Pinto-Ribeiro Filipa, Ansah Osei B, Almeida Armando, Pertovaara Antti
Biomedicum Helsinki, Institute of Biomedicine/Physiology, POB 63, University of Helsinki, 00014 Helsinki, Finland.
Brain Res. 2008 Mar 4;1197:63-75. doi: 10.1016/j.brainres.2007.12.038. Epub 2007 Dec 28.
We studied the influence of arthritis on descending modulation of nociception from the hypothalamic paraventricular nucleus (PVN) in the rat. Spinal nociception was assessed by the heat-evoked limb withdrawal in awake animals while neuronal responses were recorded in a potential brainstem relay, the rostroventromedial medulla (RVM), under pentobarbitone anesthesia. Following injection into the PVN, glutamate attenuated and lidocaine enhanced nociceptive spinal reflex responses in arthritic and control animals. In controls, PVN-induced antinociception was reversed by spinal administration of a 5-HT1A receptor or an alpha2-adrenoceptor antagonist but not by an opioid receptor antagonist. In arthritic animals, PVN-induced antinociception was not reversed by a 5-HT1A receptor antagonist, while the roles of alpha2-adrenoceptors or opioid receptors could not be assessed due to significant actions of antagonists alone. The spontaneous activity of presumably pronociceptive ON-cells of the RVM and that of antinociceptive OFF-cells was increased in arthritis. Lidocaine in the PVN increased ON-cell firing in control animals and decreased OFF-cell firing in arthritic animals, while glutamate failed to affect activity of RVM cells. The results indicate that the PVN influences phasic and tonic descending antinociception in arthritic as well as control conditions, and the RVM may contribute to the relay of this influence. In arthritis, the neurochemistry of descending antinociception differs at least partly from that in controls. Arthritis has a dual influence on the PVN-induced drive of relay cells in the RVM which reduces the arthritis-induced net change in the descending antinociceptive influence from the PVN.
我们研究了关节炎对大鼠下丘脑室旁核（PVN）下行性伤害性感受调制的影响。通过清醒动物热诱发肢体回撤评估脊髓伤害性感受，同时在戊巴比妥麻醉下，在潜在的脑干中继站延髓头端腹内侧区（RVM）记录神经元反应。向PVN注射后，谷氨酸减弱而利多卡因增强了关节炎动物和对照动物的伤害性脊髓反射反应。在对照动物中，脊髓给予5-HT1A受体拮抗剂或α2-肾上腺素能受体拮抗剂可逆转PVN诱导的镇痛作用，但阿片受体拮抗剂则不能。在关节炎动物中，5-HT1A受体拮抗剂不能逆转PVN诱导的镇痛作用，而由于拮抗剂单独作用显著，无法评估α2-肾上腺素能受体或阿片受体的作用。关节炎时，RVM中推测的促伤害性感受的ON细胞和抗伤害性感受的OFF细胞的自发活动增加。PVN中的利多卡因增加对照动物ON细胞的放电，减少关节炎动物OFF细胞的放电，而谷氨酸未能影响RVM细胞的活动。结果表明，PVN在关节炎和对照条件下均影响阶段性和紧张性下行性抗伤害感受，且RVM可能参与这种影响的中继传递。在关节炎中，下行性抗伤害感受的神经化学至少部分不同于对照。关节炎对PVN诱导的RVM中继细胞驱动有双重影响，这减少了PVN下行性抗伤害感受影响的关节炎诱导净变化。
