The rostroventromedial medulla (RVM) is an important source of descending modulatory systems that both inhibit and facilitate
pain at the level of the spinal cord. Noxious stimuli can activate serotonergic neurons in the RVM and accelerate the turnover of
5-HT in the spinal cord. While numerous studies suggest a bidirectional role for serotonergic transmission at the spinal level, the subtypes of the
5-HT receptors that are associated with descending facilitation or inhibition have not been clearly determined. Here, we explore the relative contribution of spinal 5-HT7 and 5-HT3 receptors to antinociception or
hyperalgesia associated with states of enhanced net descending inhibition or facilitation from the RVM. In uninjured rats, RVM microinjection of
morphine produced dose-dependent antinociception in the noxious thermal paw flick test while RVM microinjection of CCK produced
thermal hyperalgesia and
tactile allodynia. Spinal administration of the 5-HT7 antagonist
SB-269970, but not of the
5-HT3 antagonist ondansetron, blocked the antinociceptive effects of RVM
morphine. In contrast,
hyperalgesia induced by RVM-CCK was blocked by spinal
ondansetron, but not by
SB-269970. The antinociceptive effects of systemic
morphine were also blocked by spinal
SB-269970 but not
ondansetron while
hyperalgesia and
allodynia resulting from SNL injury were blocked by spinal
ondansetron, but not
SB-269970. These studies suggest that descending
pain inhibitory or facilitatory pathways from RVM act ultimately in the spinal cord in acute and
chronic pain states through activation of 5-HT7 and 5-HT3 receptors, respectively.