Pre- and postsynaptic localization of the 5-HT7 receptor in rat dorsal spinal cord: Immunocytochemical evidence

Abstract

Several lines of evidence indicate that 5-HT7 receptors are involved in pain control at the level of the spinal cord, although their mechanism of action is poorly understood. To provide a morphological basis for understanding the action of 5-HT on this receptor, we performed an immunocytochemical study of 5-HT7 receptor distribution at the lumbar level. 5-HT7 immunolabelling is localized mainly in the two superficial laminae of the dorsal horn and in small and medium-sized dorsal root ganglion cells, which is consistent with a predominant role in nociception. In addition, moderate labelling is found in the lumbar dorsolateral nucleus (Onuf's nucleus), suggesting involvement in the control of pelvic floor muscles. Electron microscopic examination of the dorsal horn revealed three main localizations: 1) a postsynaptic localization on peptidergic cell bodies in laminae I-III and in numerous dendrites; 2) a presynaptic localization on unmyelinated and thin myelinated peptidergic fibers (two types of axon terminals are observed, large ones, presumably of primary afferent origin, and smaller ones partially from intrinsic cells; this presynaptic labelling represents 60% and 22% of total labelling in laminae I and II, respectively); and 3) 16.9% of labelling in lamina I and 19.8% in lamina II are observed in astrocytes. Labeled astrocytes are either intermingled with neuronal elements or make astrocytic "feet" on blood vessels. In dendrites, the labelling is localized on synaptic differentiations, suggesting that 5-HT may act synaptically on the 5-HT7 receptor. This localization is compared with other 5-HT receptor localizations, and their physiological consequences are discussed.

Central modulation of pain

“…Further, systemic administration of 5-HT7 agonists blocked capsaicin-induced hyperalgesia in mice, whereas 5-HT7 antagonists elicited mechanical hypersensitivity (83). The 5-HT7 receptor has been identified in the dorsal root ganglion and on central terminals of primary afferent fibers (84,85) as well as on GABAergic interneurons in the dorsal horn of the spinal cord (84), which is consistent with a role in pain modulation (83). Although these observations indicate an important serotonergic role for pain modulation, the precise spinal mechanisms involved remain unclear.…”

Spinal 5-HT7 Receptors Are Critical for Alternating Activity During Locomotion: In Vitro Neonatal and In Vivo Adult Studies Using 5-HT7 Receptor Knockout Mice

“…Thus one possibility is that the inhibitory interneurons responsible for alternating activity during locomotion are normally controlled by 5-HT via 5-HT 7 receptors. There is one report describing 5-HT 7 receptor distribution within the spinal cord (Doly et al 2005), showing that they are confined largely to the dorsal horn, with a low level of labeling of motoneurons in lamina X of the rat lumbar cord. Our results are not consistent with an action of 5-HT on motoneurons because the major effect of 5-HT 7 receptor blockage or deletion is loss of alternating rhythmic activity, not a decrease in motoneuron output.…”

Monoaminergic Control of Cauda-Equina-Evoked Locomotion in the Neonatal Mouse Spinal Cord

“…This was not the case, and instead the rhythm was reversibly weakened after addition of 5-HT 7 agonists. Possible explanations include actions at the dorsal horn where 5-HT 7 receptors are known to be clustered in addition to the ventral horn, which could explain the concomitant reduction in polysynaptic potentials (Cina and Hochman 1998;Doly et al 2005;Schmidt and Jordan 2000).…”