Changes in long2term syna ptic plasticity in the spinal dorsal horn of neuropathic pa in rats

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1 226 ( ) JOURNAL OF PEKIN G UNIVERSITY( HEAL TH SCIENCES) Vol. 35 No. 3 J une 2003,,, (, ) [ ] / ; ; ; / [ ] :, (central sensitization) :Sprague2Dawley 5/ 6 (L5/ L6), C2, C2 L TP : (1), ( 100 Hz, 0. 5 ms, 10 V, 1 s, 10 s 4 ) C2 L TP ;, L TP, ( 3040 V, ) C2 L TP(2), C2, :, C2 L TP, [ ] R338 [ ] A [ ] X(2003) Changes in long2term syna ptic plasticity in the spinal dorsal horn of neuropathic pa in rats XIN G Guogang, L IU Fengyu, YAO Lei, WAN You,HAN Jisheng (Neuroscience Research Institute, Peking University ; Department of Neurobiology, Peking University School of Basic Medical Sciences,Beijing , China) KEY WORDS Neuralgia/ physiopathol ; Long2term potentiation ; Central sensitization ; Plasticity ; Spinal cord/ p hysiopat hol SUMMARY Objective : To observe the change in induction of long2term potentiation (L TP) of C2fiber2 evoked potentials in the spinal dorsal horn of neuropathic pain rats, examine the changes in plasticity of synaptic t ransmission, and explore t he effect s and mechanisms of cent ral sensitization and neuropat hic pain following noxious stimulation or nerve injury. Methods : Neuropat hic pain model was produced by tight ligation of the L5/ L6 spinal nerve in Sprague2Dawley rats and the control group rats were re2 ceived sham operation. The C2fiber2evoked field potentials in rat spinal dorsal horn were recorded by ext racellular recording techniques. The differences in induction of L TP of C2fiber dorsal horn field po2 tentials in sham2operated and neuropat hic pain rat s were compared. Results : (1) In neuropat hic pain rats, the L TP in the dorsal horn was induced by high2frequency, low2intensity conditioning stimula2 tion (100 Hz, 10 V, 0. 5 ms, given in 4 trains of 1 s duration at 10 s intervals) of the sciatic nerve, while the same stimulation couldn t induce L TP in sham2operated rats. The L TP could only be in2 duced by high2frequency, high2intensity conditioning stimulation (100 Hz, 3040 V, 0. 5 ms, given in 4 trains of 1 s duration at 10 s intervals) of the sciatic nerve in these control rats. (2) The thresh2 olds for evoking C2fiber dorsal horn field potentials were significantly lower and t he amplit udes tended to be higher in neuropathic pain rats as compared to controls. Conclusion : These data suggest that the nerve injury itself is likely to induce a state of hyperexcitability at the spinal nociceptive synapses, and further support the notion that the long2term synaptic plasticity and the central sensitization may con2 tribute to the development of neuropathic pain. ( J Peking U niv [ Health Sci ], 2003,35 : ) : ( G ) ( ) Supported by the National Programme for Key Basic Research Projects of China ( G ) and the National Natural Science Foundation of China ( , , ) Corresponding author , edu. cn

2 , 227,, von Frey (hyperalgesia), (allodynia), von Frey (2. 00 g), von Frey, (perip heral sensiti2 zation) ( central sensitization ) [1,2 ] Liu [326 ],, 1 ( ) C,, 4, C 30 s, (long2term potentiation, L TP), C, 50 % g L TP, 50 %, 50 % 4 g Miletic [7,8 ] [11, ] 721 d A ( long2lasting post C L TP tetanic potentiation), (1. 5 g, kg - 1,i. p. ), ; L1/ L2, ( C L4/ L5 ),, 37 L TP C2,, L5/ L6 ( 2 mg C2 L TP kg - 1,i. p. ), C2 L TP ( : 90 ; :2 1) ; ( R2R ms) ; Sprague2Dawley,, ;, ( g) von Frey, Tyrode ( ml h - 1 ) g, C L TP 1. 2 ( 13 M, Frederick Haer & 32 Co. ) C [9 ], L4/ L , L5/ L6, 6 m ; (Micro1401,mk & Spike 2, CED ), Hz ( 25,, C ) Chaplan [10 ] up and down 0. 5 ms, 1020 V, 5 min 1 50 %, 15 min, von Frey (Stoelting ) C 30 min, 30 min

3 228 ( ) JOURNAL OF PEKIN G UNIVERSITY( HEAL TH SCIENCES) Vol. 35 No. 3 J une 2003, (, 10 V, 100 Hz, 1 s, 10 s 4, ) ( 3040 V,, ) C L TP 2. 2 C ms, 1020 L TP V, 5 min 1,, 23 h C2, 6 L TP ;, (100 %), L TP, C2, C2 L TP(1) 20 %, 30 min [4 L TP ] 1. 4 Prism 3. 0, gx s t, One2way ANOVA q,p < d,,,,,,,,,, c1,after HF2L I2CS. 1 d 7 d,von Frey 1 C2 L TP 50 %, von Frey ( g), 1214 g 50 % 7 d, 50 % 2. 3 C2 ( ) g ( ) g, SNL, spinal nerve ligation ; HF2L I2CS, high frequency2low intensity conditioning stimulation ; HF2HI2CS, high frequency2high intensity con2 ditioning stimulation ;A,neuropathic pain rats ( n = 6) ;a,before condi2 tioning stimulation ; b,after conditioning stimulation ; B, sham2operated rats ( n = 5) ;a1, before conditioning stimulation ; b1,after HF2L I2CS ; Figure 1 Induction of long2term potentiation of C2fiber2evoked potentials in the spinal dorsal horn of neuropathic pain rats compared with sham2operated rats 14 g, 0. 5 ms, 100 Hz ( P < , n = 15), C2, von Frey ( ) V,

4 , 229 ( ) V, t, P < ,, tion) C2, ( ) mv L TP, ( ) mv, t, P < , ,Bliss [12 ] L TP 1982 Ito [13 ], (long2term depression, L TD) L TP L TD, L5/ L6 L TP L TD WDR C2 [16,17 L TP L TD ], [18, ], [14, ], Randic [15 ] ( hyperexcitability), L TP,,, C, C L TP, C [19 ], WDR [4,5 ] [16, ], [5,6 L TP, ],, Miletic [7,8 ] (CCI) L TP, A, ( long2lasting post2tetanic po2 tentiation),c2 L TP, CCI C2 L TP L5/ L6 C2 L TP, C2 L TP ;, L TP, C2 L TP, C2 L TP L TP, C2 L TP, (cent ral sensitiza2 [16 ] L TP C2 1 Woolf CJ. Evidence for a central component of post2injury pain hy2 persensitivity [J ]. Nature, 1983, 306 (5944) : Dubner R. Pain and hyperalgesia following tissue injury : new mechanisms and new treatments [J ]. Pain, 1991, 44 (3) : Liu XG, Sandkuhler J. Long2term potentiation of C2fiber2evoked potentials in the rat spinal dorsal horn is prevented by spinal N2 methyl2d2aspartic acid receptor blockage [J ]. Neurosci Lett, 1995, 191 (122) : Liu X, Sandkuhler J. Characterization of long2term potentiation of C2fiber2evoked potentials in spinal dorsal horn of adult rat : essential role of N K1 and N K2 receptors [J ]. J Neurophysiol, 1997, 78 (4) : Sandkuhler J, Liu X. Induction of long2term potentiation at spinal synapses by noxious stimulation or nerve injury[j ]. Eur J Neurosci, 1998, 10 (7) : Sandkuhler J. Learning and memory in pain pathways [J ]. Pain,

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