Morato Manuela, Pinho Dora, Sousa Teresa, Tavares Isaura, Albino-Teixeira António
Institute of Pharmacology and Therapeutics, Faculty of Medicine of Porto and IBMC, University of Porto, Porto, Portugal.
J Neurosci Res. 2006 Mar;83(4):647-55. doi: 10.1002/jnr.20770.
The mechanisms of hypertension-induced hypoalgesia were studied in a model of hypertension induced by adenosine receptors blockade with the non-selective antagonist 1,3-dipropyl-8-sulfophenylxanthine (DPSPX) during 7 days. Based on the positive correlation between pain thresholds and noxious-evoked expression of the c-fos protooncogene in spinal cord neurones, we used this marker of nociceptive activation of spinal neurones to evaluate the involvement of the spinal GABAergic system and the caudal ventrolateral medulla (VLM), an important inhibitory component of the supraspinal endogenous pain modulatory system. In DPSPX-treated animals, a 20% increase in blood pressure was achieved along with a decrease in Fos expression in the superficial (laminae I-II) and deep (laminae III-VII) dorsal horn. In these animals, lower percentages of neurones labeled for GABAB receptors that expressed Fos were obtained in the superficial dorsal horn. Lesioning the VLMlat with quinolinic acid prevented the decrease in Fos expression at the spinal cord of DPSPX-hypertensive rats whereas in normotensive animals, no changes in Fos expression were detected. The present results support previous findings that hypertension is associated with a decrease of nociceptive activation of spinal cord neurones, through descending inhibition exerted by the VLMlat. This study further shows that during hypertension a decrease in the expression of GABAB receptors in nociceptive spinal neurones occurs, probably due to changes in the local GABAergic inhibitory system.
在一个通过非选择性拮抗剂1,3 - 二丙基 - 8 - 磺苯基黄嘌呤（DPSPX）阻断腺苷受体诱导高血压的模型中，研究了高血压诱导痛觉减退的机制，持续7天。基于疼痛阈值与脊髓神经元中c - fos原癌基因伤害性刺激诱发表达之间的正相关关系，我们使用这种脊髓神经元伤害性激活的标志物来评估脊髓GABA能系统和延髓尾端腹外侧区（VLM）的参与情况，VLM是脊髓上源性疼痛调制系统的一个重要抑制成分。在经DPSPX处理的动物中，血压升高了20%，同时浅背角（I - II层）和深背角（III - VII层）的Fos表达降低。在这些动物中，浅背角中表达Fos的GABAB受体标记神经元的百分比更低。用喹啉酸损伤VLM外侧区可防止DPSPX高血压大鼠脊髓中Fos表达的降低，而在正常血压动物中，未检测到Fos表达的变化。目前的结果支持先前的研究发现，即高血压与脊髓神经元伤害性激活的降低有关，这是通过VLM外侧区施加的下行抑制实现的。这项研究进一步表明，在高血压期间，伤害性脊髓神经元中GABAB受体的表达会降低，这可能是由于局部GABA能抑制系统的变化所致。
