Ito A, Kumamoto E, Takeda M, Shibata K, Sagai H, Yoshimura M
Department of Physiology, Saga Medical School, Saga 849-8501, Japan.
J Neurosci. 2000 Aug 15;20(16):6302-8. doi: 10.1523/JNEUROSCI.20-16-06302.2000.
Chronic treatment with calcitonin in osteoporotic patients alleviates the pain associated with this condition by an unknown mechanism. In ovariectomized rats that develop osteoporosis and hyperalgesia, we examined whether a functional change in serotonergic systems in the spinal dorsal horn was involved, using whole-cell recordings from substantia gelatinosa neurons in spinal cord slices and [(3)H]8-hydroxy-2(di-n-propylamino)tetralin ([(3)H]8-OH-DPAT) binding. Hyperalgesia could be attributed to the elimination of presynaptic inhibition by 5-HT of glutamatergic primary C-afferent terminals and an associated decrease in the density of [(3)H]8-OH-DPAT binding sites whose receptors are neither 5-HT(1A)- nor 5-HT(7)-subtype. These changes in serotonergic systems were restored after chronic treatment with calcitonin. Reversal of 5-HT receptor changes by calcitonin treatment may provide an explanation for its analgesic actions in patients.
降钙素对骨质疏松症患者的长期治疗可通过未知机制减轻与此病症相关的疼痛。在发生骨质疏松症和痛觉过敏的去卵巢大鼠中，我们使用脊髓切片中胶状质神经元的全细胞膜片钳记录和[³H]8-羟基-2-（二正丙基氨基）四氢萘（[³H]8-OH-DPAT）结合实验，研究脊髓背角中5-羟色胺能系统的功能变化是否与之有关。痛觉过敏可能归因于5-羟色胺对谷氨酸能初级C传入终末的突触前抑制作用消除，以及与之相关的[³H]8-OH-DPAT结合位点密度降低，这些位点的受体既不是5-羟色胺1A亚型也不是5-羟色胺7亚型。降钙素长期治疗后，5-羟色胺能系统的这些变化得以恢复。降钙素治疗使5-羟色胺受体变化逆转，这可能解释了其对患者的镇痛作用。
