進階搜尋


下載電子全文  
系統識別號 U0026-2001201117171200
論文名稱(中文) 大麻系統對於三叉神經痛緩解作用之分子機制探討
論文名稱(英文) Studies on the functional role of the cannabinoid system in the trigeminal neuralgia
校院名稱 成功大學
系所名稱(中) 基礎醫學研究所
系所名稱(英) Institute of Basic Medical Sciences
學年度 99
學期 1
出版年 100
研究生(中文) 梁嫈卿
研究生(英文) Ying-Ching Liang
學號 s5894121
學位類別 博士
語文別 英文
論文頁數 144頁
口試委員 指導教授-許桂森
召集委員-黃阿敏
口試委員-蔡玉娟
口試委員-陳慶鏗
口試委員-崋瑜
中文關鍵字 三叉神經痛  痛覺過敏  第一型大麻受體 
英文關鍵字 trigeminal neuralgia  hyperalgesia  type 1 cannabinoid receptor 
學科別分類
中文摘要 三叉神經痛為一種短暫、類似電擊刺痛的臉部神經性疼痛,主因是三叉神經節受壓迫所致,然而致病原因仍不太清楚。雖然抗癲癇藥物具有良好的三叉神經痛治療效果,但是仍有病人會產生抗藥性或是耐受性。目前缺乏其他專一有效的治療藥物。而大麻物質被認為具有減輕神經痛和痛覺過度敏感的作用。此研究的主要目的在於探討大麻物質在三叉神經痛中所扮演的功能性角色為何。在此研究的第一部份,我們建立帶有下顎神經纖維的腦幹腦薄片標本來探討大麻物質對於幼鼠三叉神經尾核表層的麩氨酸神經訊息傳遞調控作用。結果發現大麻物質偏好活化小型神經纖維上的第一型大麻受體。當第一型大麻受體活化後會專一性地阻斷突觸前N-型鈣離子管道進而抑制神經傳導物質釋出的機制,減少三叉神經痛覺突觸傳導物質釋出。第二部份,我們探討合成的大麻物質WIN 55,212-2對於以眶下神經-慢性狹窄型傷害所造成的感覺異常和痛覺過敏的作用為何。主要結果發現以腹腔注射大麻物質可以增加大鼠對機械性刺激和熱刺激的閾值,並且此止痛作用會隨劑量增加而增強。此外,第一型大麻受體拮抗劑AM 251可以拮抗WIN 55,212-2的止痛作用,顯示大麻物質具有減輕三叉神經痛所引起感覺異常和痛覺過敏的行為。第三部份,我們進一步地探討大麻物質減輕三叉神疼痛的機制。我們利用活體單一胞外紀錄法探討大麻物質對於三叉神經尾核神經元wind-up現象誘發的影響,發現投予WIN 55,212-2具有明顯抑制電刺激所誘發wind-up現象的作用。此抑制作用可以被第一型大麻受體拮抗劑AM 251所阻斷,顯示大麻物質可以透過活化第一型大麻受體抑制三叉神經尾核神經元上wind-up現象的產生。最後,我們利用帶有下額神經纖維的腦幹腦薄片標本探討與慢性疼痛機制相關的長期增益現象在三叉神經尾核神經元可能的分子機轉。主要結果發現在三叉神經尾核神經元可藉由活化第五亞型代謝型麩胺酸受體,引發一連串磷脂酶C/蛋白質激脢C依賴性的訊息傳遞,進而誘發長期增益現象。此長期增益現象的表現也可能與長期三叉神經痛覺訊息產生的過程相關。總結,我們發現大麻物質具有抑制三叉神經尾核神經元上的興奮性神經傳導,以及三叉神經痛相關的機轉,並且能有效減輕三叉神經痛動物模式的感覺異常和痛覺敏感作用。此等發現支持大麻對於三叉神經痛的臨床治療上可能具有相當的潛力。
英文摘要 Trigeminal neuralgia is a disorder of paroxysmal and severely disabling facial pain. While the exact cause and pathology of this disorder is uncertain, it is thought that trigeminal neuralgia caused by the compression of the trigeminal root. Although antiepileptic drug therapy may be beneficial in the treatment of trigeminal neuralgia, some patients become refractory or intolerant to these medications. At present there are few other effective drugs. Cannabinoids are effective in alleviating neuropathic pain and hyperalgesia. Thus, the major propose of this study is to investigate the functional role of cannabinoid system in the trigeminal neuralgia. In the first part of this study, using brainstem slices with the mandibular nerve attached, we examined the effect of cannabinoids on glutamatergic transmission in superficial trigeminal caudal nucleus of juvenile rats. We found that cannabinoids preferentially activate type 1 cannabinoid receptors at the nerve terminal of small-diameter primary afferent fibers. Upon activation, type 1 cannabinoid receptors may selectively inhibit the presynaptic N-type Ca2+ channels and the exocytotic release machinery, thereby attenuating the transmitter release at the trigeminal nociceptive synapses. We next investigated the effects of the synthetic cannabinoid WIN 55,212-2 on mechanical allodynia and thermal hyperalgesia in a rat model of trigeminal neuropathic pain produced by a chronic constriction injury (CCI) of the infraorbital branch of the trigeminal nerve (ION). We found that administration of WIN 55,212-2 dose-dependently increased the mechanical and heat withdrawal thresholds, and the analgesia of WIN 55,212-2 can be blocked by type 1 cannabinoid receptor antagonist AM 251. These results suggest that cannabinoids can alleviate trigeminal nociceptive behaviors. Although cannabinoids can alleviate trigeminal nociceptive behaviors, the detail mechanism responsible for their effects is uncertain. We used extracellular single recording in the superficial layer of the trigeminal caudal nucleus to investigate the effect of WIN 55,212-2 on wind-up phenomenon in trigeminal caudal neuron. We found that systemic administration of WIN 55,212-2 can reduce the neuronal activity in win-up phenomenon and the effect of WIN 55,212-2 can be blocked by type 1 cannabinoid receptor antagonist AM 251. This indicates that cannabinoids reduce wind-up phenomenon in the trigeminal caudal nucleus through type 1 cannabinoid receptors activation. Finally, we investigated the cellular and molecular mechanisms of the other mechanism of chronic pain, long-term potentiation in trigeminal caudal nucleus. Using extracellular field potential recordings in brainstem parasagital slices of juvenile rat with the mandibular nerve attached, we found that the activation of metabotropic glutamate receptor subtype 5 (mGluR5) and in turn triggering a phospholipase C/protein kinase C (PLC/PKC)-dependent signaling cascade may contribute to the induction of long-term potentiation of primary afferent synaptic transmission in the superficial layer of trigeminal caudal nucleus of juvenile rats. In conclusion, we find cannabinoids not only can inhibit pain-related neuronal transmission but aslo the mechanisms of trigeminal pain at primary afferent fibers to trigeminal caudal neuons. Moreover, cannabinoids can alleviate the nociceptive behaviors in trigeminal pain animal model. Thus, cannabinoids may have a potential therapeutic role for the clinical management of trigeminal neuropathic pain disorders.
論文目次 Abstract in Chinese…………………………………………….……1
Abstract in English…………………………………………………..3
Contents…………………………………………………………………6
Table and Figure list…..……………………………………………8
Abbreviations…………………………………………………………11
INTRODUCTION……………………………………………………………15
1. 1. Trigeminal system……………………………………………16
1. 2. Trigeminal pain pathways…………………………………16
1. 3. Trigeminal neuralgia……………………………………….17
1. 4. Central sensitization…………………………………….20
1. 5. Cannabinoids…………………………………………………23
1. 6. Therapeutic effects of cannabinoids……………………25
1. 7. Cannabiniods in neuropathic pain………………………26
MATERIALS AND METHODS………………………………………………33
2. 1. Materials……………………………………………………….34
2. 1. 1. Animals……………………………………………….…….34
2. 1. 2. Pharmacological drugs and antibodies……………….34
2. 2. Drug treatment…………………………………………………35
2. 3. Slice preparation……………………………………………36
2. 4. Electrophysiological recordings…………………………37
2. 4. 1. In vitro electrophysiological recording……………37
2. 4. 2. In vivo extracellular recordings……………………39
2. 5. Animal model of the chronic constriction injury of the infraorbital nerve (CCI-ION)………………………………41
2. 6. Nociceptive testing………………………………………….41
2. 6. 1. Assessment of mechanical allodynia…………………41
2. 6. 2. Assessment of thermal hyperalgesia…………………42
2. 6. 3. Assessment of Motor coordination……………………43
2. 7. Hypothermia…………………………………………….………43
2. 8. Western blotting…………………………………………….43
2. 9. Immunohistochemistry………………………………………44
2. 10. Data analysis…………………………………………………45
RESULTS AND DISCUSSION…………………………….…….…..…46
3. 1. Cannabinoid-induced presynaptic inhibition at the primary afferent trigeminal synapse of juvenile rat brainstem slices……………..….…………………………..…47
3. 2. The synthetic cannabinoids attenuate allodynia and hyperalgesia in rat model of trigeminal neuropathic pain ……………………………………………………………………….66
3. 3. Cannabinoid WIN 55,212-2 reduces the wind-up of trigeminal caudal neurons……………………………………….81
3. 4. Characterization of long-term potentiation of primary afferent transmission at trigeminal synapses of juvenile rats: essential role of subtype 5 metabotropic glutamate receptors…………………..…………………………………………94
CONCLUSION……………………………………………………………114
REFERENCES……………………………………………………………120
PUBLICATIONS…………………………………………………………142
參考文獻 Ameri A (1999) The effects of cannabinoids on the brain. Prog Neurobio. 58, 315-348.
Ataka T, Kumamoto E, Shimoji K and Yoshimura M (2000) Baclofen inhibits more effectively C-afferent than A-afferent glutamatergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices. Pain. 86, 273-282.
Auclair N, Otani S, Soubrie P and Crépel F (2000) Cannabinoids modulate synaptic strength and plasticity at glutamatergic synapses of rat prefrontal cortex pyramidal neurons. J Neurophysiol. 83, 3287-3293.
Baker D, Pryce G, Giovannoni G and Thompson AJ (2003) The therapeutic potential of cannabis. Lancet Neurol. 2, 291-298.
Bao J, Li JJ and Perl ER (1998) Differences in Ca2+ channels governing generation of miniature and evoked excitatory synaptic currents in spinal laminae I and II. J Neurosci. 18, 8740-8750.
Baranauskas G and Nistri A (1996) NMDA receptor-independent mechanisms responsible for the rate of rise of cumulative depolarization evoked by trains of dorsal root stimuli on rat spinal motoneurones. Brain Res. 738, 329-332.

Barbieri M and Nistri A (2001) Depression of windup of spinal neurons in the neonatal rat spinal cord in vitro by an NK3 tachykinin receptor antagonist. J Neurophysiol. 85, 1502-15011.
Basbaum AI and Jessell TM (2000) The perception of pain. In Principles of Neural Science, 4th edn, (Kandel ER, Schwartz JH and Jessell TM eds), pp 472-491. McGraw-Hill Press.
Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, Lefkowitz L, Plasse TF and Shepard KV (1995) Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage. 10, 89-97.
Bennett GJ and Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 33, 87-107.
Bergouignan M (1942) Cures heureuses de névralgies facials essentielles par le diphenyl-hydantoinate de soude. Rev Laryngol Otol Rhinol. 63, 34-41.
Bliss TV and Collingridge GL (1993) Asynaptic model of memory: long-term potentiation in the hippocampus. Nature. 361, 31-39.
Block RI, Farinpour R and Braverman K (1992) Acute effects of marijuana on cognition: relationships to chronic effects and smoking techniques. Pharmacol Biochem Behav. 43, 907-917.
Bolton S, O’Shaughnessy CT and Goadsby PJ (2005) Properties of neuron in trigeminal nucleus caudalis responding to noxious dural and facial stimulation. Brain Res. 1046, 122-129.
Bullitt E, Tew JM and Boyd J (1986) Intracranial tumors in patients with facial pain. J Neurosurg. 64, 865-871.
Burchiel KJ and Ochoa JL (1991) Surgical management of post-traumatic neuropathic pain. Neurosurg Clin N Am. 2, 117-126.
Burchiel KJ and Slavin KV (2000) On the natural history of trigeminal neuralgia. Neurosurgery. 46, 152-154.
Burgess JM and Perl ER (1973) Cutaneous mechanoreceptors and nociceptors. In: Handbook of Sensory Physiology Volume II: Somato sensory System, (Iggo A eds), pp 29-78. Springer Press.
Calignano A, La Rana G, Giuffrida A and Piomelli D (1998) Control of pain initiation by endogenous cannabinoids. Nature. 394, 277-281.
Campbell FG, Graham JG and Zilkha KJ (1966) Clinical trial of carbazepine (tegretol) in trigeminal neuralgia. J Neurol Neurosurg Psychiatry. 29, 265-267.
Chan PK and Yung WH (1999) Inhibitory postsynaptic currents of rat substantia nigra pars reticulata neurons: role of GABA receptors and GABA uptake. Brain Res. 838, 18-26.

Cheng G and Randić M (2003) Involvement of intracellular calcium and protein phosphatases in long-term depression of A-fiber-mediated primary afferent neurotransmission. Brain Res Dev Brain Res. 144, 73-82.
Childs AM, Meaney JF, Ferrie CD and Holland PC (2000) Neurovascular compression of the trigeminal and glossopharyngeal nerve: three case reports. Arch Dis. 82, 311-315.
Compton DR, Gold LH, Ward SJ, Balster RL and Martin BR (1992) Aminoalkylindole analogs: cannabimimetic activity of a class of compounds structurally distinct from delta 9-tetrahydrocannabinol. J Pharmacol Exp Ther. 263, 1118-1126.

Costa B, Siniscalco D, Trovato AE, Comelli F, Sotgiu ML, Colleoni M, Maione S, Rossi F and Giagnoni G (2006) AM 404, an inhibitor of anandamide uptake, prevents pain behaviour and modulates cytokine and apoptotic pathways in a rat model of neuropathic pain. Br J Pharmacol. 148, 1022-1032.
Court JM (1998) Cannabis and brain function. J Paediatr Child Health. 34, 1-5.
Cusick JF (1981) Atypical trigeminal neuralgia. JAMA. 245, 2328-2329.
Dallel R, Dualé C and Molat JL (1998) Morphine administered in the substantia gelatinosa of the spinal trigeminal nucleus caudalis inhibits nociceptive activities in the spinal trigeminal nucleus oralis. J Neurosci. 18, 3529-3536.

Das B and Saha SP (2001) Trigeminal neuralgia: current concepts and management. J Indian Med Assoc. 99, 704-709.
De Petrocellis L, Orlando P and Di Marzo V (1995) Anandamide, an endogenous cannabinomimetic substance, modulates rat brain protein kinase C in vitro. Biochem Mol Biol Int. 36, 1127-1133.
Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A and Mechoulam R (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 258, 1946-1949.

Dong XW and Feldman JL (1999) Distinct subtypes of metabotropic glutamate receptors mediate differential actions on excitability of spinal respiratory motoneurons. J Neurosci. 19, 5173–5184.
Drew LJ, Harris J, Millins PJ, Kendall DA and Chapman V (2000) Activation of spinal cannabinoid 1 receptors inhibits C-fiber driven hyperexcitable neuronal responses and increases [35S]GTPS binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats. Eur J Neurosci. 12, 2079-2086.
Dudek SM and Bear MF (1993) Bidirectional long-term modification of synaptic effectiveness in the adult and immature hippocampus. J Neurosci. 13, 2910-2918.
Edwards FA, Konnerth A, Sakmann B and Takahashi T (1989) Athin slice preparation for patch clamp recordings from neurons of the mammalian central nervous system. Pflugers Arch. 414, 600-612.
Eide PK (2000) Wind-up and the NMDA receptor complex from a clinical perspective. Eur J Pain. 4, 5-15.
Elmes SJ, Winyard LA, Medhurst SJ, Clayton NM, Wilson AW, Kendall DA and Chapman V (2005) Activation of CB1 and CB2 receptors attenuates the induction and maintenance of inflammatory pain in the rat. Pain. 118, 327-335.
Endoh T (2006) Pharmacological characterization of inhibitory effects of postsynaptic opioid and cannabinoid receptors on calcium currents in neonatal rat nucleus tractus solitarius. Br J Pharmacol. 147, 391-401.
Farquhar-Smith WP and Rice AS (2001) Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder. Anesthesiology. 94, 507-513; discussion 6A.
Felder CC and Glass M (1998) Cannabinoid receptors and their endogenous agonists. Annu Rev Pharmacol Toxicol. 38, 179-200.
Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, Lai Y, Ma AL and Mitchell RL (1995) Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol. 48, 443-450.

Fezza F, Bisogno T, Minassi A, Appendino G, Mechoulam R and Di Marzo V (2002) Noladin ether, a putative novel endocannabinoid: inactivation mechanisms and a sensitive method for its quantification in rat tissues. FEBS Lett. 513, 294-298.
Filipeanu CM, de Zeeuw D and Nelemans SA (1997) Delta9-tetrahydrocannabinol activates [Ca2+]i increases partly sensitive to capacitative store refilling. Eur J Pharmacol. 336, R1-3.
Fisher K, Fundytus ME, Cahill CM and Coderre TJ (1998) Intrathecal administration of the mGluR compound, (S)-4CPG, attenuates hyperalgesia and allodynia associated with sciatic nerve constriction injury in rats. Pain. 77, 59-66.

Fisyunov A, Tsintsadze V, Min R, Burnashev N and Lozovaya N (2006) Cannabinoids modulate the P-type high-voltage-activated calcium currents in purkinje neurons. J Neurophysiol. 96, 1267-1277.
Fitzpatrick D (2001a) The somatic sensory system. In Neuroscience, 2nd edn, (Purves D, Augustine GJ, Katz L, Lamantia AS, Mcnamara JO and Williams SM eds), pp 189-208. Sinauer Press.
Fitzpatrick D (2001b) Pain. In Neuroscience, 2nd edn, (Purves D, Augustine GJ, Fitzpatrick D, Katz L, Lamantia AS, Mcnamara JO and Williams SM eds), pp 209-222. Sinauer Press.
Fitzgerald M and Gibson S (1984) The postnatal physiological and neurochemical development of peripheral sensory C fibres. Neuroscience. 13, 933–944.
Fossat P, Sibon I , Masson GL, Landry M and Nagy F (2007) L-type calsium channels and NMDA receptors: a determinant duo for short-term nociceptive plasticity. Eur J Neuroci. 25, 127-135.
Fox A, Kesingland A, Gentry C, McNair K, Patel S, Urban L and James I (2001) The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain. Pain. 92, 91-100.
Fox AP, Nowycky MC and Tsien RW (1987) Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J Physiol. 394, 149-172.
Fuentes JA, Ruiz-Gayo M, Manzanares J, Vela G, Reche I and Corchero J (1999) Cannabinoids as potential new analgesics. Life Sci. 65, 675-685.
Fulton BP (1987) Postnatal changes in conduction velocity and soma action potential parameters of rat dorsal root ganglion neurons. Neurosci Lett. 73, 125-130.
Galiegue S, Mary S, Marchand J, Dussossoy D, Carrière D, Carayon P, Bouaboula M, Shire D, Le Fur G and Casellas P (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem. 232, 254-261.
Gasser HS and Erlanger J (1927) The role played by the sizes of the constituent fibers of a nerve trunk in determining the form of its action potential wave. Am J Physiol. 80, 522-547.
Gerard CM, Mollereau C, Vassart G and Parmentier M (1991) Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J. 279, 129-134.
Gerber G, Youn DH, Hsu CH, Isaev D and Randić M (2000a) Spinal dorsal horn synaptic plasticity: involvement of group I metabotropic glutamate receptors. Prog Brain Res. 129, 115-134.
Gerber G, Zhong J, Youn D and Randić M (2000b) Group II and group III metabotropic glutamate receptor agonists depress synaptic transmission in the rat spinal cord dorsal horn. Neuroscience. 100, 393–406.
Gerdeman G and Lovinger DM (2001) CB1 cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum. J Neurophysiol. 85, 468-471.
Goeger DE, Riley RT, Dorner JW and Cole RJ (1988) Cyclopiazonic acid inhibition of the Ca2+-transport ATPase in rat skeletal muscle sarcoplasmic reticulum vesicles. Biochem Pharmacol. 37, 978-981.
Hagiwara S, Miyazaki S, Moody W and Patlak J (1978) Blocking effects of barium and hydrogen ions on the potassium current during anomalous rectification in the starfish egg. J Physiol. 279, 167-185.
Hamba M, Hisamitsu H and Muro M (1992) wind-up of tooth pulp-evoked responses and its suppression in rat trigeminal caudal neurons. Brain Res Bulletin. 29, 883-889.
Hamba M and Onimaru H (1998) Newborn rat brainstem preparation with the trigeminal nerve attached for pain study. Brain Res Brain Res Protoc. 3, 7-13.
Hamba M, Onodera K and Takahashi T (2000) Long-term potentiation of primary afferent neurotransmission at trigeminal synapses of juvenile rats. Eur J Neurosci. 12, 1128-1134.
Hayashi Y, Momiyama A, Takahashi T, Ohishi H, Ogawa-Meguro R, Shigemoto R, Mizuno N and Nakanishi S (1993) Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb. Nature. 366, 687–690.
Henry DJ and Chavkin C (1995) Activation of inwardly rectifying potassium channels (GIRK1) by co-expressed rat brain cannabinoid receptors in Xenopus oocytes. Neurosci Lett. 186, 91-94.
Herrera B, Carracedo A, Diez-Zaera M, Guzmán M and Velasco G (2005) p38 MAPK is involved in CB2 receptor-induced apoptosis of human leukaemia cells. FEBS Lett. 579, 5084-5088.
Herrero JF, Laird JMA and Lopez-Garcia JA (2000) Wind-up of spinal cord neurons and pain sensation much ado about something? Prog Neurobio. 61, 169-203.
Herzberg U, Eliav E, Bennett GJ and Kopin IJ (1997) The analgesic effects of R(+)-WIN 55,212-2 mesylate, a high affinity cannabinoid agonist, in a rat model of neuropathic pain. Neurosci Lett. 221, 157-160.
Hoffman AF and Lupica CR (2000) Mechanisms of cannabinoid inhibition of GABAA synaptic transmission in the hippocampus. J Neurosci. 20, 2470-2479.
Hohmann AG and Herkenham M (1998) Regulation of cannabinoid and -opioid receptors in rat lumbar spinal cord following neonatal capsaicin treatment. Neurosci Lett. 252, 13-16.
Honda I, Kamiya H and Yawo H (2000) Re-evaluation of phorbol ester-induced potentiation of transmitter release from mossy fiber terminals of the mouse hippocampus. J Physiol. 529, 763-776.
Howlett AC (1995) Pharmacology of cannabinoid receptors. Annu Rev Pharmacol Toxicol. 35, 607-634.
Howlett AC (2005) Cannabinoid receptor signaling. Handb Exp Pharmacol.168, 53-79.

Hu JW, Dostrovsky JO and Sessle BJ (1981) Functional properties of neurons in cat trigeminal subnucleus caudalis (medullary dorsal horn). I. Responses to oral-facial noxious and nonnoxious stimuli and projections to thalamus and subnucleus oralis. J Neurophysiol. 45, 173-192.
Hu NW, Zhang HM, Hu XD, Li MT, Zhang T, Zhou LJ and Liu XG (2003) Protein synthesis inhibition blocks the late-phase LTP of C-fiber evoked field potentials in rat spinal dorsal horn. J Neurophysiol. 89, 2354-2359.
Hua XY, Chen P and Yaksh TL (1999) Inhibition of spinal protein kinase C reduces nerve injury-induced tactile allodynia in neuropathic rats. Neurosci Lett. 276, 99-102.

Huang CC and Hsu KS (1999) Protein tyrosine kinase is required for the induction of long-term potentiation in the rat hippocampus. J Physiol. 520, 783-796.
Huang CC, Lo SW and Hsu KS (2001) Presynaptic mechanisms underlying cannabinoid inhibition of excitatory synaptic transmission in rat striatal neurons. J Physiol. 532, 731-748.
Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, Davar G, Makriyannis A, Vanderah TW, Mata HP and Malan TP JR (2005) CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc Natl Acad Sci USA. 102, 3093-3098.
Ibrahim MM, Rude ML, Stagg NJ, Mata HP, Lai J, Vanderah TW, Porreca F, Buckley NE, Makriyannis A and Malan TP Jr (2006) CB2 cannabinoid receptor mediation of antinociception. Pain. 122, 36-42.
Ikeda H, Heinke B, Ruscheweyh R and Sandkühler J (2003) Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science. 299, 1237-1240.

Ikeda H, Stark J, Fischer H, Wagner M, Drdla R, Jäger T and Sandkühler J (2006) Synaptic amplifier of inflammatory pain in the spinal dorsal horn. Science. 312, 1659-62.

Imamura Y, Kawamoto H and Nakanishi O (1997) Characterization of heat-hyperalgesia in an experimental trigeminal neuropathy in rats. Exp Brain Res. 16, 97-103.
Iversen L (2003) Cannabis and the brain. Brain. 126, 1252-1270.
Iversen L and Chapman V (2002) Cannabinoids: a real prospect for pain relief? Curr Opin Pharmacol. 2, 50-55.
Jensen TS (2002) Anticonvulsants in neuropathic pain: rationale and clinical evidence. Eur J Pain. 6, 61-68.
Jennings EA, Vaughan CW and Christie MJ (2001) Cannabinoid actions on rat superficial medullary dorsal horn neurons in vitro. J Physiol. 534, 805-812.

Ji RR, Kohno T, Moore KA and Woolf CJ (2003) Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 26, 696-705.
Ji RR and Woolf CJ (2001) Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain. Neurobiol Dis. 8, 1-10.

Jin W, Lo TM, Loh HH and Thayer SA (1994) U73122 inhibits phospholipase C-dependent calcium mobilization in neuronal cells. Brain Res. 642, 237-243.
Kajikawa Y, Saitoh N and Takahashi T (2001) GTP-binding protein beta gamma subunits mediate presynaptic calcium current inhibition by GABA(B) receptor. Proc Natl Acad Sci USA. 98, 8054-8058.

Katusic S, Beard CM, Bergstralh E and Kurland LT (1990) Incidence and clinical features of trigeminal neuralgia. Rochester, Minnesota. Ann Neurol. 27, 45-95
Katz LC and Shatz CJ (1996) Synaptic activity and the construction of cortical circuits. Science. 274, 1133-1138.
Kelly S and Chapman VJ (2001) Selective cannabinoid CB1 receptor activation inhibits spinal nociceptive transmission in vivo. Neurophysiol. 86, 3061-3064.

Kemp JA, Foster AC, Leeson PD, Priestley T, Tridgett R, Iversen LL and Woodruff GN (1988) 7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex. Proc Natl Acad Sci USA. 85, 6547-6550.
Killestein J, Uitdehaag BM and Polman CH (2004) Cannabinoids in multiple sclerosis: do they have a therapeutic role? Drugs. 64, 1-11.
Killian JM and Fromm G.H (1968) Carbamazepine in the treatment of neuralgia. Use of side effects. Arch Neurol. 19, 129-136.
Lévénés C, Daniel H, Soubrié P and Crépel F (1998) Cannabinoids decrease excitatory synaptic transmission and impair long-term depression in rat cerebellar Purkinje cells. J Physiol. 510, 867-879.

Lever IJ and Malcangio M (2002) CB1 receptor antagonist SR141716A increases capsaicin-evoked release of Substance P from the adult mouse spinal cord. Br J Pharmacol. 135, 21-24.
Li J, Daughters RS, Bullis C, Bengiamin R, Stucky MW, Brennan J and Simone DA (1999) The cannabinoid receptor agonist WIN 55,212-2 mesylate blocks the development of hyperalgesia produced by capsaicin in rats. Pain. 81, 25-33.
Liang YC, Huang CC and Hsu KS (2004a) Therapeutic potential of cannabinoids in trigeminal neuralgia. Curr Drug Targets CNS Neurol Disord. 3, 507-514.
Liang YC, Huang CC, Hsu KS and Takahashi T (2004b) Cannabinoid-induced presynaptic inhibition at the primary afferent trigeminal synapse of juvenile rat brainstem slices. J Physiol. 555, 85-96.
Liang YC, Huang CC and Hsu KS (2005) Characterization of long-term potentiation of primary afferent transmission at trigeminal synapses of juvenile rats: essential role of subtype 5 metabotropic glutamate receptors. Pain. 114, 417-428.
Liang YC, Huang CC and Hsu KS (2007) The synthetic cannabinoids attenuate allodynia and hyperalgesia in rat model of trigeminal neuropathic pain. Neuropharmacology. 53, 169-177.
Lichtman AH and Martin BR (1991) Spinal and supraspinal components of cannabinoid-induced antinociception. J Pharmacol Exp Ther. 258, 517-523.
Light AR and Perl ER (1979) Reexamination of the dorsal root projection to the spinal dorsal horn including observations on the differential termination of coarse and fine fibers. J Comp Neurol. 186, 117-131.

Lim G, Sung B, Ji RR and Mao J (2003) Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats. Pain. 105, 275-283.
Liu X and Sandkühler J (1997) Characterization of long-term potentiation of C-fiber-evoked potentials in spinal dorsal horn of adult rat: essential role of NK1 and NK2 receptors. J Neurophysiol. 78, 1973-1982.
Liu XG and Sandkühler J (1995) Long-term potentiation of C-fiber-evoked potentials in the rat spinal dorsal horn is prevented by spinal N-methyl-D-aspartic acid receptor blockage. Neurosci Lett. 191, 43-46.
Liu XG and Sandkühler J (1998) Activation of spinal N-methyl-D-aspartate or neurokinin receptors induces long-term potentiation of spinal C-fiber-evoked potentials. Neuroscience. 86, 1209-1216.
Liu XG, Morton CR, Azkue JJ, Zimmermann M and Sandkühler J (1998) Long-term depression of C-fibre-evoked spinal field potentials by stimulation of primary afferent A delta-fibres in the adult rat. Eur J Neurosci. 10, 3069-3075.

Love S and Coakham HB (2001) Trigeminal neuralgia: pathology and pathogenesis. Brain. 124, 2347-2360.
Luo C, Kumamoto E, Furue H, Chen J and Yoshimura M (2002a) Anandamide inhibits excitatory transmission to rat substantia gelatinosa neurones in a manner different from that of capsaicin. Neurosci Lett. 321, 17-20.

Luo C, Kumamoto E, Furue H, Chen J and Yoshimura M (2002b) Nociceptin inhibits excitatory but not inhibitory transmission to substantia gelatinosa neurones of adult rat spinal cord. Neuroscience. 109, 349-358.

MacDonald BK, Cockerell OC, Sander JW and Shorvon SD (2000) The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain. 123, 665-676.
Mackie K and Hille B (1992) Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci USA. 89, 3825-3829.
Mackie K, Lai Y, Westenbroek R and Mitchell R (1995) Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J Neurosci. 15, 6552-6561.

Maejima T, Hashimoto K, Yoshida T, Aiba A and Kano M. (2001) Presynaptic inhibition caused by retrograde signal from metabotropic glutamate to cannabinoid receptors. Neuron. 31, 463-75.
Mao J, Price DD, Lu J, Keniston L and Mayer DJ (2000) Two distinctive antinociceptive systems in rats with pathological pain. Neurosci Lett. 280, 13-16.

Martin WJ, Loo CM and Basbaum AI (1999) Spinal cannabinoids are anti-allodynic in rats with persistent inflammation. Pain. 82, 199-205.
Martin SJ, Grimwood PD and Morris RG (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci. 23, 649-711.
Mason WE, Kollros P and Jannetta PJ (1991) Trigeminal neuraglis and its treatment in a 13-month-old child: a review and case report. J Craniomandib Disord. 5, 213-216.
Matsuda LA, Lolait SJ, Brownstein MJ, Young AC and Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 346, 561-564.
Matwychuk MJ (2004) Diagnostic challenges of neuropathic tooth pain. J Can Dent Assoc. 70, 542-6.
Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR and Compton DR, et al. (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol. 50, 83-90.
Mendell L (1966) Physiological properties of unmyelinated fiber projection to the spinal cord. Exp Neural. 16, 316-332.
Mendell LM and Wall PD (1965) Responses of single dorsal cell to peripheral cutaneons unmyelinated fibers. Natue. 206, 97-99.
Meng ID, Manning BH, Martin WJ and Fields HL (1998) An analgesia circuit activated by cannabinoids. Nature. 395, 381-383.
Merskey H and Bogduk N (1994) Classification of chronic pain. Descriptions of Chronic Pain Syndromes and Definition of Pain Terms. pp 59. IAPS Press.
Morisset V and Nagy F (2000) Plateau potential-dependent windup of the response to primary afferent stimuli in rat dorsal horn neurons. Eur J Neurosci. 12, 3087-3095.

Morisset V and Urban L (2001) Cannabinoid-induced presynaptic inhibition of glutamatergic EPSCs in substantia gelatinosa neurons of the rat spinal cord. J Neurophysiol. 86, 40-48.
Mulkey RM and Malenka RC (1992) Mechanisms underlying induction of homosynaptic long-term depression in area CA1 of the hippocampus. Neuron. 9, 967-975.
Muňoz A, Liu XB and Jones EG (1999) Development of metabotropic glutamate receptors from trigeminal nuclei to barrel cortex in postnatal mouse. J Comp Neurol. 409, 549–566.
Munro S, Thomas KL and Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature. 365, 61-65.
Murali R (1990) Peripheral nerve injections and avulsions in the treatment of trigeminal neuralgia. In Trigeminal Neuralgia (Rovit RL, Murali R and Jannettan PJ eds), pp 95-108. Baltimore Press.
Nackley AG, Zvonok AM, Makriyannis A and Hohmann AG (2004) Activation of cannabinoid CB2 receptors suppresses C-fiber responses and windup in spinal wide dynamic range neurons in the absence and presence of inflammation. J Neurophysiol. 92, 3562-3574.

Nakatsuka T, Ataka T, Kumamoto E, Tamaki T and Yoshimura M (2000) Alteration in synaptic inputs through C-afferent fibers to substantia gelatinosa neurons of the rat spinal dorsal horn during postnatal development. Neuroscience. 99, 549–556.
Neugebauer V, Rumenapp P and Schaible HG (1996) The role of spinal neurokinin-2 receptors in the processing of nociceptive information from the joint and in the generation and maintenance of inflammation-evoked hyperexcitability of dorsal horn neurons in the rat. Eur J Neurosci. 8, 249-260.
Nicol CF (1969) A four year double-blind study of tegretol in facial pain. Headache. 9, 54-57.
Nomura H, Ogawa A, Tashiro A, Morimoto T, Hu JW and Iwata K (2002) Induction of Fos protein-like immunoreactivity in the trigeminal spinal nucleus caudalis and upper cervical cord following noxious and non-noxious mechanical stimulation of the whisker pad of the rat with an inferior alveolar nerve transection. Pain. 95, 225-238.
Notcutt W, Price M, Miller R, Newport S, Phillips C, Simmons S and Sansom C (2004) Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 'N of 1' studies. Anaesthesia. 59, 440-452.
Nurmikko TJ and Eldridge PR (2001) Trigeminal neuralgia—pathophysiology, diagonis and current treatment. Br J Anaesth. 87, 117-132.
Ohishi H, Neki A and Mizuno N (1998) Distribution of a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat and mouse: an immunohistochemical study with a monoclonal antibody. Neurosci Res. 30, 65-82.
Onodera K, Hamba M and Takahashi T (2000) Primary afferent synaptic responses recorded from trigeminal caudal neurons in a mandibular nerve-brainstem preparation of neonatal rats. J Physiol. 524, 503-512.

Palazzo E, Marabese I, de Novellis V, Oliva P, Rossi F, Berrino L, Rossi F and Maione S (2001) Metabotropic and NMDA glutamate receptors participate in the cannabinoid-induced antinociception. Neuropharmacology. 40, 319-326.

Park YK, Galik J, Ryu PD and Randić M (2004) Activation of presynaptic group I metabotropic glutamate receptors enhances glutamate release in the rat spinal cord substantia gelatinosa. Neurosci Lett. 361, 220-224.
Pascual D, Goicoechea C, Suardiaz M and Martin MI (2005) A cannabinoid agonist, WIN 55,212-2, reduces neuropathic nociception induced by paclitaxel in rats. Pain. 118, 23-34.
Patel S, Naeem S, Kesingland A, Froestl W, Capogna M, Urban L and Fox A (2001) The effects of GABA(B) agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat. Pain. 90, 217-226.
Patwardhan AM, Jeske NA, Price TJ, Gamper N, Akopian AN and Hargreaves KM (2006) The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. Proc Natl Acad Sci USA. 103, 11393-11398.
Paxinos G and Watson C (2005) The rat brain in sterotaxic coordinates, 5th ed., Academic Press.
Pertwee R (1993) The evidence for the existence of cannabinoid receptors. Gen Pharmacol. 24, 811-824.
Pertwee RG (2000) Cannabinoid receptor ligands: clinical and neuropharmacological considerations, relevant to future drug discovery and development. Exp Opin Investig Drugs. 9, 1553-1571.
Pertwee RG (2001) Cannabinoid receptors and pain. Prog Neurobiol. 63, 569-611.
Piomelli D, Giuffrida A, Calignano A and Rodríguez de Fonseca F (2000) The endocannabinoid system as a target for therapeutic drugs. Trends Pharmacol Sci. 21, 218-224.
Pin JP and Duvoisin R (1995) The metabotropic glutamate receptors: structure and functions. Neuropharmacology. 34, 1-26.
Price DD, Hu JM, Dubner R and Gracely RH (1997) Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses. Pain. 3, 57-68.
Price TJ, Helesic G, Parghi D, Hargreaves KM and Flores CM (2003) The neuronal distribution of cannabinoid receptor type 1 in the trigeminal ganglion of the rat. Neuroscience. 120, 155-162.
Price TJ, Patwardhan A, Akopian AN, Hargreaves KM and Flores CM (2004) Cannabinoid receptor-independent actions of the aminoalkylindole WIN 55,212-2 on trigeminal sensory neurons. Br J Pharmacol. 142, 257-266.
Randić M, Jiang MC and Cerne R (1993) Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord. J Neurosci. 13, 5228-5241.
Rinaldi-Carmona M, Calandra B, Shire D, Bouaboula M, Oustric D, Barth F, Casellas P, Ferrara P and Le Fur G (1996) Characterization of two cloned human CB1 cannabinoid receptor isoforms. J Pharmacol Exp Ther. 278, 871-878.
Robbe D, Alonso G, Duchamp F, Bockaert J and Manzoni OJ (2001) Localization and mechanisms of action of cannabinoid receptors at the glutamatergic synapses of the mouse nucleus accumbens. J Neurosci. 21, 109-116.
Russo RE and Hounsgaard J (1994) Short-term plasticity in turtle dorsal horn neurons mediated by L-type Ca2+ channels. Neuroscience. 61, 191-197.

Sandkühler J (1996) Neurobiology of spinal nociception: new concepts. Prog Brain Res. 110, 207-224.
Sandkühler J, Benrath J, Brechtel C, Ruscheweyh R and Heinke B (2000) Synaptic mechanisms of hyperalgesia. Prog Brain Res. 129, 81-100.

Sandkühler J, Chen JG, Cheng G and Randić M (1997) Low-frequency stimulation of afferent Adelta-fibers induces long-term depression at primary afferent synapses with substantia gelatinosa neurons in the rat. J Neurosci. 17, 6483-6491.
Sandkühler J and Liu X (1998) Induction of long-term potentiation at spinal synapses by noxious stimulation or nerve injury. Eur J Neurosci. 10, 2476-2480.
Sarlani E and Greenspan JD (2005) Why look in the brain for answers to temporomandibular disorder pain? Cells Tissues Organs. 180, 69-75.

Sessle BJ (1987) The neurobiology of facial and dental pain: present knowledge, future directions. J Dent Res. 66, 962-981.
Shen M and Thayer SA (1998) The cannabinoid agonist WIN55212-2 inhibits calcium channels by receptor-mediated and direct pathways in cultured rat hippocampal neurons. Brain Res. 783, 77-84.
Shire D, Carillon C, Kaghad M, Calandra B, Rinaldi-Carmona M, Le Fur G, Caput D and Ferrara P (1995) An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing. J Biol Chem. 270, 3726-3731.
Sidebottom A and Maxwell S (1995) The medical and surgical management of trigeminal neuralgia. J Clin Pharm Ther. 20, 31-35.
Siegling A, Hofmann HA, Denzer D, Mauler F and De Vry J (2001) Cannabinoid CB (1) receptor upregulation in a rat model of chronic neuropathic pain. Eur J Pharmacol. 415, R5-7.
Simkus CR and Stricker C (2002) The contribution of intracellular calcium stores to mEPSCs recorded in layer II neurones of rat barrel cortex. J Physiol. 545, 521–535.
Sindrup SH and Jensen TS (2002) Pharmacotherapy of trigeminal neuralgia. Clin J Pain. 18, 22-27.
Sivilotti LG, Thompson SW and Woolf CJ (1993) Rate of rise of the cumulative depolarization evoked by repetitive stimulation of small-caliber afferents is a predictor of action potential windup in rat spinal neurons in vitro. J Neurophysiol. 69, 1621-1631.

Smith FL, Fujimori K, Lowe J and Welch SP (1998) Characterization of delta9-tetrahydrocannabinol and anandamide antinociception in nonarthritic and arthritic rats. Pharmacol Biochem Behav. 60, 183-191.
Stragman NM and Walker JM (1999) Cannabinoid WIN 55,212-2 inhibits the activity-dependent facilitation of spinal nociceptive responses. J Neurophysiol. 82, 472-477.
Sugiura Y, Lee CL and Perl ER (1986) Central projections of identified, unmyelinated (C) afferent fibers innervating mammalian skin. Science. 234, 358-361.
Sullivan JM (1999) Mechanisms of cannabinoid-receptor-mediated inhibition of synaptic transmission in cultured hippocampal pyramidal neurons. J Neurophysiol. 82, 1286-94.

Svendsen F, Tjolsen A and Hole K (1998) AMPA and NMDA receptor-dependent spinal LTP after nociceptive tetanic stimulation. Neuroreport. 9, 1185-1190.
Szapiro JJr, Sindou M and Szapiro J (1985) Prognostic factors in microvascular decompression for trigeminal neuralgia. Neurosurgery. 17, 920-929.
Takahashi T, Kajikawa Y and Tsujimoto T (1998) G-Protein-coupled modulation of presynaptic calcium currents and transmitter release by a GABAB receptor. J Neurosci. 8, 3138-3146.
Takahashi T and Momiyama A (1993) Different types of calcium channels mediate central synaptic transmission. Nature. 366,156-158.
Traub RJ (1997) Spinal modulation of the induction of central sensitization. Brain Res. 778, 34-42.
Tremont-Lukats IW, Megeff C and Backonja MM (2000) Anticonvulsants for neuropathic pain syndromes: mechanisms of action and place in therapy. Drugs. 60, 1029-1052.
Tsou K, Brown S, Sanudo-Pena MC, Mackie K and Walker JM (1998) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience. 83, 393-411.
Turman JE Jr, Hiyama L, Castillo M and Chandler SH (2001) Expression of group I and II metabotropic glutamate receptors in trigeminal neurons during postnatal development. Dev Neurosci. 23, 41-54.

Twitchell W, Brown S and Mackie K (1997) Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J Neurophysiol. 78, 43-50.
Urban L, Thompson SWN and Dray A (1994) Modulation of spinal excitability: co-operation between neurokinin and excitatory amino acid neurotransmitters. Trends Neurosci. 17, 432-438.
Valjent E, Pagès C, Rogard M, Besson MJ, Maldonado R and Caboche J (2001) Delta 9-tetrahydrocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission. Eur J Neurosci. 14, 342-352.

Vaughan CW, Mcgregor IS and Christie MJ (1999) Cannabinoid receptor activation inhibits GABAergic neurotransmission in rostral ventromedial medulla neurons in vitro. Br J Pharmacol. 127, 935-940.
Vos BP, Benoist JM, Gautron M and Guilbaud G (2000) Changes in neuronal activities in the two ventral posterior medial thalamic nuclei in an experimental model of trigeminal pain in the rat by constriction of one infraorbital nerve. Somatosens Mot Res. 17, 109-122.
Vos BP, Strassman AM and Maciewicz RJ (1994) Behavioral evidence of trigeminal neuropathic pain following chronic constriction injury to the rat's infraorbital nerve. J Neurosci. 14, 2708-2723.
Walker JM, Hohmann AG, Martin WJ, Strangman NM, Huang SM and Tsou K (1999) The neurobiology of cannabinoid analgesia. Life Sci. 65, 665-673.
Walker JM, Strangman NM and Huang SM (2001) Cannabinoids and pain. Pain Res Manag. 6, 74-79.
Welch SP, Huffman JW and Lowe J (1998) Differential blockade of the antinociceptive effects of centrally administered cannabinoids by SR141716A. J Pharmacol Exp Ther. 286, 1301-1308.
Welch SP and Stevens DL (1992) Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice. J Pharmacol Exp Ther. 262, 10-18.
Williamson EM and Evans FJ (2000) Cannabinoids in clinical practice. Drugs. 60, 1303-1314.
Wilson RI, Kunos G and Nicoll RA. (2001) Presynaptic specificity of endocannabinoid signaling in the hippocampus. Neuron. 31, 453-62.

Woolf CJ and Salter MW (2000) Neuronal plasticity: increasing the gain in pain. Science. 288, 1765-1769.
Zakrzewska JM and Patsalos PN (1992) Drugs used in the management of trigeminal neuralgia. Oral Surg Oral Med Oral Pathol. 74, 439-450.
Zhang LI and Poo MM (2001) Electrical activity and development of neural circuits. Nat Neurosci. 4, 1207-1214.
Zhang X, Bao L, Shi TJ, Ju G, Elde R and Hokfelt T (1998) Down-regulation of mu-opioid receptors in rat and monkey dorsal root ganglion neurons and spinal cord after peripheral axotomy. Neuroscience. 82, 223-240.
Zhong J, Gerber G, Kojić L and Randić M (2000) Dual modulation of excitatory synaptic transmission by agonists at group I metabotropic glutamate receptors in the rat spinal dorsal horn. Brain Res. 887, 359-377.

Zhuang SY, Bridges D, Grigorenko E McCloud S, Boon A, Hampson RE and Deadwyler SA (2005) Cannabinoids produce neuroprotection by reducing intracellular calcium release from ryanodine-sensitive stores. Neuropharmacology. 48, 1086-1096.
Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sorgard M, Di Marzo V, Julius D and Hogestatt ED (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature. 400, 452-457.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2013-01-31起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2013-01-31起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw