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1 Jpn. J. Pharm. Palliat. Care Sci. 3 : 73_84 2010 73.. 2010 11 19 .. (RVM) .. RVM ERK 5-HT . RVM .. 1 .. 1 .. 641-8509 811-1 HDAC histone deacetylase HPA axis hypothalamo-pituitary adrenal axis E-mail IC insular cortex . MAPK mitogen-activated protein kinases MEK MAPK kinase 5-HT 5-hydroxy-tryptamine NA noradrenalin . ACC anterior cingulate cortex PAG periaqueductal grey . Ace central nucleus of the amygdala PFC prefrontal cortex . Ad adrenalin PPC posterior parietal cortex . BST bed nucleus of stria teminalis PVN paraventricular nucleus of hypothalamus . CRH corticotropin releasing hormone RAIC rostral agranular insular cortex DLPT dorsolateral pontine tegmentum RVM rostral ventromedial medulla.

2 ERK extracellular signal-regulated kinases SPA stimulation-produced analgesia fMRI functional magnetic resonance imaging TPH tryptophan hydroxylase . GC glucocorticoid VPM ventral posteromedial nucleus . GR glucocorticoid receptor VPL ventral posterolateral nucleus . 74 . 1 1 . 1 ACC IC .. c-fos PVN . 1 . PVN. 2 . HPA axis . 2 . Ace BST . PVN HPA axis 2 Ace . BST 3 4 . NA, Ad . 3 .. Fight or flight .. NA Ad . HPA axis glucocorticoid NA Ad GC cortisol GC . PVN . GC, corticotropin releasing hormone CRH NA, Ad T . Th1 Th2 . PVN 5 . 2 GC .. 2 . BST Ace . PVNpv HPA axis BST Ace .. 75. CA3 . CA3 . BDNF . 6 .. CA3 .. PTSD . GC MRI .. 2 . 1 .. 2.

3 Pathological pain . inflammatory pain neuropathic . pain . nociceptive 7 V WDR wide dynamic range - . VPL, VPM . SI SII .. 3 .. NA, Ad .. HPA axis . cortisol Abl: 4 . 76 . ACC BA 24 IC ACC . ACC . 8 . ACC PFC . S1 S2 PPC IC motor planning . IC Amy . serial pathway I ACC . NS nociceptive specific Tail flick . PB IC ACC RVM . parallel pathways 12 . 9, 10 . 4 ACC RVM . S1 S2 ACC IC . NMDA . PET ACC IC LTP . 11 . ACC Amy 13 . IC .. ACC IV V 14, 15 S2 . V posterior insular cortex: PIC . PAG ACC anterior insular cortex: AIC . PIC IV .. AIC . AIC ACC . IV rostral agranular insular cortex RAIC RAIC GABA dopamine RAIC . CL VPL VPM . PFC ACC RAIC.

4 RAIC . DLPT RVM IC GABA. IC . - . NA . 16 IC .. Ace parallel . path- 4 ways - - .. Ace lateral capsular subdivision serial pathway . WDR wide dynamic range - CeLC nociceptive amygdala . - pararell pathway NS nociceptive . specific 9 10 ACC. anterior cingulate cortex Amy amygdala 2 3 . BG basal ganglia HT hypothalamus LTP 17 . IC insular cortex M1 primary motor cortex PAG periaqueductal grey . PB parabrachial nucleus PCC posterior . cingulate cortex PFC prefrontal cortex . Ace LTP . PPC posterior parietal cortex SMA. supplementary motor area : 18 . 77. 3 5-HT 21-23 . RVM ON OFF. PAG RVM neutral 3 24 . 6B OFF.. PAG- ON . 19 . RVM 5 OFF . descending inhibition ON.

5 Stimulation-produced analgesia SPA descending facilitation . 20 PAG RVM DLPT . SPA PAG . RVM . DLPT PAG RVM . RVM DLPT ON - . 5-HT NA . 4 6B 5-HT neutral . RVM 5-HT RVM 20% .. 5 DRG . ACC IC Amy . PAG DLPT RVM . DLPT NA RVM 5-HT 5-HT . 19 .. 78 . 6 5-HT 5-HT3R A . 5-HT 5-HT2A R . 5-HT3R I V - . - - PAG-RVM . 5-HT3R C . vicious cycle . B PAG opioid . RVM ON OFF GABA . neutral 5-HT . ON OFF . 26 19 C RVM 5-HT . 5-HT 5-HT3R SP NK1 . I 33 . PAG 25 . 6B . ON OFF 31 RVM . neutral 5-HT 5-HT3 . 26 . ON . OFF 5-HT 32, 33 . 6C . RVM 5-HT Wei 34 RVM 5-HT . ON OFF . 27 . tryptophan hydroxylase TPH siRNA RVM . RVM 5-HT 3 5-HT . 28 .. 5,7-dihydroxytryptamine 5,7-DHT.

6 5-HT 5-HT3 RVM 5-HT .. 29 . 5-HT . 30 .. 79.. MAP MAPK .. MAPK . ex- tracellular signal-regulated kinase ERK .. RVM 5-HT ERK. 7 .. pERK 2 . pERK 5-HT . 35 . 8 % % . MAPK 5-HT TPH . 5-HT HDACs . 29, 32 . 5-HT3 . MEK (MAPK kinase) inhibitor ERK GC GR . 36 GR . RVM ERK . 6 RVM ERK 38 10 . 5-HT 1 3 . 3 arginine vasopressin AVP . 1 CpG islands DNA MeCP2 . AVP AVP . CRH HPA. axis . 39 .. 3 4 cross- 7 fostering histone deacetylase HDAC . trichostatin A .. DNA 147 DNA.. 37 . 8 H2A, DNA H2B H3 H4 . DNA N C N C .. microRNA .. histone acetyltransferase K.. DNA . CpG . islands SIN3A MeCP2 . 80 . 8 A DNA. methyltransferase DNA MeCP2 .. B . BDNF C . histone deacetylase HDAC.

7 37 .. CBP/P300 defeat . HP1 social pain ACC. 42 . social PFC 9 . defeat . S1 S2 . 40 . BDNF ACC IC . 43 .. HDACs .. ACC IC . 2 .. 7 .. 44 .. fMRI .. alexi- BA 32 thymia 45 . 41 alexithymia .. social . 81. 9 (social pain) . fMRI ACC . 42 . 2 GABA .. fMRI 1 . ACC IC diazepam . 46 . GABA-A . 3 . 49 . 47 4 . 4 3 3 . 5-HT . - . diazepam -helical CRH . 1 1 6 3 . 10 RVM . SSRI 5-HT ERK . 5-HT 50 3 . 5-HT RVM pERK 2 . 5-HT pERK 14% . 30% RVM TPH 30% . RVM 5-HT . A1- 5-HT . 5-HT . 5-HT3R . 29, 32 .. 5 10 20 110 dB 3 pERK 50 NA . 4 28 Ad .. 14 28 3 . Ad . 48 RVM. 3 1 10 2 3 20 10 . 82 . 10 A 3 forced swim sham stress na ve na ve p , . p , sham stress : p , : p B.

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