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

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 microM) significantly attenuated the dorsal root-evoked excitatory postsynaptic potential and [Sar9,Met(O2)11]-SP (2 microM) 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.

Kynurenic acid blocks nicotinic synaptic transmission to hippocampal interneurons in young rats

“…In addition to the electrophysiological characterization of cells, identity was confirmed at the end of a recording session by filling cells with biocytin by passing 500 ms pulses of 0.5 nA outward (hyperpolarizing) current (Chen et al ., 1996; Koyama et al ., 1998; Worsley et al ., 2005) through the microelectrode at 1 Hz for 5–10 min. The membrane potential was monitored throughout this procedure to ensure that penetration was maintained during filling.…”

Synaptic Connections of the Neurokinin 1 Receptor-Like Immunoreactive Neurons in the Rat Medullary Dorsal Horn

“…Serotonergic descending pathways from brainstem form an endogenous analgesic system. Electrophysiological data demonstrated that 5-HT induced inhibition on SP-sensitive (putative NK-1 receptor expressing) dorsal horn neurons in vitro [42]. We have found that 5-HT-LI terminals contact with NK1 receptor-LI somata and dendrites in the superficial dorsal horn.…”

Serotonin in a diencephalic nucleus controlling communication in an electric fish: Sexual dimorphism and relationship to indicators of dominance

“…The coexpression of two neuromodulators with opposite effects may enhance the modulation of communication signals in response to changes in social environment or reproductive condition. In other systems, serotonin and substance P often colocalize and regulate behavior and motor rhythms through divergent effects on neuronal excitability (Svensson et al, 2001;Ramirez and Viemari, 2005;Worsley et al, 2005). Furthermore, substance P acting on neurokinin-1 receptors can inhibit the release of serotonin, and serotonin can block the modulatory effects of substance P (Santarelli et al, 2001;Svensson et al, 2001;Gobbi and Blier, 2005).…”