primary afferent fibers dorsal horn lamina & synapse sensory cortex ascending pain pathways P(substance P)(glutamate) inhibitory input local interneurones 1
descending noradrenergic and serotonergic fibers Willis and Coggeshall,1979 substaintia gelatinosa spinolthalamic tract C C 0.5~2m/s P lateral spinothalamic tract, Gate-control theory Melzack, 1976 2
Ancient Sumerians poppy Joy plants poppy juice 20 1806 Serturner Morphens Morphine codeine, papaverine opiates, Reisine and Pasternak, 1995Cates Tschudi 1925-1. 3
1967 Martin nalorphine nalorphine nalorphine 1973 Pert and Snyder, 1973 ; Terenius, 1973 ; Simon, et al., 1973 [ 3 H]naloxone, [ 3 H]dihydromorphine [ 3 H]etorphine receptor competitive binding study Martin 1976 µ ketocyclazocine κ N-allylnormetazocine SKF-10,047 δ opioid receptors µ δκ µ antinociceptive areas 4
µ µ-opioid receptors µ1 µ2 Pasternak, 1988 µ3 µ3 苷 cgmp Horvath,2000 Rialas et al., 2000 δ κ enkephalins dynorphines neloxone µδκ Jaffe, 1985 Way, 1993 ; Wong et al., 2000 Wong et al., 2000 Sandra, 1996 µ (desensitization)mao et al., 1995b) Sandra, 1996 252 5
3.5mg 19.5mg Liew and Hui, 1989 (Kalso et al., 1993Steven and Yaksh, 1989Steven, 1994Saito et al., 1998aWong et al., 1993) G Wong et al., 1992a,bNMDA Mao et al., 1995aWong et al., 1994Wong et al., 1996 nnos Wong et al., 2000 酶 C Mao et al., 1995a Wong 2000 Sandra, 1996 Wong, 2002 6
Scholz, 2002 Scholz, 2002 Scholz, 2002Gasser 7
Erlanger 1929 Αδ C C fiber Gasser and Erlanger, 1929 Aδ C C Αδ 2-4 Raymond and Gissen, 1987 ; Wildsmith et al., 1987 Schmelz et al., 1997 ; Widner et al., 1999 C silent Belmonte and Cervero, 1996 ; Wall and Melzack, 1999 C Kobayashi et al., 1996 ; Quasthoff et al., 1995 8
QX314 QX314 QX314 Frazier et al., 1970 benzocaine 6 Hille, 2001 Woodhull, 1973 Strichartz, 1973 Scholz, 2002 Courtney, 1975 ; Ulbricht, 1981 Starmer et al., 1984 Raymond and Gissen, 1987 (electrical excitation threshold) (action potential) 9
Vedantham and Cannon, 1999Kimbrough and Gingrich, 2000Khodorovam et al., 2001 Strichartz et al., 2002 Attal 2000 40 Bartlett and Hutaserani, 1961 Boas et al., 1982 Shapiro et al., 1981Kalso, 1983Abboud et al., 1988Abouleish et al.,1988chadwick and Ready 1988Hjortso et al., 1989 Jayr et al., 1993Laveaux et al., 1993Burgess et al., 1994Saito et al.,1994scott et al.,1995 Hogan et al.,1991du Pen et al., 1992 Brownridge et al., 1992Cherng 2002 2 mg 2 1999 van Dongen bupivacaine bupivacaine 10
Forster and Markham, 2000van Dongen et al., 1999 John and Yaksh, 1992 bupivacaine Penning and Yaksh, 1992 myeline bupivacaine Fink and Cairns, 1983 ; Strichartz and Ritchie, 1987Saito 1998 (neurotransmitter) (hyperalgesia) (Aβ) (allodynia) 11
(spinal sensitization)mao et al., 1994 ( ) ( ( ) ( ) (Mao et al., 1994; Wegert et al., 1997 ; Vanderah et al., 2000 ; Celerier et al., 2001) Wallace et al., 1996 酶 C - (Mao et al., 1995b)Mitchell 2001 12
Hung et al., 1991 John and Yaksh, 1992 13