Instituto de Biomedicina y Biotecnología de Cantabria IBBTEC (UC-CSIC-IDICAN), Facultad de Medicina, Av. Cardenal Herrera Oria s/n, 39011 Santander (Cantabria), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain.
Neurosci Lett. 2012 May 2;515(2):181-6. doi: 10.1016/j.neulet.2012.03.050. Epub 2012 Mar 28.
Serotonin and noradrenaline reuptake inhibitors have shown to produce antinociceptive effects in several animal models of neuropathic pain. In the present work, we have analyzed the density of brain and spinal serotonin and noradrenaline transporters (5-HTT and NAT) in a rat model of neuropathic pain, the spinal nerve ligation (SNL). Quantitative autoradiography revealed a significant decrease in the density of 5-HTT ([(3)H]citalopram binding) at the level of the lumbar spinal cord following 2 weeks of neuropathic surgery (lamina V, -40%: 6.01±0.64 nCi/mg tissue in sham-animals vs 3.59±1.56 in SNL-animals; lamina X, -30%: 9.10±2.00 vs 6.40±1.93 and lamina IX, -22%: 12.01±2.41 vs 9.42±1.58). By contrast, NAT density ([(3)H]nisoxetine binding) was significantly increased (lamina I-II, +34%: 2.20±0.45 vs 2.96±0.65; lamina V, +57%: 1.34±0.28 vs 2.11±0.66; and lamina IX, +58%: 2.39±0.71 vs 3.78±1.10). At supraspinal structures, SNL induced adaptive changes only in the density of 5-HTT (septal nuclei, +33%: 10.18±2.03 vs 13.53±1.14; CA3 field of hippocampus, +18%: 6.94±1.01 vs 8.21±0.81; paraventricular thalamic nucleus, +21%: 15.18±1.88 vs 18.35±2.08; lateral hypothalamic area, +40%: 12.68±1.90 vs 17.8±2.55; ventromedial hypothalamic nuclei, +19%: 7.16±0.92 vs 8.55±0.40; and dorsal raphe nucleus, +15%: 35.22±3.88 vs 40.68±3.11). Thus, we demonstrate, in the SNL model of neuropathic pain, the existence of opposite changes in the spinal expression of 5-HTT (down-regulation) and NAT (up-regulation), and the presence of supraspinal adaptive changes (up-regulation) only on 5-HTT density. These findings may help understanding the pathogeny of neuropathic pain and the differential analgesic action of antidepressants targeting 5-HTT and/or NAT transporters.
5-羟色胺（5-HT）和去甲肾上腺素（NE）再摄取抑制剂已被证明在几种神经性疼痛的动物模型中具有抗伤害作用。在本工作中，我们分析了神经性疼痛模型（脊神经结扎，SNL）大鼠的脑和脊髓 5-羟色胺（5-HT）和去甲肾上腺素转运体（5-HTT 和 NAT）的密度。定量放射自显影显示，神经性手术后 2 周，脊髓（L5 节段，-40%：假手术动物为 6.01±0.64 nCi/mg 组织，SNL 动物为 3.59±1.56；X 节段，-30%：9.10±2.00 对 6.40±1.93 和 IX 节段，-22%：12.01±2.41 对 9.42±1.58）中 5-HTT（[3H]西酞普兰结合）的密度显著降低。相比之下，NAT 密度（[3H]去甲烟碱结合）显著增加（I-II 层，+34%：2.20±0.45 对 2.96±0.65；V 层，+57%：1.34±0.28 对 2.11±0.66；IX 层，+58%：2.39±0.71 对 3.78±1.10）。在皮质下结构中，SNL 仅诱导 5-HTT 密度发生适应性变化（隔核，+33%：10.18±2.03 对 13.53±1.14；海马 CA3 场，+18%：6.94±1.01 对 8.21±0.81；室旁丘脑核，+21%：15.18±1.88 对 18.35±2.08；外侧下丘脑区域，+40%：12.68±1.90 对 17.8±2.55；下丘脑腹内侧核，+19%：7.16±0.92 对 8.55±0.40；和中缝背核，+15%：35.22±3.88 对 40.68±3.11）。因此，我们在 SNL 神经性疼痛模型中证明，脊髓 5-HTT（下调）和 NAT（上调）表达存在相反的变化，并且仅在 5-HTT 密度上存在皮质下的适应性变化（上调）。这些发现可能有助于理解神经性疼痛的发病机制以及针对 5-HTT 和/或 NAT 转运体的抗抑郁药的差异镇痛作用。
