcitable and increase expression of voltage-gated T-type calcium channels (Cav3.2) in paclitaxel-induced peripheral neuropathy. Pain. 2017 Mar;158(3):417-429. doi: 10.1097/j.pain.0000000000000774. PubMed PMID: 27902567; PubMed Central PMCID: PMC5303135.

20: Wang X, Wang Y, Zhang C, Liu C, Yang HF, Hu WH, Zhang JG, Zhang K. Endogenous cannabinoid system alterations and their role in epileptogenesis after brain injury in rat. Epilepsy Res. 2016 Dec;128:35-42. doi: 10.1016/j.eplepsyres.2016.10.002. Epub 2016 Oct 24. PubMed PMID: 27810514.

21: Martín-Palomeque G, Castro-Ortiz A, Pamplona-Valenzuela P, Saiz-Sepúlveda MÁ, Cabañes-Martínez L, López JR. Large Amplitude Cortical Evoked Potentials in Nonepileptic Patients. Reviving an Old Neurophysiologic Tool to Help Detect CNS Pathology. J Clin Neurophysiol. 2017 Jan;34(1):84-91. doi: 10.1097/WNP.0000000000000326. PubMed PMID: 27490324.

22: Wang X, Wang Y, Zhang C, Liu C, Zhao B, Wei N, Zhang JG, Zhang K. CB1 receptor antagonism prevents long-term hyperexcitability after head injury by regulation of dynorphin-KOR system and mGluR5 in rat hippocampus. Brain Res. 2016 Sep 1;1646:174-181. doi: 10.1016/j.brainres.2016.05.055. Epub 2016 Jun 2. PubMed PMID: 27262683.

23: Alentorn A, Hoang-Xuan K, Mikkelsen T. Presenting signs and symptoms in brain tumors. Handb Clin Neurol. 2016;134:19-26. doi: 10.1016/B978-0-12-802997-8.00002-5. Review. PubMed PMID: 26948346.

24: Falnikar A, Hala TJ, Poulsen DJ, Lepore AC. GLT1 overexpression reverses established neuropathic pain-related behavior and attenuates chronic dorsal horn neuron activation following cervical spinal cord injury. Glia. 2016 Mar;64(3):396-406. doi: 10.1002/glia.22936. Epub 2015 Oct 23. PubMed PMID: 26496514; PubMed Central PMCID: PMC4703512.

25: Cordeiro Matos S, Zhang Z, Séguéla P. Peripheral Neuropathy Induces HCN Channel Dysfunction in Pyramidal Neurons of the Medial Prefrontal Cortex. J Neurosci. 2015 Sep 23;35(38):13244-56. doi: 10.1523/JNEUROSCI.0799-15.2015. PubMed PMID: 26400952; PubMed Central PMCID: PMC6605438.

26: Kras JV, Weisshaar CL, Pall PS, Winkelstein BA. Pain from intra-articular NGF or joint injury in the rat requires contributions from peptidergic joint afferents. Neurosci Lett. 2015 Sep 14;604:193-8. doi: 10.1016/j.neulet.2015.07.043. Epub 2015 Aug 1. PubMed PMID: 26240991; PubMed Central PMCID: PMC4568150.

27: Yacubian EM, Wolf P. Orofacial reflex myocloni. Definition, relation to epilepsy syndromes, nosological and prognosis significance. A focused review. Seizure. 2015 Aug;30:1-5. doi: 10.1016/j.seizure.2015.05.005. Epub 2015 May 14. Review. PubMed PMID: 26216677.

28: Mesgari M, Ghaffarian N, Khaleghi Ghadiri M, Sadeghian H, Speckmann EJ, Stummer W, Gorji A. Altered inhibition in the hippocampal neural networks after spreading depression. Neuroscience. 2015 Sep 24;304:190-7. doi: 10.1016/j.neuroscience.2015.07.035. Epub 2015 Jul 23. PubMed PMID: 26210578.

29: Winkelmann A, You X, Grünewald N, Häussler U, Krestel H, Haas CA, Schwarz G, Chen W, Meier JC. Identification of a new genomic hot spot of evolutionary diversification of protein function. PLoS One. 2015 May 8;10(5):e0125413. doi: 10.1371/journal.pone.0125413. eCollection 2015. PubMed PMID: 25955356; PubMed Central PMCID: PMC4425505.

30: Leung H, Zhu CX, Chan DT, Poon WS, Shi L, Mok VC, Wong LK. Ictal high-frequency oscillations and hyperexcitability in refractory epilepsy. Clin Neurophysiol. 2015 Nov;126(11):2049-57. doi: 10.1016/j.clinph.2015.01.009. Epub 2015 Jan 24. PubMed PMID: 25746721.

31: Crosby ND, Zaucke F, Kras JV, Dong L, Luo ZD, Winkelstein BA. Thrombospondin-4 and excitatory synaptogenesis promote spinal sensitization after painful mechanical joint injury. Exp Neurol. 2015 Feb;264:111-20. doi: 10.1016/j.expneurol.2014.11.015. Epub 2014 Dec 5. PubMed PMID: 25483397; PubMed Central PMCID: PMC4324021.

32: Althaus AL, Sagher O, Parent JM, Murphy GG. Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model. J Neurophysiol. 2015 Feb 15;113(4):1184-94. doi: 10.1152/jn.00835.2014. Epub 2014 Nov 26. PubMed PMID: 25429123; PubMed Central PMCID: PMC4329435.

33: Fang M, Wei JL, Tang B, Liu J, Chen L, Tang ZH, Luo J, Chen GJ, Wang XF. Neuroligin-1 Knockdown Suppresses Seizure Activity by Regulating Neuronal Hyperexcitability. Mol Neurobiol. 2016 Jan;53(1):270-284. doi: 10.1007/s12035-014-8999-8. Epub 2014 Nov 27. PubMed PMID: 25428619.

34: Huda S, Wong SH, Pettingill P, O'Connell D, Vincent A, Steiger M. An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre. J Neurol. 2015 Feb;262(2):418-24. doi: 10.1007/s00415-014-7588-0. Epub 2014 Nov 27. PubMed PMID: 25428531.

35: Lozovaya N, Gataullina S, Tsintsadze T, Tsintsadze V, Pallesi-Pocachard E, Minlebaev M, Goriounova NA, Buhler E, Watrin F, Shityakov S, Becker AJ, Bordey A, Milh M, Scavarda D, Bulteau C, Dorfmuller G, Delalande O, Represa A, Cardoso C, Dulac O, Ben-Ari Y, Burnashev N. Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model. Nat Commun. 2014 Aug 1;5:4563. doi: 10.1038/ncomms5563. PubMed PMID: 25081057; PubMed Central PMCID: PMC4143949.

36: Luhmann HJ, Kilb W, Clusmann H. Malformations of cortical development and neocortical focus. Int Rev Neurobiol. 2014;114:35-61. doi: 10.1016/B978-0-12-418693-4.00003-0. Review. PubMed PMID: 25078498.

37: Crosby ND, Gilliland TM, Winkelstein BA. Early afferent activity from the facet joint after painful trauma to its capsule potentiates neuronal excitability and glutamate signaling in the spinal cord. Pain. 2014 Sep;155(9):1878-87. doi: 10.1016/j.pain.2014.06.019. Epub 2014 Jun 28. PubMed PMID: 24978827; PubMed Central PMCID: PMC4157970.

38: Kahle KT, Merner ND, Friedel P, Silayeva L, Liang B, Khanna A, Shang Y, Lachance-Touchette P, Bourassa C, Levert A, Dion PA, Walcott B, Spiegelman D, Dionne-Laporte A, Hodgkinson A, Awadalla P, Nikbakht H, Majewski J, Cossette P, Deeb TZ, Moss SJ, Medina I, Rouleau GA. Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy. EMBO Rep. 2014 Jul;15(7):766-74. doi: 10.15252/embr.201438840. Epub 2014 Jun 13. PubMed PMID: 24928908; PubMed Central PMCID: PMC4196980.

39: Syré PP, Weisshaar CL, Winkelstein BA. Sustained neuronal hyperexcitability is evident in the thalamus after a transient cervical radicular injury. Spine (Phila Pa 1976). 2014 Jul 1;39(15):E870-7. doi: 10.1097/BRS.0000000000000392. PubMed PMID: 24827526.

40: Medina I, Friedel P, Rivera C, Kahle KT, Kourdougli N, Uvarov P, Pellegrino C. Current view on the functional regulation of the neuronal K(+)-Cl(-) cotransporter KCC2. Front Cell Neurosci. 2014 Feb 6;8:27. doi: 10.3389/fncel.2014.00027. eCollection 2014. Review. PubMed PMID: 24567703; PubMed Central PMCID: PMC3915100.

41: Liu B, Niu L, Shen MZ, Gao L, Wang C, Li J, Song LJ, Tao Y, Meng Q, Yang QL, Gao GD, Zhang H. Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy. Mol Neurobiol. 2014 Oct;50(2):327-38. doi: 10.1007/s12035-013-8619-z. Epub 2014 Jan 25. PubMed PMID: 24464262.

42: Weisshaar CL, Winkelstein BA. Ablating spinal NK1-bearing neurons eliminates the development of pain and reduces spinal neuronal hyperexcitability and inflammation from mechanical joint injury in the rat. J Pain. 2014 Apr;15(4):378-86. doi: 10.1016/j.jpain.2013.12.003. Epub 2014 Jan 2. PubMed PMID: 24389017; PubMed Central PMCID: PMC3972292.

43: Zhou FW, Roper SN. TRPC3 mediates hyperexcitability and epileptiform activity in immature cortex and experimental cortical dysplasia. J Neurophysiol. 2014 Mar;111(6):1227-37. doi: 10.1152/jn.00607.2013. Epub 2013 Dec 18. PubMed PMID: 24353305.

44: Kandratavicius L, Rosa-Neto P, Monteiro MR, Guiot MC, Assirati JA Jr, Carlotti CG Jr, Kobayashi E, Leite JP. Distinct increased metabotropic glutamate receptor type 5 (mGluR5) in temporal lobe epilepsy with and without hippocampal sclerosis. Hippocampus. 2013 Dec;23(12):1212-30. doi: 10.1002/hipo.22160. Epub 2013 Jul 23. PubMed PMID: 23804486; PubMed Central PMCID: PMC4165311.

45: Ma TS, Elliott RE, Ruppe V, Devinsky O, Kuzniecky R, Weiner HL, Carlson C. Electrocorticographic evidence of perituberal cortex epileptogenicity in tuberous sclerosis complex. J Neurosurg Pediatr. 2012 Nov;10(5):376-82. doi: 10.3171/2012.8.PEDS1285. Epub 2012 Sep 21. PubMed PMID: 22998031.

46: Shimizu T, Hirata K, Manaka S, Arakawa I. [Cephalic hypersensitivity syndrome]. Nihon Rinsho. 2012 Jan;70(1):145-50. Japanese. PubMed PMID: 22413510.

47: Feliciano DM, Su T, Lopez J, Platel JC, Bordey A. Single-cell Tsc1 knockout during corticogenesis generates tuber-like lesions and reduces seizure threshold in mice. J Clin Invest. 2011 Apr;121(4):1596-607. doi: 10.1172/JCI44909. Epub 2011 Mar 14. PubMed PMID: 21403402; PubMed Central PMCID: PMC3069783.

48: Miyajima M, Ohta K, Hara K, Iino H, Maehara T, Hara M, Matsuura M, Matsushima E. Abnormal mismatch negativity for pure-tone sounds in temporal lobe epilepsy. Epilepsy Res. 2011 May;94(3):149-57. doi: 10.1016/j.eplepsyres.2011.01.009. Epub 2011 Mar 1. PubMed PMID: 21367585.

49: Shams PN, Plant GT. Migraine-like visual aura due to focal cerebral lesions: case series and review. Surv Ophthalmol. 2011 Mar-Apr;56(2):135-61. doi: 10.1016/j.survophthal.2010.07.005. Review. PubMed PMID: 21335146.

50: de Lanerolle NC, Lee TS, Spencer DD. Astrocytes and epilepsy. Neurotherapeutics. 2010 Oct;7(4):424-38. doi: 10.1016/j.nurt.2010.08.002. Review. PubMed PMID: 20880506; PubMed Central PMCID: PMC5084304.

51: Benini R, Longo D, Biagini G, Avoli M. Perirhinal cortex hyperexcitability in pilocarpine-treated epileptic rats. Hippocampus. 2011 Jul;21(7):702-13. doi: 10.1002/hipo.20785. Epub 2010 Apr 13. PubMed PMID: 20865722; PubMed Central PMCID: PMC4878905.

52: Bortel A, Longo D, de Guzman P, Dubeau F, Biagini G, Avoli M. Selective changes in inhibition as determinants for limited hyperexcitability in the insular cortex of epileptic rats. Eur J Neurosci. 2010 Jun;31(11):2014-23. doi: 10.1111/j.1460-9568.2010.07225.x. Epub 2010 May 24. PubMed PMID: 20497472; PubMed Central PMCID: PMC4873281.

53: Zhou FW, Roper SN. Densities of glutamatergic and GABAergic presynaptic terminals are altered in experimental cortical dysplasia. Epilepsia. 2010 Aug;51(8):1468-76. doi: 10.1111/j.1528-1167.2010.02583.x. Epub 2010 Apr 30. PubMed PMID: 20477846.

54: Panuccio G, D'Antuono M, de Guzman P, De Lannoy L, Biagini G, Avoli M. In vitro ictogenesis and parahippocampal networks in a rodent model of temporal lobe epilepsy. Neurobiol Dis. 2010 Sep;39(3):372-80. doi: 10.1016/j.nbd.2010.05.003. Epub 2010 May 7. PubMed PMID: 20452424; PubMed Central PMCID: PMC4878916.

55: Bragin DE, Sanderson JL, Peterson S, Connor JA, Müller WS. Development of epileptiform excitability in the deep entorhinal cortex after status epilepticus. Eur J Neurosci. 2009 Aug;30(4):611-24. doi: 10.1111/j.1460-9568.2009.06863.x. Epub 2009 Aug 10. PubMed PMID: 19674083; PubMed Central PMCID: PMC2776653.

56: Young CC, Stegen M, Bernard R, Müller M, Bischofberger J, Veh RW, Haas CA, Wolfart J. Upregulation of inward rectifier K+ (Kir2) channels in dentate gyrus granule cells in temporal lobe epilepsy. J Physiol. 2009 Sep 1;587(Pt 17):4213-33. doi: 10.1113/jphysiol.2009.170746. Epub 2009 Jun 29. PubMed PMID: 19564397; PubMed Central PMCID: PMC2754361.

57: Guaranha MS, da Silva Sousa P, de Araújo-Filho GM, Lin K, Guilhoto LM, Caboclo LO, Yacubian EM. Provocative and inhibitory effects of a video-EEG neuropsychologic protocol in juvenile myoclonic epilepsy. Epilepsia. 2009 Nov;50(11):2446-55. doi: 10.1111/j.1528-1167.2009.02126.x. Epub 2009 May 12. PubMed PMID: 19453714.

58: Inaba Y, D'Antuono M, Bertazzoni G, Biagini G, Avoli M. Diminished presynaptic GABA(B) receptor function in the neocortex of a genetic model of absence epilepsy. Neurosignals. 2009;17(2):121-31. doi: 10.1159/000197864. Epub 2009 Jan 29. PubMed PMID: 19176980; PubMed Central PMCID: PMC4878904.

59: Wang G, Thompson SM. Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions. J Neurosci. 2008 Nov 12;28(46):11959-69. doi: 10.1523/JNEUROSCI.3296-08.2008. PubMed PMID: 19005061; PubMed Central PMCID: PMC2627563.

60: Pan JW, Cavus I, Kim J, Hetherington HP, Spencer DD. Hippocampal extracellular GABA correlates with metabolism in human epilepsy. Metab Brain Dis. 2008 Dec;23(4):457-68. doi: 10.1007/s11011-008-9106-5. Epub 2008 Sep 18. PubMed PMID: 18807158; PubMed Central PMCID: PMC3578212.

61: Avramescu S, Timofeev I. Synaptic strength modulation after cortical trauma: a role in epileptogenesis. J Neurosci. 2008 Jul 2;28(27):6760-72. doi: 10.1523/JNEUROSCI.0643-08.2008. PubMed PMID: 18596152; PubMed Central PMCID: PMC6670971.

62: Pan JW, Williamson A, Cavus I, Hetherington HP, Zaveri H, Petroff OA, Spencer DD. Neurometabolism in human epilepsy. Epilepsia. 2008;49 Suppl 3:31-41. doi: 10.1111/j.1528-1167.2008.01508.x. Review. PubMed PMID: 18304254; PubMed Central PMCID: PMC3657747.

63: Pallud J, Devaux B, Depaulis A. [Changes in spontaneous epileptic activity after selective intrahippocampal transection in a model of chronic mesial temporal lobe epilepsy]. Neurochirurgie. 2008 May;54(3):135-40. doi: 10.1016/j.neuchi.2008.02.002. Epub 2008 Apr 15. Review. French. PubMed PMID: 18417168.

64: Sanoja R, Vanegas H, Tortorici V. Critical role of the rostral ventromedial medulla in early spinal events leading to chronic constriction injury neuropathy in rats. J Pain. 2008 Jun;9(6):532-42. doi: 10.1016/j.jpain.2008.01.332. Epub 2008 Mar 17. PubMed PMID: 18343729.

65: de Guzman P, Inaba Y, Baldelli E, de Curtis M, Biagini G, Avoli M. Network hyperexcitability within the deep layers of the pilocarpine-treated rat entorhinal cortex. J Physiol. 2008 Apr 1;586(7):1867-83. doi: 10.1113/jphysiol.2007.146159. Epub 2008 Jan 31. PubMed PMID: 18238812; PubMed Central PMCID: PMC2375734.

66: Shetty AK, Hattiangady B. Restoration of calbindin after fetal hippocampal CA3 cell grafting into the injured hippocampus in a rat model of temporal lobe epilepsy. Hippocampus. 2007;17(10):943-56. PubMed PMID: 17604349; PubMed Central PMCID: PMC3612498.

67: Shetty AK, Hattiangady B. Concise review: prospects of stem cell therapy for temporal lobe epilepsy. Stem Cells. 2007 Oct;25(10):2396-407. Epub 2007 Jun 28. Review. PubMed PMID: 17600108; PubMed Central PMCID: PMC3612506.

68: Gwak YS, Kang J, Leem JW, Hulsebosch CE. Spinal AMPA receptor inhibition attenuates mechanical allodynia and neuronal hyperexcitability following spinal cord injury in rats. J Neurosci Res. 2007 Aug 15;85(11):2352-9. PubMed PMID: 17549753.

69: Vazquez E, Escobar W, Ramirez K, Vanegas H. A nonopioid analgesic acts upon the PAG-RVM axis to reverse inflammatory hyperalgesia. Eur J Neurosci. 2007 Jan;25(2):471-9. PubMed PMID: 17284188.

70: Kamida T, Fujiki M, Baba H, Ono T, Abe T, Kobayashi H. The relationship between paired pulse magnetic MEP and surgical prognosis in patients with intractable epilepsy. Seizure. 2007 Mar;16(2):113-9. Epub 2006 Dec 20. PubMed PMID: 17188003.

71: López-Vales R, Forés J, Navarro X, Verdú E. Chronic transplantation of olfactory ensheathing cells promotes partial recovery after complete spinal cord transection in the rat. Glia. 2007 Feb;55(3):303-11. PubMed PMID: 17096411.

72: Tran LD, Lifshitz J, Witgen BM, Schwarzbach E, Cohen AS, Grady MS. Response of the contralateral hippocampus to lateral fluid percussion brain injury. J Neurotrauma. 2006 Sep;23(9):1330-42. PubMed PMID: 16958585.

73: Ravizza T, Boer K, Redeker S, Spliet WG, van Rijen PC, Troost D, Vezzani A, Aronica E. The IL-1beta system in epilepsy-associated malformations of cortical development. Neurobiol Dis. 2006 Oct;24(1):128-43. Epub 2006 Jul 24. PubMed PMID: 16860990.

74: Wang HC, Lu CH, Lee RJ, Yang TM, Hung KS. Post-traumatic hemifacial spasm. J Clin Neurosci. 2006 Jul;13(6):681-3. PubMed PMID: 16860719.

75: Inaba Y, Biagini G, Avoli M. The H current blocker ZD7288 decreases epileptiform hyperexcitability in the rat neocortex by depressing synaptic transmission. Neuropharmacology. 2006 Sep;51(3):681-91. Epub 2006 Jun 27. PubMed PMID: 16806308.

76: Kawamata M, Sugino S, Narimatsu E, Yamauchi M, Kiya T, Furuse S, Namiki A. Effects of systemic administration of lidocaine and QX-314 on hyperexcitability of spinal dorsal horn neurons after incision in the rat. Pain. 2006 May;122(1-2):68-80. Epub 2006 Mar 9. PubMed PMID: 16524660.

77: Inaba Y, de Guzman P, Avoli M. NMDA receptor-mediated transmission contributes to network 'hyperexcitability' in the rat insular cortex. Eur J Neurosci. 2006 Feb;23(4):1071-6. PubMed PMID: 16519672.

78: Notenboom RG, Hampson DR, Jansen GH, van Rijen PC, van Veelen CW, van Nieuwenhuizen O, de Graan PN. Up-regulation of hippocampal metabotropic glutamate receptor 5 in temporal lobe epilepsy patients. Brain. 2006 Jan;129(Pt 1):96-107. Epub 2005 Nov 25. PubMed PMID: 16311265.

79: Kleinjung T, Steffens T, Langguth B, Eichhammer P, Marienhagen J, Hajak G, Strutz J. [Treatment of chronic tinnitus with neuronavigated repetitive Transcranial Magnetic Stimulation (rTMS)]. HNO. 2006 Jun;54(6):439-44. German. PubMed PMID: 16170508.

80: de Lanerolle NC, Lee TS. New facets of the neuropathology and molecular profile of human temporal lobe epilepsy. Epilepsy Behav. 2005 Sep;7(2):190-203. Review. PubMed PMID: 16098816.

81: Dobremez E, Bouali-Benazzouz R, Fossat P, Monteils L, Dulluc J, Nagy F, Landry M. Distribution and regulation of L-type calcium channels in deep dorsal horn neurons after sciatic nerve injury in rats. Eur J Neurosci. 2005 Jun;21(12):3321-33. PubMed PMID: 16026470.

82: Gasull X, Liao X, Dulin MF, Phelps C, Walters ET. Evidence that long-term hyperexcitability of the sensory neuron soma induced by nerve injury in Aplysia is adaptive. J Neurophysiol. 2005 Sep;94(3):2218-30. Epub 2005 Jun 8. PubMed PMID: 15944238.

83: Kleinjung T, Eichhammer P, Langguth B, Jacob P, Marienhagen J, Hajak G, Wolf SR, Strutz J. Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus. Otolaryngol Head Neck Surg. 2005 Apr;132(4):566-9. PubMed PMID: 15806046.

84: Ferlazzo E, Zifkin BG, Andermann E, Andermann F. Cortical triggers in generalized reflex seizures and epilepsies. Brain. 2005 Apr;128(Pt 4):700-10. Epub 2005 Feb 23. Review. PubMed PMID: 15728654.

85: Thomas PM, Phillips JP, O'Connor WT. Microdialysis of the lateral and medial temporal lobe during temporal lobe epilepsy surgery. Surg Neurol. 2005 Jan;63(1):70-9; discussion 79. PubMed PMID: 15639534.

86: Langguth B, Eichhammer P, Zowe M, Marienhagen J, Kleinjung T, Jacob P, Sand P, Hajak G. [Low frequency repetitive transcranial magnetic stimulation (rTMS) for the treatment of chronic tinnitus–are there long-term effects?]. Psychiatr Prax. 2004 Nov;31 Suppl 1:S52-4. German. PubMed PMID: 15570501.

87: Houweling AR, Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ. Homeostatic synaptic plasticity can explain post-traumatic epileptogenesis in chronically isolated neocortex. Cereb Cortex. 2005 Jun;15(6):834-45. Epub 2004 Oct 13. PubMed PMID: 15483049; PubMed Central PMCID: PMC2915841.

88: Eun JP, Choi HY, Kwak YG. Proteomic analysis of human cerebral cortex in epileptic patients. Exp Mol Med. 2004 Apr 30;36(2):185-91. PubMed PMID: 15150448.

89: Lynd-Balta E, Pilcher WH, Joseph SA. AMPA receptor alterations precede mossy fiber sprouting in young children with temporal lobe epilepsy. Neuroscience. 2004;126(1):105-14. PubMed PMID: 15145077.

90: Yang EK, Takimoto K, Hayashi Y, de Groat WC, Yoshimura N. Altered expression of potassium channel subunit mRNA and alpha-dendrotoxin sensitivity of potassium currents in rat dorsal root ganglion neurons after axotomy. Neuroscience. 2004;123(4):867-74. PubMed PMID: 14751280.

91: Topolnik L, Steriade M, Timofeev I. Hyperexcitability of intact neurons underlies acute development of trauma-related electrographic seizures in cats in vivo. Eur J Neurosci. 2003 Aug;18(3):486-96. PubMed PMID: 12911745.

92: Manrique M. [Selective dorsal rhizotomy as a therapeutic option in spasticity. Indications and results]. Rev Neurol. 2003 Jul 1-15;37(1):86-8. Spanish. Erratum in: Rev Neurol. 2003 Nov 1-15;37(9):900. PubMed PMID: 12861518.

93: de Lanerolle NC, Kim JH, Williamson A, Spencer SS, Zaveri HP, Eid T, Spencer DD. A retrospective analysis of hippocampal pathology in human temporal lobe epilepsy: evidence for distinctive patient subcategories. Epilepsia. 2003 May;44(5):677-87. Erratum in: Epilepsia. 2003 Aug;44(8):1131. Eid Toye [corrected to Eid Tore]. PubMed PMID: 12752467.

94: Krassioukov AV, Johns DG, Schramm LP. Sensitivity of sympathetically correlated spinal interneurons, renal sympathetic nerve activity, and arterial pressure to somatic and visceral stimuli after chronic spinal injury. J Neurotrauma. 2002 Dec;19(12):1521-9. PubMed PMID: 12542854.

95: Fueta Y, Fukunaga K, Ishidao T, Hori H. Hyperexcitability and changes in activities of Ca2+/calmodulin-dependent kinase II and mitogen-activated protein kinase in the hippocampus of rats exposed to 1-bromopropane. Life Sci. 2002 Dec 20;72(4-5):521-9. PubMed PMID: 12467892.

96: Veznedaroglu E, Van Bockstaele EJ, O'Connor MJ. Extravascular collagen in the human epileptic brain: a potential substrate for aberrant cell migration in cases of temporal lobe epilepsy. J Neurosurg. 2002 Nov;97(5):1125-30. PubMed PMID: 12450035.

97: Herman ST. Epilepsy after brain insult: targeting epileptogenesis. Neurology. 2002 Nov 12;59(9 Suppl 5):S21-6. Review. PubMed PMID: 12428028.

98: Shetty AK. Entorhinal axons exhibit sprouting in CA1 subfield of the adult hippocampus in a rat model of temporal lobe epilepsy. Hippocampus. 2002;12(4):534-42. PubMed PMID: 12201638.

99: Benardete EA, Kriegstein AR. Increased excitability and decreased sensitivity to GABA in an animal model of dysplastic cortex. Epilepsia. 2002 Sep;43(9):970-82. PubMed PMID: 12199722.

100: Wallin J, Cui JG, Yakhnitsa V, Schechtmann G, Meyerson BA, Linderoth B. Gabapentin and pregabalin suppress tactile allodynia and potentiate spinal cord stimulation in a model of neuropathy. Eur J Pain. 2002;6(4):261-72. PubMed PMID: 12161092.

101: Kim JY, Roh JK, Lee SK, Chung CK. Neurotrophin receptor immunoreactivity in severe cerebral cortical dysplasia. Epilepsia. 2002;43 Suppl 5:220-6. PubMed PMID: 12121325.

102: Joseph SA, Lynd-Balta E. Evidence for an anatomical substrate of hyperexcitability in human temporal lobe epilepsy: glutamate receptor alterations and reorganized circuitry. Funct Neurol. 2001 Oct-Dec;16(4):347-65. Review. PubMed PMID: 11853326.

103: D'Antuono M, Benini R, Biagini G, D'Arcangelo G, Barbarosie M, Tancredi V, Avoli M. Limbic network interactions leading to hyperexcitability in a model of temporal lobe epilepsy. J Neurophysiol. 2002 Jan;87(1):634-9. PubMed PMID: 11784779.

104: Weng HR, Mansikka H, Winchurch R, Raja SN, Dougherty PM. Sensory processing in the deep spinal dorsal horn of neurokinin-1 receptor knockout mice. Anesthesiology. 2001 Jun;94(6):1105-12. PubMed PMID: 11465604.

105: Shimizu T, Maehara T, Hino T, Komori T, Shimizu H, Yagishita A, Yokota T, Hirai S, Rossini PM. Effect of multiple subpial transection on motor cortical excitability in cortical dysgenesis. Brain. 2001 Jul;124(Pt 7):1336-49. PubMed PMID: 11408329.

106: Shetty AK, Turner DA. Glutamic acid decarboxylase-67-positive hippocampal interneurons undergo a permanent reduction in number following kainic acid-induced degeneration of ca3 pyramidal neurons. Exp Neurol. 2001 Jun;169(2):276-97. PubMed PMID: 11358442.

107: Roncarati R, Di Chio M, Sava A, Terstappen GC, Fumagalli G. Presynaptic localization of the small conductance calcium-activated potassium channel SK3 at the neuromuscular junction. Neuroscience. 2001;104(1):253-62. PubMed PMID: 11311547.

108: Vernet O, Farmer JP, Montes JL, Villemure JG, Meagher-Villemure K. Dysgenetic mesial temporal sclerosis: an unrecognized entity. Childs Nerv Syst. 2000 Nov;16(10-11):719-23. PubMed PMID: 11151722.

109: Swann JW, Al-Noori S, Jiang M, Lee CL. Spine loss and other dendritic abnormalities in epilepsy. Hippocampus. 2000;10(5):617-25. Review. PubMed PMID: 11075833.

110: Lehmann TN, Gabriel S, Kovacs R, Eilers A, Kivi A, Schulze K, Lanksch WR, Meencke HJ, Heinemann U. Alterations of neuronal connectivity in area CA1 of hippocampal slices from temporal lobe epilepsy patients and from pilocarpine-treated epileptic rats. Epilepsia. 2000;41 Suppl 6:S190-4. PubMed PMID: 10999543.

111: Mathern GW, Cepeda C, Hurst RS, Flores-Hernandez J, Mendoza D, Levine MS. Neurons recorded from pediatric epilepsy surgery patients with cortical dysplasia. Epilepsia. 2000;41 Suppl 6:S162-7. PubMed PMID: 10999538.

112: Telfeian AE, Federoff HJ, Leone P, During MJ, Williamson A. Overexpression of GluR6 in rat hippocampus produces seizures and spontaneous nonsynaptic bursting in vitro. Neurobiol Dis. 2000 Aug;7(4):362-74. PubMed PMID: 10964607.

113: Miki K, Iwata K, Tsuboi Y, Morimoto T, Kondo E, Dai Y, Ren K, Noguchi K. Dorsal column-thalamic pathway is involved in thalamic hyperexcitability following peripheral nerve injury: a lesion study in rats with experimental mononeuropathy. Pain. 2000 Mar;85(1-2):263-71. PubMed PMID: 10692627.

114: Shetty AK, Turner DA. Fetal hippocampal grafts containing CA3 cells restore host hippocampal glutamate decarboxylase-positive interneuron numbers in a rat model of temporal lobe epilepsy. J Neurosci. 2000 Dec 1;20(23):8788-801. PubMed PMID: 11102487; PubMed Central PMCID: PMC6773070.

115: Telfeian AE, Spencer DD, Williamson A. Lack of correlation between neuronal hyperexcitability and electrocorticographic responsiveness in epileptogenic human neocortex. J Neurosurg. 1999 May;90(5):939-45. PubMed PMID: 10223462.

116: Coderre TJ, Katz J. Peripheral and central hyperexcitability: differential signs and symptoms in persistent pain. Behav Brain Sci. 1997 Sep;20(3):404-19; discussion 435-513. PubMed PMID: 10097003.

117: Isnard J, Guénot M, Fischer C, Mertens P, Sindou M, Mauguière F. A stereoelectroencephalographic (SEEG) study of light-induced mesiotemporal epileptic seizures. Epilepsia. 1998 Oct;39(10):1098-103. PubMed PMID: 9776331.

118: Smith KL, Lee CL, Swann JW. Local circuit abnormalities in chronically epileptic rats after intrahippocampal tetanus toxin injection in infancy. J Neurophysiol. 1998 Jan;79(1):106-16. PubMed PMID: 9425181.

119: Pertovaara A. A neuronal correlate of secondary hyperalgesia in the rat spinal dorsal horn is submodality selective and facilitated by supraspinal influence. Exp Neurol. 1998 Jan;149(1):193-202. PubMed PMID: 9454628.

120: de Lanerolle NC, Williamson A, Meredith C, Kim JH, Tabuteau H, Spencer DD, Brines ML. Dynorphin and the kappa 1 ligand [3H]U69,593 binding in the human epileptogenic hippocampus. Epilepsy Res. 1997 Oct;28(3):189-205. PubMed PMID: 9332884.

121: Gordon SM, Dionne RA, Brahim J, Jabir F, Dubner R. Blockade of peripheral neuronal barrage reduces postoperative pain. Pain. 1997 Apr;70(2-3):209-15. PubMed PMID: 9150295.

122: Shetty AK, Turner DA. Fetal hippocampal cells grafted to kainate-lesioned CA3 region of adult hippocampus suppress aberrant supragranular sprouting of host mossy fibers. Exp Neurol. 1997 Feb;143(2):231-45. PubMed PMID: 9056386.

123: von Campe G, Spencer DD, de Lanerolle NC. Morphology of dentate granule cells in the human epileptogenic hippocampus. Hippocampus. 1997;7(5):472-88. PubMed PMID: 9347345.

124: Gao XX, Ren B, Linderoth B, Meyerson BA. Daily spinal cord stimulation suppresses autotomy behavior in rats following peripheral deafferentation. Neuroscience. 1996 Nov;75(2):463-70. PubMed PMID: 8931010.

125: Van Den Pol AN, Obrietan K, Belousov A. Glutamate hyperexcitability and seizure-like activity throughout the brain and spinal cord upon relief from chronic glutamate receptor blockade in culture. Neuroscience. 1996 Oct;74(3):653-74. PubMed PMID: 8884763.

126: Buchkremer-Ratzmann I, August M, Hagemann G, Witte OW. Electrophysiological transcortical diaschisis after cortical photothrombosis in rat brain. Stroke. 1996 Jun;27(6):1105-9; discussion 1109-11. PubMed PMID: 8650722.

127: Mathern GW, Leite JP, Babb TL, Pretorius JK, Kuhlman PA, Mendoza D, Fried I, Sakamoto AC, Assirati JA, Adelson PD, Peacock WJ. Aberrant hippocampal mossy fiber sprouting correlates with greater NMDAR2 receptor staining. Neuroreport. 1996 Apr 10;7(5):1029-35. PubMed PMID: 8804045.

128: Eide PK, Jørum E, Stenehjem AE. Somatosensory findings in patients with spinal cord injury and central dysaesthesia pain. J Neurol Neurosurg Psychiatry. 1996 Apr;60(4):411-5. PubMed PMID: 8774406; PubMed Central PMCID: PMC1073894.

129: Ishikawa M, Ohira T, Namiki J, Gotoh K, Takase M, Toya S. Electrophysiological investigation of hemifacial spasm: F-waves of the facial muscles. Acta Neurochir (Wien). 1996;138(1):24-32. PubMed PMID: 8686521.

130: Luo L, Wiesenfeld-Hallin Z. Effects of intrathecal local anesthetics on spinal excitability and on the development of autotomy. Pain. 1995 Nov;63(2):173-9. PubMed PMID: 8628582.

131: Kondoh T, Lee SH, Low WC. Alterations in striatal dopamine release and reuptake under conditions of mild, moderate, and severe cerebral ischemia. Neurosurgery. 1995 Nov;37(5):948-54. PubMed PMID: 8559344.

132: Williamson A, Spencer D. Zinc reduces dentate granule cell hyperexcitability in epileptic humans. Neuroreport. 1995 Jul 31;6(11):1562-4. PubMed PMID: 7579149.

133: Williamson A, Telfeian AE, Spencer DD. Prolonged GABA responses in dentate granule cells in slices isolated from patients with temporal lobe sclerosis. J Neurophysiol. 1995 Jul;74(1):378-87. PubMed PMID: 7472339.

134: Clatworthy AL, Walters ET. Comparative analysis of hyperexcitability and synaptic facilitation induced by nerve injury in two populations of mechanosensory neurones of Aplysia californica. J Exp Biol. 1994 May;190:217-38. PubMed PMID: 7964392.

135: Asakura T, Tokimura H, Hirahara K, Baba K. Identification of the cerebral motor cortex by focal magnetic stimulation: clinical application to neurosurgical patients. Stereotact Funct Neurosurg. 1994;63(1-4):177-81. PubMed PMID: 7624632.

136: Lahtinen H, Miettinen R, Ylinen A, Halonen T, Riekkinen PJ Sr. Biochemical and morphological changes in the rat hippocampus following transection of the fimbria-fornix. Brain Res Bull. 1993;31(3-4):311-8. PubMed PMID: 8098258.

137: Richter-Levin G, Segal M. Raphe grafts in the hippocampus, but not in the entorhinal cortex, reverse hippocampal hyperexcitability of serotonin-depleted rats and restore their responsiveness to fenfluramine. Dev Neurosci. 1992;14(2):166-72. PubMed PMID: 1396176.

138: de Lanerolle NC, Brines M, Williamson A, Kim JH, Spencer DD. Neurotransmitters and their receptors in human temporal lobe epilepsy. Epilepsy Res Suppl. 1992;7:235-50. Review. PubMed PMID: 1361331.

139: Grutsch JF, Khasawinah A. Signs and mechanisms of chlordane intoxication. Biomed Environ Sci. 1991 Sep;4(3):317-26. Review. PubMed PMID: 1764223.

140: Turner DA, Wheal HV. Excitatory synaptic potentials in kainic acid-denervated rat CA1 pyramidal neurons. J Neurosci. 1991 Sep;11(9):2786-94. PubMed PMID: 1679121; PubMed Central PMCID: PMC6575247.

141: Levitt M. The theory of chronic deafferentation dysesthesias. J Neurosurg Sci. 1990 Apr-Jun;34(2):71-98. Review. PubMed PMID: 2092098.

142: Hu JW, Sessle BJ. Effects of tooth pulp deafferentation on nociceptive and nonnociceptive neurons of the feline trigeminal subnucleus caudalis (medullary dorsal horn). J Neurophysiol. 1989 Jun;61(6):1197-206. PubMed PMID: 2746320.

143: Tenney SM, Ou LC. Hypoxic ventilatory response of cats at high altitude: an interpretation of 'blunting'. Respir Physiol. 1977 Jun;30(1-2):185-99. PubMed PMID: 877446.

144: PETSCHEK R, TIMIRAS PS. ROLE OF PITUITARY IN COLD-INDUCED BRAIN HYPEREXCITABILITY. Proc Soc Exp Biol Med. 1964 Mar;115:638-40. PubMed PMID: 14155783.


1)
Goudman L, Daenen L, Mouraux A, Nijs J, Cras P, Roussel N, Moens M, Coppieters I, Huysmans E, De Kooning M. Processing of Laser-Evoked Potentials in Patients with Chronic Whiplash-Associated Disorders, Chronic Fatigue Syndrome, and Healthy Controls: A Case-Control Study. Pain Med. 2020 Apr 14. pii: pnaa068. doi: 10.1093/pm/pnaa068. [Epub ahead of print] PubMed PMID: 32289826.
  • central_nervous_system_hyperexcitability.txt
  • Last modified: 2025/04/29 20:28
  • by 127.0.0.1