加巴喷丁对神经病理性疼痛小鼠大脑作用机制的初步探讨
|
摘要
目的：
抗癫痫药加巴喷丁对神经病理性疼痛有良好的疗效，但其作用机制仍未明了。本研究采用小鼠坐骨神经部分结扎模型，观察加巴喷丁(GBP)对大脑皮层基因差异表达的影响。
方法：
120只BALB／c雄性小鼠，体重20～22克，随机分为6组(每组n=20)：(1)CON：对照，腹腔注射生理盐水；(2)CON+GBP组：对照，腹腔注射加巴喷丁100mg／kg；(3)SHAM：假手术，腹腔注射生理盐水；(4) SHAM+GBP：假手术，腹腔注射加巴喷丁100mg／kg；(5) MOD：手术结扎部分坐骨神经，腹腔注射生理盐水；(6)MOD+GBP：手术结扎部分坐骨神经，腹腔注射加巴喷丁100mg／kg。手术前后用Von Frey纤维细丝测量机械痛阈。从手术侧足的行为学变化和机械痛阈确认神经病理性疼痛模型成功。术后第15天开始按方案腹腔注射给药四周。给药结束后将小鼠断头处死，留取大脑皮层。选择SHAM、MOD和MOD+GBP组做基因表达差异检测(01igo神经科学离子通道与载体基因芯片及0ligo神经营养素与受体基因芯片)，并根据检测结果挑选部分变化显著的基因进行实时PCR验证。同时测定SHAM、SHAM+GBP、MOD和MOD+GBP组皮层的脑啡肽含量。
结果：
和CON、CON+GBP、SHAM、SHAM+GBP组小鼠相比较，MOD和MOD+GBP组小鼠手术侧足的机械性痛阂在坐骨神经部分结扎术后极显著下降(P＜0.01)。和MOD组小鼠相比较，MOD+GBP组小鼠手术侧足的机械性痛阈在加巴喷丁给药后极显著增高(P＜0.01)。
MOD和SHAM相比较，脑源性神经生长因子(BDNF)、神经肽Y(NPY)、Pleiotrophin(PTN)等基因显著下调。MOD+GBP和MOD相比较，BDNF、NPY、PTN等基因显著上调。大脑皮层脑啡肽含量在SHAM、SHAM+GBP、MOD、MOD+GBP四组间差异无显著性。
结论：
加巴喷丁对神经病理性疼痛的镇痛机制可能与大脑皮层BDNF、NPY、PTN等基因的上调有关；其镇痛机制可能不涉及脑啡肽。
Gabapentin is an anticonvulsant that has successfully been used to treat many neuropathic pain syndromes, although the mechanism of its antihyperalgesic action remains elusive. The aim of this study was to investigate the differences of gene expression in the cerebral cortex in mice after partial sciatic nerve ligation(PSNL) with or without gabapentin administration.
120 male BALB/c mice weighing 20～22g were randomly divided into 6 groups(n=20 for each group): (1) CON: control, with intraperitoneal injection(i. p.) of saline. (2) CON+GBP: control, with gabapentin 100mg/kg i. p. (3) SHAM: sham operation, with saline i. p. (4) SHAM+GBP: sham operation, with gabapentin 100mg/kg i. p. (5) MOD: PSNL, with saline i. p. (6) MOD+GBP: PSNL, with gabapentin 100mg/kg i. p. Mechanical sensitivity was assessed with von Frey filaments before and after PSNL. Intraperitoneal injection of gabapentin or saline started from day 15 after the successful development of neuropathic pain models confirmed by behavioral changes and mechanical allodynia of the ipsilateral hind paw. After four-week administration of gabapentin, mice were sacrificed and cerebral cortex was harvested. Cerebral cortex of group SHAM, MOO, and MOD+GBP were used for gene detection(Oligo neuroscience ion channel and transporter gene array, and Oligo neurotrophin and receptors gene array), and enkephalin concentration was measured in group SHAM, SHAM+GBP, MOD, and MOD+GBP. Several genes markedly changed were selected for Real time-PCR analyses.
Compared with group CON, CON+GBP, SHAM and SHAM+GBP, mechanical sensitivity of group MOD and MOD+GBP of the ipsilateral hind paw significantly decreased after PSNL(P＜0.01). Compared with group MOD, mechanical sensitivity of group MOD+GBP of the ipsilateral hind paw significantly increased after gabapentin administration(P＞0.01).
Compared with group SHAM, several genes including brain-derived neurotrophic factor(BDNF), neuropeptide Y(NPY), and pleiotrophin markedly down-regulated in group MOD. Compared with group MOD, BDNF, NPY, and pleiotrophin markedly up-regulated in group MOD+GBP. There were no differences between group SHAM, SHAM+GBP, MOD and MOD+GBP in cortex enkephalin concentration.
BDNF, NPY, and pleiotrophin, but not enkephalin may be involved in the antihyperalgesie action of gabapentin.
抗癫痫药加巴喷丁对神经病理性疼痛有良好的疗效，但其作用机制仍未明了。本研究采用小鼠坐骨神经部分结扎模型，观察加巴喷丁(GBP)对大脑皮层基因差异表达的影响。
方法：
120只BALB／c雄性小鼠，体重20～22克，随机分为6组(每组n=20)：(1)CON：对照，腹腔注射生理盐水；(2)CON+GBP组：对照，腹腔注射加巴喷丁100mg／kg；(3)SHAM：假手术，腹腔注射生理盐水；(4) SHAM+GBP：假手术，腹腔注射加巴喷丁100mg／kg；(5) MOD：手术结扎部分坐骨神经，腹腔注射生理盐水；(6)MOD+GBP：手术结扎部分坐骨神经，腹腔注射加巴喷丁100mg／kg。手术前后用Von Frey纤维细丝测量机械痛阈。从手术侧足的行为学变化和机械痛阈确认神经病理性疼痛模型成功。术后第15天开始按方案腹腔注射给药四周。给药结束后将小鼠断头处死，留取大脑皮层。选择SHAM、MOD和MOD+GBP组做基因表达差异检测(01igo神经科学离子通道与载体基因芯片及0ligo神经营养素与受体基因芯片)，并根据检测结果挑选部分变化显著的基因进行实时PCR验证。同时测定SHAM、SHAM+GBP、MOD和MOD+GBP组皮层的脑啡肽含量。
结果：
和CON、CON+GBP、SHAM、SHAM+GBP组小鼠相比较，MOD和MOD+GBP组小鼠手术侧足的机械性痛阂在坐骨神经部分结扎术后极显著下降(P＜0.01)。和MOD组小鼠相比较，MOD+GBP组小鼠手术侧足的机械性痛阈在加巴喷丁给药后极显著增高(P＜0.01)。
MOD和SHAM相比较，脑源性神经生长因子(BDNF)、神经肽Y(NPY)、Pleiotrophin(PTN)等基因显著下调。MOD+GBP和MOD相比较，BDNF、NPY、PTN等基因显著上调。大脑皮层脑啡肽含量在SHAM、SHAM+GBP、MOD、MOD+GBP四组间差异无显著性。
结论：
加巴喷丁对神经病理性疼痛的镇痛机制可能与大脑皮层BDNF、NPY、PTN等基因的上调有关；其镇痛机制可能不涉及脑啡肽。
Gabapentin is an anticonvulsant that has successfully been used to treat many neuropathic pain syndromes, although the mechanism of its antihyperalgesic action remains elusive. The aim of this study was to investigate the differences of gene expression in the cerebral cortex in mice after partial sciatic nerve ligation(PSNL) with or without gabapentin administration.
120 male BALB/c mice weighing 20～22g were randomly divided into 6 groups(n=20 for each group): (1) CON: control, with intraperitoneal injection(i. p.) of saline. (2) CON+GBP: control, with gabapentin 100mg/kg i. p. (3) SHAM: sham operation, with saline i. p. (4) SHAM+GBP: sham operation, with gabapentin 100mg/kg i. p. (5) MOD: PSNL, with saline i. p. (6) MOD+GBP: PSNL, with gabapentin 100mg/kg i. p. Mechanical sensitivity was assessed with von Frey filaments before and after PSNL. Intraperitoneal injection of gabapentin or saline started from day 15 after the successful development of neuropathic pain models confirmed by behavioral changes and mechanical allodynia of the ipsilateral hind paw. After four-week administration of gabapentin, mice were sacrificed and cerebral cortex was harvested. Cerebral cortex of group SHAM, MOO, and MOD+GBP were used for gene detection(Oligo neuroscience ion channel and transporter gene array, and Oligo neurotrophin and receptors gene array), and enkephalin concentration was measured in group SHAM, SHAM+GBP, MOD, and MOD+GBP. Several genes markedly changed were selected for Real time-PCR analyses.
Compared with group CON, CON+GBP, SHAM and SHAM+GBP, mechanical sensitivity of group MOD and MOD+GBP of the ipsilateral hind paw significantly decreased after PSNL(P＜0.01). Compared with group MOD, mechanical sensitivity of group MOD+GBP of the ipsilateral hind paw significantly increased after gabapentin administration(P＞0.01).
Compared with group SHAM, several genes including brain-derived neurotrophic factor(BDNF), neuropeptide Y(NPY), and pleiotrophin markedly down-regulated in group MOD. Compared with group MOD, BDNF, NPY, and pleiotrophin markedly up-regulated in group MOD+GBP. There were no differences between group SHAM, SHAM+GBP, MOD and MOD+GBP in cortex enkephalin concentration.
BDNF, NPY, and pleiotrophin, but not enkephalin may be involved in the antihyperalgesie action of gabapentin.
引文
Abdulla FA, Smith PA. Nerve injury increases an excitatory action of neuropeptide Y and Y2-agonists ondorsal root ganglion neurons. Neuroscience. 1999 Mar;89(1):43-60.
Allen S: Pharmacotherapy of neuropathic pain. Contin Educ Anaesth Crit Care Pain (2005) 5(4):134-137.
Altar CA. Neurotrophins and depression. Trends Pharmacol Sci. 1999 Feb;20(2):59-61.
Armijo JA, Pena MA, Adin J, et al. Association between patient age and gabapentin serum concentration-to-dose ratio: a preliminary multivariate analysis. Ther Drug Monit. 2004 Dec;26(6):633-7.
Attal N. Chronic neuropathic pain: mechanisms and treatment. Clin J Pain. 2000 Sep;16(3 Suppl):S 118-30.
Bao L, Wang HF, Cai HJ, et al. Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord. Eur J Neurosci. 2002 Jul; 16(2): 175-85.
Balasubramaniam A. et al. Clinical potentials of neuropeptide Y family of hormones. Am J Surg. 2002 Apr;183(4):430-4.
Bennett DL, French J, Priestley JV, et al. NGF but not NT-3 or BDNF prevents the A fiber sprouting into lamina II of the spinal cord that occurs following axotomy. Mol Cell Neurosci. 1996;8(4):211-20.
Bertrand S, Ng GY, Purisai MG, et al. The anticonvulsant, antihyperalgesic agent gabapentin is an agonist at brain gamma-aminobutyric acid type B receptors negatively coupled to voltage-dependent calcium channels. J Pharmacol Exp Ther. 2001 Jul;298(1):15-24.
Bertrand S, Nouel D, Morin F, et al. Gabapentin actions on Kir3 currents and N-type Ca2+ channels via GABAB receptors in hippocampal pyramidal cells. Synapse. 2003 Nov;50(2):95-109.
Beydoun A, Backonja MM. Mechanistic stratification of antineuralgic agents. J Pain Symptom Manage. 2003 May;25(5 Suppl):S 18-30.
Bleakman D, Colmers WF, Fournier A, Miller RJ. Neuropeptide Y inhibits Ca2+ influx into cultured dorsal root ganglion neurons of the rat via a Y2 receptor. Br J Pharmacol. 1991 Jul; 103(3): 1781-9.
Blondet B, Carpentier G, Lafdil F, et al. Pleiotrophin cellular localization in nerve regeneration after peripheral nerve injury. J Histochem Cytochem. 2005 Aug;53(8):971-7.
Blum RA, Comstock TJ, Sica DA, et al. Pharmacokinetics of gabapentin in subjects with various degrees of renal function. Clin Pharmacol Ther. 1994 Aug;56(2): 154-9.
Bridges D, Thompson SW, Rice AS. Mechanisms of neuropathic pain. Br J Anaesth. 2001 Jul;87(1): 12-26.
Broqua P, Wettstein JG, Rocher MN, et al. Antinociceptive effects of neuropeptide Y and related peptides in mice. Brain Res. 1996 Jun 10;724(1):25-32.
Bowery NG, Bettler B, Froestl W, et al. International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function. Pharmacol Rev. 2002
Jun;54(2):247-64.Brown JP, Gee NS. Cloning and deletion mutagenesis of the alpha2 delta calcium channel subunit from porcine cerebral cortex. Expression of a soluble form of the protein that retains [3H]gabapentin binding activity. J Biol Chem. 1998 Sep 25;273(39):25458-65.
Carlton SM, Zhou S. Attenuation of formalin-induced nociceptive behaviors following local peripheral injection of gabapentin. Pain. 1998;76:201-207.
Cejas PJ, Martinez M, Karmally S, et al. Lumbar transplant of neurons genetically modified to secrete brain-derived neurotrophic factor attenuates allodynia and hyperalgesia after sciatic nerve constriction. Pain. 2000 May;86(1-2):195-210.
Chen B, Dowlatshahi D, MacQueen GM,et al. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry. 2001 Aug 15;50(4):260-5.
Chen SR, Eisenach JC, McCaslin PP, et al. Synergistic effect between intrathecal non-NMDA antagonist and gabapentin on allodynia induced by spinal nerve ligation in rats. Anesthesiology. 2000 Feb;92(2):500-6.
Chen SR, Xu Z, Pan HL. Stereospecific effect of pregabalin on ectopic afferent discharges and neuropathic pain induced by sciatic nerve ligation in rats. Anesthesiology. 2001;95:1473-1479.
Cheng JK, Chen CC, Yang JR, The antiallodynic action target of intrathecal gabapentin: Ca2+ channels, KATP channels or N-methyl-d-aspartic acid receptors? Anesth Analg. 2006 Jan; 102(1): 182-7.
Cheng JK, Lai YJ, Chen CC, et al. Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain. Anesthesiology. 2003 Jun;98(6): 1472-9.
Cheng JK, Lee SZ, Yang JR, et al. Does gabapentin act as an agonist at native GABAB receptors? J Biomed Sci. 2004;l 1:346-355.
Cheng JK, Pan HL, Eisenach JC. Antiallodynic effect of intrathecal gabapentin and its interaction with clonidine in a rat model of postoperative pain. Anesthesiology. 2000;92:1126-1131.
Chizh BA, Scheede M, Schlutz H. Antinociception and (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid antagonism by gabapentin in the rat spinal cord in vivo. Naunyn Schmiedebergs Arch Pharmacol. 2000;362:197-200.
Coderre TJ, Kumar N, Lefebvre CD, et al. Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal release of glutamate. J Neurochem. 2005 Aug;94(4):1131-9.
Colmers WF, Klapstein GJ, Fournier A, et al. Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor. Br J Pharmacol. 1991 Jan;102(1):41-4.
Colmers WF, Bleakman D. Effects of neuropeptide Y on the electrical properties of neurons. Trends Neurosci. 1994 Sep;17(9):373-9.
Coppell AL, Pei Q, Zetterstrom TS. Bi-phasic change in BDNF gene expression following antidepressant drug treatment. Neuropharmacology. 2003 Jun;44(7):903-10.
Costigan M, Befort K, Karchewski L, et al. Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci. 2002 Oct 25;3:16.
Cui M, Liang L, Steffery ME, et al. In vitro characterization of GABAB receptors and gabapentin effect. Soc Neurosci Abs. 2002;869:15.
Danysz W, Kozela E, Parsons CG, et al. Peripherally acting NMDA receptor/glycineB site receptor antagonists inhibit morphine tolerance. Neuropharmacology. 2005;48:360-371.
Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain. 1992;48:261-268.
De Foubert G, Carney SL, Robinson CS, et al. Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment. Neuroscience. 2004;128(3):597-604.
Dissanayake VU, Gee NS, Brown JP, et al. Spermine modulation of specific [3H]-gabapentin binding to the detergent-solubilized porcine cerebral cortex alpha 2 delta calcium channel subunit. Br J Pharmacol. 1997 Mar;120(5):833-40.
Dixit RK, Bhargava VK. Neurotransmitter mechanisms in gabapentin antinociception. Pharmacology. 2002 Aug;65(4): 198-203.
Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry. 1997 Jul;54(7):597-606.
Duggan AW, Hope PJ, Lang CW,et al. Sustained isometric contraction of skeletal muscle results in release of immunoreactive neurokinins in the spinal cord of the anaesthetized cat. Neurosci Lett. 1991 Jan 28; 122(2): 191-4.
Duman RS, Vaidya VA. Molecular and cellular actions of chronic electroconvulsive seizures. J ECT. 1998 Sep;14(3):181-93.
Eaton MJ, Blits B, Ruitenberg MJ, et al. Amelioration of chronic neuropathic pain after partial nerve injury by adeno-associated viral (AAV) vector-mediated over-expression of BDNF in the rat spinal cord. Gene Ther. 2002 Oct;9(20):1387-95.
Errante LD, Petroff OA. Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations. Seizure. 2003;12:300-306.
Errante LD, Williamson A, Spencer DD, et al. Gabapentin and vigabatrin increase GABA in the human neocortical slice. Epilepsy Res. 2002;49:203-210.
Felix R. Voltage-dependent Ca2+ channel alpha2delta auxiliary subunit: structure, function and regulation. Receptors Channels. 1999;6(5):351-62.
Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid-induced visceral nociception. Anesthesiology. 2003 Mar;98(3):729-33.
Field MJ, Hughes J, Singh L. Further evidence for the role of the alpha(2)delta subunit of voltage dependent calcium channels in models of neuropathic pain. Br J Pharmacol. 2000 Sep;131(2):282-6.
Field MJ, Holloman EF, McCleary S, et al. Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain. J Pharmacol Exp Ther. 1997;282:1242-1246.
Fink K, Dooley DJ, Meder WP, et al. Inhibition of neuronal Ca(2+) influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology. 2002 Feb;42(2):229-36.
Fink K, Meder W, Dooley DJ, et al. Inhibition of neuronal Ca(2+) influx by gabapentin and subsequent reduction of neurotransmitter release from rat neocortical slices. Br J Pharmacol. 2000 Jun;130(4):900-6.
Foster AC, Fagg GE. Neurobiology. Taking apart NMDA receptors. Nature. 1987 Oct l-7;329(6138):395-6.
Freiman TM, Kukolja J, Heinemeyer J, et al. Modulation of K+-evoked [3H]-noradrenaline release from rat and human brain slices by gabapentin: involvement of KATP channels. Naunyn Schmiedebergs Arch Pharmacol. 2001 May;363(5):537-42.
Garry EM, Delaney A, Anderson HA, et al. Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs. Pain. 2005 Nov;118(1-2):97-l 11.
Gee NS, Brown JP, Dissanayake VU, et al. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem. 1996 Mar 8;271(10):5768-76.
Goldlust A, Su TZ, Welty DF, et al. Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA. Epilepsy Res. 1995 Sep;22(1):1-11.
Gouarderes C, Cros J, Quirion R. Autoradiographic localization of mu, delta and kappa opioid receptor binding sites in rat and guinea pig spinal cord. Neuropeptides. 1985 Jul;6(4):331-42.
Grudt TJ, Henderson G. Glycine and GABAA receptor-mediated synaptic transmission in rat substantia gelatinosa: inhibition by mu-opioid and GABAB agonists. J Physiol. 1998 Mar 1;507(Pt 2):473-83.
Grudt TJ, Williams JT. kappa-Opioid receptors also increase potassium conductance. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11429-32.
Grudt TJ, Williams JT. mu-Opioid agonists inhibit spinal trigeminal substantia gelatinosa neurons in guinea pig and rat. J Neurosci. 1994 Mar; 14(3 Pt 2): 1646-54.
Gu Y, Huang LY. Gabapentin actions on N-methyl-D-aspartate receptor channels are protein kinase C-dependent. Pain. 2001 Jul;93(1):85-92.
Gu Y, Huang LY. Gabapentin potentiates N-methyl-D-aspartate receptor mediated currents in rat GABAergic dorsal horn neurons. Neurosci Lett. 2002 May 24;324(3): 177-80.
Guo W, Robbins MT, Wei F, et al. Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for descending pain facilitation. J Neurosci. 2006 Jan 4;26(1):126-37.
Ha SO, Kim JK, Hong HS, et al. Expression of brain-derived neurotrophic factor in rat dorsal root ganglia, spinal cord and gracile nuclei in experimental models of neuropathic pain. Neuroscience. 2001;107(2):301-9.
Hansen C, Gilron I, Hong M. The effects of intrathecal gabapentin on spinal morphine tolerance in the rat tail-flick and paw pressure tests. Anesth Analg. 2004;99:1180-1184.
Hill DR, Suman-Chauhan N, Woodruff GN. Localization of [3 H] gabapentin to a novel site in rat brain: autoradiographic studies. Eur J Pharmacol. 1993 Feb 15;244(3):303-9.
Honmou O, Oyelese AA, Kocsis JD. The anticonvulsant gabapentin enhances promoted release of GABA in hippocampus: a field potential analysis. Brain Res. 1995 Sep 18;692(1-2):273-7.
Hori Y, Endo K, Takahashi T. Presynaptic inhibitory action of enkephalin on excitatory transmission in superficial dorsal horn of rat spinal cord. J Physiol. 1992 May;450:673-85.
Hua XY, Boublik JH, Spicer MA,et al. The antinociceptive effects of spinally administered neuropeptide Y in the rat:systematic studies on structure-activity relationship. J Pharmacol Exp Ther. 1991 Jul 1;258(1):243-8.
Hwang JH, Yaksh TL. Effect of subarachnoid gabapentin on tactile-evoked allodynia in a surgically induced neuropathic pain model in the rat. Reg Anesth. 1997 May-Jun;22(3):249-56.
Jensen AA, Mosbacher J, Elg S, et al. The anticonvulsant gabapentin (neurontin) does not act through gamma-aminobutyric acid-B receptors. Mol Pharmacol. 2002 Jun;61(6):1377-84.
Jessell TM, Iversen LL. Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature. 1977 Aug 11;268(5620):549-51.
Jun JH, Yaksh TL. The effect of intrathecal gabapentin and 3-isobutyl gamma-aminobutyric acid on the hyperalgesia observed after thermal injury in the rat. Anesth Analg. 1998;86:348-354.
Kanai A, Sarantopoulos C, McCallum JB, et al. Painful neuropathy alters the effect of gabapentin on sensory neuron excitability in rats. Acta Anaesthesiol Scand. 2004;48:507-512.
Kalra S, Cashman NR, Caramanos Z, et al. Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy. AJNR Am J Neuroradiol. 2003;24:476-480.
Kar S, Quirion R. Quantitative autoradiographic localization of [125I]neuropeptide Y receptor binding sites in rat spinal cord and the effects of neonatal capsaicin, dorsal rhizotomy and peripheral axotomy. Brain Res. 1992 Mar 6;574(1-2):333-7.
Kato A, Ohkubo T, Kitamura K. Algogen-specific pain processing in mouse spinal cord: differential involvement of voltage-dependent Ca(2+) channels in synaptic transmission. Br J Pharmacol. 2002 Mar; 135(5): 1336-42.
Kleckner NW, Dingledine R. Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes. Science. 1988;241:835-837.
Kocsis JD, Honmou O. Gabapentin increases GABA-induced depolarization in rat neonatal optic nerve. Neurosci Lett. 1994 Mar 14;169(1-2):181-4.
Kohno T, Kumamoto E, Higashi H,et al. Actions of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord. J Physiol. 1999 Aug 1;518 (Pt 3):803-13.
Kubo T, Yamashita T, Yamaguchi A, et al. Analysis of genes induced in peripheral nerve after axotomy using cDNA microarrays. J Neurochem. 2002 Sep;82(5):1129-36.
Kuzniecky R, Ho S, Pan J, et al. Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults. Neurology. 2002 Feb 12;58(3):368-72.
Lanneau C, Green A, Hirst WD, et al. Gabapentin is not a GABAB receptor agonist. Neuropharmacology. 2001 Dec;41(8):965-75.
Lekan HA, Carlton SM, Coggeshall RE. Sprouting of A beta fibers into lamina II of the rat dorsal horn in peripheral neuropathy. Neurosci Lett. 1996 Apr 26;208(3): 147-50.
Li CY, Song YH, Higuera ES, et al. Spinal dorsal horn calcium channel alpha2delta-l subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J Neurosci. 2004 Sep 29;24(39):8494-9.
Li YS, Milner PG, Chauhan AK, et al. Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity. Science. 1990 Dec 21;250(4988): 1690-4.
Loscher W, Honack D, Taylor CP. Gabapentin increases aminooxyacetic acid-induced GABA accumulation in several regions of rat brain. Neurosci Lett. 1991 Jul 22;128(2):150-4.
Luo ZD, Chaplan SR, Higuera ES, et al. Upregulation of dorsal root ganglion (alpha)2(delta) calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J Neurosci. 2001 Mar 15;21(6): 1868-75.
Malcangio M, Lessmann V. A common thread for pain and memory synapses? Brain-derived neurotrophic factor and trkB receptors. Trends Pharmacol Sci. 2003 Mar;24(3): 116-21.
Malmberg AB, Basbaum AI. Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates. Pain. 1998 May; 76(1-2): 215-22.
Malberg JE, Eisch AJ, Nestler EJ, et al. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci. 2000 Dec 15;20(24):9104-10.
Maneuf YP, Hughes J, McKnight AT. Gabapentin inhibits the substance P-facilitated K(+)-evoked release of [(3)H]glutamate from rat caudial trigeminal nucleus slices. Pain. 2001 Aug;93(2): 191-6.
Mantyh PW, Allen CJ, Rogers S, et al. Some sensory neurons express neuropeptide Y receptors: potential paracrineinhibition of primary afferent nociceptors following peripheral nerve injury. J Neurosci. 1994 Jun;14(6):3958-68.
Matzner O, Devor M. Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels. J Neurophysiol. 1994;72:349-359. Max MB. Clarifying the definition of neuropathic pain. Pain. 2002 Apr;96(3):406-7. Merskey H. Clarifying definition of neuropathic pain. Pain. 2002 Apr;96(3):408-9. Merskey H. Classification of chronic pain. 2~(nd) edn. Seattle: IASP Press. 1994:40-43.
Misgeld U, Bijak M, Jarolimek W. A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Prog Neurobiol. 1995 Jul;46(4):423-62.
Mixcoatl-Zecuatl T, Medina-Santillan R, Reyes-Garcia G, et al. Effect of K+ channel modulators on the antiallodynic effect of gabapentin. Eur J Pharmacol. 2004;484:201-208.
Moore KA, Kohno T, Karchewski LA, et al. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J Neurosci. 2002 Aug 1;22(15):6724-31.
Moran TD, Colmers WF, Smith PA. Opioid-like actions of neuropeptide Y in rat substantia gelatinosa: Y1 suppression of inhibition and Y2 suppression of excitation. J Neurophysiol. 2004 Dec;92(6):3266-75. 2004 Aug 4.
Munglani R, Harrison SM, Smith GD,et al. Neuropeptide changes persist in spinal cord despite resolving hyperalgesia in arat model of mononeuropathy. Brain Res. 1996 Dec 16;743(1-2):102-8.
Nachshen DA. Regulation of Cytosolic calcium concentration in presynaptic nerve endings isolated from rat brain. J Physiol. 1985 Jun;363:87-101.
Naveilhan P, Hassani H, Lucas G,et al. Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor. Nature. 2001 Jan 25;409(6819):513-7.
Nestler EJ, Barrot M, DiLeone RJ, et al. Neurobiology of depression. Neuron. 2002 Mar 28;34(1):13-25.
Ng GY, Bertrand S, Sullivan R, et al. Gamma-aminobutyric acid type B receptors with specific heterodimer composition and postsynaptic actions in hippocampal neurons are targets of anticonvulsant gabapentin action. Mol Pharmacol. 2001 Jan;59(1): 144-52.
Nicholson B. Gabapentin use in neuropathic pain syndromes. Acta Neurol Scand. 2000 Jun;101(6):359-71.
Obara I, Przewlocki R, Przewlocka B. Local peripheral effects of mu-opioid receptor agonists in neuropathic pain in rats. Neurosci Lett. 2004 Apr 22;360(1-2):85-9.
Obata K, Yamanaka H, Kobayashi K, et al. The effect of site and type of nerve injury on the expression of brain-derived neurotrophic factor in the dorsal root ganglion and on neuropathic pain behavior. Neuroscience. 2006a Feb; 137(3):961-70.
Obata K, Noguchi K. BDNF in sensory neurons and chronic pain. Neurosci Res. 2006b May;55(1):1-10.
Ochoa J, Torebjork HE, Culp WJ, et al. Abnormal spontaneous activity in single sensory nerve fibers in humans. Muscle Nerve. 1982;5(9S):S74-7.
Omura T, Sano M, Omura K, et al. Different expressions of BDNF, NT3, and NT4 in muscle and nerve after various types of peripheral nerve injuries. J Peripher Nerv Syst. 2005 Sep;10(3):293-300.
Pan HL, Eisenach JC, Chen SR. Gabapentin suppresses ectopic nerve discharges and reverses allodynia in neuropathic rats. J Pharmacol Exp Ther. 1999;288:1026-1030.
Parker DA, Ong J, Marino V, et al. Gabapentin activates presynaptic GABAB heteroreceptors in rat cortical slices. Eur J Pharmacol. 2004 Jul 14;495(2-3): 137-43.
Partridge BJ, Chaplan SR, Sakamoto E, Yaksh TL. Characterization of the effects of gabapentin and 3-isobutyl-gammaaminobutyric acid on substance P-induced thermal hyperalgesia. Anesthesiology. 1998;88:196-205.
Pasero C. Pathophysiology of neuropathic pain. Pain Manag Nurs. 2004 Dec;5(4 Suppl 1):3-8.
Patel S, Naeem S, Kesingland A, et al. The effects of GABAB agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat. Pain. 2001 ;90:217-226.
Petroff OA, Rothman DL, Behar KL, et al. The effect of gabapentin on brain gamma-aminobutyric acid in patients with epilepsy. Ann Neurol. 1996 Jan;39(1):95-9.
Pinzon-Duarte G, Arango-Gonzalez B, Guenther E, et al. Effects of brain-derived neurotrophic factor on cell survival, differentiation and patterning of neuronal connections and Muller glia cells in the developing retina. Eur J Neurosci. 2004 Mar;19(6):1475-84.
Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science. 2000 Jun 9;288(5472): 1769-72.
Qian J, Colmers WF, Saggau P. Inhibition of synaptic transmission by neuropeptide Y in rat hippocampal area CA1: modulation of presynaptic Ca2+ entry. J Neurosci. 1997 Nov 1 ;17(21):8169-77.
Rao ML, Clarenbach P, Vahlensieck M, et al. Gabapentin augments whole blood serotonin in healthy young men. J Neural Transm. 1988;73(2): 129-34.
Rauvala H, Vanhala A, Castren E, et al. Expression of HB-GAM (heparin-binding growth-associated molecules) in the pathways of developing axonal processes in vivo and neurite outgrowth in vitro induced by HB-GAM. Brain Res Dev Brain Res. 1994 Jun 17;79(2): 157-76.
Redwine KE, Trujillo KA. Effects of NMDA receptor antagonists on acute mu-opioid analgesia in the rat. Pharmacol Biochem Behav. 2003;76:361-372.
Rock DM, Kelly KM, Macdonald RL. Gabapentin actions on ligand- and voltage-gated responses in cultured rodent neurons.Epilepsy Res. 1993;16:89-98.
Rode F, Jensen DG, Blackburn-Munro G, et al. Centrally-mediated antinociceptive actions of GABA(A) receptor agonists in the rat spared nerve injury model of neuropathic pain. Eur J Pharmacol. 2005 Jun 1;516(2): 131-8.
Rose MA, Kam PC. Gabapentin: pharmacology and its use in pain management. Anaesthesia. 2002 May;57(5):451-62.
Sarantopoulos C, McCallum B, Sapunar D, et al. ATP-sensitive potassium channels in rat primary afferent neurons: the effect of neuropathic injury and gabapentin. Neurosci Lett. 2003;343:185-189.
Satzinger G. Antiepileptics from gamma-aminobutyric acid. Arzneimittelforschung. 1994 Mar;44(3):261-6.
Schwarz JB, Gibbons SE, Graham SR, et al. Novel cyclopropyl beta-amino acid analogues of pregabalin and gabapentin that target the alpha2-delta protein. J Med Chem. 2005 Apr 21;48(8):3026-35.
Seltzer Z, Dubner R, Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain. 1990 Nov;43(2):205-18.
Shimoyama M, Shimoyama N, Hori Y. Gabapentin affects glutamatergic excitatory neurotransmission in the rat dorsal horn. Pain. 2000;85:405-414.
Shinder V, Govrin-Lippmann R, Cohen S, et al. Structural basis of sympathetic-sensory coupling in rat and human dorsal root ganglia following peripheral nerve injury. J Neurocytol. 1999 Sep;28(9):743-61.
Siddall PJ, Cousins MJ. Spinal pain mechanisms. Spine. 1997 Jan l;22(1):98-104.
Sills GJ. Not another gabapentin mechanism! Epilepsy Curr. 2005 Mar-Apr;5(2):75-7.
Silos-Santiago I, Yeh HJ, Gurrieri MA, et al. Localization of pleiotrophin and its mRNA in subpopulations of neurons and their corresponding axonal tracts suggests important roles in neural-glial interactions during development and in maturity. J Neurobiol. 1996 Nov;31(3):283-96.
Sivilotti L, Woolf CJ. The contribution of GABAA and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J Neurophysiol. 1994 Jul;72(1): 169-79.
Smiley MM, Lu Y, Vera-Portocarrero LP, et al. Intrathecal gabapentin enhances the analgesic effects of subtherapeutic dose morphine in a rat experimental pancreatitis model. Anesthesiology. 2004;101:759-765.
Stefani A, Spadoni F, Bernardi G. Gabapentin inhibits calcium currents in isolated rat brain neurons. Neuropharmacology. 1998;37(1):83-91.
Stefani A, Spadoni F, Giacomini P, et al. The effects of gabapentin on different ligand- and voltage-gated currents in isolated cortical neurons. Epilepsy Res. 2001 Mar;43(3):239-48.
Sweatt AJ, Garcia-Espinosa MA, Wallin R, et al. Branched-chain amino acids and neurotransmitter metabolism:expression of Cytosolic branched-chain aminotransferase(BCATc) in the cerebellum and hippocampus. J Comp Neurol.2004;477:360-370.
Stewart BH, Kugler AR, Thompson PR,et al. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. Pharm Res. 1993 Feb;10(2):276-81.
Su TZ, Lunney E, Campbell G, et al. Transport of gabapentin, a gamma-amino acid drug, by system 1 alpha-amino acid transporters: a comparative study in astrocytes, synaptosomes, and CHO cells. J Neurochem. 1995 May;64(5):2125-31.
Suarez LM, Suarez F, Del Olmo N, et al. Presynaptic NMDA autoreceptors facilitate axon excitability: a new molecular target for the anticonvulsant gabapentin. Eur J Neurosci. 2005 ;21:197-209.
Suman-Chauhan N, Webdale L, Hill DR, et al. Characterisation of [3H]gabapentin binding to a novel site in rat brain: homogenate binding studies. Eur J Pharmacol. 1993 Feb 15;244(3):293-301.
Suszkiw JB, Murawsky MM, Shi M. Further characterization of phasic calcium influx in rat cerebrocortical synaptosomes: inferences regarding calcium channel type(s) in nerve endings. J Neurochem. 1989 Apr;52(4): 1260-9.
Sutton KG, Martin DJ, Pinnock RD, et al. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol. 2002 Jan;135(1):257-65.
Suzdak PD, Jansen JA. A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor. Epilepsia. 1995 Jun;36(6):612-26.
Singh L, Field MJ, Ferris P, et al. The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed by D-serine. Psychopharmacology (Berl). 1996 Sep;127(1):1-9.
Sutton KG, Martin DJ, Pinnock RD, et al. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol.2002; 135:257-265.
Taiwo OB, Taylor BK. Antihyperalgesic effects of intrathecal neuropeptide Y during inflammation are mediated by Y1 receptors. Pain. 2002 Apr;96(3):353-63.
Tatemoto K, Carlquist M, Mutt V. et al. Neuropeptide Y-a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature. 1982 Apr 15;296(5858):659-60.
Taylor CP. Emerging perspectives on the mechanism of action of gabapentin. Neurology. 1994 Jun;44(6 Suppl 5):S10-6; discussion S31-2.
Taylor CP, Gee NS, Su TZ, et al. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res. 1998 Feb;29(3):233-49.
Taylor MT, Bonhaus DW. Allosteric modulation of [(3)H]gabapentin binding by ruthenium red. Neuropharmacology. 2000 Apr 27;39(7): 1267-73.
Thoenen H. Neurotrophins and neuronal plasticity. Science. 1995 Oct 27;270(5236):593-8.
Toth PT, Bindokas VP, Bleakman D, et al.Mechanism of presynaptic inhibition by neuropeptide Y at sympathetic nerve terminals. Nature. 1993 Aug 12;364(6438):635-9.
Vacher CM, Bettler B. GABA(B) receptors as potential therapeutic targets. Curr Drug Targets CNS Neurol Disord. 2003 Aug;2(4):248-59.
Vollmer KO, von Hodenberg A, Kolle EU.Pharmacokinetics and metabolism of gabapentin in rat, dog and man. Arzneimittelforschung. 1986 May;36(5):830-9.
Wakisaka S, Kajander KC, Bennett GJ. Increased neuropeptide Y (NPY)-like immunoreactivity in rat sensory neurons following peripheral axotomy. Neurosci Lett. 1991 Apr 1;124(2):200-3.
Wamil AW, McLean MJ. Limitation by gabapentin of high frequency action potential firing by mouse central neurons in cell culture. Epilepsy Res. 1994; 17:1-11.
Wanaka A, Carroll SL, Milbrandt J. Developmentally regulated expression of pleiotrophin, a novel heparin binding growth factor, in the nervous system of the rat. Brain Res Dev Brain Res. 1993 Mar 19;72(1):133-44.
Wang H, Sun H, Delia Penna K, et al. Chronic neuropathic pain is accompanied by global changes in gene expression and shares pathobiology with neurodegenerative diseases. Neuroscience. 2002;l 14(3):529-46.
Welty DF, Schielke GP, Vartanian MG, et al. Gabapentin anticonvulsant action in rats: disequilibrium with peak drug concentrations in plasma and brain microdialysate. Epilepsy Res. 1993 Dec; 16(3): 175-81.
Wilson SP, Yeomans DC, Bender MA, et al. Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes virus. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3211-6.
Wong MO, Eldon MA, Keane WF, et al. Disposition of gabapentin in anuric subjects on hemodialysis. J Clin Pharmacol. 1995 Jun;35(6):622-6.
Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472): 1765-9.
Woolf CJ, Shortland P, Coggeshall RE. Peripheral nerve injury triggers central sprouting of myelinated afferents.Nature.1992 Jan 2;355(6355):75-8.
Xiao HS, Huang QH, Zhang FX, et al. Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8360-5.
Xiao WH, Bennett GJ. Synthetic omega-conopeptides applied to the site of nerve injury suppress neuropathic pains in rats. J Pharmacol Exp Ther. 1995 Aug;274(2):666-72.
Xu XJ, Hao JX, Hokfelt T,et al. The effects of intrathecal neuropeptide Y on the spinal nociceptive flexor reflex in rats with intact sciatic nerves and after peripheral axotomy. Neuroscience. 1994 Dec;63(3):817-26.
Xu IS, Hao JX, Xu XJ,et al. The effect of intrathecal selective agonists of Y1 and Y2 neuropeptide Y receptors on the flexor reflex in normal and axotomized rats. Brain Res. 1999 Jul 3;833(2):251-7.
Xu M, Petraschka M, McLaughlin JP, et al. Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance. J Neurosci. 2004 May 12;24(19):4576-84.
Xu Y, Oz G, LaNoue KF, et al. Whole-brain glutamate metabolism evaluated by steadystate kinetics using a double-isotope procedure: effects of gabapentin. J Neurochem. 2004;90:1104-1116.
Yatham LN. Newer anticonvulsants in the treatment of bipolar disorder. J Clin Psychiatry. 2004;65 Suppl 10:28-35.
Yoon MH, Bae HB, Choi JI. Antinociceptive interactions between intrathecal gabapentin and MK801 or NBQX in rat formalin test. J Korean Med Sci. 2005;20:307-312.
Yoon MH, Choi JI, Jeong SW. Spinal gabapentin and antinociception: mechanisms of action. J Korean Med Sci. 2003 Apr;18(2):255-61
Yoshimura M, North RA. Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature. 1983 Oct 6-12;305(5934):529-30.
Zahn PK, Brennan TJ. Lack of effect of intrathecally administered N-methyl-D-aspartate receptor antagonists in a rat model for postoperative pain. Anesthesiology. 1998;88:143-156.
Zhang X, Xiao HS. Gene array analysis to determine the components ofneuropathic pain signaling. Curr Opin Mol Ther. 2005 Dec; 7(6): 532-7.
Zhou XF, Chie ET, Deng YS, Injured primary sensory neurons switch phenotype for brain-derived neurotrophic factor in the rat. Neuroscience. 1999; 92(3): 841-53.
Zidichouski JA, Chen H, Smith PA. Neuropeptide Y activates inwardly-rectifying K(+)-channels in C-cells of amphibian sympathetic ganglia. Neurosci Lett. 1990 Sep 4; 117(1-2): 123-8.
Zimmermann M. Pathobiology of neuropathic pain. Eur J Pharmacol. 2001 Oct 19; 429(1-3): 23-37.
安珂，田玉科，杨辉。鞘内移植人前脑啡肽原基因修饰的永生化大鼠星形胶质细胞株对大鼠慢性神经痛的镇痛作用。中华医学杂志。2005：85(38)：2711-2714。
何展文，罗向阳。神经肽Y在癫痫发病机制中的作用。中国病理生理杂志。2004：20(3)：489-492．
李功迎，李凌江，孔媛。脑源性神经营养因子与应激。中国行为医学科学。2005；14(12)：1134—1135。
刘国凯，黄宇光，罗爱伦。神经病理性疼痛动物模型及其评价。中国临床药理学与治疗学。2005：10(6)：601-603。
Allen S: Pharmacotherapy of neuropathic pain. Contin Educ Anaesth Crit Care Pain (2005) 5(4):134-137.
Altar CA. Neurotrophins and depression. Trends Pharmacol Sci. 1999 Feb;20(2):59-61.
Armijo JA, Pena MA, Adin J, et al. Association between patient age and gabapentin serum concentration-to-dose ratio: a preliminary multivariate analysis. Ther Drug Monit. 2004 Dec;26(6):633-7.
Attal N. Chronic neuropathic pain: mechanisms and treatment. Clin J Pain. 2000 Sep;16(3 Suppl):S 118-30.
Bao L, Wang HF, Cai HJ, et al. Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord. Eur J Neurosci. 2002 Jul; 16(2): 175-85.
Balasubramaniam A. et al. Clinical potentials of neuropeptide Y family of hormones. Am J Surg. 2002 Apr;183(4):430-4.
Bennett DL, French J, Priestley JV, et al. NGF but not NT-3 or BDNF prevents the A fiber sprouting into lamina II of the spinal cord that occurs following axotomy. Mol Cell Neurosci. 1996;8(4):211-20.
Bertrand S, Ng GY, Purisai MG, et al. The anticonvulsant, antihyperalgesic agent gabapentin is an agonist at brain gamma-aminobutyric acid type B receptors negatively coupled to voltage-dependent calcium channels. J Pharmacol Exp Ther. 2001 Jul;298(1):15-24.
Bertrand S, Nouel D, Morin F, et al. Gabapentin actions on Kir3 currents and N-type Ca2+ channels via GABAB receptors in hippocampal pyramidal cells. Synapse. 2003 Nov;50(2):95-109.
Beydoun A, Backonja MM. Mechanistic stratification of antineuralgic agents. J Pain Symptom Manage. 2003 May;25(5 Suppl):S 18-30.
Bleakman D, Colmers WF, Fournier A, Miller RJ. Neuropeptide Y inhibits Ca2+ influx into cultured dorsal root ganglion neurons of the rat via a Y2 receptor. Br J Pharmacol. 1991 Jul; 103(3): 1781-9.
Blondet B, Carpentier G, Lafdil F, et al. Pleiotrophin cellular localization in nerve regeneration after peripheral nerve injury. J Histochem Cytochem. 2005 Aug;53(8):971-7.
Blum RA, Comstock TJ, Sica DA, et al. Pharmacokinetics of gabapentin in subjects with various degrees of renal function. Clin Pharmacol Ther. 1994 Aug;56(2): 154-9.
Bridges D, Thompson SW, Rice AS. Mechanisms of neuropathic pain. Br J Anaesth. 2001 Jul;87(1): 12-26.
Broqua P, Wettstein JG, Rocher MN, et al. Antinociceptive effects of neuropeptide Y and related peptides in mice. Brain Res. 1996 Jun 10;724(1):25-32.
Bowery NG, Bettler B, Froestl W, et al. International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function. Pharmacol Rev. 2002
Jun;54(2):247-64.Brown JP, Gee NS. Cloning and deletion mutagenesis of the alpha2 delta calcium channel subunit from porcine cerebral cortex. Expression of a soluble form of the protein that retains [3H]gabapentin binding activity. J Biol Chem. 1998 Sep 25;273(39):25458-65.
Carlton SM, Zhou S. Attenuation of formalin-induced nociceptive behaviors following local peripheral injection of gabapentin. Pain. 1998;76:201-207.
Cejas PJ, Martinez M, Karmally S, et al. Lumbar transplant of neurons genetically modified to secrete brain-derived neurotrophic factor attenuates allodynia and hyperalgesia after sciatic nerve constriction. Pain. 2000 May;86(1-2):195-210.
Chen B, Dowlatshahi D, MacQueen GM,et al. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry. 2001 Aug 15;50(4):260-5.
Chen SR, Eisenach JC, McCaslin PP, et al. Synergistic effect between intrathecal non-NMDA antagonist and gabapentin on allodynia induced by spinal nerve ligation in rats. Anesthesiology. 2000 Feb;92(2):500-6.
Chen SR, Xu Z, Pan HL. Stereospecific effect of pregabalin on ectopic afferent discharges and neuropathic pain induced by sciatic nerve ligation in rats. Anesthesiology. 2001;95:1473-1479.
Cheng JK, Chen CC, Yang JR, The antiallodynic action target of intrathecal gabapentin: Ca2+ channels, KATP channels or N-methyl-d-aspartic acid receptors? Anesth Analg. 2006 Jan; 102(1): 182-7.
Cheng JK, Lai YJ, Chen CC, et al. Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain. Anesthesiology. 2003 Jun;98(6): 1472-9.
Cheng JK, Lee SZ, Yang JR, et al. Does gabapentin act as an agonist at native GABAB receptors? J Biomed Sci. 2004;l 1:346-355.
Cheng JK, Pan HL, Eisenach JC. Antiallodynic effect of intrathecal gabapentin and its interaction with clonidine in a rat model of postoperative pain. Anesthesiology. 2000;92:1126-1131.
Chizh BA, Scheede M, Schlutz H. Antinociception and (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid antagonism by gabapentin in the rat spinal cord in vivo. Naunyn Schmiedebergs Arch Pharmacol. 2000;362:197-200.
Coderre TJ, Kumar N, Lefebvre CD, et al. Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal release of glutamate. J Neurochem. 2005 Aug;94(4):1131-9.
Colmers WF, Klapstein GJ, Fournier A, et al. Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor. Br J Pharmacol. 1991 Jan;102(1):41-4.
Colmers WF, Bleakman D. Effects of neuropeptide Y on the electrical properties of neurons. Trends Neurosci. 1994 Sep;17(9):373-9.
Coppell AL, Pei Q, Zetterstrom TS. Bi-phasic change in BDNF gene expression following antidepressant drug treatment. Neuropharmacology. 2003 Jun;44(7):903-10.
Costigan M, Befort K, Karchewski L, et al. Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci. 2002 Oct 25;3:16.
Cui M, Liang L, Steffery ME, et al. In vitro characterization of GABAB receptors and gabapentin effect. Soc Neurosci Abs. 2002;869:15.
Danysz W, Kozela E, Parsons CG, et al. Peripherally acting NMDA receptor/glycineB site receptor antagonists inhibit morphine tolerance. Neuropharmacology. 2005;48:360-371.
Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain. 1992;48:261-268.
De Foubert G, Carney SL, Robinson CS, et al. Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment. Neuroscience. 2004;128(3):597-604.
Dissanayake VU, Gee NS, Brown JP, et al. Spermine modulation of specific [3H]-gabapentin binding to the detergent-solubilized porcine cerebral cortex alpha 2 delta calcium channel subunit. Br J Pharmacol. 1997 Mar;120(5):833-40.
Dixit RK, Bhargava VK. Neurotransmitter mechanisms in gabapentin antinociception. Pharmacology. 2002 Aug;65(4): 198-203.
Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry. 1997 Jul;54(7):597-606.
Duggan AW, Hope PJ, Lang CW,et al. Sustained isometric contraction of skeletal muscle results in release of immunoreactive neurokinins in the spinal cord of the anaesthetized cat. Neurosci Lett. 1991 Jan 28; 122(2): 191-4.
Duman RS, Vaidya VA. Molecular and cellular actions of chronic electroconvulsive seizures. J ECT. 1998 Sep;14(3):181-93.
Eaton MJ, Blits B, Ruitenberg MJ, et al. Amelioration of chronic neuropathic pain after partial nerve injury by adeno-associated viral (AAV) vector-mediated over-expression of BDNF in the rat spinal cord. Gene Ther. 2002 Oct;9(20):1387-95.
Errante LD, Petroff OA. Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations. Seizure. 2003;12:300-306.
Errante LD, Williamson A, Spencer DD, et al. Gabapentin and vigabatrin increase GABA in the human neocortical slice. Epilepsy Res. 2002;49:203-210.
Felix R. Voltage-dependent Ca2+ channel alpha2delta auxiliary subunit: structure, function and regulation. Receptors Channels. 1999;6(5):351-62.
Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid-induced visceral nociception. Anesthesiology. 2003 Mar;98(3):729-33.
Field MJ, Hughes J, Singh L. Further evidence for the role of the alpha(2)delta subunit of voltage dependent calcium channels in models of neuropathic pain. Br J Pharmacol. 2000 Sep;131(2):282-6.
Field MJ, Holloman EF, McCleary S, et al. Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain. J Pharmacol Exp Ther. 1997;282:1242-1246.
Fink K, Dooley DJ, Meder WP, et al. Inhibition of neuronal Ca(2+) influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology. 2002 Feb;42(2):229-36.
Fink K, Meder W, Dooley DJ, et al. Inhibition of neuronal Ca(2+) influx by gabapentin and subsequent reduction of neurotransmitter release from rat neocortical slices. Br J Pharmacol. 2000 Jun;130(4):900-6.
Foster AC, Fagg GE. Neurobiology. Taking apart NMDA receptors. Nature. 1987 Oct l-7;329(6138):395-6.
Freiman TM, Kukolja J, Heinemeyer J, et al. Modulation of K+-evoked [3H]-noradrenaline release from rat and human brain slices by gabapentin: involvement of KATP channels. Naunyn Schmiedebergs Arch Pharmacol. 2001 May;363(5):537-42.
Garry EM, Delaney A, Anderson HA, et al. Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs. Pain. 2005 Nov;118(1-2):97-l 11.
Gee NS, Brown JP, Dissanayake VU, et al. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem. 1996 Mar 8;271(10):5768-76.
Goldlust A, Su TZ, Welty DF, et al. Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA. Epilepsy Res. 1995 Sep;22(1):1-11.
Gouarderes C, Cros J, Quirion R. Autoradiographic localization of mu, delta and kappa opioid receptor binding sites in rat and guinea pig spinal cord. Neuropeptides. 1985 Jul;6(4):331-42.
Grudt TJ, Henderson G. Glycine and GABAA receptor-mediated synaptic transmission in rat substantia gelatinosa: inhibition by mu-opioid and GABAB agonists. J Physiol. 1998 Mar 1;507(Pt 2):473-83.
Grudt TJ, Williams JT. kappa-Opioid receptors also increase potassium conductance. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11429-32.
Grudt TJ, Williams JT. mu-Opioid agonists inhibit spinal trigeminal substantia gelatinosa neurons in guinea pig and rat. J Neurosci. 1994 Mar; 14(3 Pt 2): 1646-54.
Gu Y, Huang LY. Gabapentin actions on N-methyl-D-aspartate receptor channels are protein kinase C-dependent. Pain. 2001 Jul;93(1):85-92.
Gu Y, Huang LY. Gabapentin potentiates N-methyl-D-aspartate receptor mediated currents in rat GABAergic dorsal horn neurons. Neurosci Lett. 2002 May 24;324(3): 177-80.
Guo W, Robbins MT, Wei F, et al. Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for descending pain facilitation. J Neurosci. 2006 Jan 4;26(1):126-37.
Ha SO, Kim JK, Hong HS, et al. Expression of brain-derived neurotrophic factor in rat dorsal root ganglia, spinal cord and gracile nuclei in experimental models of neuropathic pain. Neuroscience. 2001;107(2):301-9.
Hansen C, Gilron I, Hong M. The effects of intrathecal gabapentin on spinal morphine tolerance in the rat tail-flick and paw pressure tests. Anesth Analg. 2004;99:1180-1184.
Hill DR, Suman-Chauhan N, Woodruff GN. Localization of [3 H] gabapentin to a novel site in rat brain: autoradiographic studies. Eur J Pharmacol. 1993 Feb 15;244(3):303-9.
Honmou O, Oyelese AA, Kocsis JD. The anticonvulsant gabapentin enhances promoted release of GABA in hippocampus: a field potential analysis. Brain Res. 1995 Sep 18;692(1-2):273-7.
Hori Y, Endo K, Takahashi T. Presynaptic inhibitory action of enkephalin on excitatory transmission in superficial dorsal horn of rat spinal cord. J Physiol. 1992 May;450:673-85.
Hua XY, Boublik JH, Spicer MA,et al. The antinociceptive effects of spinally administered neuropeptide Y in the rat:systematic studies on structure-activity relationship. J Pharmacol Exp Ther. 1991 Jul 1;258(1):243-8.
Hwang JH, Yaksh TL. Effect of subarachnoid gabapentin on tactile-evoked allodynia in a surgically induced neuropathic pain model in the rat. Reg Anesth. 1997 May-Jun;22(3):249-56.
Jensen AA, Mosbacher J, Elg S, et al. The anticonvulsant gabapentin (neurontin) does not act through gamma-aminobutyric acid-B receptors. Mol Pharmacol. 2002 Jun;61(6):1377-84.
Jessell TM, Iversen LL. Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature. 1977 Aug 11;268(5620):549-51.
Jun JH, Yaksh TL. The effect of intrathecal gabapentin and 3-isobutyl gamma-aminobutyric acid on the hyperalgesia observed after thermal injury in the rat. Anesth Analg. 1998;86:348-354.
Kanai A, Sarantopoulos C, McCallum JB, et al. Painful neuropathy alters the effect of gabapentin on sensory neuron excitability in rats. Acta Anaesthesiol Scand. 2004;48:507-512.
Kalra S, Cashman NR, Caramanos Z, et al. Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy. AJNR Am J Neuroradiol. 2003;24:476-480.
Kar S, Quirion R. Quantitative autoradiographic localization of [125I]neuropeptide Y receptor binding sites in rat spinal cord and the effects of neonatal capsaicin, dorsal rhizotomy and peripheral axotomy. Brain Res. 1992 Mar 6;574(1-2):333-7.
Kato A, Ohkubo T, Kitamura K. Algogen-specific pain processing in mouse spinal cord: differential involvement of voltage-dependent Ca(2+) channels in synaptic transmission. Br J Pharmacol. 2002 Mar; 135(5): 1336-42.
Kleckner NW, Dingledine R. Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes. Science. 1988;241:835-837.
Kocsis JD, Honmou O. Gabapentin increases GABA-induced depolarization in rat neonatal optic nerve. Neurosci Lett. 1994 Mar 14;169(1-2):181-4.
Kohno T, Kumamoto E, Higashi H,et al. Actions of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord. J Physiol. 1999 Aug 1;518 (Pt 3):803-13.
Kubo T, Yamashita T, Yamaguchi A, et al. Analysis of genes induced in peripheral nerve after axotomy using cDNA microarrays. J Neurochem. 2002 Sep;82(5):1129-36.
Kuzniecky R, Ho S, Pan J, et al. Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults. Neurology. 2002 Feb 12;58(3):368-72.
Lanneau C, Green A, Hirst WD, et al. Gabapentin is not a GABAB receptor agonist. Neuropharmacology. 2001 Dec;41(8):965-75.
Lekan HA, Carlton SM, Coggeshall RE. Sprouting of A beta fibers into lamina II of the rat dorsal horn in peripheral neuropathy. Neurosci Lett. 1996 Apr 26;208(3): 147-50.
Li CY, Song YH, Higuera ES, et al. Spinal dorsal horn calcium channel alpha2delta-l subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J Neurosci. 2004 Sep 29;24(39):8494-9.
Li YS, Milner PG, Chauhan AK, et al. Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity. Science. 1990 Dec 21;250(4988): 1690-4.
Loscher W, Honack D, Taylor CP. Gabapentin increases aminooxyacetic acid-induced GABA accumulation in several regions of rat brain. Neurosci Lett. 1991 Jul 22;128(2):150-4.
Luo ZD, Chaplan SR, Higuera ES, et al. Upregulation of dorsal root ganglion (alpha)2(delta) calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J Neurosci. 2001 Mar 15;21(6): 1868-75.
Malcangio M, Lessmann V. A common thread for pain and memory synapses? Brain-derived neurotrophic factor and trkB receptors. Trends Pharmacol Sci. 2003 Mar;24(3): 116-21.
Malmberg AB, Basbaum AI. Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates. Pain. 1998 May; 76(1-2): 215-22.
Malberg JE, Eisch AJ, Nestler EJ, et al. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci. 2000 Dec 15;20(24):9104-10.
Maneuf YP, Hughes J, McKnight AT. Gabapentin inhibits the substance P-facilitated K(+)-evoked release of [(3)H]glutamate from rat caudial trigeminal nucleus slices. Pain. 2001 Aug;93(2): 191-6.
Mantyh PW, Allen CJ, Rogers S, et al. Some sensory neurons express neuropeptide Y receptors: potential paracrineinhibition of primary afferent nociceptors following peripheral nerve injury. J Neurosci. 1994 Jun;14(6):3958-68.
Matzner O, Devor M. Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels. J Neurophysiol. 1994;72:349-359. Max MB. Clarifying the definition of neuropathic pain. Pain. 2002 Apr;96(3):406-7. Merskey H. Clarifying definition of neuropathic pain. Pain. 2002 Apr;96(3):408-9. Merskey H. Classification of chronic pain. 2~(nd) edn. Seattle: IASP Press. 1994:40-43.
Misgeld U, Bijak M, Jarolimek W. A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Prog Neurobiol. 1995 Jul;46(4):423-62.
Mixcoatl-Zecuatl T, Medina-Santillan R, Reyes-Garcia G, et al. Effect of K+ channel modulators on the antiallodynic effect of gabapentin. Eur J Pharmacol. 2004;484:201-208.
Moore KA, Kohno T, Karchewski LA, et al. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J Neurosci. 2002 Aug 1;22(15):6724-31.
Moran TD, Colmers WF, Smith PA. Opioid-like actions of neuropeptide Y in rat substantia gelatinosa: Y1 suppression of inhibition and Y2 suppression of excitation. J Neurophysiol. 2004 Dec;92(6):3266-75. 2004 Aug 4.
Munglani R, Harrison SM, Smith GD,et al. Neuropeptide changes persist in spinal cord despite resolving hyperalgesia in arat model of mononeuropathy. Brain Res. 1996 Dec 16;743(1-2):102-8.
Nachshen DA. Regulation of Cytosolic calcium concentration in presynaptic nerve endings isolated from rat brain. J Physiol. 1985 Jun;363:87-101.
Naveilhan P, Hassani H, Lucas G,et al. Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor. Nature. 2001 Jan 25;409(6819):513-7.
Nestler EJ, Barrot M, DiLeone RJ, et al. Neurobiology of depression. Neuron. 2002 Mar 28;34(1):13-25.
Ng GY, Bertrand S, Sullivan R, et al. Gamma-aminobutyric acid type B receptors with specific heterodimer composition and postsynaptic actions in hippocampal neurons are targets of anticonvulsant gabapentin action. Mol Pharmacol. 2001 Jan;59(1): 144-52.
Nicholson B. Gabapentin use in neuropathic pain syndromes. Acta Neurol Scand. 2000 Jun;101(6):359-71.
Obara I, Przewlocki R, Przewlocka B. Local peripheral effects of mu-opioid receptor agonists in neuropathic pain in rats. Neurosci Lett. 2004 Apr 22;360(1-2):85-9.
Obata K, Yamanaka H, Kobayashi K, et al. The effect of site and type of nerve injury on the expression of brain-derived neurotrophic factor in the dorsal root ganglion and on neuropathic pain behavior. Neuroscience. 2006a Feb; 137(3):961-70.
Obata K, Noguchi K. BDNF in sensory neurons and chronic pain. Neurosci Res. 2006b May;55(1):1-10.
Ochoa J, Torebjork HE, Culp WJ, et al. Abnormal spontaneous activity in single sensory nerve fibers in humans. Muscle Nerve. 1982;5(9S):S74-7.
Omura T, Sano M, Omura K, et al. Different expressions of BDNF, NT3, and NT4 in muscle and nerve after various types of peripheral nerve injuries. J Peripher Nerv Syst. 2005 Sep;10(3):293-300.
Pan HL, Eisenach JC, Chen SR. Gabapentin suppresses ectopic nerve discharges and reverses allodynia in neuropathic rats. J Pharmacol Exp Ther. 1999;288:1026-1030.
Parker DA, Ong J, Marino V, et al. Gabapentin activates presynaptic GABAB heteroreceptors in rat cortical slices. Eur J Pharmacol. 2004 Jul 14;495(2-3): 137-43.
Partridge BJ, Chaplan SR, Sakamoto E, Yaksh TL. Characterization of the effects of gabapentin and 3-isobutyl-gammaaminobutyric acid on substance P-induced thermal hyperalgesia. Anesthesiology. 1998;88:196-205.
Pasero C. Pathophysiology of neuropathic pain. Pain Manag Nurs. 2004 Dec;5(4 Suppl 1):3-8.
Patel S, Naeem S, Kesingland A, et al. The effects of GABAB agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat. Pain. 2001 ;90:217-226.
Petroff OA, Rothman DL, Behar KL, et al. The effect of gabapentin on brain gamma-aminobutyric acid in patients with epilepsy. Ann Neurol. 1996 Jan;39(1):95-9.
Pinzon-Duarte G, Arango-Gonzalez B, Guenther E, et al. Effects of brain-derived neurotrophic factor on cell survival, differentiation and patterning of neuronal connections and Muller glia cells in the developing retina. Eur J Neurosci. 2004 Mar;19(6):1475-84.
Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science. 2000 Jun 9;288(5472): 1769-72.
Qian J, Colmers WF, Saggau P. Inhibition of synaptic transmission by neuropeptide Y in rat hippocampal area CA1: modulation of presynaptic Ca2+ entry. J Neurosci. 1997 Nov 1 ;17(21):8169-77.
Rao ML, Clarenbach P, Vahlensieck M, et al. Gabapentin augments whole blood serotonin in healthy young men. J Neural Transm. 1988;73(2): 129-34.
Rauvala H, Vanhala A, Castren E, et al. Expression of HB-GAM (heparin-binding growth-associated molecules) in the pathways of developing axonal processes in vivo and neurite outgrowth in vitro induced by HB-GAM. Brain Res Dev Brain Res. 1994 Jun 17;79(2): 157-76.
Redwine KE, Trujillo KA. Effects of NMDA receptor antagonists on acute mu-opioid analgesia in the rat. Pharmacol Biochem Behav. 2003;76:361-372.
Rock DM, Kelly KM, Macdonald RL. Gabapentin actions on ligand- and voltage-gated responses in cultured rodent neurons.Epilepsy Res. 1993;16:89-98.
Rode F, Jensen DG, Blackburn-Munro G, et al. Centrally-mediated antinociceptive actions of GABA(A) receptor agonists in the rat spared nerve injury model of neuropathic pain. Eur J Pharmacol. 2005 Jun 1;516(2): 131-8.
Rose MA, Kam PC. Gabapentin: pharmacology and its use in pain management. Anaesthesia. 2002 May;57(5):451-62.
Sarantopoulos C, McCallum B, Sapunar D, et al. ATP-sensitive potassium channels in rat primary afferent neurons: the effect of neuropathic injury and gabapentin. Neurosci Lett. 2003;343:185-189.
Satzinger G. Antiepileptics from gamma-aminobutyric acid. Arzneimittelforschung. 1994 Mar;44(3):261-6.
Schwarz JB, Gibbons SE, Graham SR, et al. Novel cyclopropyl beta-amino acid analogues of pregabalin and gabapentin that target the alpha2-delta protein. J Med Chem. 2005 Apr 21;48(8):3026-35.
Seltzer Z, Dubner R, Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain. 1990 Nov;43(2):205-18.
Shimoyama M, Shimoyama N, Hori Y. Gabapentin affects glutamatergic excitatory neurotransmission in the rat dorsal horn. Pain. 2000;85:405-414.
Shinder V, Govrin-Lippmann R, Cohen S, et al. Structural basis of sympathetic-sensory coupling in rat and human dorsal root ganglia following peripheral nerve injury. J Neurocytol. 1999 Sep;28(9):743-61.
Siddall PJ, Cousins MJ. Spinal pain mechanisms. Spine. 1997 Jan l;22(1):98-104.
Sills GJ. Not another gabapentin mechanism! Epilepsy Curr. 2005 Mar-Apr;5(2):75-7.
Silos-Santiago I, Yeh HJ, Gurrieri MA, et al. Localization of pleiotrophin and its mRNA in subpopulations of neurons and their corresponding axonal tracts suggests important roles in neural-glial interactions during development and in maturity. J Neurobiol. 1996 Nov;31(3):283-96.
Sivilotti L, Woolf CJ. The contribution of GABAA and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J Neurophysiol. 1994 Jul;72(1): 169-79.
Smiley MM, Lu Y, Vera-Portocarrero LP, et al. Intrathecal gabapentin enhances the analgesic effects of subtherapeutic dose morphine in a rat experimental pancreatitis model. Anesthesiology. 2004;101:759-765.
Stefani A, Spadoni F, Bernardi G. Gabapentin inhibits calcium currents in isolated rat brain neurons. Neuropharmacology. 1998;37(1):83-91.
Stefani A, Spadoni F, Giacomini P, et al. The effects of gabapentin on different ligand- and voltage-gated currents in isolated cortical neurons. Epilepsy Res. 2001 Mar;43(3):239-48.
Sweatt AJ, Garcia-Espinosa MA, Wallin R, et al. Branched-chain amino acids and neurotransmitter metabolism:expression of Cytosolic branched-chain aminotransferase(BCATc) in the cerebellum and hippocampus. J Comp Neurol.2004;477:360-370.
Stewart BH, Kugler AR, Thompson PR,et al. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. Pharm Res. 1993 Feb;10(2):276-81.
Su TZ, Lunney E, Campbell G, et al. Transport of gabapentin, a gamma-amino acid drug, by system 1 alpha-amino acid transporters: a comparative study in astrocytes, synaptosomes, and CHO cells. J Neurochem. 1995 May;64(5):2125-31.
Suarez LM, Suarez F, Del Olmo N, et al. Presynaptic NMDA autoreceptors facilitate axon excitability: a new molecular target for the anticonvulsant gabapentin. Eur J Neurosci. 2005 ;21:197-209.
Suman-Chauhan N, Webdale L, Hill DR, et al. Characterisation of [3H]gabapentin binding to a novel site in rat brain: homogenate binding studies. Eur J Pharmacol. 1993 Feb 15;244(3):293-301.
Suszkiw JB, Murawsky MM, Shi M. Further characterization of phasic calcium influx in rat cerebrocortical synaptosomes: inferences regarding calcium channel type(s) in nerve endings. J Neurochem. 1989 Apr;52(4): 1260-9.
Sutton KG, Martin DJ, Pinnock RD, et al. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol. 2002 Jan;135(1):257-65.
Suzdak PD, Jansen JA. A review of the preclinical pharmacology of tiagabine: a potent and selective anticonvulsant GABA uptake inhibitor. Epilepsia. 1995 Jun;36(6):612-26.
Singh L, Field MJ, Ferris P, et al. The antiepileptic agent gabapentin (Neurontin) possesses anxiolytic-like and antinociceptive actions that are reversed by D-serine. Psychopharmacology (Berl). 1996 Sep;127(1):1-9.
Sutton KG, Martin DJ, Pinnock RD, et al. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol.2002; 135:257-265.
Taiwo OB, Taylor BK. Antihyperalgesic effects of intrathecal neuropeptide Y during inflammation are mediated by Y1 receptors. Pain. 2002 Apr;96(3):353-63.
Tatemoto K, Carlquist M, Mutt V. et al. Neuropeptide Y-a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature. 1982 Apr 15;296(5858):659-60.
Taylor CP. Emerging perspectives on the mechanism of action of gabapentin. Neurology. 1994 Jun;44(6 Suppl 5):S10-6; discussion S31-2.
Taylor CP, Gee NS, Su TZ, et al. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res. 1998 Feb;29(3):233-49.
Taylor MT, Bonhaus DW. Allosteric modulation of [(3)H]gabapentin binding by ruthenium red. Neuropharmacology. 2000 Apr 27;39(7): 1267-73.
Thoenen H. Neurotrophins and neuronal plasticity. Science. 1995 Oct 27;270(5236):593-8.
Toth PT, Bindokas VP, Bleakman D, et al.Mechanism of presynaptic inhibition by neuropeptide Y at sympathetic nerve terminals. Nature. 1993 Aug 12;364(6438):635-9.
Vacher CM, Bettler B. GABA(B) receptors as potential therapeutic targets. Curr Drug Targets CNS Neurol Disord. 2003 Aug;2(4):248-59.
Vollmer KO, von Hodenberg A, Kolle EU.Pharmacokinetics and metabolism of gabapentin in rat, dog and man. Arzneimittelforschung. 1986 May;36(5):830-9.
Wakisaka S, Kajander KC, Bennett GJ. Increased neuropeptide Y (NPY)-like immunoreactivity in rat sensory neurons following peripheral axotomy. Neurosci Lett. 1991 Apr 1;124(2):200-3.
Wamil AW, McLean MJ. Limitation by gabapentin of high frequency action potential firing by mouse central neurons in cell culture. Epilepsy Res. 1994; 17:1-11.
Wanaka A, Carroll SL, Milbrandt J. Developmentally regulated expression of pleiotrophin, a novel heparin binding growth factor, in the nervous system of the rat. Brain Res Dev Brain Res. 1993 Mar 19;72(1):133-44.
Wang H, Sun H, Delia Penna K, et al. Chronic neuropathic pain is accompanied by global changes in gene expression and shares pathobiology with neurodegenerative diseases. Neuroscience. 2002;l 14(3):529-46.
Welty DF, Schielke GP, Vartanian MG, et al. Gabapentin anticonvulsant action in rats: disequilibrium with peak drug concentrations in plasma and brain microdialysate. Epilepsy Res. 1993 Dec; 16(3): 175-81.
Wilson SP, Yeomans DC, Bender MA, et al. Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes virus. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3211-6.
Wong MO, Eldon MA, Keane WF, et al. Disposition of gabapentin in anuric subjects on hemodialysis. J Clin Pharmacol. 1995 Jun;35(6):622-6.
Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472): 1765-9.
Woolf CJ, Shortland P, Coggeshall RE. Peripheral nerve injury triggers central sprouting of myelinated afferents.Nature.1992 Jan 2;355(6355):75-8.
Xiao HS, Huang QH, Zhang FX, et al. Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8360-5.
Xiao WH, Bennett GJ. Synthetic omega-conopeptides applied to the site of nerve injury suppress neuropathic pains in rats. J Pharmacol Exp Ther. 1995 Aug;274(2):666-72.
Xu XJ, Hao JX, Hokfelt T,et al. The effects of intrathecal neuropeptide Y on the spinal nociceptive flexor reflex in rats with intact sciatic nerves and after peripheral axotomy. Neuroscience. 1994 Dec;63(3):817-26.
Xu IS, Hao JX, Xu XJ,et al. The effect of intrathecal selective agonists of Y1 and Y2 neuropeptide Y receptors on the flexor reflex in normal and axotomized rats. Brain Res. 1999 Jul 3;833(2):251-7.
Xu M, Petraschka M, McLaughlin JP, et al. Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance. J Neurosci. 2004 May 12;24(19):4576-84.
Xu Y, Oz G, LaNoue KF, et al. Whole-brain glutamate metabolism evaluated by steadystate kinetics using a double-isotope procedure: effects of gabapentin. J Neurochem. 2004;90:1104-1116.
Yatham LN. Newer anticonvulsants in the treatment of bipolar disorder. J Clin Psychiatry. 2004;65 Suppl 10:28-35.
Yoon MH, Bae HB, Choi JI. Antinociceptive interactions between intrathecal gabapentin and MK801 or NBQX in rat formalin test. J Korean Med Sci. 2005;20:307-312.
Yoon MH, Choi JI, Jeong SW. Spinal gabapentin and antinociception: mechanisms of action. J Korean Med Sci. 2003 Apr;18(2):255-61
Yoshimura M, North RA. Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature. 1983 Oct 6-12;305(5934):529-30.
Zahn PK, Brennan TJ. Lack of effect of intrathecally administered N-methyl-D-aspartate receptor antagonists in a rat model for postoperative pain. Anesthesiology. 1998;88:143-156.
Zhang X, Xiao HS. Gene array analysis to determine the components ofneuropathic pain signaling. Curr Opin Mol Ther. 2005 Dec; 7(6): 532-7.
Zhou XF, Chie ET, Deng YS, Injured primary sensory neurons switch phenotype for brain-derived neurotrophic factor in the rat. Neuroscience. 1999; 92(3): 841-53.
Zidichouski JA, Chen H, Smith PA. Neuropeptide Y activates inwardly-rectifying K(+)-channels in C-cells of amphibian sympathetic ganglia. Neurosci Lett. 1990 Sep 4; 117(1-2): 123-8.
Zimmermann M. Pathobiology of neuropathic pain. Eur J Pharmacol. 2001 Oct 19; 429(1-3): 23-37.
安珂，田玉科，杨辉。鞘内移植人前脑啡肽原基因修饰的永生化大鼠星形胶质细胞株对大鼠慢性神经痛的镇痛作用。中华医学杂志。2005：85(38)：2711-2714。
何展文，罗向阳。神经肽Y在癫痫发病机制中的作用。中国病理生理杂志。2004：20(3)：489-492．
李功迎，李凌江，孔媛。脑源性神经营养因子与应激。中国行为医学科学。2005；14(12)：1134—1135。
刘国凯，黄宇光，罗爱伦。神经病理性疼痛动物模型及其评价。中国临床药理学与治疗学。2005：10(6)：601-603。