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╙ 28 ࿁㎾∩⮎䊶䉥䊏䉥䉟䊄䊕䊒䉼䊄䉲䊮䊘䉳䉡䊛㐿௅䈮䈅䈢䈦䈩䈗᜿ᜦ㩷 㩷 㩷 㩷 㩷 ઍ⴫਎⹤ੱ㩷 ਗᧁᤘ⟵䋨ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮ቇ⻠ᐳ䋩㩷㩷 䈖䈱ᐲ䇮╙ 㪉㪏 ࿁㎾∩⮎䊶䉥䊏䉥䉟䊄䊕䊒䉼䊄䉲䊮䊘䉳䉡䊛䉕ᧅᏻ䈪㐿௅䈪䈐䉁䈜䈖䈫䉕༑䈹䈫䈫䉅䈮శᩕ䈮ᕁ䈦䈩䈍䉍䉁䈜䇯䈖䈱⎇ⓥળ䈲ක䊶ᱤ䊶⮎䈱ᄢቇ䈍䉋䈶⵾⮎ળ␠䈱⎇ⓥᚲ䈱⎇ⓥ⠪䈠䈚䈩⥃ᐥක䈏ෳട䈜䉎ቇ㓙⊛䈭䉅䈱䈪䈅䉍䉁䈜䇯䈠䈖䈪䈲䈠䉏䈡䉏䈱ಽ㊁䈪䈱⍮⼂䇮ᚻᛛ䇮ᖱႎ䈮䈧䈇䈩⊒⴫䇮⸛⺰䈏䈭䈘䉏䉎䈱䈪ീᒝ䈮䈭䉍᦭⋉䈪䈅䉍䉁䈜䇯䈚䈎䈚䉁䈣䉁䈣ฦಽ㊁㑆䈪චಽ䈮ℂ⸃䈚ว䈋䈩䈇䈭䈇䈱䈏⃻⁁䈫䈇䈋䉁䈜䇯੹࿁䈱䉲䊮䊘䉳䉡䊛䈪䈲㎾∩⮎䊶䉥䊏䉥䉟䊄䈮㑐䈚䈩䉋䉍⥃ᐥ㕙䉕ᒝ⺞䈚䇮⥃ᐥ䈪໧㗴䈮䈭䈦䈩䈇䉎䈖䈫䇮䉁䈢᳞䉄䉌䉏䈩䈇䉎䈖䈫䈮㊀ὐ䉕䈍䈇䈩䊜䉟䊮䊁䊷䊙
䉕䇸㎾∩⮎䊶䉥䊏䉥䉟䊄ᴦ≮䈱ᣂ䈢䈭น⢻ᕈ䇹䈫䈚䈩䊒䊨䉫䊤䊛䉕ડ↹䈚䉁䈚䈢䇯․೎⻠Ṷ䈲ᦥᩮᢎ᝼䈱䇸䉥䊏䉥䉟䊄ᗵฃᕈ䈱ㆮવ⊛୘ੱᏅ䇹䈪䈅䉍䇮䉲䊮䊘䉳䉡䊛䈲䇸⣄㜑䉋䉍਄૏ਛᨔ䈪䈱䉥䊏䉥䉟䊄䈱૞↪䇹䇮䇸䉥䊏䉥䉟䊄ଐሽ䊶⠴ᕈ䈱ᦨㄭ䈱⍮⷗䋺⥃ᐥ䉕〯䉁䈋䈢ᣂ䈚䈇⸃㉼䇹䇮䇸㎾∩䉺䊷䉭䉾䊃䈫䈚䈩䈱䉦䊮䊅䊎䊉䉟䊄䊧䉶䉺䈱น⢻ᕈ䇹䈫−∩ቇ䇮−∩ක≮䉕ⴕ䈉䉅䈱䈮䈫䈦䈩㊀ⷐ䈪⥝๧䈅䉎䊁䊷䊙䈪䈅䉍䉁䈜䇯䊤䊮䉼䊢䊮䈫䉟䊑䊆䊮䉫䉶䊚䊅䊷䈪䈲−∩ක≮䈮䈍䈔䉎ታᖱ䉕⥃ᐥએᄖ䈱ળຬ䈮䉅ℂ
⸃䈚䈩䉅䉌䈉䈢䉄䈮 㪊 䊁䊷䊙䉕ข䉍਄䈕䈩䈇䉁䈜䇯৻⥸Ṷ㗴䈲ฦᣉ⸳䈎䉌 㪈㪌 㗴䈱ᔕ൐䈏䈅䉍䇮ᵴ⊒䈪೨ะ䈐䈭⸛⺰䉕ᦼᓙ䈚䈩䈇䉁䈜䇯╙ 㪈 ᣣ䈱ቇⴚ䊒䊨䉫䊤䊛⚳ੌᓟ䈮ળຬ⋧੕䈱ᗧ⷗੤឵䉇੤ᵹ䉕ᷓ䉄䉎䈢䉄䈮䉰䉾䊘䊨䊎䊷䊦࿦䈪䈱ᙣⷫળ䉕ડ↹䈚䈩䈇䉁䈜䇯ᅗ䈦䈩ᓮෳട䈒䈣䈘䈇䇯㪏 ᦬䈱ᧅᏻ䈲⚛᥍䉌䈚䈇ቄ▵䈪䈅䉍䇮ᄐ䈱ⷰశ䉲䊷䉵䊮䈪䈜䈱䈪䇮ᄢ䈇䈮⧷᳇䉕㙃䈇ᭉ䈚䉖䈪䈇䈎䉏䉎䈖䈫䉕㗿䈦䈩䈍䉍䉁䈜䇯㩷

 

㩷

㎾∩⮎䊶䉥䊏䉥䉟䊄䊕䊒䉼䊄䉲䊮䊘䉳䉡䊛㩷 ਎⹤ੱ᦭↰㩷 ⧷ሶ

JR ᧲੩✚ว∛㒮䊶㤗㈮/ᣣᧄᄢ䊶ක䊶㤗㈮ᳰ↰㩷 ๺㓉

᧲੩ㇺ♖␹කቇ✚ว⎇ⓥᚲᬀ↰㩷 ᒄᏧ

㐳ፒᄢ䊶කᱤ⮎䊶ಽሶ⮎ℂጟ 㩷 ື㓶᧲ᶏᄢ䊶ක䊶⮎ℂዊᎹ㩷 ▵ᦶ

ᣣᧄᄢ䊶ක䊶㤗㈮ዊ㊁㩷 ⑲᮸

ฬฎደᏒᄢ䊶⮎䊶ਛᨔ␹⚻ᯏ⢻⮎ℂ㊄ሶ㩷 ๟ม

੩ㇺᄢቇ䊶⮎䊶↢૕ᯏ⢻⸃ᨆ੉੗㩷 ᷕਃ

ᤊ⮎ᄢ䊶⮎䊶⮎‛ᴦ≮ጯጟ㩷 ผ㇢

๺᱌ጊකᄢ䊶ක䊶⮎ℂୖ⍹㩷  ᵏንጊක⮎ᄢ䊶⮎䊶⮎ຠ૞↪

ᰞ↰㩷  ᔋ᧲ർ⮎ᄢ䊶⮎䊶ᯏ⢻ᒻᘒᰞ↰㩷  ม╙৻⮎ᄢ䊶⮎䊶↢ൻ૒⮮㩷 ౏㆏

቟↰ᅚሶᄢ䊶⮎ਅጊ㩷 ⋥ੱ

࿖┙䈏䉖䉶䊮䉺䊷䊶✭๺ක≮㋈ᧁ㩷  ീᤊ⮎ᄢ䊶⮎䊶⮎ຠᲥᕈᦥ⦟㩷 ৻㇢

ർᄢ䊶ක䊶♖␹␹⚻↢‛㜞ᯅ㩷 ᱜస

㐳ፒᄢ䊶ᄢቇᢎ⢒ᯏ⢻㐿⊒䉶䊮䉺䊷ᓼጊ㩷 ዏ๋

␹ᚭቇ㒮ᄢ䊶⮎䊶⥃ᐥ⮎ቇ࿯⢈㩷 ୃม

ጘ㒂ᄢ䊶ක䊶㤗㈮−∩೙ᓮ㐳ἑ㩷  ඳർ㉿ᄢ䊶⮎䊶↢๮⮎ൻቇਗᧁ㩷 ᤘ⟵

ᧅᏻකᄢ䊶ක䊶㤗㈮ᚑ↰㩷  ᐕᤊ⮎ᄢ䊶⮎䊶⮎ຠᲥᕈ

㊁ፒ㩷 ᱜൎ↢↥㐿⊒⑼ቇ⎇䊶⮎ℂ⧎ጟ㩷 ৻㓶

JR ᧲੩✚ว∛㒮䊶㤗㈮ධ 㩷 㓷ᢥർᶏ㆏ᄢ䊶⮎䊶⮎ℂศᎹ㩷 ᱜ᣿

੩ㇺᄢ䊶ㄘ䊶㘩ຠ↢‛
䋨2007 ᐕ 8 ᦬⃻࿷㩷 ੖ච㖸㗅㩷 ᢘ⒓⇛䋩⎇ⓥળ੐ോዪ䋨੐ോዪ㐳䋺੉੗ᷕਃ䋩੩ㇺ䊥䉰䊷䉼䊌䊷䉪䋨ᩣ䋩䉮䊮䊔䊮䉲䊢䊮䉼䊷䊛ౝ
䇾600-8813 ੩ㇺᐭ੩ㇺᏒਅ੩඙ਛၴኹධ↸ 134
TEL䋺075-315-8697㩷 Fax䋺075-314-2968
e-mail: jnrc@krp.co.jp

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ᏻකᄢ࡮ක࡮㤗㈮㧕 ╙ 28 ࿁㎾∩⮎䊶䉥䊏䉥䉟䊄䊕䊒䉼䊄䉲䊮䊘䉳䉡䊛᭎ⷐ
䊁䊷䊙䋺㎾∩⮎䊶䉥䊏䉥䉟䊄ᴦ≮䈱ᣂ䈢䈭น⢻ᕈᣣᤨ䋺ᐔᚑ 19 ᐕ 8 ᦬ 31 ᣣ (㊄) - 9 ᦬ 1 ᣣ (࿯)႐ᚲ䋺䇾060-8543
ᧅᏻᏒਛᄩ඙ධ䋱᧦⷏ 16 ৼ⋡㩷 ᧅᏻක⑼ᄢቇ⥃ᐥᢎ⢒⎇ⓥ᫟ 1F ⻠ၴ䋨᩺ౝ㩷 ೎⚕䋩ෳട⾌䋺৻⥸ 6,000 ౞䋬ቇ↢ 3,000 ౞਎⹤ੱળ䋺ᧅᏻක⑼ᄢቇ⥃ᐥᢎ⢒⎇ⓥ᫟ 1F ౒↪ታ⠌ቶ
8 ᦬ 31 ᣣ (㊄) 8䋺30䌾9䋺20਎⹤ੱળႎ๔䋺ળ႐8 ᦬ 31 ᣣ (㊄) 13䋺35䌾13䋺45

ቇⴚ䊒䊨䉫䊤䊛
1䋮․೎⻠Ṷ䋺䇸䉥䊏䉥䉟䊄ᗵฃᕈ䈱ㆮવ⊛୘ੱᏅ䇹㩷 㩷 ᧲ർᄢቇ㩷 ♖␹␹⚻↢‛ቇಽ㊁㩷 ᦥ⦟৻㇢2䋮䉲䊮䊘䉳䉡䊛㩷䌉䋺䇸਄૏ਛᨔ䈪䈱∩䉂ᖱႎવ㆐䊶೙ᓮ䈱䊜䉦䊆䉵䊛䇹II䋺䇸䉥䊏䉥䉟䊄ଐሽ䊶⠴ᕈ䈱ᦨㄭ䈱⍮⷗䋺⥃ᐥ䉕〯䉁䈋䈢ᣂ䈚䈇⸃㉼䇹
III:䇸㎾∩䉺䊷䉭䉾䊃䈫䈚䈩䈱䉦䊮䊅䊎䊉䉟䊄䊧䉶䊒䉺䈱น⢻ᕈ䇹
3. 䉶䉾䉲䊢䊮 I-III㩷 ৻⥸Ṷ㗴
4䋮䊤䊮䉼䊢䊮䉶䊚䊅䊷䋬䉟䊑䊆䊮䉫䉶䊚䊅䊷䊤䊮䉼䊢䊮䉶䊚䊅䊷䌉䋺㩷 䇸⥃ᐥ䈮䈍䈔䉎䉥䊏䉥䉟䊄♽㎾∩⮎䈱૶䈇ᣇ䈫໧㗴ὐ䇹 ੩ㇺᐭ┙ක⑼ᄢቇ㤗㈮⑼㩷 ⚦Ꮉ㩷 ⼾ผ䉟䊑䊆䊮䉫䉶䊚䊅䊷䋺䇸䊧䊚䊐䉢䊮䉺䊆䊦䈱ၮ␆䈫⥃ᐥ䇹㩷 㩷 㩷 䊟䊮䉶䊮䊐䉜䊷䊙ᩣᑼળ␠㩷 ᪊੗┨ᙗ㩷 㩷 㩷 ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮⑼㩷 ጊ⬺㆏᣿䊤䊮䉼䊢䊮䉶䊚䊅䊷II䋺䇸✭๺ක≮䈮䈍䈔䉎䉥䊏䉥䉟䊄⵾೷䈱૏⟎䈨䈔䌾࿷ቛ✭๺䉬䉝䇮ක≮ㅪ៤䉅฽䉄䈩䌾䇹ⷐ↸∛㒮೽㒮㐳㩷 ศỈ᣿ቁ
䋨ᢘ⒓⇛䋩5䋮ᙣⷫળ䋺8 ᦬ 31 ᣣ䋨㊄䋩19䋺30䌾㩷䉰䉾䊘䊨䊎䊷䊦࿦㩷 㩷 ᧅᏻᏒ᧲඙ർ䋷᧦᧲ 9 ৼ⋡ 2-10㩷 㩷 㩷 TEL䋺0120-150-550ળ⾌䋺৻⥸ 3,000 ౞㩷 㩷 㩷 ቇ↢㩷 2,000 ౞ળ⾌䈲੐೨䈮⻠Ṷળળ႐ฃઃ䈮䈩䈍ᡰᛄ䈇䈒䈣䈘䈇䋮↢䊤䊛䉳䊮䉩䉴䉦䊮䋬὾䈐㊁⩿䋬䉲䊷䊐䊷䊄䋬㘩䈼᡼㗴䋬㘶䉂᡼㗴䈪䈜䋮ቇળ႐䈎䉌⾉ಾ䊋䉴䈮䈩ᙣⷫળળ႐䉁䈪䈗ㅍㄫ䈇䈢䈚䉁䈜䋮ᙣⷫળ⚳ੌᓟ䈲⃻࿾⸃ᢔ䈫䈭䉍䉁䈜䋮䊋䉴䊶䉺䉪䉲䊷䈲ળ႐䈎䉌⊒⌕䈚䈩䈍䉍䉁䈜䋮䈍໧䈇ว䉒䈞వ䋺
䇾060-8543
ᧅᏻᏒਛᄩ඙ධ䋱᧦⷏ 16 ৼ⋡㩷 ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮ቇ⻠ᐳ╙ 28 ࿁㎾∩⮎䊶䉥䊏䉥䉟䊄䊕䊒䉼䊄䉲䊮䊘䉳䉡䊛੐ോዪᐙ੐㩷 Ꮉ⌀↰᮸ੱ
TEL䋺011-611-2111䋨ౝ✢ 3568䋩
FAX䋺011-631-9683
E-mail䋺kosugiya@sapmed.ac.jp

 

㩷㩷㩷㩷

╙ 28 ࿁㎾∩⮎䊶䉥䊏䉥䉟䊄䊕䊒䉼䊄䉲䊮䊘䉳䉡䊛ᣣ⒟⴫㩷 (╙ 1 ᣣ)ળ႐䋨䋱F㩷 ⻠ၴ䋩

1F㩷 ౒↪ታ⠌ቶ䈍䉋䈶⻠ၴ೨
8䋺30䌾9䋺20਎⹤ੱળ

9䋺20䌾9䋺25㩷 㐿ળ䈱᜿ᜦዷ␜㩷 䉮䊷䊍䊷䉰䊷䊎䉴

9䋺25䌾10䋺30㩷 䉶䉾䉲䊢䊮 Iᐳ㐳㩷 ੉੗ᷕਃ䋬ᰞ↰ม
10䋺35䌾12䋺35㩷 䉲䊮䊘䉳䉡䊛 Iᐳ㐳㩷 ᬀ↰ᒄᏧవ↢㩷 ධ㓷ᢥ12䋺40䌾13䋺30㩷 䊤䊮䉼䊢䊮䉶䊚䊅䊷Iᐳ㐳㩷 ⧎ጟ৻㓶Ṷ⠪㩷 ⚦Ꮉ⼾ผ13䋺35䌾13䋺45㩷 ਎⹤ੱળႎ๔
13䋺50䌾䋱4䋺55㩷 䉶䉾䉲䊢䊮 IIᐳ㐳㩷 㩷 ㋈ᧁീ㩷 ጯጟผ㇢15䋺00䌾䋱7䋺00㩷 䉲䊮䊘䉳䉡䊛 IIᐳ㐳㩷 ᚑ↰ᐕ㩷 ਄࿦଻ੳ17:05䌾18:05㩷 ․೎⻠Ṷᐳ㐳㩷 ਗᧁᤘ⟵Ṷ⠪㩷 ᦥ⦟৻㇢㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷㩷㩷㩷㩷㩷

18:10䌾19:00㩷 䉟䊑䊆䊮䉫䉶䊚䊅䊷ᐳ㐳㩷 ችᧄ◊Ṷ⠪㩷 ᪊੗┨ᙗ㩷 㩷 㩷 㩷 ጊ⬺㆏᣿

19:30䌾㩷 ᙣⷫળ ╙ 28 ࿁㎾∩⮎䊶䉥䊏䉥䉟䊄䊕䊒䉼䊄䉲䊮䊘䉳䉡䊛ᣣ⒟⴫㩷 (╙䋲ᣣ)
ળ႐䋨䋱F㩷 ⻠ၴ䋩

1F㩷 ౒↪ታ⠌ቶ䈍䉋䈶⻠ၴ೨ዷ␜㩷 䉮䊷䊍䊷䉰䊷䊎䉴

8䋺40䌾9䋺45㩷 䉶䉾䉲䊢䊮 IIIᐳ㐳㩷 ୖ⍹ᵏ䋬ᳰ↰๺㓉
9䋺50䌾11䋺50㩷 䉲䊮䊘䉳䉡䊛 IIIᐳ㐳㩷 ᷰㄝ㓷ᒾ㩷 ጊᧄ⚻ਯ
11䋺55䌾12䋺05ᰴ࿁ઍ⴫਎⹤ੱ᜿ᜦ
12:10䌾12䋺15㩷 㐽ળ䈱᜿ᜦዷ␜᠗෰

12䋺20䌾13䋺20㩷 䊤䊮䉼䊢䊮䉶䊚䊅䊷IIᐳ㐳㩷 ዊᎹ▵㇢䋨ᢘ⒓⇛䋩Ṷ⠪㩷 ศỈ᣿ቁ 䉲䊮䊘䉳䉡䊛ㆇ༡ⷐ㗄
A.

䉲䊮䊘䉳䉡䊛ෳട䈱⊝᭽䈻ෳട⊓㍳䈲 8 ᦬ 31 ᣣ䋨㊄䋩㩷 8:00 a䌭䉋䉍䋬ᧅᏻක⑼ᄢቇ⥃ᐥᢎ⢒⎇ⓥ᫟ 1F ⻠ၴ䈱ฃઃ䈪ⴕ䈇䉁䈜䋮ળ႐䈪䈲䊈䊷䊛䉦䊷䊄䉕䈍ઃ䈔䈒䈣䈘䈇䋮៤Ꮺ㔚⹤䋬䊘䉬䉾䊃䊔䊦䈱ળ႐ౝ䈪䈱૶↪䈲䈍ប䈋ਅ䈘䈇䋮B.

Ṷ⠪䋨౒หṶ⠪䉕฽䉃䋩䈱ᣇ䇱䈻ᧄ⎇ⓥળ䈪⊒⴫䈘䉏䉎ᣇ䈲ᧄ⎇ⓥળળຬ䈮㒢䉍䉁䈜䋮ળຬ䈪䈭䈇ᣇ䈲㎾∩⮎䊶䉥䊏䉥䉟䊄䊕䊒䉼䊄䉲䊮䊘䉳䉡䊛䋨੐ോዪ䋺䌊䌎䌒䌃੐ോዪ 䇾600-8813 ੩ㇺᐭ੩ㇺᏒਅ੩඙ਛၴኹධ
↸ 134 ੩ ㇺ 䊥 䉰 䊷 䉼 䊌 䊷 䉪 䋨 ᩣ 䋩 䉮 䊮 䊔 䊮 䉲 䊢 䊮 䉼 䊷 䊛 ౝ TEL 䋺 075-315-8697 㩷 Fax:
075-314-2968 e-mail: jnrc@krp.co.jp䋩䈻౉ળ䈚䈩ਅ䈘䈇䋮ᣂ౉ળຬ䈱ฃ䈔ઃ䈔䈲ᒰᣣળ႐䈪䉅ⴕ䈇䉁䈜䋮

C.

Ṷ⠪䋨⊒⴫⠪䋩䈱ᣇ䈻䉲䊮䊘䉳䉡䊛 I,II,III ⊒⴫

1.

⊒⴫䈲 PC 䊒䊧䉷䊮䊁䊷䉲䊢䊮䈪䈍㗿䈇䈚䉁䈜䋮

2.

⊒⴫ᤨ㑆䈲Ṷ⠪䈮䉋䈦䈩⧯ᐓ⇣䈭䉍䉁䈜䋮ᐳ㐳䈮ᓮ⏕⹺ਅ䈘䈇䋮⊒⴫ᤨ㑆䈲෩቞䈚䈩ਅ䈘䈇䋮ᐳ㐳䈱ᜰ␜䈏䈅䉎႐ว䈮䈲䈠䉏䈮ᓥ䈦䈩ਅ䈘䈇䋮

3.

⊒⴫ᤨ㑆䈱 10 ಽ೨䉁䈪䈮䇸ᰴṶ⠪Ꮸ䇹䈮䈍⌕䈐ਅ䈘䈇䋮

4.

Microsoft PowerPoint 2003 䈏 䉟 䊮 䉴 䊃 䊷 䊦 䈘 䉏 䈢 䊉 䊷 䊃 䊌 䉸 䉮 䊮 䉕 ⸳ ⟎ 䈇 䈢 䈚 䉁 䈜䋨Windows XP䋩䋮䈖䈱ⅣႺ䈱䊉䊷䊃䊌䉸䉮䊮䈪↹㕙䈮ਇㇺว䈏䈭䈇䈖䈫䉕੍䉄䈗⏕⹺ਅ䈘䈇䋮
Microsoft PowerPoint 䈪૞ᚑ䈘䉏䈢⊒⴫䉴䊤䉟䊄ේⓂ䉕 USB 䊐䊤䉾䉲䊠䊜䊝䊥䊷䈪䈍ᜬ䈤䈮䈭䉎䈎䋬䈗⥄り䈱䉮䊮䊏䊠䊷䉺䉕⋥ធ䈍ᜬㄟ䉂ਅ䈘䈇䋮䈗⥄り䈱䉮䊮䊏䊠䊷䉺䉕䈍ᜬ䈤䈮䈭䉎႐ว䋬ળ႐䈪䈲䊚䊆 D䋭SUB15 䊏䊮䋨䉥䉴䋩䈱䉬䊷䊑䊦䉕↪ᗧ䈚䉁䈜䈱䈪䋬䉮䊮䊏䊠䊷䉺䈮䊚䊆 D䋭SUB15 䊏䊮䋨䊜䉴䋩䈱┵ሶ䈏䈅䉎䈖䈫䉕䈗⏕⹺ਅ䈘䈇䋮PC ⊒⴫䈱 30 ಽ೨䉁䈪䈮䉼䉢䉾䉪䉕䈍㗿䈇䈚䉁䈜䋮

5.

ᤋ௝⸃௝ᐲ䈱ၮᧄ䈲 1024 X 768 䈪䈜䋮䈖䉏એ਄䈱⸃௝ᐲ䈱ᓮᏗᦸ䈱႐ว䈲䈅䉌䈎䈛䉄ᓮㅪ⛊ਅ䈘䈇䋮

6.

䉰䉴䊕䊮䊄䊝䊷䊄䋨䉴䊥䊷䊒䋩䉇䉴䉪䊥䊷䊮䉶䉟䊋䊷䈏૞േ䈜䉎䈫⸳ቯ䈏ᄌᦝ䈘䉏䉎႐ว䉅䈅䉍䉁䈜䋮䈖䉏䉌䈱ᯏ⢻䈲䈅䉌䈎䈛䉄 OFF 䈮䈚䈩䈍䈇䈩ਅ䈘䈇䋮䉶䉾䉲䊢䊮 I,II,III ⊒⴫㪈㪅⊒⴫ᒻᑼ䈲䉲䊮䊘䉳䉡䊛䈫ห᭽䈪䋬PC 䊒䊧䉷䊮䊁䊷䉲䊢䊮䈪䈍㗿䈇䈚䉁䈜䋮㪉㪅⊒⴫ᤨ㑆䈲ญṶ 10 ಽ㩷 ⾰⇼ᔕ╵ 3 ಽ㩷 ⸘ 13 ಽ䈪䈜䋮Ṷ⊒⴫ᤨ㑆䈲෩቞䈚䈩ਅ䈘䈇䋮ᐳ㐳䈱ᜰ␜䈏䈅䉎႐ว䈮䈲䈠䉏䈮ᓥ䈦䈩ਅ䈘䈇䋮 ᐳ㐳䈻䈱䈍㗿䈇㩷 䈗ᜂᒰ䉶䉾䉲䊢䊮㐿ᆎ 10 ಽ೨䈮ฦળ႐䈱ᰴᐳ㐳Ꮸ䈱೨䈮䈍⿧䈚䈒䈣䈘䈇䋮ቯೞ䈮䈭䉏䈳䉲䊮䊘䉳䉡䊛䊶䉶䉾䉲䊢䊮䉕㐿ᆎ䈚䈩ਅ䈘䈇䋮⸛⺰⠪䈻䈱䈍㗿䈇㩷 ળ႐䈪⾰໧䊶ㅊട䈭䈬䈱⊒⸒䉕䈘䉏䉎ᣇ䈲೨䉅䈦䈩䊙䉟䉪䈱೨䈮䈍┙䈤ਅ䈘䈇䋮⊒⸒䈲ᚲዻ䊶᳁ฬ䉕᣿䉌䈎䈮䈚䈩䈎䉌ⴕ䈦䈩ਅ䈘䈇䋮⊒⸒䈱ណุ䈮䈧䈇䈩䈲ᐳ㐳䈱ᜰ␜䈮ᓥ䈦䈩ਅ䈘䈇䋮 ળ႐๟ㄝ࿑
٨ળ႐ᧅᏻක⑼ᄢቇ⥃ᐥᢎ⢒⎇ⓥ᫟ 1F ⻠ၴ䇾060-8543 ᧅᏻᏒਛᄩ඙ධ 1 ᧦⷏ 16 ৼ⋡
TEL 011-611-2111 (ౝ✢ 3568)

ධ 1 ᧦ㅢ䉍䈎䉌∛㒮䈮ะ䈎䈦䈩ㅴ䉂䋬㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 ᦨೋ䈱Ꮐᚻ䈱ᑪ‛䋱F

੤ㅢᧅᏻ㚞䈎䉌䉺䉪䉲䊷䈪⚂ 10 ಽ䋨⚂ 1,000 ౞䋩࿾ਅ㋕᧲⷏✢䇸⷏ 18 ৼ⋡㚞䇹䋬䋵⇟䋶⇟಴ญ䈎䉌ᓤᱠ 2 ಽ ╙ 28 ࿁㎾∩⮎䊶䉥䊏䉥䉟䊄䊕䊒䉼䊄䉲䊮䊘䉳䉡䊛䊒䊨䉫䊤䊛8 ᦬ 31 ᣣ (㊄)

9䋺20

㐿ળ䈱᜿ᜦ
ઍ⴫਎⹤ੱ㩷 ਗᧁᤘ⟵㩷

9:25䋭10:30

䉶䉾䉲䊢䊮 䌉㩷 ৻⥸Ṷ㗴ᐳ㐳䋺ᤊ⮎⑼ᄢቇ⮎‛ᴦ≮㩷 ੉੗ᷕਃ╙৻⮎⑼ᄢቇ⮎ℂቇ㩷 ᰞ↰ ม
SI-1㩷 ␹⚻㓚ኂᕈ−∩ਅ䈮䈍䈔䉎䉥䉨䉲䉮䊄䊮䈍䉋䈶䊝䊦䊍䊈䈱㎾∩ലᨐ⊒⃻ᯏᐨ䈱⋧㆑ᤊ⮎⑼ᄢቇ㩷 ⮎ຠᲥᕈቇᢎቶ㩷 ਛ㇍◊ผSI-2㩷 ␹⚻࿃ᕈ−∩䈮ኻ䈜䉎(+)-pentazocine ᧃ᪳ᛩਈ䈱ലᨐᤊ⮎⑼ᄢቇ㩷 ⮎‛ᴦ≮ቇᢎቶ㩷 ᨋ㩷 㓳テ
SI-3㩷 Jak-STAT ⚻〝䈱ᵴᕈൻ䈲␹⚻࿃ᕈ−∩䉕⺞▵䈜䉎๺᱌ጊ⋵┙ක⑼ᄢቇ⮎ℂቇ㩷 ೨↰ᱞᒾSI-4㩷 −∩೙ᓮᯏ᭴䈮㑐䈜䉎⎇ⓥ(╙ 73 ႎ); ␹⚻㓚ኂᕈ−∩ᒻᚑ䈮䈍䈔䉎⣄㜑ౝ IP 䈍䉋䈶 EPฃኈ૕䈱ᄌൻ䈫␹⚻㓚ኂᕈ−∩䈮ኻ䈜䉎 beraprost sodium 䈱᦭↪ᕈᤊ⮎⑼ᄢቇ ⮎ຠᲥᕈቇᢎቶ㩷 ㋈ᧁ㓷⟤SI-5㩷 Morphine-3-gluculonide 䈱䊙䉡䉴⣄㜑ౝᛩਈ䈮઻䈉䉝䊨䊂䉞䊆䉝⊒⃻ᯏ᭴䈱⸃ᨆ╙৻⮎⑼ᄢቇ㩷 ⮎ℂቇ㩷 ዊ᧻㩷 ↢᣿

10:35䋭12:35

䉲䊮䊘䉳䉡䊛䌉

䇸਄૏ਛᨔ䈪䈱∩䉂ᖱႎવ㆐䊶೙ᓮ䈱䊜䉦䊆䉵䊛䇹ᐳ㐳䋺㐳ፒᄢቇᄢቇ㒮කᱤ⮎ቇ✚ว⎇ⓥ⑼ಽሶ⮎ℂቇಽ㊁㩷 ᬀ↰ᒄᏧർᶏ㆏ᄢ㒮䊶⮎䊶⮎ℂ㩷 ධ㩷 㓷ᢥ
10䋺35䋭11䋺05
SSI-1

PAG 䈮䈍䈔䉎 BDNF 䈱ᨐ䈢䈜䊝䊦䊍䊈㎾∩⠴ᕈ⛽ᜬᯏ᭴㐳ፒᄢቇᄢቇ㒮කᱤ⮎ቇ✚ว⎇ⓥ⑼ಽሶ⮎ℂቇಽ㊁㩷 ᧻ਅᵗテ

11䋺05䋭11䋺35
SSI-2∩䉂䈮䉋䉎ਇᔟᖱേ↢ᚑ䈮䈍䈔䉎ಽ⇇᧦ᐥᩭ䈱ᓎഀർᶏ㆏ᄢ㒮䊶⮎䊶⮎ℂ㩷 ධ㓷ᢥ11䋺35䋭11䋺55㩷
SSI-3

ㆮવ⊛⢛᥊䈮䉋䉎⣄㜑ᓟⷺ䊶่஥ᑧ㜑⣻ౝ஥ㇱ䊆䊠䊷䊨䊮䈱ᯏ⢻․ᕈ ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮㩷 Ꮉ⌀↰᮸ੱ
11䋺55䋭12䋺35
SSI-4

ᘟᕈ∩䈮઻䈉ᖱേᄌൻ䈱␹⚻ᯏ᭴᧲੩ᘏᕺળක⑼ᄢቇ䊶␹⚻↢ℂቇ⎇ⓥቶ㩷 ട⮮✚ᄦ

12:40䋭13:30

䊤䊮䉼䊢䊮䉶䊚䊅䊷I

ᐳ㐳䋺䌊䌒᧲੩∛㒮㩷 ⧎ጟ৻㓶Ṷ⠪䋺੩ㇺᐭ┙ක⑼ᄢቇ㤗㈮⑼㩷 ⚦Ꮉ⼾ผ䇸⥃ᐥ䈮䈍䈔䉎䉥䊏䉥䉟䊄♽㎾∩⮎䈱૶䈇ᣇ䈫໧㗴ὐ䇹౒௅䋺Ⴎ㊁⟵⵾⮎ᩣᑼળ␠䊶䊛䊮䊂䉞䊐䉜䊷䊙ᩣᑼળ␠13䋺35䋭13䋺45㩷 ਎⹤ੱળႎ๔
13:50䋭14:55

䉶䉾䉲䊢䊮 II㩷 ৻⥸Ṷ㗴ᐳ㐳䋺ᤊ⮎⑼ᄢቇ⮎ຠᲥᕈ㩷 ㋈ᧁ㩷 ീ
๺᱌ጊක⑼ᄢቇකቇㇱ⮎ℂቇ㩷 ጯጟผ㇢SII-1㩷 ᣂⷙ dermorphin N ᧃ┵䊁䊃䊤䊕䊒䉼䊄⺃ዉ૕䈪䈅䉎 amidino-TAPA 䈱਄૏ਛᨔ䈮䈍䈔䉎᛫ଚኂ૞↪䈫േᯏઃ䈔ലᨐ᧲ർ⮎⑼ᄢቇ㩷 ᯏ⢻ᒻᘒቇᢎቶ㩷 ศጟ㤗਽
SII-2㩷 㔚᳇䈔䈇䉏䉖≮ᴺ䈲᳞ᔃ〝ㆤᢿᕈ−∩䈫䊝䊦䊍䊈⠴ᕈ䉕シᷫ䈜䉎⨙ၔ⋵┙෹ㇱ∛㒮㩷 ࿯੗᳗ผSII-3㩷 㔚᳇∨ᡨ≮ᴺ䈱䊝䊦䊍䊈⠴ᕈ䈮ਈ䈋䉎ᓇ㗀᧲੩ㇺකቇ⎇ⓥᯏ᭴᧲੩ㇺ♖␹කቇ✚ว⎇ⓥᚲ㩷 ጤ↰㩷 ஜ
SII-4㩷 䊝䊦䊍䊈䈱㎾∩⠴ᕈᒻᚑᯏ᭴䈮䈍䈔䉎 NCAM-FGFR 㑆⋧੕૞↪䈱ᓎഀ␹ᚭቇ㒮ᄢቇ⮎ቇㇱ⥃ᐥ⮎ቇ⎇ⓥቶ㩷 ựㆻ๺᱌ሶ
SII-5㩷 µ 䉥䊏䉥䉟䊄ฃኈ૕ㆮવሶᰳ៊䊙䉡䉴䉕↪䈇䈢㤗⮎ᜟ᛫ᕈ㎾∩⮎䈱᛫ଚኂฃኈ૞↪䈱⹏ଔᐢፉ࿖㓙ᄢቇ⮎ቇㇱ䊶␹⚻⮎ℂቇᢎቶ㩷 ੗ᚻ㩷 ⡡৻㇢

15:00䋭17䋺00㩷 䉲䊮䊘䉳䉡䊛 II䋺䇸䉥䊏䉥䉟䊄ଐሽ䊶⠴ᕈ䈱ᦨㄭ䈱⍮⷗䋺⥃ᐥ䉕〯䉁䈋䈢ᣂ䈚䈇⸃㉼䇹ᐳ㐳䋺ᤊ⮎⑼ᄢቇ⮎ຠᲥᕈቇᢎቶ㩷 ᚑ↰㩷 ᐕ㐳ፒᄢቇᄢቇ㒮කᱤ⮎ቇ✚ว⎇ⓥ⑼ ਄࿦଻ੳ15䋺00䋭15䋺30

 

SSII-1⥃ᐥ䈎䉌⷗䈢−∩ਅ䈮䈍䈔䉎䉥䊏䉥䉟䊄ଐሽ䊶⠴ᕈ࿖┙䈏䉖䉶䊮䉺䊷ਛᄩ∛㒮㤗㈮䊶✭๺䉬䉝⑼㩷 ᦯ㇱ᡽ᴦ

15䋺30䋭16:00
SSII-2−∩ਅ䈮䈍䈔䉎䊝䊦䊍䊈♖␹ଐሽਇᒻᚑᯏ᭴䈱⸃ᨆᤊ⮎⑼ᄢቇ⮎ຠᲥᕈቇᢎቶ ᣂୖᘮ৻16䋺00䋭16䋺30㩷
SSII-3ᘟᕈἻ∝ᕈ−∩ਅ䈮䈍䈔䉎 morphine 䈍䉋䈶 fentanyl ⺃⊒㎾∩⠴䈍䉋䈶䈠䈱ಽሶᯏ᭴䈱⋧㆑㗅ᄤၴᄢቇකቇㇱ⣖␹⚻ౝ⑼ ੹੗ືม16䋺30䋭17䋺00
SSII-4䉥䊏䉥䉟䊄ฃኈ૕䈱⊒⃻᭽ᑼ䈱㆑䈇䈏䇮⒳䇱䈱䉥䊏䉥䉟䊄⵾೷䈱㎾∩ലᨐ䇮⠴ᕈ䈱㆑䈇䉕↢䉃䋿 – ၮ␆ታ㛎䈎䉌䈱䉝䊒䊨䊷䉼 –㐳ፒᄢቇᄢቇ㒮කᱤ⮎ቇ✚ว⎇ⓥ⑼㩷 ਄࿦଻ੳ17:05䋭18:05․೎⻠Ṷᐳ㐳䋺ᧅᏻක⑼ᄢቇ㤗㈮ቇ⻠ᐳ㩷 ਗᧁᤘ⟵Ṷ⠪䋺᧲ർᄢቇᄢቇ㒮㩷 ♖␹␹⚻↢‛ቇಽ㊁㩷 ᦥ⦟৻ᦶ䇸䉥䊏䉥䉟䊄ᗵฃᕈ䈱ㆮવ⊛୘ੱᏅ䇹

18:10䋭19:00

䉟䊑䊆䊮䉫䉶䊚䊅䊷ᐳ㐳䋺ᧅᏻක⑼ᄢቇ∛㒮⮎೷ㇱ㩷 ችᧄ◊Ṷ⠪䋺䊟䊮䉶䊮䊐䉜䊷䊙ᩣᑼળ␠㩷 ᪊੗┨ᙗ㩷 㩷 㩷 ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮ቇ⻠ᐳ㩷 ጊ⬺㆏᣿䇸䊧䊚䊐䉢䊮䉺䊆䊦䈱ၮ␆䈫⥃ᐥ䇹౒௅䋺䊟䊮䉶䊮䊐䉜䊷䊙ᩣᑼળ␠㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷㩷

19:30䋭ᙣⷫળ䉰䉾䊘䊨䊎䊷䊦࿦䈮䈩䋨೎⚕ෳᾖ䋩
9 ᦬ 1 ᣣ (࿯)

8:40䋭9:45

㩷 䉶䉾䉲䊢䊮 III㩷 ৻⥸Ṷ㗴ᐳ㐳䋺ንጊᄢቇ⮎ቇㇱ⮎ຠ૞↪㩷 ୖ⍹㩷 ᵏ㩷 㩷 㩷 㩷 ᧲੩ㇺ┙♖␹කቇ✚ว⎇ⓥᚲ㩷 ᳰ↰๺㓉
SIII-1㩷 −∩㑐ㅪਇᔟᖱേ෻ᔕ䈮䈍䈔䉎⣻஥ಽ⇇᧦ᐥᩭౝ protein kinase A 䈱ᓎഀ ർᶏ㆏ᄢ㒮䊶⮎䊶⮎ℂ㩷 ಴ጊ⻀ม
SIII-2㩷 Morphine 䈲⣄㜑៊்ᕆᕈᦼ䈱ㆇേ㤗∽䉕Ⴧᖡ䈘䈞䉎
ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮ቇ⻠ᐳ㩷 ᧖ጊ↱♿
SIII-3㩷 㛽䈏䉖ᕈ−∩䊝䊂䊦䈮䈍䈔䉎 MOR1 ⊒⃻䈫䊝䊦䊍䊈㎾∩ലᨐᧅᏻක⑼ᄢቇකቇㇱ㤗㈮ቇ⻠ᐳ㩷 ጊᧄ㩷 ⚐SIII-4㩷 㛽䈏䉖ᕈ−∩䊝䊂䊦䈮䈍䈔䉎 CB1 ฃኈ૕૞േ⮎䈱㎾∩ലᨐᧅᏻක⑼ᄢቇකቇㇱ㤗㈮ቇ⻠ᐳ㩷 ฎἑ᤯๋SIII-5㩷 CB1 ฃኈ૕ᜟ᛫⮎䈱⣄㜑䈒䉅⤑ਅ⣧ౝᛩਈ䈮䉋䉎−∩㑐ㅪⴕേ䈱⊒⃻䈮䈧䈇䈩᧲ർ⮎⑼ᄢቇ㩷 ᯏ⢻ᒻᘒቇᢎቶ㩷 㐳ጟ㜞ผ

9:50䋭11:50

䉲䊮䊘䉳䉡䊛 III

䇸㎾∩䉺䊷䉭䉾䊃䈫䈚䈩䈱䉦䊮䊅䊎䊉䉟䊄䊧䉶䊒䉺䈱น⢻ᕈ䇹ᐳ㐳䋺ർᶏ㆏ᄢቇකቇ⎇ⓥ⑼㩷 ⸃೬⊒↢ቇಽ㊁㩷 ᷰㄝ㓷ᒾ㩷 㩷 㩷 㩷 㐳ፒ࿖㓙ᄢቇ⮎ቇㇱ⮎ℂቇ⎇ⓥቶ㩷 ጊᧄ⚻ਯ
9䋺50䋭10䋺25㩷
SSIII-1 㩷 㩷 㩷 ␹⚻♽䈮䈍䈔䉎ౝ࿷ᕈ䉦䊮䊅䊎䊉䉟䊄䈱วᚑ䊶ಽ⸃䈫䈠䈱↢ℂ૞↪
㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 ർᶏ㆏ᄢቇකቇ⎇ⓥ⑼㩷 ⸃೬⊒↢ቇಽ㊁㩷 ᷰㄝ㓷ᒾ10䋺25䋭11䋺00㩷
SSIII-2 㩷 㩷 㩷 ౝ࿷ᕈ䉦䊮䊅䊎䊉䉟䊄䈱ᓎഀ䈫䈠䈱⎕✋䋭ഃ⮎䈫䈚䈩䈱น⢻ᕈ䋭䉕ត䉎㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㐳ፒ࿖㓙ᄢቇ⮎ቇㇱ⮎ℂቇ⎇ⓥቶ㩷 ጊᧄ⚻ਯ
11䋺00䋭11䋺25
SSIII-3 㩷 㩷 㩷 ৻ᰴ⍮ⷡ␹⚻䈱 CB1 ฃኈ૕䈮䉋䉎∩ⷡฃኈ䈱⺞▵㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 ੩ㇺᐭ┙ක⑼ᄢቇ㤗㈮ቇᢎቶ䊶㓸ਛᴦ≮ㇱ㩷 ᄤ⼱ᢥ᣽
11䋺25䋭11䋺50
SSIII-4 㩷 㩷 㩷 ർᶏ㆏䈮䈍䈔䉎㊁↢ᄢ㤗䈱⃻⁁䈫⺖㗴㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 㩷 ർᶏ㆏଻ஜ⑔␩ㇱකോ⮎ോ⺖㩷 ㊁ዥᓆ↢11:55䋭12:05

ᰴ࿁ઍ⴫਎⹤ੱ᜿ᜦ

ᰴ࿁ઍ⴫਎⹤ੱ㩷 ୖ⍹ᵏ

12:10䋭12:15㐽ળ䈱᜿ᜦઍ⴫਎⹤ੱ㩷 ਗᧁᤘ⟵㩷

12:20䋭13:20㩷 䊤䊮䉼䊢䊮䉶䊚䊅䊷II㩷 䋨╙ 23 ࿁ർᶏ㆏䊕䉟䉪䊥䊆䉾䉪ቇળ䈫วห㐿௅䋩ᐳ㐳䋺ᣣᧄᄢቇකቇㇱ㤗㈮⑼㩷 ዊᎹ▵㇢Ṷ⠪䋺ⷐ↸∛㒮㩷 ೽㒮㐳㩷 ศỈ᣿ቁ䇸✭๺ක≮䈮䈍䈔䉎䉥䊏䉥䉟䊄⵾೷䈱૏⟎䈨䈔䌾࿷ቛ✭๺䉬䉝䇮ක≮ㅪ៤䉅฽䉄䈩䌾䇹౒௅䋺ᱞ↰⮎ຠᎿᬺᩣᑼળ␠ 

․೎⻠Ṷ㩷 䇸䉥䊏䉥䉟䊄ᗵฃᕈ䈱ㆮવ⊛୘ੱᏅ䇹ᦥ⦟৻㇢᧲ർᄢቇᄢቇ㒮කቇ♽⎇ⓥ⑼䊶♖␹␹⚻↢‛ቇಽ㊁
Genetic difference of individual sensitivity to opiates
Ichiro Sora
Department of Biological Psychiatry, Tohoku University Graduate School of Medicine䊝䊦䊍䊈䉕ઍ⴫䈫䈜䉎䉥䊏䉥䊄㘃䈲ଐሽᕈ⮎‛䈱৻䈧䈪䈅䉍䇮ᒝജ䈭㎾∩ലᨐ䉕᦭䈜䉎䇯䉥䊏䉥䉟䊄䈻䈱ᗵฃᕈ䈱୘ੱᏅ䈮䉋䉍䇮චಽ䈭㎾∩ലᨐ䈏ᓧ䉌䉏䈝䇮೽૞↪䈱಴⃻䈏ലᨐ⊛䈭−∩ᴦ≮䈱ᅹ䈕䈫䈭䉎႐ว䈏䈅䉎䇯୘䇱ੱ䈻䈱䉥䊏䉥䉟䊄䈱⥋ㆡ↪㊂䉕᳿ቯ䈜䉎䈢䉄䈮䈲䇮䈇䉁䈱䈫䈖䉐⹜ⴕ㍲⺋䉕➅䉍㄰䈜ᔅⷐ䈏䈅䉎䇯䈖䉏䉌䉥䊏䉥䉟䊄ᗵฃᕈ䈱୘ੱᏅ䈮䈲ㆮવⷐ࿃䈏㑐ਈ䈜䉎䈫⠨䈋䉌䉏䉎䈏䇮䈠䈱䊜䉦䊆䉵䊛䈲චಽ䈮᣿䉌䈎䈮䈲䈘䉏䈩䈇䈭䈇䇯ᚒ䇱䈲䇮ㆮવሶᰳ៊䊙䉡䉴䊝䊂䊦䈱⸃ᨆ䈮䉋䉍 µ 䉥䊏䉥䉟䊄ฃኈ૕䈏䉥䊏䉥䉟䊄ᗵฃᕈ䈮㊀ⷐ䈪
䈅䉎䈖䈫䉕␜䈚䇮䊍䊃䉥䊏䉥䉟䊄ฃኈ૕䈱ㆮવሶᄙဳ䈏ଐሽᕈ⮎‛䈱ലᨐ䈫㑐ㅪ䈜䉎䈖䈫䉕␜䈚䈢䇯䈖䉏䉌䈱⚿ᨐ䈲䉥䊏䉥䉟䊄ฃኈ૕䈱ㆮવ⊛୘ੱᏅ䉕᣿䉌䈎䈮䈜䉎䈖䈫䈮䉋䉍䇮୘ੱ⊛䈭䉥䊏䉥䉟䊄ᗵฃᕈ䉕੍᷹䈚䇮୘䇱䈱ᖚ⠪䈮ᔅⷐ䈭䉥䊏䉥䉟䊄䈱ᔅⷐ㊂䉕ផቯ䈪䈐䉎น⢻ᕈ䉕␜ໂ䈚䈩䈇䉎䇯䉥䊏䉥䉟䊄♽䈱䊐䉜䊷䊙䉮䉳䉢䊈䊁䉞䉪䉴䉕⸃᣿䈜䉎䈖䈫䈲䇮✭๺ක≮䈭䈬䈱⥃ᐥ⃻႐䈮䈍䈔䉎୘䇱䈱ᖚ⠪䈮හ䈚䈢䊁䊷䊤䊷䊜䉟䊄ක≮䈱ታ⃻䈮⽸₂䈪䈐䉎䈫⠨䈋䉌䉏䉎䇯 䉲䊮䊘䉳䉡䊛䌉䋺䇸਄૏ਛᨔ䈪䈱∩䉂ᖱႎવ㆐䊶೙ᓮ䈱䊜䉦䊆䉵䊛䇹
SSI-1

PAG 䈮䈍䈔䉎 BDNF 䈱ᨐ䈢䈜䊝䊦䊍䊈㎾∩⠴ᕈ⛽ᜬᯏ᭴᧻ਅᵗテ䇮੗਄⺈䇮ᬀ↰ᒄᏧ㐳ፒᄢቇ㩷 ᄢቇ㒮කᱤ⮎ቇ✚ว⎇ⓥ⑼㩷 ಽሶ⮎ℂቇಽ㊁
BDNF maintains morphine analgesic tolerance in PAG
Yosuke Matsushita, Makoto Inoue and Hiroshi Ueda
Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of
BioMedical Sciences㩷 䊝䊦䊍䊈䉕ᆎ䉄䈫䈜䉎䉥䊏䉥䉟䊄䈲ᦨㄭ䈱᰷☨䈪䈲≸ᕈ−∩䈱䉂䈭䉌䈝ᘟᕈ−∩䈭䈬䈮䉅ᐢ䈒↪
䈇䉌䉏䉎䉋䈉䈮䈭䈦䈩䈐䈩䈇䉎䇯䈖䈉䈚䈢∩䉂䈪䈲ᴦ≮䈏㐳ᦼ䈮䉒䈢䉎䈢䉄䇮䈠䈱᦭ലᕈ䈫౒䈮䇮䈠䈱⠴ᕈ䊶ଐሽᕈᒻᚑ䈭䈬䈱೽૞↪໧㗴䈏ᡷ䉄䈩㊀ⷐ䈭⺖㗴䈫䈚䈩ข䉍਄䈕䉌䉏䈩䈇䉎䇯䉋䉍቟ᔃ䈚䈩䉥䊏䉥䉟䊄ᴦ≮䉕ⴕ䈉䈢䉄䇮⠴ᕈ䊶ଐሽᕈᒻᚑ䉕ᛥ೙䈜䉎⮎೷䈱㐿⊒䈮ᦼᓙ䈏ነ䈞䉌䉏䈧䈧䈅䉎䇯ᓥ᧪䉋䉍䈭䈘䉏䈩䈇䉎䇮ଐሽᒻᚑ⢻䈱ૐ䈇䉥䊏䉥䉟䊄䈮䉋䉎⟎឵≮ᴺ䈲 QOL 䈱ὐ䈮䈍䈇䈩ᧄ⾰⊛䈭⸃᳿䈫䈭䉌䈭䈇䇯ᧄ⎇ⓥ⠪䉌䈏ឭ໒䈚䈩䈇䉎䈱䈲䇮⠴ᕈ䊶ଐሽᕈᒻᚑ䈮䈱䉂䈮௛䈐䇮QOL
਄ᄢ䈐䈭㓚ო䈮䈭䉌䈭䈇䇮䉝䊮䉼䉥䊏䉥䉟䊄ᯏ᭴䉕ㆤᢿ䈜䉎ᴦ≮ᴺ䈪䈅䉎䇯䉝䊮䉼䉥䊏䉥䉟䊄ᯏ᭴䈮䈧䈇䈩䈲䇮䈖䉏䉁䈪ᄙ䈒䈱㑐ㅪ䈜䉎䊜䉦䊆䉵䊛䈏ឭ໒䈘䉏䈩䈐䈢䈏䇮䉫䊦䉺䊚䊮㉄䊶NMDA ฃኈ૕ᯏ᭴䈏ᦨ䉅䉋䈒⎇ⓥ䈘䉏䈩䈍䉍䇮䈠䈱㑐ਈ䉅᣿⏕䈪䈅䉎䇯⪺⠪䉌䈱⎇ⓥ䈪䈲䇮NMDA ฃኈ૕䉰䊑䊡䊆䉾䊃 NR2A 䈱ㆮવሶᰳ៊േ‛䈲䊝䊦䊍䊈㎾∩⠴ᕈ䊶ଐሽᕈᒻᚑ䉕␜䈘䈭䈇䈚䇮⣖ PAG 䈮䊧䉴䉨䊠䊷䈜䉎䈣䈔䈪⪺᣿䈭⠴ᕈ䊶ଐሽ䈏ౣ⃻䈪䈐䈢䇯⠴ᕈ䊶ଐሽᤨ䈮䈲⣖䈱․ቯ㗔ၞ䈮 NR2A ⊒⃻਄᣹䈏ⷰኤ䈘䉏䉎䈖䈫䈏䈠䈱ಽሶᯏ᭴䈫⠨䈋䈩䈇䉎䈏䇮䈠䈱⹦⚦䈲⸃᣿䈘䉏䈩䈇䈭䈇䇯⪺⠪䉌䈲䇮
BDNF 䈏 NR2A ⊒⃻਄᣹䉕⺃⊒䈜䉎䈖䈫䈮⌕⌒䈚䇮BDNF 䈱⊒⃻䉇䈠䈱ๆ෼᛫૕䈱䊝䊦䊍䊈⠴ᕈᒻᚑ䈮ኻ䈜䉎ᓎഀ䉕⸃ᨆ䈚䈢䇯ᧄ⎇ⓥ䈮䈍䈔䉎䇮㊀ⷐ䈭⊒⷗䈲 BDNF 䈏䊝䊦䊍䊈⠴ᕈ䈱⛽ᜬᯏ᭴䈮௛䈒䈫䈇䈉⍮⷗䈪䈅䉎䇯੹ᓟ䇮䈘䉌䈭䉎ᖱႎવ㆐ᯏ᭴䈱⸃᣿䉕ㅢ䈛䈩䇮ᣂ䈚䈇㎾∩⵬ഥ⮎䈱ឭ᩺䉕ⴕ䈦䈩䉉䈐䈢䈇䇯 

SSI-2∩䉂䈮䉋䉎ਇᔟᖱേ↢ᚑ䈮䈍䈔䉎ಽ⇇᧦ᐥᩭ䈱ᓎഀධ㩷 㓷ᢥർᶏ㆏ᄢ㒮䊶⮎䊶⮎ℂ
Role of the bed nucleus of the stria terminalis in pain-induced aversion in rats
Masabumi Minami
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University㩷 ᚒ䇱䈲䇮∩䉂䈮䉋䉎ਇᔟᖱേ↢ᚑᯏ᭴䈮䈧䈇䈩䇮䈖䉏䉁䈪䈮ᖱേ䈫䈱㑐ㅪ䈏ᒝ䈒␜ໂ䈘䉏䈩䈇䉎ᚳ ᩶ ૕ 䋨amygdala䋩䈮ὶ ὐ 䉕䈅䈩䈢⎇ ⓥ 䉕ⴕ 䈇䇮䊖䊦䊙䊥䊮ᓟ⢇⊹ਅᛩਈ䈮䉋䉎૕ᕈ∩ᤨ䈱ਇᔟᖱേ↢ᚑ䈮ᚳ᩶૕ၮᐩᄖ஥ᩭౝ NMDA ฃኈ૕䉕੺䈚䈢䉫䊦䉺䊚䊮㉄␹⚻ᖱႎવ㆐䈏㊀ⷐ
䈪䈅䉎䈖䈫䉕᣿䉌䈎䈮䈚䈩䈇䉎䋨Neurosci. Res., in press䋩䇯ᧄ⻠Ṷ䈪䈲䇮ㄭᐕ䇮䇸extended amygdala䇹䉕᭴ᚑ䈜䉎⣖㗔ၞ䈫䈚䈩䇮ਇᔟᖱേ↢ᚑ䈮䈍䈔䉎ᓎഀ䈏ᵈ⋡䈘䉏䈩䈇䉎ಽ⇇᧦ᐥᩭ䈮䈍䈇䈩䇮䉮䊦䉼䉮䊃䊨䊏䊮᡼಴࿃ሶ䋨CRF䋩䉇䊉䊦䉝䊄䊧䊅䊥䊮䋨NA䋩䈮䉋䉎␹⚻ᖱႎવ㆐䈏∩䉂䈮䉋䉎ਇᔟᖱേ↢ᚑ䈮㑐ਈ䈚䈩䈇䉎䈖䈫䉕␜䈜ᚒ䇱䈱ᦨㄭ䈱⎇ⓥᚑᨐ䈮䈧䈇䈩⚫੺䈜䉎䇯䈜䈭䉒䈤䇮ಽ⇇᧦ᐥᩭ⢛஥䈻䈱 CRF ฃኈ૕ᜟ᛫⮎ᛩਈ䇮䈅䉎䈇䈲ಽ⇇᧦ᐥᩭ⣻஥䈻䈱 β 䉝䊄䊧䊅䊥䊮ฃኈ૕ᜟ᛫⮎ᛩਈ䈲䇮䊖䊦䊙䊥䊮ᓟ⢇⊹ਅᛩਈ䈮䉋䉎ଚኂฃኈⴕേ䉕ᛥ೙䈜䉎䈖䈫䈭䈒䇮᧦ઙઃ䈔႐ᚲህᖡᕈ
䋨CPA䋩䉕ᛥ೙䈚䈢䇯䈘䉌䈮䇮ಽ⇇᧦ᐥᩭ⣻஥䈻䈱 β ฃኈ૕૞േ⮎ᛩਈ䈮䉋䉍 CPA 䈏ᗖ⿠䈘䉏䈢䇯䈖䉏䉌䈱⚿ᨐ䈲䇮ಽ⇇᧦ᐥᩭౝ䈮䈍䈔䉎 CRF 䈍䉋䈶 NA ␹⚻ᖱႎવ㆐䈱੣ㅴ䈏∩䉂䈮䉋䉎ਇᔟᖱേ↢ᚑ䈮㊀ⷐ䈭ᓎഀ䉕ᨐ䈢䈚䈩䈇䉎䈖䈫䉕␜ໂ䈚䈩䈇䉎䇯 

SSI-3㩷 㩷 ㆮવ⊛⢛᥊䈮䉋䉎⣄㜑ᓟⷺ䈍䉋䈶่஥ᑧ㜑⣻ౝ஥ㇱ䊆䊠䊷䊨䊮䈱ᯏ⢻․ᕈᎹ⌀↰᮸ੱ‫᧖ޔ‬㊁❥৻‫ޔ‬ਗᧁᤘ⟵
ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮ቇ⻠ᐳGenetic variation in response properties of spinal dorsal horn neurons and rostral ventromedial
medulla neurons in different mouse strain
Mikito Kawamata, Shigekazu Sugino, Akiyoshi Namiki
Department of Anesthesiology, Sapporo Medical University School of Medicine
㩷 䈘䉁䈙䉁䈭−∩䈮䈍䈇䈩䋬䈠䈱ᗵฃᕈ䈮䈲ᄢ䈐䈭୘ੱᏅ䈏䈅䉍䋬䈖䉏䈏−∩ᴦ≮䉕࿎㔍䈫䈚䈩䈇䉎৻࿃䈪䈅䉎䋮䈖䈉䈚䈢−∩ᗵฃᕈ䈱Ꮕ⇣䈲ᄙ࿃ሶᕈᒻ⾰䈫⠨䈋䉌䉏䋬䈠䈱⸃ᨆ䈮䈲ㄭ੤♽䊙䉡䉴䈏᦭↪䈪䈅䉎䋮䉒䉏䉒䉏䈲ㄭ੤♽䊙䉡䉴䈱⣄㜑ᓟⷺ䋨V ጀ䋬II ጀ䋩䈍䉋䈶่஥ᑧ㜑⣻ౝ஥ㇱ
䋨Rostral Ventromedial medulla䋺RVM䋩䊆䊠䊷䊨䊮䈎䉌 in vivo ⸥㍳䉕ⴕ䈇䋬䈠䉏䉌䈱ᯏ⢻․ᕈ䈱Ꮕ⇣䉕ᬌ⸛䈚䈩䈐䈢䋮䈠䈱⚿ᨐ䋬Ἳ∝ᕈ−∩䊝䊂䊦䉇ⴚᓟ∩䊝䊂䊦䈮䈍䈔䉎ⴕേ↢ℂቇ⊛䈭෻ᔕ䈫䋬⣄㜑䊆䊠䊷䊨䊮䈍䉋䈶 RVM 䊆䊠䊷䊨䊮䈱ᔕ╵ᄌൻ䈏䉋䈒⋧㑐䈜䉎䈖䈫䈏␜ໂ䈘䉏䋬−∩ᗵฃᕈ䈱Ꮕ⇣䈲䈖䉏䉌∩ⷡ䊒䊨䉶䉴䈱਄ⴕ〝䈍䉋䈶ਅⴕ〝䈱䊆䊠䊷䊨䊮․ᕈ䈮⿠࿃䈜䉎䈖䈫䈏␜䈘䉏䈢䋮㩷 ৻ᣇ−∩䈮䉋䉎ᖱേᄌൻ䉕 in vivo 䈮䈍䈔䉎㔚᳇↢ℂቇᚻᴺ䈪ᬌ⸛䈜䉎䈢䉄䋬䉁䈝䈲䊤䉾䊃ᚳ᩶૕ਛᔃᩭ䈅䉎䈇䈲ಽ⇇᧦ᐥᩭ䈎䉌䈱⚦⢩ᄖ⸥㍳䉕⹜䉂䈢䋮䈖䈉䈚䈢 in vivo ⸥㍳䈮䉋䉎䋬਄૏ਛᨔ䈪䈱−∩䈱⹺⍮䊶ᖱേᄌൻ䈱⎇ⓥ䈱น⢻ᕈ䈮䈧䈇䈩䉅⠨䈋䈩䉂䈢䈇䋮 

SSI-4ᘟᕈ∩䈮઻䈉ᖱേᄌൻ䈱␹⚻ᯏ᭴ട⮮✚ᄦ᧲੩ᘏᕺળක⑼ᄢቇ䊶␹⚻↢ℂቇ⎇ⓥቶ
∩䉂䈱ᧄ⾰䈲ਇᔟ䈭䇸ᖱേ⊛૕㛎䇹䈪䈅䉍䇮ᘟᕈ∩䈱⥃ᐥකቇ⊛໧㗴䈱ᩭᔃ䈲䇮ේ⊒∝⁁ᶖㅌᓟ䉅ᜬ⛯䈜䉎䈠䈱⧰∩䉇ਇᔟᗵ䇮ਇ቟䈭䈬䈱ᖱേ⊛஥㕙䈮䈅䉎䇯∩䉂䈱ᖱേᚑಽ䈱ᚑ┙䈮㑐ਈ䈜䉎␹⚻࿁〝䈫䈚䈩䇮Bernard 䉌䈲⣄㜑ᓟⷺᵻጀ−∩․⇣⊛䊆䊠䊷䊨䊮䈎䉌਄ⴕ䈚ㅒ஥ᯅ⣉றᩭᄖ஥ㇱ䋨PB䋩䈪䉲䊅䊒䉴䉕੺䈚䈢ᓟ䈮ᚳ᩶૕ਛᔃᩭᄖ஥ᄖ൮ㇱ䋨CeLC䋩䈻䈫⥋䉎 spino-limbic
pathway 䉕หቯ䈚䈢䋨Exp Physiol, 87:251-, 2002䋩䇯CeLC 䈲䇸nociceptive amygdala䇹䈫䉅๭䈳䉏䈠䈱
78%䈱䊆䊠䊷䊨䊮䈏ଚኂೝỗ䈮䉋䈦䈩⥝ᅗ䈜䉎䇯⣄㜑␹⚻⚿⚤␹⚻࿃ᕈ−∩䊝䊂䊦䉕૞ᚑ䈚䇮
allodynia ᔕ╵䉕ቯ㊂⹏ଔ䈚䈢ᓟ䇮⣖䉴䊤䉟䉴䉕૞ᚑ䈚䈩 PB-CeLC ⥝ᅗᕈ䉲䊅䊒䉴વ㆐䉕⸥㍳䊶⸃ᨆ䈚䈢⚿ᨐ䇮CeLC 䈮䈍䈔䉎䉲䊅䊒䉴વ㆐䈏 allodynia ᚑ┙䈱ᒝᐲ䈮ଐሽ䈚䈩Ⴧᒝ䈘䉏䉎੐ታ䉕⷗಴䈚䈢䇯䈘䉌䈮䇮䈖䈱䉲䊅䊒䉴Ⴧᒝ䈲 allodynia 䈱ᡷༀᓟ䉅ᱷሽ䈚䇮∩䉂䈱ᗵⷡᚑಽ䈫ᖱേᚑಽ䈱ਵ㔌䈏⹺䉄䉌䉏䈢䇯䈖䉏䉌䈱੐ታ䈲䇮−∩౉ജ䈱㐳ᦼൻ䈮઻䈉 CeLC 䉲䊅䊒䉴વ㆐Ⴧᒝ䈱䇸࿕ቯൻ䇹䈏ᘟᕈ∩䈮䈍䈔䉎ᜬ⛯⊛ᖱേ㓚ኂ䈱ᯏ⢻⊛ၮ⋚䉕᭴ᚑ䈚䈩䈇䉎น⢻ᕈ䉕␜䈚䈩䈇䉎䇯౒ห⎇ⓥ⠪䋺ᳰ↰㩷 ੫䋨᧲੩ᘏᕺળක⑼ᄢቇ䊶ᢛᒻᄖ⑼䋩䇮㜞ᯅ↱㚅㉿䋨ห䊶␹⚻↢ℂቇ䋩䇮ጤἑ✍
ਫ䋨ห䋩䇯

 

䉲䊮䊘䉳䉡䊛 II䋺䇸䉥䊏䉥䉟䊄ଐሽ䊶⠴ᕈ䈱ᦨㄭ䈱⍮⷗䋺⥃ᐥ䉕〯䉁䈋䈢ᣂ䈚䈇⸃㉼䇹
SSII-1⥃ᐥ䈎䉌⷗䈢−∩ਅ䈮䈍䈔䉎䉥䊏䉥䉟䊄ଐሽ䊶⠴ᕈ࿖┙䈏䉖䉶䊮䉺䊷ਛᄩ∛㒮㤗㈮䊶✭๺䉬䉝⑼✭๺ක≮䉼䊷䊛㩷᦯ㇱ㩷 ᡽ᴦ
Opioid addiction and tolerance in cancer pain management: Clinical view
Seiji Hattori, National Cancer Center Hospital, Tokyo, Japan
Division of Anesthesiology and Palliative Medicine
㩷 1980 ᐕઍᓟඨ䈮䊝䊦䊍䊈ᓢ᡼⵾೷䈏⊒ᄁ䈘䉏䇮䈏䉖䈱∩䉂䈮⧰䈚䉃ᄙ䈒䈱ᖚ⠪䈘䉖䈱䌑䌏䌌䉕ᡷༀ䈚䈢䈱䈲๟⍮䈱䈖䈫䈪䈅䉎䇯䊝䊦䊍䊈න⁛䈪䈅䈦䈢ᤨઍ䈲䈏䉖−∩䈱䈢䉄䈮䊝䊦䊍䊈䉕Ⴧ㊂䈚䈩䉅䇮䈾䈎䈮ᚻᲑ䈏䈭䈇䈫䈇䈉䈖䈫䈪ᄤ੗⍮䉌䈝䈮Ⴧ㊂䈚䈩䈇䈢䉬䊷䉴䉅ዋ䈭䈒䈭䈎䈦䈢䈫⡞䈒䇯−∩䈏䈅䉎㒢䉍䈲䉥䊏䉥䉟䊄䈱ଐሽ䈲⿠䈖䉍䈮䈒䈇䇮⠴ᕈ䉕ᒻᚑ䈚䈮䈒䈇䈫䈇䈉䈖䈫䈎䉌∩䉂䈏Ⴧᒝ䈚䈢႐ว䈮Ⓧᭂ⊛䈮Ⴧ㊂䈚䈩䈐䈢䇯䈢䈣䈚䇮⥃ᐥ䈱⃻႐䈪䈲䇸∩䉂䈱⹏ଔ䇹䈫䈇䈉䉅䈱䈏᳿䈚䈩 Logic 䈪䈲䈭䈒䇮ᖚ⠪䈘䉖ฦ䇱䈪䈠䈱⴫⃻䈲⇣䈭䉎䈢䉄䇮ᔅ䈝䈚䉅∩䉂䈱Ⴧᒝ䈮ኻ䈚䈩ㆡᱜ䈮Ⴧ㊂䈚䈩䈇䈭䈎䈦䈢น⢻ᕈ䉅ุቯ䈪䈐䈭䈇䇯
2002 ᐕએ㒠䊐䉢䊮䉺䊆䊦䇮䉥䉨䉲䉮䊄䊮䉕ਥᚑಽ䈫䈜䉎ᓢ᡼⵾೷䈏⋧ᰴ䈇䈪⊒ᄁ䈘䉏䇮䈏䉖−∩䈱ᴦ≮䈲䈘䉌䈮㘧べ⊛䈮ㅴᱠ䈚䈢䇯⚻⊹ๆ෼ဳ䊐䉢䊮䉺䊆䊦⾍ઃ೷䈲䇮ૐኈ㊂䈪䈲䊝䊦䊍䊈䊶䉥䉨䉲䉮䊄䊮䉋䉍䉅೽૞↪䈪䈅䉎ଢ⒁䈏಴⃻䈚䈮䈒䈒䇮䉁䈢⚻ญਇ⢻䈫䈭䈦䈢ᖚ⠪䈪䉥䊏䉥䉟䊄䈱⚻⊹ๆ෼䉕น⢻䈫䈚䈢ὐ䈪䈠䈱⽸₂ᐲ䈲ᄢ䈐䈇䇯৻ᣇ䈪䇮䈠䈱ⷙᩰ᏷䈏ᄢ䈐䈇䈢䉄∩䉂䈱ᄌൻ䈮ᔕ䈛䈢↪㊂䈱⺞▵ᕈ䈲ਲ䈚䈒䇮䈠䈱૶↪㊂䈏㕖Ᏹ䈮ᄙ䈒䈭䉎䈫䈇䈉ᗧ⷗䉅⡞䈒䇯⥃ᐥ䈱⃻႐䈪䈲䇮ᄤ੗ലᨐ䉇⠴ᕈᒻᚑ䈏䈅䉎䈱䈪䈲䈫䈇䈉ჿ䉅⡞䈎䉏䉎䉋䈉䈮䈭䈦䈢䇯䊐䉢䊮䉺䊆䊦䈮㒢䉌䈝䉥䊏䉥䉟䊄䈱૶↪ᣇᴺ䈮ේ࿃䈏䈅䉎䈱䈎䇮䈏䉖−∩▤ℂ䈏ᵈ⋡䈘䉏䉎䉋䈉䈮䈭䈦䈢䈢䉄䈮ᶋ䈐ᓂ䉍䈮䈭䈦䈢䈣䈔䈭䈱䈎䈲ቯ䈎䈪䈲䈭䈇䈏䇮⥃ᐥ䈪䈱⇼໧ὐ䉕ႎ๔䈘䈞䈩䈇䈢䈣䈐䈢䈇䇯 

SSII-2−∩ਅ䈮䈍䈔䉎䊝䊦䊍䊈♖␹ଐሽਇᒻᚑᯏ᭴䈱⸃ᨆᣂୖᘮ৻䇮ᚑ↰㩷 ᐕ䇮ᚑ↰㆏ሶ䇮ਛ㇍◊ผ䇮ዊᨋᵏਭ䇮㋈ᧁ㓷⟤䇮㋈ᧁ㩷 ീᤊ⮎⑼ᄢቇ䊶⮎ຠᲥᕈቇᢎቶ
Molecular mechanism of the suppression of morphine-induced rewarding effect under a pain-likestate
Keiichi Niikura, Minoru Narita, Michiko Narita, Atsushi Nakamura, Yasuhisa Kobayashi, Masami
Suzuki, Tsutomu Suzuki
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences㩷 ක≮↪㤗⮎䈪䈅䉎 morphine 䈲䈏䉖−∩䈭䈬䈱ᘟᕈ−∩䈱✭๺䈱䈢䉄䈮ㆡᱜ૶↪䈘䉏䈢႐ว䇮
morphine 䈮䉋䉎♖␹ଐሽ䈲໧㗴䈮䈭䉌䈭䈇䈖䈫䈏᏷ᐢ䈇⥃ᐥ⚻㛎䈎䉌᣿䉌䈎䈫䈭䈦䈩䈇䉎䇯䈖䉏䉁䈪䈮ᚒ䇱䈲䇮␹⚻㓚ኂᕈ−∩േ‛䊝䊂䊦䉕↪䈇䈩䇮␹⚻㓚ኂᕈ−∩ਅ䈪䈲 morphine 䈮䉋䉎♖␹ଐሽ䈏ᒻᚑ䈘䉏䈭䈇䈖䈫䉕⷗䈇䈣䈚䈩䈍䉍䇮䈖䈱ᯏᐨ䈫䈚䈩䇮ਛ⣖ㄝ✼䊄䊌䊚䊮␹⚻♽䈱⿠ᆎᩭ䈪䈅䉎⣻஥ⵍ⬄㊁䈮䈍䈔䉎 µ-䉥䊏䉥䉟䊄ฃኈ૕䈱ᯏ⢻ᄌൻ䈏৻ㇱ㑐ਈ䈚䈩䈇䉎䈖䈫䉕᣿䉌䈎䈮䈚䈩䈇䉎䇯䈖䈉䈚䈢ਛ⣖ㄝ✼㗔ၞ䈮䈍䈔䉎 µ-䉥䊏䉥䉟䊄ฃኈ૕䈱ᯏ⢻ૐਅ䈲䇮⣄㜑䈎䉌䈱ᜬ⛯⊛䈭∩䉂ೝỗ䈮ኻ䈜䉎↢ℂ⊛䈭෻ᔕ䈫䈚䈩ᜬ⛯⊛䈮ㆆ㔌䈘䉏䉎ౝ࿃ᕈ䉥䊏䉥䉟䊄䊥䉧䊮䊄䈮⿠࿃䈜䉎䇯䈖䈱䉋䈉䈮ᘟᕈ−∩䈲ᧃ᪳䈎䉌䈱⋥ធ౉ജㇱ૏䈪䈅䉎⣄㜑䈱䉂䈭䉌䈝䇮਄૏ਛᨔ䈪䈅䉎⣖䈮䉅ᄢ䈐䈭ᓇ㗀䉕ਈ䈋䉎䈖䈫䈏⠨䈋䉌䉏䉎䇯䈚䈎䈚䈭䈏䉌䇮⣖䈮ὶὐ䉕ᒰ䈩䈢ᘟᕈ−∩䈱⎇ⓥ䈲ዋ䈭䈒䇮ᘟᕈ−∩䈏⣖䈮ਈ䈋䉎ᓇ㗀䈲䈅䉁䉍᣿⏕䈮䈘䉏䈩䈇䈭䈇䇯ᘟᕈ−∩䈏⣖ౝ␹⚻࿁〝䈮ਈ䈋䉎ᓇ㗀䉕⸃ᨆ䈜䉎䈖䈫䈲䇮∩䉂䈮䉋䈦䈩ᒁ䈐⿠䈖䈘䉏䉎᭽䇱䈭ᄌൻ䉕⸃᣿䈜䉎਄䈪㕖Ᏹ䈮㊀ⷐ䈪䈅䉎䈫⠨䈋䉌䉏䉎䇯㩷 ᧄ䉲䊮䊘䉳䉡䊛䈪䈲䇮䈖䈉䈚䈢ᯏ᭴䈱ಽሶ䊜䉦䊆䉵䊛䈎䉌⣖ౝ␹⚻࿁〝✂䈱ᄌൻ䈮䈧䈇䈩ᯏ⢻⸃೬䈭ᦨᣂ䈱⍮⷗䉕⚫੺䈜䉎䇯 

SSII-3ᘟᕈἻ∝ᕈ−∩ਅ䈮䈍䈔䉎 morphine 䈍䉋䈶 fentanyl ⺃⊒㎾∩⠴ᕈ䈍䉋䈶䈠䈱ಽሶᯏ᭴䈱⋧㆑੹੗ືม 1)2)䇮ᚑ↰㩷 ᐕ 2)䇮ਛ㇍◊ผ 2)䇮ਃᅢ㩷 ᱑ 2)䇮㋈ᧁ㓷⟤ 2)䇮㋈ᧁ㩷 ീ 2)1)㗅ᄤၴᄢቇකቇㇱ䊶⣖␹⚻ౝ⑼䇮2)ᤊ⮎⑼ᄢቇ䊶⮎ຠᲥᕈቇᢎቶ

Differences in tolerance to anti-hyperalgesic effects between chronic treatment with morphine andfentanyl under a chronic pain-like state
Satoshi Imai 1)2), Minoru Narita2), Atsushi Nakamura2), Kan Miyoshi2), Masami Suzuki2), Tsutomu
Suzuki2)
1) Department of Neurology, Juntendo University, School of Medicine 2) Department of Toxicology,
Hoshi University School of Pharmacy and Pharmaceutical Sciences㩷 ᧄ⎇ⓥ䈪䈲䇮complete Freund’s adjuvant (CFA) 䉕䊙䉡䉴ᓟ⢇⿷ぞ⊹ਅ䈮ᛩਈ䈚૞⵾䈚䈢ᘟᕈἻ∝ᕈ−∩䊝䊂䊦䉕↪䈇䈩䇮㒰∩↪㊂䈱 morphine 䈅䉎䈇䈲 fentanyl ෻ᓳ⊹ਅᛩਈ䈮䉋䉎㎾∩⠴
ᕈᒻᚑ⢻䈮䈧䈇䈩Ყセᬌ⸛䈚䈢䇯CFA 䈱ᓟ⢇⿷ぞ⊹ਅᛩਈᓟ䈮䇮morphine 䉕 14 ᣣ㑆෻ᓳ⊹ਅᛩਈ䈚䈩䉅චಽ䈭㎾∩ലᨐ䈏⹺䉄䉌䉏䈢䈱䈮ኻ䈚䇮fentanyl ᛩਈ⟲䈪䈲ᣧᦼ䈎䉌㎾∩⠴ᕈᒻᚑ䈏⹺䉄䉌䉏䈢䇯µ-Opioid ฃኈ૕ (MOR) 䈲㐳ᦼ⊛䈭૞േ⮎䈱ೝỗ䈮䉋䉍䇮ฃኈ૕䈱 C ᧃ┵䈏䊥䊮㉄ൻ䈘䉏⚦⢩ౝ⒖ⴕ䈜䉎䇯䈠䈱ᓟ䇮䊥䊮㉄ൻ MOR (p-MOR) 䈲 protein phosphatase 2A (PP2A)
䈮䉋䈦䈩⣕䊥䊮㉄ൻ䈘䉏䈢ᓟ䈮䇮Rab4 ଐሽ⊛䈮ౣᗵ૞䈘䉏䉎䇯⥝๧ᷓ䈇䈖䈫䈮䇮CFA 䉕⿷ぞ⊹ਅᛩਈ䈚䈢 fentanyl ෻ᓳ⊹ਅᛩਈ⟲䈮䈍䈇䈩䈱䉂䇮⣄㜑⚦⢩⤑ಽ↹䈪䈱 p-MOR ㊂䈱᦭ᗧ䈭Ⴧട䇮ਇᵴᕈဳ PP2A ㊂䈱Ⴧട䈭䉌䈶䈮 Rab4 ⊒⃻㊂䈱ᷫዋ䈏⹺䉄䉌䉏䈢䇯એ਄䈱⚿ᨐ䈎䉌䇮ᘟᕈἻ∝ᕈ−∩ਅ䈪䈲䇮fentanyl 䉕෻ᓳ⊹ਅᛩਈ䈜䉎䈖䈫䈮䉋䉍㎾∩⠴ᕈ䈏ᒻᚑ䈘䉏䇮䈖䈱⃻⽎䈮䈲⣄㜑䈮䈍䈔䉎 PP2A 䈱ਇᵴᕈൻ䈮ଐሽ䈚䈢 p-MOR 䈱Ⴧട䈍䉋䈶 Rab4 䈱ᷫዋ䈮઻䈦䈢ฃኈ૕ౣᗵ૞ല₸䈱ૐਅ䈏৻ㇱ㑐ਈ䈚䈩䈇䉎䈖䈫䈏᣿䉌䈎䈫䈭䈦䈢䇯 

SSII-4㩷 䉥䊏䉥䉟䊄ฃኈ૕䈱⊒⃻᭽ᑼ䈱㆑䈇䈏䇮⒳䇱䈱䉥䊏䉥䉟䊄⵾೷䈱㎾∩ലᨐ䇮⠴ᕈ䈱㆑䈇䉕↢䉃䋿 – ၮ␆ታ㛎䈎䉌䈱䉝䊒䊨䊷䉼 –㐳ፒᄢቇᄢቇ㒮කᱤ⮎ቇ✚ว⎇ⓥ⑼䊶↢๮ක⑼ቇ䊶ౝ⤳⮎ℂቇ
਄࿦଻ੳ䇮ർ᪯⟤⢻⇐䇮቟⮮ఝሶ
Involvement of diverse expression patterns of opioid receptors in the different efficacy of analgesia
and tolerance of several opioid drugs – approaches from basic medical sciences -Nagasaki University Graduate School of Biomedical Sciences, Department of Pharmacology andTherapeutics.
㩷 ᣣᧄ䈮䈍䈇䈩䈲䊝䊦䊍䊈䇮䉥䉨䉲䉮䊄䊮䇮䊐䉢䊮䉺䊆䊦⵾೷䈏ක≮↪㤗⮎䈫䈚䈩૶↪䈘䉏䇮⠴ᕈ䊶೽૞↪䈱ዋ䈭䈇ಣᣇ䈫䈚䈩䇮ฦ⒳⮎‛䈱․ᕈ䉕೑↪䈚䈢䉥䊏䉥䉟䊄䊨䊷䊁䊷䉲䊢䊮䈏ⴕ䉒䉏䈩䈇䉎䇯ක≮↪㤗⮎䈲ਥ䈮 µ 䉥䊏䉥䉟䊄ฃኈ૕(µOR)䈮૞↪䈜䉎䈏䇮ㄭᐕ µOR 䈫 δ 䉥䊏䉥䉟䊄ฃኈ૕(δ-OR)䈏䊓䊁䊨ੑ㊂૕(µ-δOR)䉕↢૕ౝ䈪ᒻᚑ䈚䇮න⁛䈱ฃኈ૕䈫䈲⇣䈭䉎⮎ℂቇ⊛․ᕈ䉕␜䈜䈖䈫䈏䉒䈎䈦䈩䈐䈢䇯⮎‛⠴ᕈ䈱㆑䈇䈲䇮µOR 䈱⚦⢩ౝ⒖ⴕ (internalization)䈱㆑䈇䈮䉋䉎䈫䈜䉎ႎ๔䈏䈅䉎䈏⹦⚦䈲ਇ᣿䈪䈅䉎䇯⑳䈢䈤䈲䊝䊦䊍䊈䈭䉌䈶䈮䊐䉢䊮䉺䊆䊦䈱䇮ੑ㊂૕ൻ µ-δOR 䈱internalization䇮internalization 䈮䈍䈔䉎 β-arrestin2 䈱㑐ਈ䇮䈘䉌䈮⚦⢩ౝ䉲䉫䊅䊦䈱㆑䈇䈮䈧䈇䈩ᬌ⸛䉕ⴕ䈦䈢䇯㩷 䈠䈱⚿ᨐ䊐䉢䊮䉺䊆䊦䈲䇮µOR䇮ੑ㊂૕ൻ µ-δOR 䈱 internalization 䉕ᒁ䈐⿠䈖䈜䈱䈮ኻ䈚䇮䊝䊦䊍䊈䈲 µOR 䉕 internalization 䈞䈝䇮ੑ㊂૕ൻ µ-δOR 䈱䉂ᒁ䈐⿠䈖䈜䈖䈫䈏䉒䈎䈦䈢䇯䉁䈢ੑ㊂૕ൻµ-δOR 䉕੺䈚䈢⚦⢩ౝ䉲䉫䊅䊦䇮䈭䉌䈶䈮 β-arrestin2 䈱㑐ਈ䉅⇣䈭䈦䈩䈇䉎䈖䈫䈏್᣿䈚䈢䇯ක≮↪㤗⮎䈱ᜬ䈧⇣䈭䉎⮎ല䇮⮎‛⠴ᕈ䈱㆑䈇䈮䇮ੑ㊂૕ൻ µ-δOR 䈱ሽ࿷䈫䈠䉏䉌ฃኈ૕䈱
internalization 䈱㆑䈇䈏㑐ਈ䈜䉎น⢻ᕈ䈏⠨䈋䉌䉏䈢䇯 䉲䊮䊘䉳䉡䊛 III㩷 ㎾∩䉺䊷䉭䉾䊃䈫䈚䈩䈱䉦䊮䊅䊎䊉䉟䊄䊧䉶䊒䉺䈱น⢻ᕈ
SSIII-1␹⚻♽䈮䈍䈔䉎ౝ࿷ᕈ䉦䊮䊅䊎䊉䉟䊄䈱วᚑ䊶ಽ⸃䈫䈠䈱↢ℂ૞↪

ᷰㄝ㓷ᒾർᶏ㆏ᄢቇකቇ⎇ⓥ⑼㩷 ⸃೬⊒↢ቇಽ㊁⣖ౝ䊙䊥䊐䉜䊅ฃኈ૕䈫䈚䈩หቯ䈘䉏䈢 CB䋱ฃኈ૕䈏䇮䉲䊅䊒䉴䈱ㅒⴕᕈવ㆐⺞▵䈮㑐ਈ䈜䉎ฃኈ૕䈪䈅䉎䈖䈫䈏䋲䋰䋰䋱ᐕ䈮⊒⷗䈘䉏䈢䇯␹⚻ᵴേ䈮઻䈇⣕ಽᭂ䈫 Gq ౒ᓎဳฃኈ૕䈱ᵴᕈൻ䈏หᦼ䈚䈩⿠䈖䉎䈫䇮䊘䉴䊃஥䊆䊠䊷䊨䊮䈪 2-䉝䊤䉨䊄䊉䉟䊦䉫䊥䉶䊨䊷䊦䋨2-AG䋩䉕ਛᔃ䈫䈚䈢ౝ࿷ᕈ䉦䊮䊅䊎䊉䉟䊄䈏วᚑ䈘䉏䇮䊒䊧䉲䊅䊒䉴䈮⊒⃻䈜䉎 CB1 ฃኈ૕䉕ᵴᕈൻ䈚䇮␹⚻વ㆐‛⾰᡼಴䉕ㅒⴕᕈ䈮ᛥ೙䈜䉎䇯ᚒ䇱䈲䇮CB䋱ฃኈ૕䈮ട䈋䇮2-AG วᚑ㉂⚛䈪䈅䉎䉳䉝䉲䊦䉫䊥䉶䊨䊷䊦䊥䊌䊷䉷䋨DGL䋩䇮2-AG ಽ⸃㉂⚛䈪䈅䉎䊝䊉䉝䉲䊦䉫䊥䉶䊨䊷䊦䊥䊌䊷䉷䋨MGL䋩䇮䈘䉌䈮䈖䉏䉌䈫 Gq ౒ᓎဳฃኈ૕䈫䈱ಽሶዪ࿷㑐ଥ䉕ㅊ᳞䈚䈩䈐䈢䇯䈠䈱⚿ᨐ䇮㗔ၞᲤ䈮ㆬᛯ⊛䈭⚦⢩⊒⃻⺞▵䈏ⷰኤ䈘䉏䇮䉲䊅䊒䉴࿁〝䈮ᔕ䈛䈢Ꮑᅱ䈭ዪ࿷⺞▵䈏௛䈇䈩䈇䉎䈖䈫䈏್᣿䈚䈢䇯ዊ⣖䉕଀䈮䈫䉎䈫䇮ઍ⻢ဳ䉫䊦䉺䊚䊮㉄ฃኈ૕ mGluR1 䈲⥝ᅗᕈ౉ജ䉕ฃ䈔䉎䊒䊦䉨䊮䉣⚦⢩䈱᫚⓭⿠䊓䉾䊄䈮㓸ਛ䈜䉎䈏䇮วᚑ㉂⚛ DGLa 䈲᫚䈱䊈䉾䉪㗔ၞ䈮ᦨᄢዪ࿷䉕␜䈜䇯৻ᣇ䇮CB䋱ฃኈ૕䈲䇮⥝ᅗᕈ⚳ᧃ䉋䉍䉅ᛥ೙ᕈ⚳ᧃ䈱⴫㕙䈮⼾ን䈮⊒⃻䈜䉎䈏䇮ಽ⸃㉂⚛ MGL 䈲ᛥ೙ᕈ⚳ᧃ䉋䉍䉅⥝ᅗᕈ⚳ᧃ䈱ౝㇱ䈮⼾ን䈮ሽ࿷䈜䉎䇯䈖䉏䉌䈱ಽሶ㈩⟎䈎䉌䇮ౝ࿷ᕈ䉦䊮䊅䊎䊉䉟䊄䈮䉋䉎ㅒⴕᕈ䉲䊅䊒䉴વ㆐ᛥ೙䈏䇮⥝ᅗᕈ䉲䊅䊒䉴ᵴേ䈮㓙䈚䈩⿠䈖䉍䉇䈜䈇䉋䈉䈮䇮䈠䈱૞↪䈏⥝ᅗ䈫ᛥ೙䈱䊋䊤䊮䉴䉕࿑䉏䉎䉋䈉䈮䇮䈠䈱૞↪▸࿐䈏ዪᚲ࿁〝䈮㒢ቯ䈘䉏䉎䉋䈉䈮઀⚵䉁䉏䈩䈇䉎䈖䈫䉕␜ໂ䈚䈩䈇䉎䇯 

SSIII-2

ౝ࿷ᕈ䉦䊮䊅䊎䊉䉟䊄䈱ᓎഀ䈫䈠䈱⎕✋䋭ഃ⮎䈫䈚䈩䈱น⢻ᕈ䉕ត䉎䋭ጊᧄ⚻ਯ㐳ፒ࿖㓙ᄢቇ⮎ቇㇱ⮎ℂቇ⎇ⓥቶ䉦䊮䊅䊎䊉䉟䊄⎇ⓥ䈲ᬀ‛䈫䈚䈩䈱ᄢ㤗䈱ᵴᕈᚑಽ䈱․⇣䈭♖␹૞↪䈱⸃᣿䈮ᆎ䉁䉍䇮1980 ᐕᧃ䈮↢૕ౝ䈪䈱䉦䊮䊅䊎䊉䉟䊄ฃኈ૕䈫䈠䈱ౝ࿷ᕈ‛⾰䈱⊒⷗䈎䉌䇮⎇ⓥᜰะ䈏৻ᄌ䈚䈢䇯䈠䈱╙৻䈱⎇ⓥ䈲䇮ౝ࿃ᕈ䉦䊮䊅䊎䊉䉟䊄 / 䉦䊮䊅䊎䊉䉟䊄ฃኈ૕䈱↢૕ౝ䈮䈍䈔䉎ᯏ⢻⊛ᓎഀ䉕᣿䉌䈎䈮䈜䉎੐䈪䈅䉎䇯䈖䈱⎇ⓥ䈲หᤨ䈮䇮䈠䈱ᓎഀ䈱⎕✋䈏ᅤ૗䈭䉎∔ᖚ䈫⚿䈶䈧䈒䈱䈎䋭䈱໧䈇䈮╵䈋䉎੐䈮䉅䈭䉎䇯䉦䊮䊅䊎䊉䉟䊄ฃኈ૕䈮䈲䉰䊑䉺䉟䊒䈏ሽ࿷䈚䇮CB1 ฃኈ૕䈲∩ⷡવ㆐⚻〝䈮ዪ࿷䈚䇮ᧃ᪳䇮⣄㜑䈍䉋䈶⣖䈱 CB1 ฃኈ૕䈱ᵴᕈൻ䈮䉋䉍−∩✭๺䈱ᓎഀ䉕ᜂ䈦䈩䈇䉎䈫⠨䈋䉌䉏䈩䈇䉎䇯৻ᣇ䇮ᧃ᪳䈱఺∉⚦⢩╬䈱㕖␹⚻ᕈ⚦⢩䈮ሽ࿷䈜䉎 CB2 ฃኈ૕䉅䇮䈠䈱ᵴᕈൻ䈮䉋䈦䈩䊍䉴䉺䊚䊮╬䈱Ἳ∝䊜䊂䉞䉣䊷䉺䊷䈱ㆆ㔌䉕ᛥ೙䈚৻ᰴଚኂ᳞ᔃ✢⛽䉕੺䈜䉎−∩ᖱႎ䉕ᷫᒙ䈘䈞䉎੐䈏⍮䉌䉏䈩䈇䉎䇯৻ᣇ䇮䊝䊦䊍䊈ㅌ⮎∝୥䈏ౝ࿃ᕈ䉦䊮䊅䊎䊉䉟䊄䋲-AG 䈮䉋䈦䈩ᛥ೙䈘䉏䉎੐䇮䉁䈢ㅒ䈮 CB1 ฃኈ૕ᜟ᛫⮎䈮䉋䈦䈩ㅌ⮎∝୥䈏⊒⃻䈜䉎੐䈎䉌䇮⣖ౝႎ㈽♽䈮䈍䈇䈩䉥䊏䉥䉟䊄䉲䉴䊁䊛䈫䉦䊮䊅䊎䊉䉟䊄䉲䉴䊁䊛䈏䉪䊨䉴䊃䊷䉪䈚䈩䈇䉎น⢻ᕈ䈏␜ໂ䈘䉏䈩䈇䉎䇯╙ੑ䈱⎇ⓥ䈲䇮ᄖ࿃ᕈ䊶ౝ࿃ᕈ䉕໧䉒䈝䉦䊮䊅䊎䊉䉟䊄䈱ක⮎ຠ䈫䈚䈩䈱㐿⊒䈱⹜䉂䈪䈅䉎䇯⃻࿷䇮᦭ല䈭ᴦ≮⮎䈱ή䈇␹⚻࿃ᕈ−∩䉇ᄙ⊒ᕈ⎬ൻ∝䈏䉦䊮䊅䊎䊉䉟䊄䈮䉋䈦䈩✭๺䈘䉏䉎䈫䈱⥝๧䈅䉎⍮⷗䉅ႎ๔䈘䉏䈩䈇䉎䇯ᧄ⻠Ṷ䈪䈲䇮䉦䊮䊅䊎䊉䉟䊄䈱ක⮎ຠ㐿⊒䈱⃻⁁䈪䈱໧㗴ὐ䉅ว䉒䈞䈩᭎⺑䈚䈢䈇䇯

 

SSIII-3

৻ᰴ⍮ⷡ␹⚻䈱 CB1 ฃኈ૕䈮䉋䉎∩ⷡฃኈ䈱⺞▵ᄤ⼱ᢥ᣽੩ㇺᐭ┙ක⑼ᄢቇ㤗㈮ቇᢎቶ䊶㓸ਛᴦ≮ㇱ
Role of peripheral CB1 receptor to control pain perception
Department of Anesthesiology, Kyoto Prefectural University of Medicine৻ᰴ⍮ⷡ␹⚻䈮䈍䈔䉎 CB1 䉦䊮䊅䊎䊉䉟䊄ฃኈ૕䈱ᓎഀ䉕᣿䉌䈎䈮䈜䉎䈢䉄䇮䊤䉾䊃䈍䉋䈶䊃䊤䊮䉴䉳䉢䊆䉾䉪䊙䉡䉴䉕↪䈇䈢⸃ᨆ䈮䉋䈦䈩৻ᰴ⍮ⷡ␹⚻䈱 CB1 ฃኈ૕䈱∩ⷡવ㆐䈻䈱㑐ਈ䈮䈧䈇䈩ᬌ⸛䈚䈢䇯
CB1 㓁ᕈ⚦⢩䈱ᄙ䈒䈲∩ⷡવ㆐䉕ᜂ䈉 C-✢⛽䇮A-delta ✢⛽䉕ᜬ䈧䊆䊠䊷䊨䊮䈪䈅䈦䈢䇯
CB1mRNA 䈲䊤䉾䊃৻ᰴ⍮ⷡ␹⚻䈱䈍䉋䈠 30%䈮⹺䉄䉌䉏䈢䈏䇮䈠䈱⊒⃻䈲Ἳ∝ೝỗ䈮䉋䉍Ⴧട
䈚䈢䇯CB1 㓁ᕈ⚦⢩䈱Ⴧട䈲Ἳ∝ᕈ−∩䈱ේ࿃䈫䈭䉎 TRPV1 ⊒⃻䊆䊠䊷䊨䊮䈮䈍䈇䈩․䈮⪺䈚䈎䈦䈢䇯CB1 ㆬᛯ⊛䉝䉯䊆䉴䊃 ACEA 䈱⿷ᐩᛩਈ䈲Ἳ∝ᕈ−∩䈮ኻ䈚㎾∩ലᨐ䉕␜䈚䇮䈠䈱૞↪
䈲 CB1 mRNA 䈱⊒⃻Ⴧട䈮઻䈦䈩Ⴧᒝ௑ะ䉕␜䈚䈢䇯৻ᣇ䇮৻ᰴ⍮ⷡ␹⚻䈱 CB1 䈱䉂䉕ㆬᛯ⊛䈮䊉䉾䉪䉝䉡䊃䈚䈢䊃䊤䊮䉴䉳䉢䊆䉾䉪䊙䉡䉴䈪䈲䇮䉦䊮䊅䊎䊉䉟䊄䈮䉋䉎㎾∩ലᨐ䈏ᷫᒙ䈜䉎䈱䉂䈭䉌䈝䇮−∩㑣୯⥄૕䈏⪺䈚䈒ૐਅ䈜䉎䈖䈫䈏ⷰኤ䈘䉏䈢䇯䊉䉾䉪䉝䉡䊃䊙䉡䉴䈮䈍䈔䉎∩ⷡㆊᢅ䈲−∩䊝䊂䊦૞ᚑᓟ䈣䈔䈪䈭䈒ᧂಣ⟎䈭䊙䉡䉴䈮䈍䈇䈩䉅⹺䉄
䉌䉏䇮CB1 䈏৻ᰴ⍮ⷡ␹⚻䈱␹⚻વ㆐䉕ᛥ೙䈜䉎䈖䈫䈪∩ⷡવ㆐䈏ᱜᏱ䈮ⴕ䉒䉏䈩䈇䉎䈖䈫䈏␜䈘䉏䈢䇯䈖䉏䉌䈱⚿ᨐ䈎䉌䇮৻ᰴ⍮ⷡ␹⚻䈱 CB1 䈲ଚኂฃኈ␹⚻䈮ሽ࿷䈚䇮CB1 䉝䉯䊆䉴䊃䈱ዪᚲᛩਈ䈮
䉋䉎㎾∩૞↪䉕䉅䈢䉌䈜৻ᣇ䈪䇮ౝ࿃ᕈ䉦䊮䊅䊎䊉䉟䊄䈫䈫䉅䈮∩ⷡવ㆐䈱೙ᓮ䈮䈎䈎䉒䈦䈩䈇䉎䉅䈱䈫⠨䈋䉌䉏䉎䇯

 

SSIII-4

ർᶏ㆏䈮䈍䈔䉎㊁↢ᄢ㤗䈱⃻⁁䈫⺖㗴㊁ዥᓆ↢ർᶏ㆏଻ஜ⑔␩ㇱ଻ஜක≮ዪකോ⮎ോ⺖⮎ോ䉫䊦䊷䊒ਥᩏ䋨㤗⮎䋩㩷
Trend and its countermeasures against wild cannabis in Hokkaido
Department of Health and Welfare, Bureau of Health and Medical Affairs, Medical andPharmaceutical Affairs Division, Pharmaceutical Groupsᄢ㤗䈫䈲䇮䇺ᄢ㤗ข✦ᴺ䇻䈮䈍䈇䈩䇮䇸ᄢ㤗⨲䋨䉦䊮䊅䊎䉴䊶䉰䊁䉞䊋䊶䉣䊦䋩෸䈶䈠䈱⵾ຠ䉕䈇䈉䇯䈢䈣䈚䇮ᄢ㤗⨲䈱ᚑᾫ䈚䈢⨍෸䈶䈠䈱⵾ຠ䋨᮸⢽䉕㒰䈒䇯䋩ਗ䈶䈮ᄢ㤗⨲䈱⒳ሶ෸䈶䈠䈱⵾ຠ䉕㒰䈒䇯䇹䈫ቯ⟵䈘䉏䈩䈇䉎䇯ᄢ㤗䈲䇮ᄢ㤗ขᛒ⠪䈱఺⸵䉕᦭䈜䉎䇸ᄢ㤗ᩱၭ⠪䇹෸䈶䇸ᄢ㤗⎇ⓥ⠪䇹એᄖ䈲䇮ᚲᜬ䇮ᩱၭ䇮⼑ᷰ䇮⼑ฃ䈏⑌ᱛ䈘䉏䈩䈇䉎䈏䇮఺⸵䉕᦭䈜䉎⠪䈪䈅䈦䈩䉅ᱜⷙ䈱⋡⊛એᄖ䈱૶↪䉇ක⮎ຠ䈫䈚䈩䈱૶↪䈏⑌ᱛ䈘䉏䈩䈇䉎䇯ᄢ㤗䈲䇮╙䋲ᰴ਎⇇ᄢᚢ⚳ੌ೨䈱ᣣᧄ䈮䈍䈇䈩䈲䇮⴩᦯䉇✽䈱ේᢱ䈫䈚䈩䈱૶↪䉇৻ㇱ䈪␹੐䈭䈬䈮↪䈇䉌䉏䈩䈇䈢䈣䈔䈣䈦䈢䈏䇮ᢌᚢ䈮䉋䉎ᷙੂ䈫ㅌᑄ䈱␠ળᖱ൓䉇⻉ᄖ࿖䈱ᓇ㗀䈭䈬䈎䉌ᣣᧄੱ䈮䉋䉎ੂ↪䈏ᓢ䇱䈮ᆎ䉁䈦䈢䇯ർᶏ㆏䈮䈍䈇䈩䈲䇮Ფᐕ䇸㊁↢ᄢ㤗䊶ਇᱜ䈔䈚ᠡṌㆇേ䇹䉕ዷ㐿䈚䇮㒰෰ᧄᢙ䈲ᓢ䇱䈮ᷫዋ䈚䈩䈇䉎䈏䇮ᧄ㆏䈮䈍䈔䉎㊁↢ᄢ㤗䈱ਇᱜណข੐‽䈏ᧂ䈣ᓟ䉕⛘䈢䈭䈇⃻⁁䉇ㄭᐕ䇮ో࿖⊛䈮ᄢ㤗੐‽䈮䉋䉎ᬌ᜼⠪䈏Ⴧട䈚䈩䈇䉎䈖䈫䇮ੂ↪⠪䈱⧯ᐕൻ䈭䈬䈏໧㗴䈫䈭䈦䈩䈇䉎䇯ᐔᚑ䋱䋷ᐕᐲ䈱ᧄ㆏䈮䈍䈔䉎㊁↢ᄢ㤗䈱㒰෰ᧄᢙ䈲⚂䋹䋰ਁᧄ䈪ో࿖䈱⚂䋸䋰䋦䈮⋧ᒰ䈜䉎䈖䈫䈎䉌䇮੹ᓟ䉅㊁↢ᄢ㤗ᠡṌኻ╷䉕䉋䉍৻ጀផㅴ䈜䉎ᔅⷐ䈏䈅䉎䈫⠨䈋䉎䇯

 

SI-1
␹⚻㓚ኂᕈ−∩ਅ䈮䈍䈔䉎䉥䉨䉲䉮䊄䊮䈍䉋䈶䊝䊦䊍䊈䈱㎾∩ലᨐ⊒⃻ᯏᐨ䈱⋧㆑ਛ㇍◊ผ 1)2)䇮ᚑ↰㩷 ᐕ 1)䇮દ⮮ਭೣ 2)䇮የ㑐䈅䉉䉂 1)䇮ᅏᵤᄢ᮸ 1)䇮ἏᎹ㓶⾆ 1)䇮㋈ᧁ㓷⟤ 1)䇮ട⮮㩷 ᤩ 2)䇮㋈ᧁ㩷 ീ 1)1)ᤊ⮎⑼ᄢቇ㩷 ⮎ຠᲥᕈቇᢎቶ䇮2)Ⴎ㊁⟵⵾⮎ᩣᑼળ␠㩷 ഃ⮎⎇ⓥᚲ
Different antinociceptive property of oxycodone or morphine under a neuropathic pain-like state
Atsushi Nakamura1)2), Minoru Narita1), Hisanori Ito2), Ayumi Ozeki1), Daiki Okutsu1), Yuki
Takigawa1), Masami Suzuki1), Akira Kato2), Tsutomu Suzuki1)
1) Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences 2)
Discovery ReserchLaboratories, SHIONOGI Co.,LTD䇼✜⸒䇽䉥䉨䉲䉮䊄䊮䈲㐿⊒એ᧪⚂ 100 ᐕㄭ䈒䈱ᱧผ䉕᦭䈜䉎䉅䈱䈱䇮䈠䈱ၮ␆⎇ⓥ䈮䈧䈇䈩䈲䈾䈫䉖䈬ᬌ⸛䈘䉏䈩䈇䈭䈇䈱䈏⃻⁁䈪䈅䉎䇯䈠䈖䈪ᧄ⎇ⓥ䈪䈲䇮䉥䉨䉲䉮䊄䊮䈱␹⚻㓚ኂᕈ−∩䈮ኻ䈜䉎䉥䉨䉲䉮䊄䊮䈍䉋䈶䊝䊦䊍䊈䈱㎾∩ലᨐ⊒⃻ᯏᐨ䈱⋧㆑䈮䈧䈇䈩⹦⚦䈮ᬌ⸛䈚䈢䇯䇼⚿ᨐ䈍䉋䈶⠨ኤ䇽ฃኈ૕⚿วታ㛎䈱⚿ᨐ䈎䉌䇮䉥䉨䉲䉮䊄䊮䈲ਥ䈮 µ-opioid ฃኈ૕䈮⚿ว䈜䉎䈖䈫䉕␜䈚䈢䇯␹⚻㓚ኂᕈ−∩䊝䊂䊦䊙䉡䉴䉕↪䈇䈩䉥䉨䉲䉮䊄䊮䇮䊝䊦䊍䊈䈍䉋䈶 M-6-G 䈱⊹ਅ䈍䉋䈶㜑⣧ౝᛩਈ䈮䉋䉎㎾∩ലᨐ䈮䈧䈇䈩ᬌ⸛䈚䈢䈫䈖䉐䇮⊹ਅᛩਈ䈮䉋䉎䉥䉨䉲䉮䊄䊮䈱㎾∩
ലᨐ䈱ᷫᒙ䈲⹺䉄䉌䉏䈭䈎䈦䈢䈏䇮䊝䊦䊍䊈䈍䉋䈶 M-6-G 䈱㎾∩ലᨐ䈲᦭ᗧ䈮ᷫᒙ䈚䈢䇯䉁䈢䇮㜑⣧ౝᛩਈ䈮䉋䉎䉥䉨䉲䉮䊄䊮䈍䉋䈶䊝䊦䊍䊈䈱㎾∩ലᨐ䈲⦟ᅢ䈮⊒⃻䈚䈢䈏䇮M-6-G 䈱ലᨐ䈲᦭ᗧ䈮ᷫᒙ䈚䈢䇯䈘䉌䈮䈲䇮[35S]GTPγS ⚿วታ㛎䈮䉋䉍䇮ထ㛽␹⚻⚿⚤䊙䉡䉴⣄㜑䈮䈍䈔䉎䉥䉨䉲䉮䊄䊮䈍䉋䈶䊝䊦䊍䊈䈱 G 䉺䊮䊌䉪⾰ᵴᕈൻ૞↪䈲㕖⚿⚤⟲䈫Ყセ䈚ᄌൻ䈏⹺䉄䉌䉏䈭䈎䈦䈢䉅䈱䈱䇮M-6-G 䈱૞↪䈲㕖⚿⚤⟲䈫Ყセ䈚᦭ᗧ䈮ૐਅ䈚䈢䇯䈖䉏䉌䈱䈖䈫䈎䉌䇮␹⚻㓚ኂᕈ−∩䈮ኻ䈚䈩䉥䉨䉲䉮䊄䊮䈲⪺ല䈜䉎䈖䈫䈏᣿䉌䈎䈫䈭䈦䈢䇯䉁䈢䇮␹⚻㓚ኂᕈ−∩ਅ䈪䊝䊦䊍䊈䉕㜑⣧ౝᛩਈ䈚䈢㓙䈮䈲ᒝᐲ䈱㎾∩ലᨐ䈏ᓧ䉌䉏䈢䈖䈫䈎䉌䇮䊝䊦䊍䊈䉅ᧃ᪳ᛩਈ䈪䈲䈭䈒䇮䈒䉅⤑ਅᛩਈ䈮ᄌᦝ䈚䈢႐ว䈮䈲⦟ᅢ䈭㎾∩ലᨐ䈏ᓧ䉌䉏䉎น⢻ᕈ䈏⠨䈋䉌䉏䉎䇯

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SI-2
␹⚻࿃ᕈ−∩䈮ኻ䈜䉎(+)-pentazocine ᧃ᪳ᛩਈ䈱ലᨐᨋ㩷 㓳テ䇮ᄢỈ㩷 ආᒄ䇮๺↰㩷 ᤯䇮ች↰㩷 ⨃㓶䇮੉੗㩷 ᷕਃᤊ⮎⑼ᄢቇ㩷 ⮎‛ᴦ≮ቇᢎቶ
Effect of peripherally administered (+)-pentazocine on partial sciatic nerve injury-induced
mechanical allodynia in miceShun-suke Hayashi, Masahiro Ohsawa, Susumu Wada, Shigeo Miyata, Junzo Kamei
Department of Pathophysiology and Therapeutics, Hoshi University␹⚻㓚ኂ䈮䉋䉎−∩䈲᭽䇱䈭ᯏᐨ䈮䉋䉍⊒⃻䈜䉎䈖䈫䈏⍮䉌䉏䈩䈇䉎䇯․䈮䇮␹⚻㓚ኂ䈮䉋䉍৻㉄ൻ⓸⚛䋨NO䋩วᚑ㉂⚛䋨NOS䋩䈱⊒⃻㊂䈏⣄㜑ᓟᩮ␹⚻▵䈮䈍䈇䈩਄᣹䈜䉎䈖䈫䈏᣿䉌䈎䈮䈘䉏䈩䈍䉍䇮䈖䈱 NOS ⊒⃻㊂䈱਄᣹䈏␹⚻㓚ኂ䈮䉋䉎∩ⷡㆊᢅ䈱⊒⃻䈮৻ㇱ㑐ਈ䈚䈩䈇䉎䈖䈫䈏␜ໂ䈘䉏䈩䈇䉎䇯σ1 ฃኈ૕૞േ⮎䈲 NOS ᵴᕈ䉕ᛥ೙䈜䉎䈖䈫䈏᣿䉌䈎䈮䈘䉏䈩䈇䉎䇯䈠䈖䈪ᧄ⎇ⓥ䈪䈲䇮␹⚻㓚ኂ䈮䉋䉎䉝䊨䊂䉞䊆䉝䈍䉋䈶ᧃ᪳䈪䈱 NO ㊂䈱ᄌൻ䈮ኻ䈜䉎 σ1 ฃኈ૕ೝỗ䈱ᓇ㗀䈮䈧䈇䈩ᬌ⸛䉕ⴕ䈦䈢䇯ထ㛽␹⚻ㇱಽ⚿⚤ 2 ㅳ㑆ᓟ䈱䊙䉡䉴䈮䈍䈇䈩䇮ᯏ᪾ೝỗ䈮ኻ䈜䉎䉝䊨䊂䉞䊆䉝䈍䉋䈶⿷ㇱ䈮䈍䈔䉎 NO ㊂䈱਄᣹䈏⹺䉄䉌䉏䈢䇯䈖䈱␹⚻㓚ኂ䈮䉋䉎䉝䊨䊂䉞䊆䉝䈭䉌䈶䈮NO ㊂䈱਄᣹䈲䇮σ1 ฃኈ૕૞േ⮎䈪䈅䉎(+)-pentazocine䋨PTZ䋩䈱⿷⢛ㇱ䈻䈱ᛩਈ䈮䉋䉍ᛥ೙䈘䉏䈢䇯৻ᣇ䇮PTZ 䈱ಣ⟎䈲䇮௾ᚻⴚ⟲䈱ᯏ᪾ೝỗ䈮ኻ䈜䉎෻ᔕᕈ䈍䉋䈶⿷ㇱ䈱 NO ㊂䈮ኻ䈚䈩᦭ᗧ䈭ᓇ㗀䉕ਈ䈋䈭䈎䈦䈢䇯ထ㛽␹⚻ㇱಽ⚿⚤䊙䉡䉴䈮䈍䈔䉎 PTZ 䈱᛫䉝䊨䊂䉞䊆䉝૞↪䈭䉌䈶䈮⿷ㇱ䈪䈱 NO ↥↢ᛥ೙૞↪䈲䇮ㆬᛯ⊛ σ1 ฃኈ૕ᜟ᛫⮎䈪䈅䉎 BD1047 䈱⿷⢛ㇱ䈻䈱೨ಣ⟎䈮䉋䉍ᛥ೙䈘䉏䈢䈏䇮䉥䊏䉥䉟䊄 κ ฃኈ૕ᜟ᛫⮎䈪䈅䉎 nor-binaltorphimine 䈱⊹ਅ䈻䈱೨ಣ⟎䈪䈲᦭ᗧ䈭ᓇ㗀䈏⹺䉄䉌䉏䈭䈎䈦䈢䇯䈖䉏䉌䈱䈖䈫䈎䉌䇮PTZ 䈱␹⚻㓚ኂ䈮䉋䉎ᯏ᪾ೝỗ䈮ኻ䈜䉎䉝䊨䊂䉞䊆䉝䈱ᡷༀ䈮䇮␹⚻㓚ኂᤨ䈪䈱ᧃ᪳䈮䈍䈔䉎 σ1 ฃኈ૕ೝỗ䉕੺䈚䈢 NO ↥↢ᛥ೙૞↪䈏৻ㇱ㑐ਈ䈚䈩䈇䉎䈖䈫䈏᣿䉌䈎䈮䈭䈦䈢䇯

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SI-3
Jak-STAT ⚻〝䈱ᵴᕈൻ䈲␹⚻࿃ᕈ−∩䉕⺞▵䈜䉎೨↰ᱞᒾ䇮ᧁญ୶৻䇮ᢕ⾐⟤ᕺ䇮ጯጟผ㇢๺᱌ጊ⋵┙ක⑼ᄢቇ⮎ℂቇ
Activated Jak-STAT pathway modulates neuropathic pain

Takehiko Maeda, Norikazu Kiguchi, Mie Tsuruga, Shiroh Kishioka
Department of Pharmacology, Wakayama Medical University䇼⋡⊛䇽␹⚻࿃ᕈ−∩䋨NP䋩䊝䊂䊦䈮䈍䈔䉎 IL-6 ⊒⃻Ⴧട䈏䊕䊦䉥䉨䉲䉸䊷䊛Ⴧᱺ࿃ሶᵴᕈൻฃ
ኈ૕ γ䋨PPARγ䋩ೝỗ⮎䊏䉥䉫䊥䉺䉹䊮ᛩਈ䈮䉋䉍ᷫᒙ䈜䉎䈖䈫䉕᣿䉌䈎䈮䈚䈩䈐䈢䇯䈚䈎䈚䇮䈠䈱⚦⢩ౝ䉲䉫䊅䊦⚻〝䈱ᵴᕈ䈫−∩ᒻᚑ䈫䈱㑐ଥ䈮䈧䈇䈩䈲␜䈘䉏䈩䈇䈭䈇䇯ᧄ⎇ⓥ䈪䈲䇮Ძ᭽૕␹⚻ᩕ㙃࿃ሶ䊐䉜䊚䊥䊷䈮ዻ䈜䉎 IL-6 䈍䉋䈶䊧䊒䉼䊮䈱 NP 䊝䊂䊦䈮䈍䈔䉎⚦⢩ౝ䉲䉫䊅䊦 Janus
kinase (Jak)-signal transducer and activator of transcription 䋨STAT䋩⚻〝䈱ᵴᕈ䈮䈧䈇䈩ᬌ⸛䈚䈢䇯
䇼ᣇᴺ䇽䊙䉡䉴䋨ICR ♽㓶ᕈ䋩䈱ထ㛽␹⚻䋨SCN䋩䉕ㇱಽ⚿⚤䋨PSL䋩䈜䉎䈖䈫䈮䉋䉍䇮NP 䊝䊂䊦䉕૞⵾
䈚䈢䇯Jak-2 䈍䉋䈶 STAT3 䈱ᵴᕈဳ䈪䈅䉎䊥䊮㉄ൻ૕䋨pJak-2 䈍䉋䈶 pSTAT3䋩䇮IL-6䇮䊧䊒䉼䊮䇮PPARγ 䈭䉌䈶䈮 F4/80䋨䊙䉪䊨䊐䉜䊷䉳䈱䊙䊷䉦䊷䋩䈱⊒⃻䉕 SCN 䈮䈍䈇䈩⹏ଔ䈚䈢䇯ᓟ⢇⿷ᐩ䈮ኻ䈜䉎 von Frey 䊐䉞䊤䊜䊮䊃䈮䉋䉎⸅ೝỗ䈍䉋䈶 Hargreaves ᴺ䈮䉋䉎ᾲೝỗ䈮䉋䉍ᗖ⿠䈘䉏䉎−∩෻ᔕ䉕᷹ቯ䈚䈢䇯AG490䋨Jak-2 㒖ኂ⮎䇮i.p.䋩䇮IL-6 ᛫૕䋨SCN ๟࿐ᛩਈ䋩䇮䊧䊒䉼䊮䋨i.p.䋩䈍䉋䈶䊏䉥䉫䊥䉺䉹䊮䋨PIO䇮p.o.䋩ᛩਈ䈱−∩෻ᔕ䈮෸䈿䈜ᓇ㗀䉕ᬌ⸛䈚䈢䇯䇼⚿ᨐ䈍䉋䈶⠨ኤ䇽PSL 䈮䉋䉎∩ⷡㆊᢅ෻ᔕ䈱ᒻᚑ䈮઻䈇䇮IL-6䇮䊧䊒䉼䊮䇮pJak-2䇮pSTAT3 䈭䉌䈶䈮 PPARγ 䈱⊒⃻㊂䈏Ⴧട䈚䈢䇯PSL ஥ SCN 䈮⷗䉌䉏䉎 F4/80 㓁ᕈ⚦⢩䈲䌰STAT3 䈍䉋䈶PPARγ 䉕⊒⃻䈚䈩䈇䈢䇯IL-6 ᛫૕䇮AG490 䈍䉋䈶 PIO ᛩਈ䈲∩ⷡㆊᢅ෻ᔕ䈭䉌䈶䈮 pSTAT3 ⊒⃻Ⴧട䉕ᷫᒙ䈚䈢䈏䇮ኻᾖ⊛䈮䇮䊧䊒䉼䊮ᛩਈ䈲䈠䉏䉌䉕Ⴧᒝ䈚䈢䇯એ਄䈱⚿ᨐ䈲䇮SCN 䈱 PSL
䈮䉋䉎 Jak-STAT ⚻〝ᵴᕈൻ䈲䇮∩ⷡㆊᢅ෻ᔕ䉕ଦㅴᕈ䈮⺞▵䈜䉎䈖䈫䉕␜ໂ䈜䉎䇯

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SI-4
−∩೙ᓮᯏ᭴䈮㑐䈜䉎⎇ⓥ(╙ 73 ႎ); ␹⚻㓚ኂᕈ−∩ᒻᚑ䈮䈍䈔䉎⣄㜑ౝ IP 䈍䉋䈶 EP ฃኈ૕䈱ᄌൻ䈫␹⚻㓚ኂᕈ−∩䈮ኻ䈜䉎 beraprost sodium 䈱᦭↪ᕈ
㋈ᧁ㓷⟤䇮ᚑ↰ ᐕ䇮㜞ᧁᥓ⛗䇮ᅏᵤᄢ᮸䇮ᱞ↰ᵏሶ䇮ᚑ↰㆏ሶ䇮㋈ᧁ ീᤊ⮎⑼ᄢቇ ⮎ຠᲥᕈቇᢎቶ
Change in spinal prostaglandin receptors in the development of the neuropathic pain-like state inmice

Masami Suzuki, Minoru Narita, Tomoe Takagi, Daiki Okutsu, Yasuko Takeda, Michiko Narita,
Tsutomu Suzuki
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences
Prostaglandin I2 (PGI2) ⺃ዉ૕⵾೷䈪䈅䉎 beraprost sodium (BPS) 䈲䇮ਥ䈮 IP ฃኈ૕䈮⚿ว䈚䇮
EP3 ฃኈ૕䈮䉅ᒙ䈇ⷫ๺ᕈ䉕␜䈜䈖䈫䈏⍮䉌䉏䈩䈍䉍䇮ⴊ▤᜛ᒛ૞↪䈍䉋䈶ⴊዊ᧼ಝ㓸ᛥ೙૞↪䉕᦭䈜䉎䈖䈫䈎䉌䇮⥃ᐥ䈮䈍䈇䈩ᘟᕈേ⣂㐽Ⴇ∝䉇ේ⊒ᕈ⢖㜞ⴊ࿶∝䈮ㆡ↪䈘䉏䈩䈇䉎䇯䉁䈢䇮
ᧃ᪳ᓴⅣᡷༀ૞↪䈮䉋䉍⣶ᬁ∔ᖚ䈍䉋䈶㗪ᬁ∔ᖚ䈭䈬䈱∩䉂䈮ኻ䈚䈩૶↪䈘䉏䈩䈇䉎䈏䇮䈠䈱૞↪ᯏᐨ䈱⹦⚦䈲᣿䉌䈎䈮䈘䉏䈩䈇䈭䈇䇯䈠䈖䈪ᧄ⎇ⓥ䈪䈲䇮BPS 䈱␹⚻㓚ኂᕈ−∩䈮ኻ䈜䉎᦭ലᕈ䉕ᬌ⸛䈚䈢䇯ထ㛽␹⚻⚿⚤䈮䉋䉎ᾲ∩ⷡㆊᢅ෻ᔕ䈲䇮BPS 䉕ᧃ᪳䈅䉎䈇䈲㜑⣧ౝᛩਈ䈜䉎䈖䈫䈮䉋䉍᦭ᗧ䈮ᛥ೙䈘䉏䈢䇯ᰴ䈮䇮ထ㛽␹⚻⚿⚤ᓟ䈱⣄㜑⤑ᮡᧄ䉕↪䈇䈩 EP1-4 ฃኈ૕䈭䉌䈶䈮 IP ฃኈ૕䈱Ⱞ⊕⾰㊂䈱ᄌൻ䉕ᬌ⸛䈚䈢䈫䈖䉐䇮EP2 ฃኈ૕䈮䈍䈇䈩䈱䉂᦭ᗧ䈭Ⴧട䈏⹺䉄䉌䉏䈢䇯䈘䉌䈮 BPS䇮EP2 ฃኈ૕૞േ⮎䈭䉌䈶䈮 EP3 ฃኈ૕૞േ⮎⺃⊒ G Ⱞ⊕⾰ᵴᕈൻ૞↪䈱ᄌൻ䉕ᬌ⸛䈚䈢䈫䈖䉐䇮BPS ⺃⊒ G Ⱞ⊕⾰ᵴᕈൻ૞↪䈱ᷫᒙ䈫䇮EP2 䈍䉋䈶 EP3 ฃኈ૕ᯏ⢻䈱੣ㅴ䈏⹺䉄䉌䉏䈢䇯એ਄䈱⚿ᨐ䈎䉌䇮␹⚻㓚ኂᕈ−∩ਅ䈪䈲⣄㜑䈮䈍䈔䉎 IP ฃኈ૕䈱ᯏ⢻ૐਅ䇮EP2 ฃኈ૕䈍䉋䈶 EP3 ฃኈ૕䈱ᯏ⢻੣ㅴ䈏ᒁ䈐⿠䈖䈘䉏䈩䈇䉎䈖䈫䈏᣿䉌䈎䈫䈭䈦䈢䇯䉁䈢䇮BPS 䈲 IP ฃኈ૕䈱ᯏ⢻䉕ᤚᱜ䈚䇮䈎䈧 EP3 ฃኈ૕䈱ᵴᕈൻ䉕৻ㇱㆤᢿ䈜䉎䈖䈫䈮䉋䉍
EP2 ฃኈ૕䉕੺䈚䈢෻ᔕ䉕↢ℂ⊛䈮ᛥ೙䈜䉎น⢻ᕈ䈏␜ໂ䈘䉏䇮䈖䈉䈚䈢 BPS 䈱૞↪䈏␹⚻㓚ኂᕈ−∩䈱ᡷༀ䈮㑐ਈ䈚䈩䈇䉎䉅䈱䈫⠨䈋䉌䉏䉎䇯

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SI-5
Morphine-3-gluculonide 䈱䊙䉡䉴⣄㜑ౝᛩਈ䈮઻䈉䉝䊨䊂䉞䊆䉝⊒⃻ᯏ᭴䈱⸃ᨆዊ᧻㩷 ↢᣿䋱)䇮ầᐔ㩷 ⧷㇢ 2)䇮ᰞ↰㩷 ᔋ 3)䇮ᰞ↰㩷 ม䋱)1)╙৻⮎⑼ᄢቇ㩷 ⮎ℂቇ(㸇)䇮2)⑔ጟᄢቇ㩷 ⥃ᐥ⮎‛ᴦ≮ቇ䇮3)᧲ർ⮎⑼ᄢቇ㩷 ᯏ⢻ᒻᘒቇ
Mechanim of allodynia in mice evoked by intrathecal morphine-3-gluculonide
Takaaki Komatsu䋱), Hideo Shiohira2), Shinobu Sakurada3), Tsukasa Sakurada䋱)1) First Department of pharmacology, Daiichi College of Pharmaceutical Sciences, 2) Departmentof Clinical Pharmacology, Fukuoka University, 3) Department of Physiology and Anatomy, Tohoku
Pharmaceutical University↢૕ౝ䈪䈱䊝䊦䊍䊈ਥઍ⻢↥‛䈪䈅䉎 Morphine-3-glucuronide (M3G) (3nmol/5µl)䉕䊙䉡䉴⣄㜑䉪䊝⤑ਅ⣧ౝ(i.t.)䈮ᛩਈ䈜䉎䈫䇮䉝䊨䊂䉞䊆䉝䋨5 - 90 ಽ㑆䋩䈏⊒⃻䈜䉎䇯䈠䈖䈪䇮ᧄ⎇ⓥ䈪䈲䇮M3G ⺃⊒ᕈ䉝䊨䊂䉞䊆䉝−∩ᯏ᭴䈱⸃᣿䉕⋡ᜰ䈚䇮⸃ᨆ䉕ⴕ䈦䈢䇯䉁䈝䇮䈲䈛䉄䈮䇮M3G ⺃⊒ᕈ䉝䊨䊂䉞䊆䉝䈮䈍䈔䉎⣄㜑ᓟⷺౝ䈱 ERK 䈱㑐ਈ䉕ᬌ⸛䈚䈢䈫䈖䉐䇮M3G ᛩਈ 5 - 15 ಽᓟ䉁䈪⪺䈚䈇 ERK 䈱䊥䊮㉄ൻ䈏⹺䉄䉌䉏䈢䇯䈠䈖䈪䇮ERK 䊥䊮㉄ൻ䉕㒖ኂ䈜䉎 MEK 㒖ኂ⮎ U0126 䈫䈱૬↪ታ㛎䉕ⴕ䈦䈢䈫䈖䉐䇮䉝䊨䊂䉞䊆䉝䈲ᛩਈ 5 ಽᓟ䈎䉌᦭ᗧ䈭ᛥ೙䈏⹺䉄䉌䉏䈢䇯䈘䉌䈮䇮M3G ⺃⊒ᕈ䉝䊨䊂䉞䊆䉝䈏 NO-cGMP/PKG 䉦䉴䉬䊷䊄䈮ነਈ䈚䈩䈇䉎䈎ุ䈎䉕᣿䉌䈎䈮䈜䉎䈢䉄䈮䇮M3G 䈫㕖┹ว⊛ NOS 㒖ኂ⮎䈪䈅䉎 L-NAME䇮TRIM䇮ㆬᛯ⊛ nNOS䇮iNOS 㒖ኂ⮎䈪䈅䉎 N-Propyl-L-Arginie䇮W1400䇮นṁᕈ䉫䉝䊆䊦㉄䉲䉪䊤䊷䉷㒖ኂ⮎䈪䈅䉎 ODQ䇮PKG 㒖ኂ⮎䈪䈅䉎 KT-5823 䈫䈱૬↪ታ㛎䉕ⴕ䈦䈢䈫䈖䉐䇮M3G ⺃⊒ᕈ䉝䊨䊂䉞䊆䉝䈭䉌䈶䈮 5 ಽᓟ䈱⣄㜑ᓟⷺౝ ERK 䈱䊥䊮㉄ൻ䈲䇮䈇䈝䉏䈱૬↪⮎‛䈮䈍䈇䈩䉅᦭ᗧ䈮ᛥ೙䈘䉏䈢䇯䈚䈢䈏䈦䈩䇮M3G i.t.
ᛩਈ䈮઻䈉䉝䊨䊂䉞䊆䉝ೋᦼ䈱⺃⊒ᯏ᭴䈮䈲䇮NO-cGMP/PKG 䉦䉴䉬䊷䊄䈮䉋䈦䈩ᒁ䈐⿠䈖䈘䉏䉎
ERK 䈱䊥䊮㉄ൻ䈏㊀ⷐ䈪䈅䉎䈫⠨䈋䉌䉏䈢䇯 

SII-1
ᣂⷙ dermorphin N ᧃ┵䊁䊃䊤䊕䊒䉼䊄⺃ዉ૕䈪䈅䉎 amidino-TAPA 䈱਄૏ਛᨔ䈮䈍䈔䉎᛫ଚኂ૞↪䈫േᯏઃ䈔ലᨐศጟ㤗਽䇮Ḵญᐢ৻䇮ᷰㄝජኼሶ䇮☨Ỉ┨ᒾ䇮ᰞ↰ᔋ᧲ർ⮎⑼ᄢቇ㩷 ᯏ⢻ᒻᘒቇᢎቶSupraspinal antinociception and motivational effect induced by the novel dermorphin tetrapeptide
analog amidino-TAPA

Yoshioka M, Mizoguchi H, Watanabe C, Yonezawa A, Sakurada S
Department of Physiology and Anatomy, Tohoku Pharmaceutical Universityᚒ䇱䈲ㄭᐕ䇮µ ฃኈ૕䈮ㆬᛯᕈ䈏㜞䈒䇮ᧃ᪳ᛩਈ䈮䈍䈇䈩䉅ᒝജ䈭᛫ଚኂ૞↪䉕⊒⃻䈜䉎ᣂ
ⷙ dermorphin N ᧃ┵䊁䊃䊤䊕䊒䉼䊄⺃ዉ૕䈪䈅䉎 amidino-TAPA 䉕㐿⊒䈚䈢䇯ᧄ⎇ⓥ䈪䈲䇮
amidino-TAPA 䈱਄૏ਛᨔ䈮䈍䈔䉎᛫ଚኂ૞↪䉕⸃ᨆ䈜䉎䈫䈫䉅䈮䈠䈱♖␹ଐሽᕈ䈮䈧䈇䈩ᬌ⸛䈚䈢䇯ታ㛎䈮䈲 ddY ♽㓶ᕈ䊙䉡䉴䈭䉌䈶䈮 prodynorphin ᰳ៊㓶ᕈ䊙䉡䉴䉕↪䈇䇮᛫ଚኂ૞↪䈱⹏ଔ䈮 tail-flick ᴺ䇮♖␹ଐሽᕈ䈱⹏ଔ䈮᧦ઙઃ䈔႐ᚲ༵ᅢᕈ⹜㛎䉕↪䈇䈢䇯Amidino-TAPA 䈱⣖ቶౝᛩਈ䈮䉋䉍⺃⊒䈘䉏䉎᛫ଚኂ૞↪䈲䇮µ ฃኈ૕ᜟ᛫⮎䈪䈅䉎 CTOP䇮κ ฃኈ૕ᜟ᛫⮎䈪䈅䉎
nor-binaltorphimine 䈮䉋䉍᦭ᗧ䈮ᛥ೙䈘䉏䈢䈏䇮δ ฃኈ૕ᜟ᛫⮎䈪䈅䉎 naltrindole 䈮䉋䉎ᓇ㗀䈲䉂䉌䉏䈭䈎䈦䈢䇯䉁䈢䇮ౝ࿃ᕈ κ 䉥䊏䉥䉟䊄䊕䊒䉼䊄䈪䈅䉎 dynorphinA䇮dynorphinB 䈱ฦ᛫૕䈮䉋䉍䈠䈱᛫ଚኂ૞↪䈲᦭ᗧ䈮ᛥ೙䈘䉏䈢䈏䇮ౝ࿃ᕈ κ 䉥䊏䉥䉟䊄䊕䊒䉼䊄䈪䈅䉎 α-neo-endorphin䇮ౝ࿃ᕈ δ 䉥䊏䉥䉟䊄䊕䊒䉼䊄䈪䈅䉎[Leu5]enkephalin䇮[Met5]enkephalin 䈱ฦ᛫૕䈮䉋䉎ᓇ㗀䈲䉂䉌䉏䈭䈎䈦䈢䇯৻ᣇ䇮⊹ਅᛩਈ䈮䈍䈇䈩⚂ 80䋦䈱᛫ଚኂ૞↪䉕␜䈜↪㊂䈱 amidino-TAPA 䈲䇮ddY 䊙䉡䉴䈪䈲ႎ㈽ലᨐ䉕⊒⃻䈚䈭䈎䈦䈢䈏䇮prodynorphin ᰳ៊䊙䉡䉴䈮䈍䈇䈩᦭ᗧ䈭ႎ㈽ലᨐ䉕⊒⃻䈚䈢䇯એ਄䈱⚿ᨐ䉋䉍䇮amidino-TAPA 䈲⣖ౝ䈱 µ ฃኈ૕䉕੺䈚䈩 dynorphinA䇮dynorphinB 䉕ㆆ㔌䈚䈩䈍䉍䇮䈖䈱ㆆ㔌䈏 amidino-TAPA 䈱᛫ଚኂ૞↪䈱⊒⃻䉇ႎ㈽ലᨐ䈱ᰳᅤ䈮ነਈ䈚䈩䈇䉎䈖䈫䈏᣿䉌䈎䈮䈭䈦䈢䇯 

SII-2㔚᳇䈔䈇䉏䉖≮ᴺ䈲᳞ᔃ〝ㆤᢿᕈ−∩䈫䊝䊦䊍䊈⠴ᕈ䉕シᷫ䈜䉎࿯੗᳗ผ 1)7)䇮☨⦟ੳᔒ 2)䇮↢ᣇ␭੺ 2)䇮⺪⸰ᶈ 3)䇮㞯ፉ㆐ᄦ 4)䇮ਛ᧛ḩ 4)䇮৻ἑ㇌ᒄ 4)䇮
⥓੗ජᕺ 5)䇮ጤ↰ஜ 6)7)䇮ᳰ↰๺㓉 7)1)⨙ၔ⋵┙෹ㇱ∛㒮䇮2)᧲੩ㇺ଻ஜක≮౏␠⨶ේ∛㒮㤗㈮⑼䇮3)ห♖␹⑼䇮4)ㇺ┙⼾ፉ∛㒮␹⚻⑼䇮5)㗅ᄤၴᄢቇකቇㇱ䇮6)ㇺ┙ᐢየ∛㒮␹⚻⑼䇮7)᧲੩ㇺ♖␹කቇ✚ว⎇ⓥᚲ

Electroconvulsive therapy reduces deafferentation pain and morphine tolerance

Nagafumi Doi1)7), Hitoshi Mera2), Yusuke Ubukata2), Hiroshi Suwa3), Tatsuo Sameshima4), Mitsuru
Nakamura4), Kunihiro Isse4), Chie Usui5), Ken Iwata6)7), Kazutaka Ikeda7)1) Ibaraki Prefectural Tomobe Hospital 2) Dept. of Anesthesiology, Tokyo Metropolitan Ebara
Hospital 3) Dept. of Psychiatry, Tokyo Metropolitan Ebara Hospital 4) Dept. of Psychiatry, Tokyo
Metropolitan Toshima Hospital 5) Faculty of Medicine, Juntendo University 6) Dept. of Psychiatry,Tokyo Metropolitan Hiroo Hospital 7) Tokyo Institute of Psychiatryⷞᐥ∩䇮Ꮺ⁁∊∐ᓟ␹⚻∩䈭䈬䈱᳞ᔃ〝ㆤᢿᕈ−∩䈲䇮ㅢᏱ㊂䈱 morphine 䈮෻ᔕ䈚䈭䈇䇯䈖䉏䉌䈱㔍ᴦᕈ−∩䈮ኻ䈚䈩䇮㔚᳇∨ᡨ≮ᴺ(ECT)䈲ఝ䉏䈢㎾∩ലᨐ䉕ᜬ䈧䈖䈫䈏䇮ᦨㄭ䈱Ṷ⠪䉌䈱⎇ⓥ䈪᣿䉌䈎䈫䈭䈦䈢䇯䈖䈱䈫䈐ኻ஥ⷞᐥ䈱ᓴⅣઍ⻢䈲∩䉂䈱ᶖᄬ䋯ౣΆ䈫䈫䉅䈮ᡷༀ䋯ૐਅ䈜䉎䇯৻ᣇ䇮ECT 䈲 µ agonist 䈱㎾∩ലᨐ䉕Ⴧᒝ䈜䉎䇯એ਄䈱⥃ᐥ⍮⷗䉕ឭ␜䈚䇮䇸᳞ᔃ〝ㆤᢿᕈ−∩䈪䈲ኻ஥ⷞᐥ䈱 opioid ♽䇮䈫䈒䈮 µ ฃኈ૕ኒᐲ䈮ᄌൻ䈏↢䈛䈩䈍䉍䇮ECT 䈲䈖䉏䉕࿁ᓳ䈜䉎䈖䈫
䈪㎾∩ലᨐ䉕⊒ើ䈜䉎䇹䈫䈇䈉૞ᬺ઒⺑䉕ឭ໒䈜䉎䇯 

SII-3㔚᳇∨ᡨ≮ᴺ䈱䊝䊦䊍䊈⠴ᕈ䈮ਈ䈋䉎ᓇ㗀ጤ↰㩷 ஜ 1)2)䇮ጊᧄ⑲ሶ 1)䇮㜞᧻ᐘ㓶 1)䇮࿯੗᳗ผ 1)3)䇮ᳰ↰๺㓉 1)1)᧲੩ㇺකቇ⎇ⓥᯏ᭴᧲੩ㇺ♖␹කቇ✚ว⎇ⓥᚲ䇮2)ㇺ┙ᐢየ∛㒮␹⚻⑼䇮3)⨙ၔ⋵┙෹ㇱ∛㒮The effect of electroconversion therapy on morphine-tolerance
Ken Iwata1)2), Hideko Yamamoto1), Yukio Takamatsu1), Nagafumi Doi1)3), Kazutaka Ikeda1)
1) Tokyo Institute of Psychiatry 2) Department of Neuro-psychiatry, Tokyo Metropolitan Hiroo
General Hospital 3) Ibaragi prefectural Tomobe hospital㩷 ECT䋨㔚᳇∨ᡨ≮ᴺ䋩䈲․䈮㊀∝䈱䈉䈧∛䈮ኻ䈚䈩ᐢ䈒૶䉒䉏䈩䈇䉎ᴦ≮ᴺ䈪⮎‛≮ᴺ䈫Ყ䈼䈩䉅቟ోᕈ䈏㜞䈇䈫䈘䉏䈩䈇䉎䇯ᦨㄭ䇮䈖䈱 ECT 䈏⥃ᐥ⊛䈮␹⚻࿃ᕈ−∩䈮ኻ䈚䈩㎾∩ലᨐ䈏䈅䉎䈫ႎ๔䈘䉏䈩䈇䉎䇯䈚䈎䈚䇮䈖䈱ᴦ≮ലᨐ⊒⃻ᯏᐨ䈮㑐䈜䉎⎇ⓥ⊒⴫䈲䈾䈫䉖䈬䈭䈇䇯㩷 ␹⚻࿃ᕈ−∩䈱ᚑ┙ᯏᐨ䈲᣿䉌䈎䈪䈲䈭䈇䈏䇮䊝䊦䊍䊈䈱ᘟᕈᛩਈ䈏∩䉂䈱ᗵฃᕈ䉕਄䈕䉎䈫䈇䈉ႎ๔䉇䇮␹⚻࿃ᕈ−∩䈱∛ᘒᯏ᭴䈮䈲䊝䊦䊍䊈䈮ኻ䈜䉎⠴ᕈ䈏㑐ਈ䈚䈩䈇䉎䈫䈜䉎✚⺑⺰ᢥ䈏䈅䉎䇯ᚒ䇱䈲䇮ECT 䈱㎾∩ലᨐ䈲䇮ECT 䈏䊝䊦䊍䊈⠴ᕈ䉕㒖ኂ䈚䈩䈍䈐䉎䈫䈇䈉઒⺑䉕┙䈩䇮
ECT 䈱䊝䊦䊍䊈⠴ᕈ䈮ኻ䈜䉎ലᨐ䉕䇮䊙䉡䉴䉕૶䈦䈩⺞䈼䈢䇯㩷 䊝䊦䊍䊈䋨10 mg/kg䋩䉕⊹ਅᛩਈ䈚䊖䉾䊃䊒䊧䊷䊃⹜㛎䈮䉋䈦䈩䋦MPE 䉕䉅䈫䉄䇮24 ᤨ㑆ᓟ䈮ౣ䈶䊝䊦䊍䊈䉕ᛩਈ䈚䈩䋦MPE 䉕䉅䈫䉄䈩Ყセ䈚䈢䇯㔚᳇ೝỗ䈲䊙䉡䉴䈱ਔ⡊䈮㔚ᭂ䉕䈧䈔䈩ਈ䈋䈢䇯㔚᳇ೝỗ䉕ਈ䈋䈭䈇႐ว䈲䇮⠴ᕈ䈏ⷰኤ䈘䉏䈢䇯㔚᳇ೝỗ䈱䉺䉟䊚䊮䉫䈏䇮ೋ࿁䊝䊦䊍䊈ᛩਈ䈱䇮
6 ᤨ㑆೨䇮1 ᤨ㑆೨䇮1 ᤨ㑆ᓟ䇮3 ᤨ㑆ᓟ䈱⟲䈪䈲䇮⠴ᕈ䈏ⷰኤ䈘䉏䈭䈎䈦䈢䈏䇮18 ᤨ㑆ᓟ䇮23 ᤨ㑆ᓟ䈪䈲䇮⠴ᕈ䈏ⷰኤ䈘䉏䈢䇯䉁䈢䇮3 ᣣ㑆䊝䊦䊍䊈䉕ㅪ⛯ᛩਈ䈚䇮24 ᤨ㑆ᓟ䈮 ECT 䉕ⴕ䈇䇮䈘䉌
䈮 24 ᤨ㑆ᓟ䈮䊝䊦䊍䊈䉕ᛩਈ䈚䈢䈫䈖䉐䇮⠴ᕈ䈏ⷰኤ䈘䉏䈢䇯㩷 䈖䉏䉌䈱⚿ᨐ䈎䉌䇮ECT 䈲䊝䊦䊍䊈⠴ᕈᒻᚑ䉕㒖ኂ䈜䉎䈖䈫䇮䈍䉋䈶䈖䈱 ECT 䈱ലᨐ䈮䈲ಣ⟎ᤨ㑆䈱䉺䉟䊚䊮䉫䈏㊀ⷐ䈪䈅䉎䈖䈫䈏⠨䈋䉌䉏䈢䇯 

SII-4䊝䊦䊍䊈䈱㎾∩⠴ᕈᒻᚑᯏ᭴䈮䈍䈔䉎 NCAM-FGFR 㑆⋧੕૞↪䈱ᓎഀựㆻ๺᱌ሶ䇮ጊᩮ⵨ਯ䇮ᓼጊዏ๋␹ᚭቇ㒮ᄢቇ⮎ቇㇱ⥃ᐥ⮎ቇ⎇ⓥቶ
The effect of repeated morphine administration on the interaction between NCAM and FGFR

Wakako Hamabe, Hiroyuki Yamane, Shogo Tokuyama
Department of Clinical Pharmacy, Kobe Gakuin University Faculty of Pharmaceutical Sciences㩷 ᚒ䇱䈲䈖䉏䉁䈪䈮䇮䊝䊦䊍䊈䈱෻ᓳᛩਈ䈮䉋䉎㎾∩⠴ᕈᒻᚑ䈮䇮␹⚻⚦⢩ធ⌕ಽሶ (NCAM)
䈏㊀ⷐ䈭ᓎഀ䉕ᜂ䈉䈖䈫䉕ឭ໒䈚䈩䈐䈢䇯ᦨㄭ NCAM 䈲䇮❫⛽⧘⚦⢩Ⴧᱺ࿃ሶฃኈ૕ (FGFR) 䈫⇣⒳ⷫ๺ᕈ䈮⋧੕૞↪䈚䇮⸥ᙘᒻᚑ䈭䈬䈱␹⚻䈱น႟⊛ᄌൻ䉕ᒁ䈐⿠䈖䈜䈖䈫䈏ႎ๔䈘䉏䈩䈇䉎䇯⥝๧ᷓ䈇䈖䈫䈮䇮ᚒ䇱䈲એ೨䇮FGFR 䈱㒖ኂ⮎䈲䊝䊦䊍䊈㎾∩⠴ᕈᒻᚑ䉕ᛥ೙䈜䉎䈖䈫䉕᣿䉌䈎䈮䈚䈢䇯䈖䈱䈖䈫䈲䇮NCAM 䈫 FGFR 䈱⋧੕૞↪䈏䊝䊦䊍䊈㎾∩⠴ᕈᒻᚑᯏ᭴䈮䉅㑐ਈ䈜䉎น⢻ᕈ䉕␜ໂ䈚䈩䈇䉎䇯䈠䈖䈪ᧄ⎇ⓥ䈪䈲䇮NCAM 䈫 FGFR 䈱 in vivo 䈮䈍䈔䉎ⶄว૕ᒻᚑ䈫䇮䈠䉏䈮෸䈿䈜䊝䊦䊍䊈෻ᓳᛩਈ䈱ᓇ㗀䈮䈧䈇䈩ᬌ⸛䈚䈢䇯㩷 ታ㛎䈮䈲 4 ㅳ㦂䈱 ddY ♽㓶ᕈ䊙䉡䉴䉕↪䈇䇮䊝䊦䊍䊈 (10 mg/kg, s.c.) 䉕 1 ᣣ 1 ࿁ 5 ᣣ㑆෻ᓳᛩਈ䈚䈢䇯ᦨ⚳ᛩਈ 24 ᤨ㑆ᓟ䈮䈍䈇䈩䇮ਛ⣖⚵❱᛽಴ᶧ䉕⺞ᢛ䈚䇮఺∉ᴉ㒠ᴺ䈮䉋䉍
NCAM-FGFR ⶄว૕䉕ᬌ಴䈚䈢䇯৻ᣇ䇮䊝䊦䊍䊈䈱㎾∩ലᨐ䈲䇮tail-flick ᴺ䉕↪䈇䈩ⴕേቇ⊛䈮⸃ᨆ䈚䈢䇯㩷 䈠䈱⚿ᨐ䇮䊝䊦䊍䊈䈱෻ᓳᛩਈ䈮䉋䉍㎾∩ലᨐ䈲᦭ᗧ䈮ᷫᒙ䈚䇮㎾∩⠴ᕈᒻᚑ䈏⹺䉄䉌䉏䈢䇯䈘䉌䈮䇮䈖䈱䈫䈐 NCAM 䈫 FGFR 䈱ⶄว૕ᒻᚑ䈲ᛥ೙䈘䉏䈩䈇䈢䇯䈖䉏䉌䈱⍮⷗䈎䉌䇮䊝䊦䊍䊈䈱෻ᓳᛩਈ䈲 NCAM 䈫 FGFR 䈱⋧੕૞↪䈮ᓇ㗀䉕෸䈿䈚䇮㎾∩⠴ᕈᒻᚑ䉕⺃ዉ䈜䉎น⢻ᕈ䈏␜ໂ䈘
䉏䈢䇯

 

SII-5µ 䉥䊏䉥䉟䊄ฃኈ૕ㆮવሶᰳ៊䊙䉡䉴䉕↪䈇䈢㤗⮎ᜟ᛫ᕈ㎾∩⮎䈱᛫ଚኂฃኈ૞↪䈱⹏ଔ੗ᚻ㩷 ⡡৻㇢ 1)2)䇮ධ㩷 㓷ᢥ 3)䇮⍹ේ㩷 ᾢኼ 1)䇮George R Uhl4)䇮૒⮮㩷 ౏㆏ 5)䇮ᦥ⦟㩷 ৻㇢ 6)䇮ᳰ↰㩷๺㓉 2)1)ᐢፉ࿖㓙ᄢቇ⮎ቇㇱ䊶␹⚻⮎ℂቇᢎቶ䇮2)᧲੩ㇺ♖␹කቇ✚ว⎇ⓥᚲ䊶♖␹↢‛ቇ⎇ⓥಽ㊁䇮3)ർᶏ㆏ᄢቇᄢቇ㒮⮎ቇ⎇ⓥ⑼䊶⮎ℂቇಽ㊁ 4) MNB䊶NIDA/IRP䇮5)቟↰ᅚሶᄢቇ⮎ቇㇱ䇮6)᧲ർᄢቇකቇ⎇ⓥ⑼䊶♖␹␹⚻↢‛ቇಽ㊁
Analyses of antinociceptive effects of mu-opioid receptor partial agonists in mu-opioid receptor
knockout mice
Soichiro Ide1)2), Masabumi Minami3), Kumatoshi Ishihara1), George R Uhl4), Masamichi Satoh5),
Ichiro Sora6), Kazutaka Ikeda2)
1) Laboratory of Neuropharmacology, Faculty of Pharmaceutical Sciences, Hiroshima International
University 2) Division of Psychobiology, Tokyo Institute of Psychiatry 3) Department ofPharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University 4) Molecular
Neurobiology, National Institute on Drug Abuse 5) Department of Pharmacy, Yasuda Women’s
University 6) Division of Psychobiology, Department of Neuroscience, Tohoku University Graduate
School of Medicine⃻࿷ᧄ㇌䈮䈍䈇䈩䇮ⶄᢙ䈱㤗⮎ᜟ᛫ᕈ㎾∩⮎䈏−∩✭๺䉕⋡⊛䈫䈚䈩⥃ᐥ૶↪䈘䉏䈩䈇䉎䈏䇮䉥䊏䉥䉟䊄ฃኈ૕䈱ฦ䉰䊑䉺䉟䊒ㆮવሶ䈏หቯ䈘䉏䉎એ೨䈎䉌૶↪䈘䉏䈩䈇䉎⮎䉅ᄙ䈒䇮䈠䈱ಽሶᯏ᭴䈮䈲䇮ᧂ䈣ਇ᣿⍎䈭ὐ䈏ᄙ䈒ᱷ䈘䉏䈩䈇䉎䇯ᧄ⎇ⓥ䈪䈲䇮4 ⒳䈱㤗⮎ᜟ᛫ᕈ㎾∩⮎䇮䊃䊤䊙䊄䊷䊦䇮䊑䊃䊦䊐䉜䊉䊷䊦䇮䊑䊒䊧䊉䊦䊐䉞䊮䇮䊕䊮䉺䉹䉲䊮䇮䈮㑐䈚䈩䇮න৻ฃኈ૕䉰䊑䉺䉟䊒䉕ᒝ೙⊒⃻䈘䈞䈢ၭ㙃⚦⢩䉕↪䈇䈢ฃኈ૕૞↪䈱⸃ᨆ䇮ਗ䈶䈮 µ 䉥䊏䉥䉟䊄ฃኈ૕ㆮવሶᰳ៊
䋨MOR-KO䋩䊙䉡䉴䉕↪䈇䈢᛫ଚኂฃኈ૞↪䈱⸃ᨆ䉕ⴕ䈦䈢䇯䊑䊃䊦䊐䉜䊉䊷䊦䇮䊑䊒䊧䊉䊦䊐䉞䊮䇮䊕䊮䉺䉹䉲䊮䈲䇮δ ෸䈶 κ 䉥䊏䉥䉟䊄ฃኈ૕䈮ኻ䈜䉎૞↪․ᕈ䈮⧯ᐓ䈱Ꮕ⇣䈏⹺䉄䉌䉏䈢䈏䇮µ 䉥䊏䉥䉟䊄ฃኈ૕䈮ኻ䈜䉎ㇱಽ૞േ⮎䈪䈅䈦䈢䇯ฦ⮎‛䈱㎾∩૞↪䉕ᬌ⸛䈚䈢䈫䈖䉐䇮䊃䊤䊙䊄䊷䊦䉕㒰䈒 3 ⒳䈱⮎‛䈪䇮䊖䊝 MOR-KO 䊙䉡䉴䈮䈍䈔䉎᦭ᗧ䈭᛫ᾲ⊛ਗ䈶䈮᛫ᯏ᪾⊛ଚኂฃኈ૞↪
䈲⏕⹺䈘䉏䈭䈎䈦䈢䇯৻ᣇ䇮᛫ൻቇ⊛ଚኂฃኈ૞↪䈲䇮µ 䉥䊏䉥䉟䊄ฃኈ૕䈱ㆮવሶଐሽ⊛䈮ᷫᒙ䈏⷗䉌䉏䈢䈏䇮䊖䊝 MOR-KO 䊙䉡䉴䈮䈍䈇䈩䉅᦭ᗧ䈭㎾∩ലᨐ䈏⏕⹺䈘䉏䇮䈠䈱૞↪䈲 κ 䉥䊏䉥䉟䊄ฃኈ૕ᜟ᛫⮎䈱೨ಣ⟎䈮䉋䉍ᶖᄬ䈚䈢䇯䈖䉏䉌䈱⚿ᨐ䈲䇮㤗⮎ᜟ᛫ᕈ㎾∩⮎䈮䈍䈇䈩䉅䇮䈠
䈱㎾∩૞↪䈮䈲 µ 䉥䊏䉥䉟䊄ฃኈ૕䈏ਥ䈢䉎ᓎഀ䉕ᨐ䈢䈚䈩䈍䉍䇮᛫ൻቇ⊛ଚኂฃኈ૞↪䈮䈲 κ䉥䊏䉥䉟䊄ฃኈ૕䉅㑐ਈ䈚䈩䈇䉎䈖䈫䉕␜ໂ䈚䈩䈇䉎䇯 

SIII-1−∩㑐ㅪਇᔟᖱേ෻ᔕ䈮䈍䈔䉎⣻஥ಽ⇇᧦ᐥᩭౝ protein kinase A 䈱ᓎഀ಴ጊ⻀ม 1)2)䇮 ጊ⾆ඳ 1)䇮ਛᎹ⾆ਯ 2)䇮㊄ሶ๟ม 2)䇮ጊญᜏ 3)䇮ศጟలᒄ 3)䇮ධ㓷ᢥ 1)1)ർᶏ㆏ᄢ㒮䊶⮎䊶⮎ℂ䇮2)੩ㇺᄢ㒮䊶⮎䊶↢૕ᯏ⢻⸃ᨆ䇮3)ർᶏ㆏ᄢ㒮䊶ක䊶␹⚻⮎ℂ

Role of protein kinase A within the ventral bed nucleus of the stria terminalis in pain-related
aversion in rats
Satoshi Deyama1)2), Takahiro Katayama1), Takayuki Nakagawa2), Shuji Kaneko2), Taku Yamaguchi3),
Mitsuhiro Yoshioka3), Masabumi Minami1)
 Dept. Pharmacol., Grad. Sch. Pharm. Sci., Hokkaido Univ. 2) Dept. Mol. Pharmacol., Grad. Sch.
Pharm. Sci., Kyoto Univ. 3) Dept. Neuropharmacol., Grad. Sch. Med., Hokkaido Univ.
䇸∩䉂䇹䈲ᗵⷡ⊛ᚑಽ䈫ᖱേ⊛ᚑಽ䉋䉍䈭䉎䈏䇮ᖱേ⊛ᚑಽ䉕ᜂ䈉‛⾰⊛ၮ⋚䈮㑐䈜䉎⎇ⓥ䈲ᧂ䈣✜䈮䈧䈇䈢䈳䈎䉍䈪䈅䉎䇯ᚒ䇱䈲䈖䉏䉁䈪䈮⣻஥ಽ⇇᧦ᐥᩭ䋨vBST䋩䈮䈍䈔䉎 β 䉝䊄䊧䊅䊥䊮ฃኈ૕䉕੺䈚䈢 NA ␹⚻ᖱႎવ㆐੣ㅴ䈏䇮∩䉂䈮䉋䉎ਇᔟᖱേ↢ᚑ䈮㊀ⷐ䈪䈅䉎䈖䈫䉕␜ໂ䈜䉎⚿ᨐ䉕ᓧ䈩䈇䉎䇯䈠䈖䈪ᧄ⎇ⓥ䈪䈲䇮β ฃኈ૕䉕੺䈚䈢⚦⢩ౝᖱႎવ㆐䈱ਅᵹ䈮૏⟎䈜䉎 protein
kinase A䋨PKA䋩䈱−∩㑐ㅪਇᔟᖱേ↢ᚑ䈻䈱㑐ਈ䈮䈧䈇䈩ᬌ⸛䈚䈢䇯ታ㛎䈮䈲㓶ᕈ SD ♽䊤䉾䊃䉕↪䈇䇮᧦ઙઃ䈔႐ᚲህᖡᕈ䋨CPA䋩⹜㛎䈮䉋䉍ਇᔟᖱേ䈱⹏ଔ䉕ⴕ䈦䈢䇯β ฃኈ૕૞േ⮎isoproterenol 䈱 vBST ౝᛩਈ䈮䉋䉎᧦ઙઃ䈔䉕ⴕ䈦䈢⚿ᨐ䇮↪㊂ଐሽ⊛䈮 CPA 䈏ᗖ⿠䈘䉏䈢䇯䉁䈢䇮䈖䈱 CPA 䈲 PKA 㒖ኂ⮎ Rp-cAMPS 䈱 vBST ౝหᤨᛩਈ䈮䉋䉍ᶖᄬ䈚䈢䇯ᰴ䈮䇮䊖䊦䊙䊥䊮ᓟ⢇⿷ᐩౝᛩਈ䈮䉋䉍ᗖ⿠䈘䉏䉎 CPA 䈍䉋䈶ଚኂฃኈⴕേ䈮ኻ䈜䉎 vBST ౝ Rp-cAMPS ᛩਈ䈱ലᨐ䈮䈧䈇䈩ᬌ⸛䈚䈢䇯䈠䈱⚿ᨐ䇮䊖䊦䊙䊥䊮ᛩਈ 10 ಽ೨䈮 vBST ౝ䈮 Rp-cAMPS 䉕ᛩਈ䈜䉎䈖䈫䈮䉋䉍䇮䊖䊦䊙䊥䊮⺃⊒ CPA 䈲↪㊂ଐሽ⊛䈮ᷫᒙ䈘䉏䈢䈏䇮䊖䊦䊙䊥䊮ᛩਈ䈮䉋䉎ଚኂฃኈⴕേ䈲ᓇ㗀䉕ฃ䈔䈭䈎䈦䈢䇯એ਄䈱⚿ᨐ䈎䉌䇮ଚኂೝỗ䈮䉋䉎 vBST ౝ PKA ᵴᕈൻ䈏∩䉂䈮䉋䉎ਇᔟᖱേ↢ᚑ䈮㊀ⷐ䈭ᓎഀ䉕ᜂ䈦䈩䈇䉎䈖䈫䈏␜ໂ䈘䉏䈢䇯 

SIII-2Morphine 䈲⣄㜑៊்ᕆᕈᦼ䈱ㆇേ㤗∽䉕Ⴧᖡ䈘䈞䉎᧖ጊ↱♿䇮Ꮉ⌀↰᮸ੱ䇮᧖㊁❥৻䇮ᧁ⼱෹ᵗ䇮ᚑ᧻⧷ᥓ䇮ਗᧁᤘ⟵
ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮ቇ⻠ᐳ
Spinal morphine exacerbates motor dysfunction after traumatic spinal cord contusion injury

Yuki Sugiyama, Mikito Kawamata, Shigekazu Sugino, Tomohiro Kiya, Eichi Narimatsu, Akiyoshi
Namiki
Department of Anesthesiology, Sapporo Medical University School of Medicine䇼䈲䈛䉄䈮䇽⣄㜑⯯ⴊᓟ䋬morphine䋨Mor䋩䉕ోり䋬䈅䉎䈇䈲⣄㜑ᛩਈ䈚䈢႐ว䋬ㆇേ㤗∽䉕ᖡൻ䈘䈞䉎น⢻ᕈ䈏䈅䉎䋨Kakinohana et al., 2003䋩䋮䈠䈖䈪ᯏ᪾⊛䈭⣄㜑៊்䋨SCI䋩ᤨ䈱 Mor ᛩਈ䈱ᓇ㗀䈮䈧䈇䈩ᬌ⸛䈚䈢䋮䇼ᣇᴺ䇽㓶ᕈ SD 䊤䉾䊃䋨250-300 g䋩䈱⣶ㇱ⣄㜑䈒䉅⤑ਅ⣧䈮 PE10 䉦䊁䊷䊁䊦䉕ᝌ౉䊶⇐⟎䈚䈢䋮2䋭3 ᣣᓟ䋬ㆇേ䊶⍮ⷡ㓚ኂ䈏䈭䈇䈖䈫䉕⏕⹺ᓟ䋬䊊䊨䉺䊮㤗㈮ਅ䈪䋬⣄㜑ಽ▵T12-13 㗔ၞ䈮ਛ╬ᐲ䈱⣄㜑ᝂ்䋨BBB 䉴䉮䉝䋺7䋭8䋩䉕 New York Univ. device 䉕ᮨ䈚䈢ᣇᴺ䈮䉋
䉍૞⵾䈚䋨10g, 10 mm 㜞䋩䋬૞⵾ 2 ᤨ㑆ᓟ䈮 Mor䋨1䋭30 µg/10 µl䋩䉕䈒䉅⤑ਅᛩਈ䈚䈢䋮䈘䉌䈮 Mor㐳ᦼᛩਈ䈱ᓇ㗀䉕ᬌ⸛䈜䉎䈢䉄䇮න࿁ᛩਈ䋨30 µg/10 µl䋩䈮ᒁ䈐⛯䈐 3 µg/µl Mor 䉕 2 µl/hr 䈪 3 ᣣ㑆ᛩਈ䈚䈢䋮ㆇേ㓚ኂ∽䈱⒟ᐲ䈲 BBB 䉴䉮䉝䈍䉋䈶 Yaksh 䉌䈱ᣇᴺ䋨Kakinohana et al., 2003䋩䈪
⹏ଔ䈚䈢䋮䉁䈢ᜬ⛯ᛩਈ଀䈪䈲䋬⣶ㇱ⣄㜑䋨L3-6䋩䉕 HE 䈍䉋䈶 KB ᨴ⦡䈚䋬Motoneuron 䈱ᒻᘒቇ⊛ᄌൻ䉕ᬌ⸛䈚䋬䈘䉌䈮 GFAP ᨴ⦡䈫 Iba㵥1 ᨴ⦡䉕ⴕ䈦䈢䋮䇼⚿ᨐ䇽SCI ૞⵾ 2 ᤨ㑆ᓟ䈱 Mor ᛩਈ䈲 SCI ᓟ䈱ㆇേ㓚ኂ䉕᦭ᗧ䈮ᖡൻ䈘䈞䋬䈖䈱ᖡൻ䈲 naroxone ᛩਈ䈮䉋䉍࿁ᓳ䈚䈢䋮Mor ᜬ⛯ᛩਈ䈮䉋䉍ㆇേ㓚ኂ䈱Ⴧᖡ䈏ᜬ⛯䈚䈢䋮Mor ᜬ⛯ᛩਈ⟲䈪䈲䉮䊮䊃䊨䊷䊦⟲䈮Ყ䈼䋬ᒻᘒᄌൻ䉕⹺䉄䈢 motoneuron 䈱ഀว䈏Ⴧട௑ะ䈮䈅䉍䋬GFAP䋬Iba-1 㓁ᕈ⚦⢩䉅Ⴧട䈚䈩䈇䈢䋮䇼⚿⺆䇽SCI ᣧᦼ
䈮䈲䋬Mor ᛩਈ䈮䉋䉍ㆇേ㤗∽䈏Ⴧᖡ䈜䉎น⢻ᕈ䈏䈅䉎䋮 

SIII-3㛽䈏䉖ᕈ−∩䊝䊂䊦䈮䈍䈔䉎 MOR1 ⊒⃻䈫䊝䊦䊍䊈㎾∩ലᨐጊᧄ㩷 ⚐䇮Ꮉ⢆⍮ਯ䇮ᣂጊᐘବ䇮⴫㩷 ࿻৻䇮ਗᧁᤘ⟵
ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮ቇ⻠ᐳ
Mu-opioid receptor-1 expression and analgesic effect of morphine on bone cancer pain model

Jun Yamamoto, Tomoyuki Kawamata, Yukitoshi Niiyama, Keiichi Omote, Akiyoshi Namiki
Department of Anesthesiology, Sapporo Medical University School of Medicine䈲䈛䉄䈮䋺㛽䈏䉖䈍䉋䈶䈏䉖䈱㛽ォ⒖䈮䉋䉎−∩䈲䋬䈠䈱䉮䊮䊃䊨䊷䊦䈮㔍ᷦ䈜䉎䈖䈫䈏ᄙ䈇䋮੹࿁䋬ᚒ䇱䈲㛽䈏䉖ᕈ−∩䊝䊂䊦䉕↪䈇䈩 MOR1 ⊒⃻䈫䊝䊦䊍䊈㎾∩ലᨐ䈮䈧䈇䈩ᬌ⸛䈚䋬䈘䉌䈮Ἳ∝ᕈ−∩䈮䈍䈔䉎 MOR1 ⊒⃻䈫䊝䊦䊍䊈㎾∩ലᨐ䈫Ყセᬌ⸛䈚䈢䋮ᣇ ᴺ 䋺 㛽 䈏 䉖 䊝 䊂 䊦 䈫 䈚 䈩 䋬 ో り 㤗 ㈮ ਅ 䈮 㓶 䈱 C3H/HeJ 䊙 䉡 䉴 䈱 Ꮐ ᄢ ⣽ 㛽 ㆙ ૏ ┵ 䈮osteosarconma ⚦⢩䉕ᵈ౉䈚䈢䋮ኻᾖ䊙䉡䉴䈮䈲ၭ㙃ᶧ䈱䉂䈱ᛩਈ䈫䈚䈢䋮ᛩਈ 14 ᣣᓟ䋬䊐䊥䊮䉼࿁ᢙ䋬቟㕒ᤨ䈍䉋䈶ᒝ೙ᤨ䈱ᱠⴕ⁁ᘒ䉕⸥㍳䈚䈢ᓟ䈮䋬osteosarconma ⚦⢩䉁䈢䈲ၭ㙃ᶧᵈ౉஥
䈱 L2䋬3䋬4DRG 䈫 L3䋬4 䊧䊔䊦䈱⣄㜑䉕ណข䈚䈢䋮⣄㜑䈲ណขᓟ䋬ᵈ౉஥䈫䈠䈱෻ኻ஥䈮 2 ಽഀ䈚䈢䋮RT-PCR䋬Western blot 䉕䈍䈖䈭䈇䋬MOR1 ⊒⃻䈮䈧䈇䈩ᬌ⸛䈚䈢䋮䉁䈢䋬䊝䊦䊍䊈䉕䉪䊝⤑ਅ
ᛩਈ䈚㎾∩ലᨐ䉕Ἳ∝ᕈ−∩䊝䊂䊦䈫Ყセᬌ⸛䈚䈢䋮⚿ᨐ䋺ᛩਈ 14 ᣣᓟ䋬䊝䊂䊦䊙䉡䉴䈪䈲᦭ᗧ䈭䊐䊥䊮䉼࿁ᢙ䈱Ⴧട䈫䋬቟㕒ᤨ䈍䉋䈶ᒝ೙ᤨᱠⴕ㓚ኂ䉕⹺䉄䈢䋮ኻᾖ䊙䉡䉴䈮Ყ䈼䋬䊝䊂䊦䊙䉡䉴 DRG 䈪䈱 MOR 䉺䊮䊌䉪⊒⃻㊂䈍䉋䈶 mRNA ㊂䈱ૐਅ䈏⹺䉄䉌䉏䈢䋮ᵈ౉஥⣄㜑䈪䈲ኻᾖ䊙䉡䉴䈮Ყ䈼䈩䋬䊝䊂䊦䊙䉡䉴䈪 MOR 䉺䊮䊌䉪⊒⃻㊂䈱ૐਅ䈏⹺䉄䉌䉏䈢䈏 mRNA ㊂䈲ᄌ䉒䉌䈭䈎䈦䈢䋮䉁䈢䋬䊐䊥䊮䉼䈮ኻ䈜䉎䉪䊝⤑ਅ䊝䊦䊍䊈䈱ലᨐ䈲Ἳ∝ᕈ−∩䊝䊂䊦䈮Ყ䈼㛽䈏䉖䊝䊂䊦䈪᦭ᗧ䈮ᷫᒙ䈚䈢䋮⚿⺰䋺㛽䈏䉖ᕈ−∩䊝䊂䊦䈮䈍䈇䈩ᧃ᪳␹⚻䈪䈱 MOR1 䈱⊒⃻䈏ォ౮䊧䊔䊦䈪ᛥ೙䈘䉏䈩䈇䉎䋮䈖䉏䈲㛽䈏䉖䈍䉋䈶䈏䉖䈱㛽ォ⒖䈮䉋䉎−∩䈏䉥䊏䉥䉟䊄ᛶ᛫ᕈ䈪䈅䉎䈖䈫䈱䋱䈧䈱ᯏᐨ䈪䈅䉎䈖䈫䈏ផ᷹䈘䉏䈢䋮 

SIII-4㛽䈏䉖ᕈ−∩䊝䊂䊦䈮䈍䈔䉎 CB1 ฃኈ૕૞േ⮎䈱㎾∩ലᨐฎἑ᤯๋ 1)䇮Ꮉ⢆⍮ਯ 1)䇮ᷰㄝ㓷ᒾ 2)䇮ᣂጊᐘବ 1)䇮ጊᧄ㩷 ⚐ 1)䇮ਗᧁᤘ⟵ 1)1)ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮ቇ⻠ᐳ䇮2)ർᶏ㆏ᄢቇᄢቇ㒮කቇ⎇ⓥ⑼⸃೬⊒↢ቇಽ㊁

Activation of spinal CB1 receptor reduces bone cancer-related pain
Shiongo Furuse1), Tomoyuki Kawamata1), Masahiko Watanabe2), Yukitoshi Niiyama1), Jun
Yamamoto1), Akiyoshi Namiki1)
1) Department of Anesthesiology, Sapporo Medical University School of Medicine 2) Department of
Anatomy and Embryology, Hokkaido University Graduate School of Medicine䇼䈲䈛䉄䈮䇽
䈏䉖ᕈ−∩䈱ਛ䈪䉅㛽ォ⒖ᕈ䈱∩䉂䈲ᴦ≮䈮㔍ᷦ䈜䉎䈖䈫䈏ᄙ䈒䇮−∩✭๺䉕ⴕ䈉਄䈪ᦨ䉅࿎㔍䈭−∩䈱䈵䈫䈧䈪䈅䉎䇯੹࿁䇮ᚒ䇱䈲 CB1 ฃኈ૕䈮⌕⋡䈚䇮䊙䉡䉴㛽䈏䉖ᕈ−∩䊝䊂䊦䉕↪䈇䈩䈠䈱⊒⃻䈫 CB1 ฃኈ૕૞േ⮎䈱㎾∩ലᨐ䈮䈧䈇䈩ᬌ⸛䈚䈢䇯䇼ኻ⽎䊶ᣇᴺ䇽㓶ᕈ C3H/HeJ 䊙䉡䉴䉕↪䈇䈢䋮ోり㤗㈮ਅ䈮 L5/6 䈎䉌䈒䉅⤑ਅ䉦䊁䊷䊁䊦䉕ᝌ౉䊶⇐⟎ᓟ䋬Ꮐᄢ⣽㛽㆙૏┵䈮 osteosarcoma ⚦⢩䉕ᵈ౉䈚㛽䈏䉖−∩䊝䊂䊦䉕૞⵾䈚䈢䇯䊝䊂䊦૞ᚑ 14 ᣣᓟ䈮
CB1 ฃኈ૕૞േ⮎ ACEA 䉕䈒䉅⤑ਅᛩਈ䈚䋬−∩㑐ㅪⴕേ䈮෸䈿䈜ലᨐ䉕ᬌ⸛䈚䈢䋮䉁䈢䇮఺∉⚵❱ൻቇ⊛䈮䉋䉍⣄㜑䈮䈍䈔䉎 CB1 ฃኈ૕䈱ಽᏓ䉕ᬌ⸛䈚䈢䇯䇼⚿ᨐ䇽ⴕേቇ⊛⸃ᨆ䈮䈍䈇䈩䇮ṁᇦᛩਈ䈮Ყ䈼 ACEA ᛩਈ䈮䉋䉍↪㊂ଐሽᕈ䈮−∩㑐ㅪⴕേ䈲ᷫᒙ䈚䈢䋮䉁䈢䋬ACEA 䈱ലᨐ䈲ㆬᛯ⊛ CB1 ฃኈ૕ᜟ᛫⮎ AM251 䈱หᤨᛩਈ䈜䉎䈖䈫䈮䉋䉍ᜟ᛫䈘䉏䈢䇯఺∉⚵❱ൻቇ⊛⸃ᨆ䈮䉋䉍⣄㜑⴫ጀ䊶ᷓጀ䋬ਛᔃ▤๟࿐䈍䉋䈶 DLF 䈮ᒝ䈇 CB1 ఺∉෻ᔕ䉕⹺䉄䈢䇯CB1 ⊒⃻ಽᏓ䊶ᒝᐲ䈲䊝䊂䊦䊙䉡䉴䈫ኻᾖ䊙䉡䉴䈪ห᭽䈪䈅䈦䈢䋮䉁䈢䋬CB1 䈲ਥ䈮
VGLUT2 䈫䈱౒ሽ䈏⹺䉄䉌䉏䈢䋮䇼⚿⺰䇽
CB1 ฃኈ૕䈱ᵴᕈൻ䈮䉋䉍 3 䈧䈱−∩㑐ㅪⴕേ䈲ᛥ೙䈘䉏䈢䇯㛽㜑−∩ᴦ≮䈮ኻ䈚 CB1 ฃኈ૕૞േ⮎䈱᦭ലᕈ䈏␜ໂ䈘䉏䈢䇯 

SIII-5
CB1 ฃኈ૕ᜟ᛫⮎䈱⣄㜑䈒䉅⤑ਅ⣧ౝᛩਈ䈮䉋䉎−∩㑐ㅪⴕേ䈱⊒⃻䈮䈧䈇䈩㐳ጟ㜞ผ 1)䇮ᷰㄝජኼሶ 1)䇮Ḵญᐢ৻ 1)䇮☨Ỉ┨ᒾ 1)䇮ዊ᧻↢᣿ 2)䇮ᰞ↰㩷 ม 2)䇮
ᰞ↰㩷 ᔋ 1)1)᧲ർ⮎⑼ᄢቇᯏ⢻ᒻᘒቇᢎቶ䇮2)╙৻⮎⑼ᄢቇ⮎ℂቇ(㸇)ᢎቶ

Characterization of nociceptive behavior evoked by intrathecal administration of CB1 receptor
antagonist
Nagaoka K1), Watanabe C1), Mizoguchi H1), Yonezawa A1), Komatsu T2), Sakurada T2),
Sakurada S1)
1) Department of Physiology and Anatomy, Tohoku Pharmaceutical University 2) First Departmentof Pharmacology, Daiichi College of Pharmaceutical Sciences
䇼✜⸒䇽Cannabinoid ฃኈ૕䈮䈲 CB1 ෸䈶 CB2 ฃኈ૕䈏ሽ࿷䈚䇮䈠䉏䈡䉏⇣䈭䉎↢ℂᯏ⢻䉕᦭䈜䉎䈖䈫䈏ႎ๔䈘䉏䈩䈇䉎䇯․䈮 CB1 ฃኈ૕䈲⣄㜑ᓟⷺ䈮ᄙ䈒ሽ࿷䈚䇮᛫ଚኂ૞↪䈱⊒⃻䈮ᷓ䈒㑐ਈ䈚䈩䈇䉎䈖䈫䈏⍮䉌䉏䈩䈇䉎䇯৻ᣇ䇮CB1 ฃኈ૕ᜟ᛫⮎䈱න⁛⣄㜑䈒䉅⤑ਅ⣧ౝ(i.t.)ᛩਈ䈮䉋䉍∩ⷡㆊᢅ⃻⽎䉕⿠䈖䈜䈖䈫䉅ႎ๔䈘䉏䈩䈇䉎䇯䈖䉏䉌䈱ႎ๔䉕䉅䈫䈮 CB1 ฃኈ૕ᜟ᛫⮎䈱 i.t.ᛩਈ䈮䉋䉎ᬌ⸛䉕ⴕ䈦䈢䈫䈖䉐䇮Scratching䇮Biting䇮Licking 䈎䉌䈭䉎․ᓽ⊛䈭−∩㑐ㅪⴕേ(SBL ⴕേ)䈏⊒⃻䈜䉎䈖䈫䉕⷗䈇಴䈚䈢䇯䈠䈖䈪䇮䈖䈱 SBL ⴕേ䈱⊒⃻ᯏᐨ䉕⸃᣿䈜䉎⋡⊛䈪䇮⣄㜑ౝ−∩೙ᓮ䈮䈍䈇䈩㊀ⷐ䈭ᓎഀ䉕ᜂ䈦䈩䈇䉎 NMDA ෸䈶 NK1 ฃኈ૕䈱㑐ਈ䈮䈧䈇䈩ᬌ⸛䉕ⴕ䈦䈢䇯䇼ᣇᴺ䇽ታ㛎䈮䈲䇮ddY ♽㓶ᕈ䊙䉡䉴䉕↪䈇䈢䇯ฦ⮎‛䈲 CB1 ฃኈ૕ᜟ᛫⮎(AM251)䈫 i.t.䈻หᤨᛩਈ䈚䇮ᛩਈ⋥ᓟ䈎䉌 30 ಽ㑆䇮SBL ⴕേ䉕᷹ቯ䈚䈢䇯䇼⚿ᨐ෸䈶⠨ኤ䇽AM251 䈱න⁛ i.t.ᛩਈ䈮䉋䉍↪㊂ଐሽ⊛䈭 SBL ⴕേ䈏⊒⃻䈚䈢䇯AM251 䈮䉋䈦䈩ᒁ䈐⿠䈖䈘䉏䉎 SBL ⴕേ䈲 CB1 ฃኈ૕૞േ⮎䈱ᛩਈ䈮䉋䉍᦭ᗧ䈮ᛥ೙䈘䉏䇮NMDA ฃኈ૕ᜟ᛫⮎䇮NK1 ฃኈ૕ᜟ᛫⮎䇮NO วᚑ㉂⚛㒖ኂ⮎䈱หᤨᛩਈ䈮䈍䈇䈩䉅ᛥ೙䈘䉏䈢䇯੹࿁䈱⚿ᨐ䈎䉌䇮CB1 ฃኈ૕ᜟ᛫⮎䈱 i.t ᛩਈ䈮䉋䉍䇮䉰䊑䉴䉺䊮䉴 P 䉇䉫䊦䉺䊚䊮㉄䈭䈬䈱␹⚻વ㆐‛⾰䈱ㆆ㔌䈏ଦㅴ䈘䉏䇮NK1 ෸䈶 NMDA ฃኈ૕䉕੺䈚䈩−∩㑐ㅪⴕേ䈏⊒⃻䈚䈩䈇䉎䈖䈫䈏␜ໂ䈘䉏䈢䇯 䊤䊮䉼䊢䊮䉶䊚䊅䋭I
䇸⥃ᐥ䈮䈍䈔䉎䉥䊏䉥䉟䊄♽㎾∩⮎䈱૶䈇ᣇ䈫໧㗴ὐ䇹⚦Ꮉ⼾ผ੩ㇺᐭ┙ක⑼ᄢቇᄢቇ㒮කቇ⎇ⓥ⑼㩷 㤗㈮⑼ቇᢎቶ
੩ㇺᐭ┙ක⑼ᄢቇ㒝ዻ∛㒮㩷 −∩✭๺ක≮ㇱ䊕䉟䊮䉪䊥䊆䉾䉪䈪䈲䇮㗡䈱䊁䉾䊕䊮䈎䉌ᚻ⿷ᜰ䈱వ䈦䉀䉁䈪䇮䈅䉌䉉䉎∩䉂䈮ኻಣ䈚䈩䈇䉎䇯ᢛ
ᒻᄖ⑼䉕ਛᔃ䈮䇮␹⚻ౝ⑼䇮⊹⤏⑼䇮ᄖ⑼䇮ฦౝ⑼䈎䉌∩䉂䈱ᴦ≮䈫⸻ᢿ䉕᳞䉄䈩ᖚ⠪䈘䉖䈏⚫
੺䈘䉏䈩䈒䉎䇯ฦ⒳䈱␹⚻䊑䊨䉾䉪䈲䈖䉏䉌䈱∩䉂䈱ᴦ≮䉇㐓೎⸻ᢿ䈮᦭↪䈪䈲䈅䉎䈏䇮䈖䉏䈱䉂䈪䈱ኻᔕ䈲ਇน⢻䈪䈅䉎䇯䈖䈱䈢䉄䇮䉣䊏䊄䊤䉴䉮䊏䊷䋨ౝⷞ㏜ਅ⎬⤑ᄖ≹⌕೸㔌ⴚ䋩䉇䌓䌃䌓䋨⎬⤑ᄖ⣄㜑ೝỗ㔚ᭂၒ䉄ㄟ䉂ⴚ䋩䇮⚻⊹⊛ᬁ૕ᒻᚑⴚ䈭䈬䈱ᴦ≮䉕Ⓧᭂ⊛䈮ⴕ䈇䈧䈧䇮శ✢≮ᴺ
䋨ૐ෻ᔕ䊧䊔䊦䊧䊷䉱䊷䇮䉨䉶䊉䊮䇮⋥✢஍శㄭ⿒ᄖ✢䋩䉇䌓䌓䌐䋬䌔䌅䌎䌓䋬㎞ἲ䈭䈬ᖚ⠪䈘䉖䈮ఝ䈚䈇㕖ଚⷅ⊛ᴦ≮䉅ข䉍౉䉏䈩䈇䉎䇯䈠䈚䈩㎾∩⮎䇮㎾∩⵬ഥ⮎䇮ṽᣇ⮎䈭䈬䉅᦭ജ䈭ᴦ≮ᚻᲑ䈫䈭䉎䇯䊕䉟䊮䉪䊥䊆䉾䉪䈲ᭂ䉄䈩⥃ᐥ⊛䈭ㇱ㐷䈪䈅䉎䇯䈎䈧䈩⮎ℂቇ⊛⎇ⓥ䉇∩䉂䈱ၮ␆⎇ⓥ䈱⊒⴫䉇⻠Ṷ䉕⡬䈇䈩䉅䇮⥃ᐥ䈫䈲䈎䈔㔌䉏䈢䈫䈖䉐䈮䈅䉎䈫ᗵ䈛䈢䉅䈱䈣䈏䇮ㄭᐕᴦ≮䈮䈲䉣䊎䊂䊮䉴䈏ᰳ䈎䈞䈭䈇䈖䈫䇮ㅒ䈮ၮ␆ㇱ㐷䈪䉅䇮⥃ᐥ䈮ᓎ┙䈢䈭䈇⎇ⓥ䈪䈲ᗧ๧䈏⷗಴䈞䈭䈇䈫䈱⹺⼂䈎䉌䇮ᕆㅦ䈮䈠䈱㑆㓗䈏ၒ䉄䉌䉏䈢䈳䈎䉍䈪䈭䈒䇮䉥䊷䊋䊷䊤䉾䊒䈜䉎㗔ၞ䈏ᄙ䈒⷗ฃ䈔䉌䉏䉎䇯䈖䈱䉶䊚䊅䊷䈪䈲䇮NSAID䌳䈱૶䈇ᣇ䈫೽૞↪䈱⃻⁁䇮䉥䊏䉥䉟䊄䈱૶䈇ಽ䈔䈫೽૞↪ኻ╷䈍䉋䈶䉣䊎䊂䊮䉴䈱ਇ᣿䈭䉥䊏䉥䉟䊄䈱⚻㛎ೣ䇮㎾∩⵬ഥ⮎䈱ᮡḰ⊛૶䈇ಽ䈔䈫ᗧᄖ䈭ㆡᔕ䈠䈚䈩⥃ᐥ૶↪䈪䈱᳇䉕䈧䈔䉎䈼䈐䈖䈫䇮ᣂ⮎䈮ᦼᓙ䈜䉎䈖䈫䈭䈬䈮䈧䈇䈩䈍⹤䈚䉁䈜䇯 䉟䊑䊆䊮䉫䉶䊚䊅䊷䇸䊧䊚䊐䉢䊮䉺䊆䊦䈱ၮ␆䈫⥃ᐥ䇹ᐳ㐳䋺ᧅᏻකᄢ∛㒮⮎೷ㇱᢎ᝼㩷 ችᧄ◊వ↢Ṷ⠪䋺䊟䊮䉶䊮䊐䉜䊷䊙ᩣᑼળ␠㩷 ᪊੗┨ᙗవ↢㩷 㩷 㩷 㩷 ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮⑼㩷 ጊ⬺㆏᣿వ↢䋱䋮ోり㤗㈮↪㎾∩೷㩷 䊧䊚䊐䉢䊮䉺䊆䊦Ⴎ㉄Ⴎ䋨໡ຠฬ㩷 䉝䊦䉼䊋®䋩᪊੗㩷 ┨ᙗ䋨䊟䊮䉶䊮 䊐䉜䊷䊙ᩣᑼળ␠䋩㩷 䊧䊚䊐䉢䊮䉺䊆䊦Ⴎ㉄Ⴎ䋨໡ຠฬ䋺䉝䊦䉼䊋®䋩䈲䋬วᚑ䈘䉏䈢⿥⍴ᤨ㑆૞↪ᕈ䈱䉥䊏䉥䉟䊄㎾∩⮎䋨㤗⮎ᕈ㎾∩⮎䋩䈪䈅䉎䇯㩷 ㎾∩૞↪䈱⊒⃻ਗ䈶䈮ᶖᄬ䈏䈫䉅䈮ㅦ䉇䈎䈭⿥⍴ᤨ㑆૞↪ᕈ䈱䉥䊏䉥䉟䊄䉕㐿⊒䈜䉎⋡⊛䈪䋬ㆬᛯ⊛ µ-䉥䊏䉥䉟䊄ฃኈ૕䉝䉯䊆䉴䊃䈫䈚䈩䈱⮎ℂቇ⊛૞↪䉕⛽ᜬ䈜䉎䈫หᤨ䈮䋬ⴊᶧਛ෸䈶⚵❱ౝ䈮ሽ࿷䈜䉎㕖․⇣⊛䉣䉴䊁䊤䊷䉷䈮䉋䉎ઍ⻢䉕ฃ䈔ᤃ䈒䈜䉎䈢䉄䈮䋬䊏䊕䊥䉳䊮Ⅳ
䈱ฦ૏⟎䈮⒳䇱䈱䉝䊦䉨䊦䉣䉴䊁䊦⟎឵ၮ䉕᦭䈜䉎৻ㅪ䈱 4-䉝䊆䊥䊄䊏䊕䊥䉳䊮ൻว‛䉕วᚑ䈚䈢䇯㩷 วᚑ䈘䉏䈢৻ㅪ䈱ൻว‛䈱䉥䊏䉥䉟䊄ฃኈ૕䈮ኻ䈜䉎૞േᕈ䈲䊝䊦䊝䉾䊃៰಴࿁⣺䉕↪䈇䈩ᬌ⸛䈘䉏䋬㎾∩૞↪䈱ᜬ⛯ᕈ䈮䈧䈇䈩䈲䊤䉾䊃䉕↪䈇䈢ユ኿ᾲᴺ䈮䉋䉍䋬䈘䉌䈮䋬ઍ⻢ㅦᐲ䈮䈧䈇䈩䈲䊍䊃ⴊᶧ䉕↪䈇䈢⹜㛎╬䈮䉋䉍᷹ቯ䈘䉏䈢䇯䈖䉏䉌䈱⹜㛎ਗ䈶䈮ฦ⒳䈱 in vitro ෸䈶䊝䊂䊦േ‛䉕↪䈇䈢⹜㛎䈮䉋䈦䈩䋬ᒝജ䈭㎾∩૞↪䉕᦭䈚䋬䈎䈧૞↪ᜬ⛯ᤨ㑆䈱ᭂ䉄䈩⍴䈇ൻว‛䈪䈅䉎䊧䊚䊐䉢䊮䉺䊆䊦䈏⊒⷗䈘䉏䋬1991 ᐕ䈮 Feldman PL 䉌䈏䊧䊚䊐䉢䊮䉺䊆䊦䈱
วᚑᴺ䋬⮎ℂቇ⊛․ᓽ╬䈮䈧䈇䈩ႎ๔䈚䈢䇯㩷 ᶏᄖ䈪䈲 1996 ᐕ䈮䊄䉟䉿䈮䈍䈇䈩ᛚ⹺䈘䉏䋬⃻࿷䋬⚂ 69 䉦࿖䈪ਥ䈮䇸ోり㤗㈮ᤨ䈱㎾∩⮎䇹䈫䈚䈩⥃ᐥ૶↪䈘䉏䋬᦭↪ᕈ䈏ᄙᢙႎ๔䈘䉏䈩䈇䉎䇯㩷 ᧄ㇌䈪䈲䋬1995 ᐕ䉋䉍⥃ᐥ⹜㛎䉕㐿ᆎ䈚䋬2006 ᐕ 10 ᦬䈮䇺ోり㤗㈮䈱ዉ౉෸䈶⛽ᜬ䈮䈍䈔䉎㎾∩䇻䈱ല⢻䊶ലᨐ䈪⵾ㅧᛚ⹺䈘䉏䋬2007 ᐕ 1 ᦬䈮⊒ᄁ䈜䉎䈮⥋䈦䈢䇯 䋲䋮䊧䊚䊐䉢䊮䉺䊆䊦䈱⥃ᐥᴦ㛎䊶Ꮢ⽼ᓟ⥃ᐥ૶↪䉕⚻㛎䈚䈩ጊ⬺㩷 ㆏᣿䋨ᧅᏻක⑼ᄢቇකቇㇱ㤗㈮⑼䋩
㩷 ⿥⍴ᤨ㑆૞↪ᕈ䉥䊏䉥䉟䊄㎾∩⮎䊧䊚䊐䉢䊮䉺䊆䊦䈱⥃ᐥᴦ㛎䈮ෳട䈘䈞䈩䈇䈢䈣䈇䈢䈱䈲䋬⑳䈏☨࿖⇐ቇ䈎䉌Ꮻ࿖䈚䈢 1996 ᐕ䈱䈖䈫䈪䈅䈦䈢䋮䈖䈱ᒰᤨ䈲䋬ᣥ GCP䋨ක⮎ຠ⥃ᐥ⹜㛎䈱ታᣉၮḰ䋩ਅ䈱⥃ᐥᴦ㛎䈪䈅䉍䋬䈎䈧䊧䊚䊐䉢䊮䉺䊆䊦䈏㤗⮎▤ℂ䈫䈭䈦䈩䈇䈭䈎䈦䈢䈢䉄䋬ᖚ⠪䈘䉖䈎䉌䈱หᗧ䈲㕖Ᏹ䈮◲ଢ䈭䉅䈱䈪䈅䉍䋬䈎䈧ᴦ㛎⮎䉕㎛䈱䈭䈇⥄ಽ䈱᧍䈱ਛ䈮▤ℂ䈚䈩䈍䈇䈢䈱䉕ⷡ䈋䈩䈇䉎䋮㩷 䈘䈩䋬ᧄ⮎೷䉅ᣣᧄ䈪䈱㐳ᦼ㑆䈮䉒䈢䉎⥃ᐥᴦ㛎䉕䉋䈉䉇䈒⚳ੌ䈚䋬᰷☨䈎䉌 10 ᐕㆃ䉏䈩⥃ᐥ૶↪䈪䈐䉎䉋䈉䈮䈭䈦䈢䋮㤗⮎ᕈ㎾∩⮎䈫䈚䈩䊝䊦䊍䊈䈫䊐䉢䊮䉺䊆䊦䈚䈎૶↪䈪䈐䈭䈎䈦䈢⃻⁁䈎䉌䋬䉴䊐䉢䊮䉺䊆䊦䉇䉝䊦䊐䉢䊮䉺䊆䊦䉕ㅢ䉍⿧䈚䈩䋬䈖䈱⿥⍴ᤨ㑆૞↪ᕈ䉥䊏䉥䉟䊄㎾∩⮎䊧䊚䊐䉢䊮䉺䊆䊦䉕ᚻ䈮䈚䈢䉒䈔䈪䈅䉎䋮⥃ᐥᴦ㛎 46 ∝଀䈱㤗㈮䉕⚻㛎䈚䈩ᗵ䈛䉎䈖䈫䈲䋬䉇䈲䉍䈠䈱“⺞▵ᕈ”䈱⦟䈘䈪䈅䉎䋮ᜬ⛯ᛩਈ䈪㐿ᆎ䈚䈩䉅ㅦ䉇䈎䈮ⴊਛ䊶⣖ౝỚᐲ䈏਄᣹䈚䋬
ㆡಾ䈭㎾∩䉕ᓧ䉎䈖䈫䈏䈪䈐䉎䋮ᛩਈ䉕ਛᱛ䈜䉏䈳䋬ㅦ䉇䈎䈮૞↪䈏ᶖᄬ䈜䉎䋮ඨᷫᦼ䈲 3ޯ
8 ಽ䈫ᭂ䉄䈩⍴䈇䋮ઍ⻢䈲䋬ⴊਛ䊶⚵❱ਛ䈮ᐢ䈒ሽ࿷䈜䉎㕖․⇣⊛䉣䉴䊁䊤䊷䉷䈪ಽ⸃䈘䉏䉎䈢䉄䋬䈠䈱ᣧ䈇ઍ⻢ㅦᐲ䈲ᛩਈ㊂䉇ᛩਈᤨ㑆䈅䉎䈇䈲⢄⣢ᯏ⢻䈮ଐሽ䈚䈭䈇䋮䈧䉁䉍䋬䈠䈱⺞▵ᕈ䈱⦟䈘䈲䈅䈢䈎䉅ᒝജ䈭੝㉄ൻ⓸⚛䉕ᛒ䈉䈗䈫䈒䈪䈅䉎䋮䈖䈱䉋䈉䈭⺞▵ᕈ䈱䉋䈇ᒝജ䈭
㎾∩⮎䉕ᚻ䈮䈜䉏䈳䋬㎾㕒䊶㎾∩䊶╭ᒆ✭䈫䈇䈉ోり㤗㈮䈱ⷐ⚛䉕䈇䈦䈠䈉⠨ᘦ䈚䈢㤗㈮䋬䈇
䉒䉉䉎䊋䊤䊮䉴㤗㈮䈏䉋䉍᥉෸䈚䈩䈇䈐䋬ᖚ⠪䈘䉖䈮䈫䈦䈩䉅቟ో䈪ᔟㆡ䈭㤗㈮▤ℂ䈏䉁䈜䉁䈜ㅴ䉃䈖䈫䈏ᦼᓙ䈘䉏䉎䋮㩷 ᵈᗧὐ䉕䈇䈒䈧䈎᜼䈕䈢䈇䋮䊐䉢䊮䉺䊆䊦䈫ห᭽䋬䊧䊚䊐䉢䊮䉺䊆䊦䉅 µ ฃኈ૕䉕ೝỗ䈜䉎䈖䈫䈮䉋䈦䈩䈠䈱૞↪䉕⊒⃻䈜䉎䈢䉄䋬㋦▤⃻⽎䉇೽੤ᗵೝỗ૞↪䉕䉅䈧䋮䈠䈱૞↪䈲䊐䉢䊮䉺䊆䊦䉋䉍䉅ᣧ䈒⊒⃻䈜䉎䈢䉄䋬න࿁ᛩਈ䉕↪䈇䉎႐ว䈮䈲╭ᒆ✭⮎䈱ㆡಾ䈭૶↪䉇㜞ᐲᓢ⣂䈮ኻ䈜䉎ᵈᗧ䈏ᔅⷐ䈪䈅䉎䋮䉁䈢䋬䊧䊚䊐䉢䊮䉺䊆䊦䈱․ᓽ䈪䉅䈅䉎ㅦ䉇䈎䈭૞↪䈱ᶖᄬ䈱䈢䉄䋬ㅦ䉇䈎䈭ⷡ㉕䈏ᓧ䉌䉏䉎৻ᣇ䋬ⴚᓟ䈱㎾∩䉕චಽ䈮⠨ᘦ䈜䉎ᔅⷐ䈏䈅䉎䋮 䊤䊮䉼䊢䊮䉶䊚䊅䊷II✭๺ක≮䈮䈍䈔䉎䉥䊏䉥䉟䊄⵾೷䈱૏⟎䈨䈔䌾࿷ቛ✭๺䉬䉝䇮ක≮ㅪ៤䉅฽䉄䈩䌾ศỈ᣿ቁⷐ↸∛㒮䊶ⷐ↸䊖䊷䊛䉬䉝䉪䊥䊆䉾䉪੹ᐕ䈱 4 ᦬䈎䉌䈏䉖ኻ╷ၮᧄᴺ䈏㐿ᆎ䈘䉏䇮䈠䈱ਛ䈱ᩇ䈱৻䈧䈫䈚䈩ᣧᦼ䈎䉌䈱✭๺䉬䉝䈱᥉෸䇮࿷ቛ✭๺䉬䉝䈫䈱ㅪ៤䉕ⷐઙ䈱৻䈧䈮ข䉍਄䈕䇮≸ㅪ៤᜚ὐ∛㒮䈱೙ቯ䉕ⴕ䈇䇮䈠䈖䉕ਛᔃ䈮䈏䉖ᴦ≮䈱ဋ䈩䉖ൻ䉕࿑䉎᭴ᗐ䈪䈅䉎䇯䈚䈎䈚䇮✭๺䉬䉝᥉෸䈱⃻⁁䇮䈠䉏䈮ኻ䈜䉎᡽╷䈏䈅䉁䉍䈲䈦䈐䉍౏㐿䈘䉏䈝䇮⃻࿷䉥䊏䉥䉟䊄䈱⒳㘃䇮೷ဳ䈫䉅䈮Ⴧ䈋䈧䈧䈅䉍䈠䈱૶䈇ಽ䈔䈮䇮⧰ᘦ䈘䉏䉎వ↢ᣇ䉅ᄙ䈇䈫⠨䈋䉎䇯੹࿁ 1 ᣣ 1 ࿁⵾೷䈪ㅦ᡼ᕈ䋫ᓢ᡼ᕈ䉕૬䈞ᜬ䈧⵾೷䊌䉲䊷䊐㿙䈱૶↪
⚻㛎䉕〯䉁䈋䈠䈱᦭↪ᕈ䈫ઁ೷䈱․ᓽ䉕Ყセᬌ⸛䈚䈩䉂䈢䈇䇯✭๺䉬䉝䈮㒢䉌䈝䇮ක≮䈲ᖚ⠪᭽ਛᔃ䈮ⴕ䉒䉏䈭䈔䉏䈳ᚑ䉌䈭䈇䈱䈏ᒰ䈢䉍೨䈱䈲䈝䈪䈅䉎䈏䇮ታ㓙䉥䊏䉥䉟䊄⵾೷䈮㑐䈚䈩䈲ᖚ⠪᭽ਛᔃ䈪䈭䈒䇮㒮ౝ▤ℂ䈭䈬䈏ఝవ䈚䇮ᖚ⠪᭽䈮ว䉒䈞䈢⮎೷ㆬᛯ䇮૶↪ᣇᴺ䈏ⴕ䉒䉏䈩䈇䈭䈇⃻⁁䉅⧰⸒䈮䈲䈭䉎䈏ႎ๔䈮౉䉏䈩䉂䈢䈇䇯෶࿷ቛ✭๺䉬䉝䈫ක≮ㅪ៤䈮䈧䈇䈩䉅ᤨ㑆䈱⸵䈜㒢䉍䇮ႎ๔䈚䈢䈇䈫⠨䈋䈩䈇䉎䇯ቱ䈚䈒䈍㗿䈇䈇䈢䈚䉁䈜䇯

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㩷 ╙ 28 ࿁㎾∩⮎䊶䉥䊏䉥䉟䊄䊕䊒䉼䊄䉲䊮䊘䉳䉡䊛䈱ㆇ༡䈮䈅䈢䉍䋬ක⑼䈱

࿅૕䈭䉌䈶䈮ડᬺ䉋䉍ᄙᄢ䈭䈗េഥ䉕䈇䈢䈣䈐䉁䈚䈢䋮䈖䈖䈮ᷓ↟䈭䉎ᗵ⻢䈱ᗧ䉕⴫䈚䉁䈜䋮ഥᚑ
⽷࿅ᴺੱᧅᏻක⑼ᄢቇቇⴚᝄ⥝ળ㩷 㩷 㩷 㩷 㩷 㩷 ᧅᏻක⑼ᄢቇකᏧળද⾥ᱞ↰⮎ຠᩣᑼળ␠
䊟䊮䉶䊮䊐䉜䊷䊙ᩣᑼળ␠Ⴎ㊁⟵⵾⮎ᩣᑼળ␠
䊛䊮䊂䉞䊐䉜䊷䊙ᩣᑼળ␠ᩣᑼળ␠㩷 䊛䊃䉡䊐䉜䉟䉱䊷ᩣᑼળ␠
ᩣᑼળ␠䉣䉴䉣䊛䉲䊷ᄢᣣᧄ૑෹⵾⮎ᩣᑼળ␠Ꮲ࿡⵾⮎ᩣᑼળ␠ද๺⊒㉂Ꮏᬺᩣᑼળ␠
╙৻ਃ౒ᩣᑼળ␠
䊋䉪䉴䉺䊷ᩣᑼળ␠䊜䊂䉞䉬䊷䉲䊢䊮䊂䊥䊋䊥䊷੐ᬺㇱᣣᧄൻ⮎ᩣᑼળ␠
ᣣᧄᣂ⮎ᩣᑼળ␠
䉝䉴䊁䊤䉴⵾⮎ᩣᑼળ␠ᩣᑼળ␠㩷 ┻ጊ䊁䊦䊝ᩣᑼળ␠
ਭశ⵾⮎ᩣᑼળ␠ 