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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Brain Stem / cytology
-
Brain Stem / drug effects
-
Brain Stem / metabolism*
-
Efferent Pathways / cytology
-
Efferent Pathways / drug effects
-
Efferent Pathways / metabolism*
-
Hyperalgesia / metabolism
-
Hyperalgesia / physiopathology
-
Immunohistochemistry
-
Immunotoxins
-
Male
-
Nerve Fibers, Myelinated / drug effects
-
Nerve Fibers, Myelinated / metabolism
-
Nerve Fibers, Unmyelinated / drug effects
-
Nerve Fibers, Unmyelinated / metabolism
-
Neural Inhibition / drug effects
-
Neural Inhibition / physiology
-
Pain / metabolism*
-
Pain / physiopathology
-
Pain Measurement / drug effects
-
Pain Threshold / drug effects
-
Pain Threshold / physiology
-
Posterior Horn Cells / cytology
-
Posterior Horn Cells / drug effects
-
Posterior Horn Cells / metabolism*
-
Proto-Oncogene Proteins c-fos / metabolism
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, Neurokinin-1 / drug effects
-
Receptors, Neurokinin-1 / metabolism*
-
Receptors, Serotonin / drug effects
-
Receptors, Serotonin / metabolism
-
Receptors, Serotonin, 5-HT3
-
Ribosome Inactivating Proteins, Type 1
-
Saporins
-
Serotonin Antagonists / pharmacology
-
Substance P / analogs & derivatives
-
Substance P / metabolism*
-
Synaptic Transmission / drug effects
-
Synaptic Transmission / physiology
Substances
-
Immunotoxins
-
Proto-Oncogene Proteins c-fos
-
Receptors, Neurokinin-1
-
Receptors, Serotonin
-
Receptors, Serotonin, 5-HT3
-
Ribosome Inactivating Proteins, Type 1
-
Serotonin Antagonists
-
substance P-saporin
-
Substance P
-
Saporins