Besse D, Lombard M C, Perrot S, Besson J M
Unité de Recherche de Physiopharmacologie du Système Nerveux (INSERM, U. 161), Ecole Pratique des Hautes Etudes, Paris, France.
Neuroscience. 1992 Oct;50(4):921-33. doi: 10.1016/0306-4522(92)90215-n.
The aim of the present study was to quantify time-related modifications in mu and delta opioid binding sites in the superficial layers (laminae I and II) of the L4 lumbar segment in a rat model of mononeuropathy induced by loose ligation of the sciatic nerve. We have shown a 28% (P < 0.01) and 24% (P < 0.01) decrease in ipsi/contralateral side binding ratios for tritiated (Tyr*-D-Ala-Gly-NMe-Phe-Gly-ol) ([3H]DAMGO) and tritiated (Tyr*-D-Thr-Gly-Phe-Leu-Thr) ([3H]DTLET) respectively, at two weeks postlesion which correspond to the delay of maximal hyperalgesia and of maximal alteration of fine diameter primary afferent fibers. In contrast, no change in [3H]U.69593 specific binding could be detected at this postlesion delay. For longer survival delays (four, eight and 15 weeks postlesion), mu and delta binding ratios return towards control values (approximately equal to 1), probably reflecting the occurrence of a long-term neuroplasticity (i.e. a new equilibrium in the metabolism of primary neurons, or collateral sprouting from intact primary afferents) following loose nerve ligation. In addition, a comparison of the results obtained in this model with those measured after sciatic nerve section and lumbar dorsal rhizotomy was performed in order to compare the degree of loss in opioid binding sites in these three types of lesion. The section of the sciatic nerve induced at eight days postlesion an 18% (P < 0.01) and 28% (P < 0.01) decrease in binding ratio for [3H]DAMGO and [3H]DTLET, respectively. At two weeks postlesion the loss was 24% (P < 0.01) for the two ligands, and at longer delays (four and 12 weeks), a progressive recovery in binding ratio was observed. Thus, it appears that both sciatic nerve lesions we have studied result in mu and delta binding modifications which have similar intensity and similar time course from two to 12-15 weeks postlesion. In contrast, the unilateral rhizotomy of nine consecutive dorsal roots (T13-S2), which is known to induce a massive degeneration of fine diameter primary afferent fibers, is followed by a dramatic decrease in binding ratios for [3H]DAMGO (53%, P < 0.001) and [3H]DTLET (45%, P < 0.001) at two weeks postlesion. These data suggest that the more deprived the dorsal horn is of fine diameter primary afferent fibers, the more dramatic is the opioid binding loss in the ipsilateral side as compared to the contralateral side.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究的目的是在坐骨神经松结扎诱导的单神经病变大鼠模型中,量化L4腰段浅层(I层和II层)中μ和δ阿片样物质结合位点随时间的变化。我们发现,在损伤后两周,与最大痛觉过敏和细直径初级传入纤维最大改变的延迟相对应,氚标记的(酪氨酰-D-丙氨酰-甘氨酰-N-甲基苯丙氨酰-甘氨醇)([3H]DAMGO)和氚标记的(酪氨酰-D-苏氨酰-甘氨酰-苯丙氨酰-亮氨酰-苏氨酸)([3H]DTLET)同侧/对侧结合比率分别下降了28%(P<0.01)和24%(P<0.01)。相比之下,在该损伤后延迟时,未检测到[3H]U.69593特异性结合的变化。对于更长的存活延迟时间(损伤后4周、8周和15周),μ和δ结合比率恢复到对照值(约等于1),这可能反映了在神经松结扎后发生了长期神经可塑性(即初级神经元代谢中的新平衡,或完整初级传入纤维的侧支发芽)。此外,将该模型中获得的结果与坐骨神经切断和腰背部背根切断后测量的结果进行比较,以比较这三种损伤类型中阿片样物质结合位点的损失程度。损伤后8天进行坐骨神经切断,[3H]DAMGO和[3H]DTLET的结合比率分别下降了18%(P<0.01)和28%(P<0.01)。损伤后两周,两种配体的损失率为24%(P<0.01),在更长的延迟时间(4周和12周),观察到结合比率逐渐恢复。因此,似乎我们研究的两种坐骨神经损伤都会导致μ和δ结合的改变,从损伤后2周到12 - 15周,其强度和时间进程相似。相比之下,连续切断9个背根(T13 - S2)的单侧背根切断术,已知会导致细直径初级传入纤维大量变性,损伤后两周,[3H]DAMGO(53%,P<0.001)和[3H]DTLET(45%,P<0.001)的结合比率显著下降。这些数据表明,背角中细直径初级传入纤维缺失越多,与对侧相比,同侧阿片样物质结合损失就越显著。(摘要截断于400字)