Department of Animal Morphology and Physiology, College of Agricultural and Veterinarian Sciences, São Paulo State University, Jaboticabal, SP, 14884-900, Brazil.
National Institute of Science and Technology in Comparative Physiology (INCT-Fisiologia Comparada), Jaboticabal, SP, Brazil.
Pflugers Arch. 2017 Sep;469(9):1151-1161. doi: 10.1007/s00424-017-1966-2. Epub 2017 Apr 4.
The periaqueductal gray matter (PAG) is rich in mu and kappa opioid receptors, and this system is involved in thermoregulation, analgesia, and defensive behaviors. No study approached the involvement of the PAG opioids in body temperature (Tb) regulation during psychological stress such as restraint. Because activation of mu and kappa receptors increases and reduces Tb, respectively, we tested the hypothesis that they exert excitatory and inhibitory modulation, respectively, of the restraint-induced fever in rats. To this end, Tb, heat loss index (HLI, inference for peripheral vasoconstriction/vasodilation), and oxygen consumption (inference for thermogenesis) were monitored in unanesthetized rats, restrained or unrestrained, before and after intra-PAG microinjection of the selective mu opioid receptor antagonist (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH cyclic, CTAP; 1 and 10 μg/100 nL) or the selective kappa opioid receptor antagonist (nor-binaltorphimine dihydrochloride, nor-BNI; 1 and 4 μg/100 nL) or saline (100 nL). CTAP and nor-BNI did not change the Tb or HLI of euthermic animals. During restraint, Tb increased (1.0 ± 0.1 °C) in all groups; however, this effect was lower in those animals treated with CTAP and higher in animals treated with nor-BNI. The HLI decreased during restraint and increased after animals were released, but this response was not affected by any treatment. Restraint stress increased oxygen consumption (35.9 ± 3.9% elevation), but this response was diminished by CTAP and overstimulated by nor-BNI. Confirming our hypothesis, the results indicate that the mu and kappa opioid receptors in the PAG of rats play a pyrogenic and antipyretic role, respectively, during fever induced by restraint by affecting the thermogenic but not the heat conservation effector.
导水管周围灰质（periaqueductal gray matter，PAG）富含μ和κ阿片受体，该系统参与体温调节、镇痛和防御行为。没有研究探讨 PAG 阿片系统在束缚等心理应激下对体温（Tb）调节的作用。由于激活μ和κ受体分别增加和降低 Tb，我们假设它们分别对束缚诱导的发热产生兴奋和抑制调节作用。为此，我们在未麻醉大鼠中监测 Tb、热损失指数（HLI，推测为外周血管收缩/扩张）和耗氧量（推测为产热），在束缚或不束缚之前和之后，分别在 PAG 内微量注射选择性μ阿片受体拮抗剂（D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH 环，CTAP；1 和 10μg/100nL）或选择性κ阿片受体拮抗剂（nor-binaltorphimine dihydrochloride，nor-BNI；1 和 4μg/100nL）或生理盐水（100nL）。CTAP 和 nor-BNI 未改变体温正常大鼠的 Tb 或 HLI。在束缚期间，所有组的 Tb 均升高（1.0±0.1°C）；然而，用 CTAP 处理的动物的这种作用较低，用 nor-BNI 处理的动物的作用较高。在束缚期间，HLI 降低，在动物释放后增加，但这种反应不受任何处理的影响。束缚应激增加耗氧量（增加 35.9±3.9%），但 CTAP 减弱，nor-BNI 过度刺激这种反应。证实了我们的假设，结果表明，大鼠 PAG 中的 μ 和 κ 阿片受体在束缚引起的发热中分别发挥发热和退热作用，通过影响产热而不是热保存效应器。
