Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways.
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.
Suzuki
Rie
R
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. ucklrsu@ucl.ac.uk
Morcuende
Sara
S
Webber
Mark
M
Hunt
Stephen P
SP
Dickenson
Anthony H
AH
D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004525:Efferent Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D000922:Immunotoxins; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012702:Serotonin Antagonists / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000922:Immunotoxins; D016760:Proto-Oncogene Proteins c-fos; D018040:Receptors, Neurokinin-1; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D054789:Ribosome Inactivating Proteins, Type 1; D012702:Serotonin Antagonists; C468274:substance P-saporin; D013373:Substance P; D000076985:Saporins