Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Aomori, Japan.
Mol Pain. 2011 Oct 18;7:79. doi: 10.1186/1744-8069-7-79.
Phospholipase C-related inactive protein (PRIP) plays important roles in trafficking to the plasma membrane of GABA(A) receptor, which is involved in the dominant inhibitory neurotransmission in the spinal cord and plays an important role in nociceptive transmission. However, the role of PRIP in pain sensation remains unknown. In this study, we investigated the phenotypes of pain behaviors in PRIP type 1 knockout (PRIP-1 (-/-)) mice. The mutant mice showed hyperalgesic responses in the second phase of the formalin test and the von Frey test as compared with those in wild-type mice. In situ hybridization studies of GABA(A) receptors revealed significantly decreased expression of γ2 subunit mRNA in the dorsal and ventral horns of the spinal cord in PRIP-1 (-/-) mice, but no difference in α1 subunit mRNA expression. β2 subunit mRNA expression was significantly higher in PRIP-1 (-/-) mice than in wild-type mice in all areas of the spinal cord. On the other hand, the slow decay time constant for the spontaneous inhibitory current was significantly increased by treatment with diazepam in wild-type mice, but not in PRIP-1 (-/-) mice. These results suggest that PRIP-1 (-/-) mice exhibit the changes of the function and subunits expression of GABA(A) receptor in the spinal cord, which may be responsible for abnormal pain sensation in these mice.
磷酯酶 C 相关无活性蛋白 (PRIP) 在 GABA(A) 受体向质膜转运中发挥重要作用，GABA(A) 受体参与脊髓中的主要抑制性神经传递，在痛觉传递中起重要作用。然而，PRIP 在痛觉感知中的作用尚不清楚。在本研究中，我们研究了 PRIP 型 1 敲除 (PRIP-1(-/-)) 小鼠的疼痛行为表型。与野生型小鼠相比，突变小鼠在福尔马林试验和 von Frey 试验的第二阶段表现出痛觉过敏反应。原位杂交研究表明，PRIP-1(-/-) 小鼠脊髓背角和腹角的 γ2 亚基 mRNA 表达显著降低，但 α1 亚基 mRNA 表达无差异。PRIP-1(-/-) 小鼠脊髓各区域的 β2 亚基 mRNA 表达明显高于野生型小鼠。另一方面，在野生型小鼠中，地西泮处理显著增加了自发性抑制电流的缓慢衰减时间常数，但在 PRIP-1(-/-) 小鼠中没有增加。这些结果表明，PRIP-1(-/-) 小鼠表现出脊髓中 GABA(A) 受体功能和亚基表达的变化，这可能是这些小鼠异常痛觉感知的原因。
