Influence of arthritis on descending modulation of nociception from the paraventricular nucleus of the hypothalamus

Abstract

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 α2-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 α2-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.