We studied the influence of arthritis on descending modulation of pain originating in the paraventricular nucleus (PVN) of the hypothalamus and relaying through the medial medulla to the spinal cord. Unilateral arthritis of the knee joint was induced by intra-articular injection of carrageenan and kaolin in the rat. The influence of glutamate injection into the PVN on responses of nociceptive medial medullary and spinal dorsal horn wide-dynamic range neurons was determined under pentobarbitone anesthesia in arthritic and control animals. In arthritic animals, spontaneous activity of medullary neurons giving excitatory responses to nociceptive stimulation was increased. Glutamate in the PVN reduced heat-evoked excitatory responses of nociceptive medial medullary and spinal dorsal horn neurons. This glutamate-induced antinociceptive effect was attenuated following arthritis. The results indicate that arthritis induces a change in the efficacy of the descending pain inhibitory pathway originating in the PVN.