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Serotoninergic-mediated inhibition of substance P sensitive deep dorsal horn neurons: a combined electrophysiological and morphological study in vitro

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Abstract

Dorsal horn neurons that express the neurokinin 1 receptor (NK-1R) play an important role in nociceptive processing. The targetting of NK-1R neurons by serotoninergic (5-hydroxytryptamine, 5-HT) axons would provide a straightforward means to exert an inhibitory analgesic effect at spinal level. This study used single cell electrophysiology to analyse and correlate the responses of rat deep DH neurons in vitro to both 5-HT and the NK-1R agonist [Sar9,Met(O2)11]-substance P (SP). Subsequently a combination of immunocytochemistry and confocal imaging was applied to biocytin-filled laminae III–VI neurons to reveal putative 5-HT innervation in this neuronal sample. A population of neurons was identified in which 5-HT (50 µM) significantly attenuated the dorsal root-evoked excitatory postsynaptic potential and [Sar9,Met(O2)11]-SP (2 µM) induced a direct tetrodotoxin-resistant depolarisation. Immunolabelling revealed that all of these neurons were inhibited by 5-HT, including those that were excited by [Sar9,Met(O2)11]-SP, were overlaid by a plexus of 5-HT immunoreactive fibres and in some instances, closely apposed putative contacts with somata and proximal dendrites identified although their incidence was low. Inhibition by 5-HT of deep DH neurons directly responsive to SP may account at least in part for monoamine-induced modulation of nociceptive processing in the spinal cord.

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Acknowledgements

We are grateful to The Wellcome Trust for financial support. M.A. Worsley was in receipt of a University of Leeds Postgraduate Studentship. Technical assistance was provided by Mrs. J. Daniel.

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Authors and Affiliations

  1. School of Biomedical Sciences, University of Leeds, Leeds, LS2 9NQ, UK

    Matthew A. Worsley & Anne E. King

  2. Spinal Cord Group, Institute of Biomedical and Life Sciences, University of Glasgow, West Medical Building, Glasgow, G12 8QQ, UK

    Andrew J. Todd

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  1. Matthew A. Worsley
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  2. Andrew J. Todd
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Correspondence to Anne E. King.

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Worsley, M.A., Todd, A.J. & King, A.E. Serotoninergic-mediated inhibition of substance P sensitive deep dorsal horn neurons: a combined electrophysiological and morphological study in vitro. Exp Brain Res 160, 360–367 (2005). https://doi.org/10.1007/s00221-004-2018-7

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  • DOI: https://doi.org/10.1007/s00221-004-2018-7

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