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Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways

Abstract

The increase in pain sensitivity that follows injury is regulated by superficially located projection neurons in the dorsal horn of the spinal cord that express the neurokinin-1 (NK1) receptor. After selective ablation of these neurons in rats, we identified changes in receptive field size, mechanical and thermal coding and central sensitization of deeper dorsal horn neurons that are important for both pain sensations and reflexes. We were able to reproduce these changes by pharmacological block of descending serotonergic facilitatory pathways. Using Fos histochemistry, we found changes in the activation of serotonergic neurons in the brainstem as well as evidence for a loss of descending control of spinal excitability. We conclude that NK1-positive spinal projection neurons, activated by primary afferent input, project to higher brain areas that control spinal excitability—and therefore pain sensitivity—primarily through descending pathways from the brainstem.

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Figure 1: SP-SAP infusion ablates lamina I/III NK1-R neurons.
Figure 2: SP-SAP attenuates CFA-induced mechanical hyperalgesia, RF size, formalin evoked activity and wind-up of deep dorsal horn neurons.
Figure 3: Deficits in the neuronal coding of mechanical stimuli in SP-SAP treated rats.
Figure 4: Disruption of the stimulus response relation for thermal stimuli in SP-SAP treated rats.
Figure 5: Block of the 5HT3-R mimics the effect of SP-SAP on mechanical/thermal coding and formalin response in SAP injected rats.
Figure 6: SP-SAP reduces descending control onto spinal neurons.
Figure 7: 5HT positive RMg neurons label with Fos following peripheral formalin injection.

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Acknowledgements

This work was supported by the Wellcome Trust, London Pain Consortium and by the European Community Marie Curie Fellowship.

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Correspondence to Rie Suzuki.

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Suzuki, R., Morcuende, S., Webber, M. et al. Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways. Nat Neurosci 5, 1319–1326 (2002). https://doi.org/10.1038/nn966

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