Activation of the dorsomedial nucleus of the hypothalamus (
DMH) by
galanin (GAL) induces behavioural
hyperalgesia. Since
DMH neurones do not project directly to the spinal cord, we hypothesized that the medullary dorsal reticular nucleus (DRt), a pronociceptive region projecting to the spinal dorsal horn (SDH) and/or the serotoninergic raphe-spinal pathway acting on the spinal
5-HT3 receptor (5HT3R) could relay descending nociceptive facilitation induced by GAL in the
DMH. Heat-evoked paw-withdrawal latency (PWL) and activity of SDH neurones were assessed in monoarthritic (ARTH) and control (
SHAM) animals after pharmacological manipulations of the
DMH, DRt and spinal cord. The results showed that GAL in the
DMH and
glutamate in the DRt lead to behavioural
hyperalgesia in both
SHAM and ARTH animals, which is accompanied particularly by an increase in heat-evoked responses of wide-dynamic range neurons, a group of nociceptive SDH neurones. Facilitation of
pain behaviour induced by GAL in the
DMH was reversed by
lidocaine in the DRt and by
ondansetron, a 5HT3R antagonist, in the spinal cord. However, the
hyperalgesia induced by
glutamate in the DRt was not blocked by spinal
ondansetron. In addition, in ARTH but not
SHAM animals PWL was increased after
lidocaine in the DRt and
ondansetron in the spinal cord. Our data demonstrate that GAL in the
DMH activates two independent descending facilitatory pathways: (i) one relays in the DRt and (ii) the other one involves
5-HT neurones acting on spinal 5HT3Rs. In experimental ARTH, the tonic
pain-facilitatory action is increased in both of these descending pathways.