Immediate inhibition of spinal secretory phospholipase A2 prevents the pain and elevated spinal neuronal hyperexcitability and neuroimmune regulatory genes that develop with nerve root compression.
Neuroreport
; 31(15): 1084-1089, 2020 10 14.
Article
in En
| MEDLINE
| ID: mdl-32881777
ABSTRACT
Cervical nerve root injury induces a host of inflammatory mediators in the spinal cord that initiate and maintain neuronal hyperexcitability and pain. Secretory phospholipase A2 (sPLA2) is an enzyme that has been implicated as a mediator of pain onset and maintenance in inflammation and neural injury. Although sPLA2 modulates nociception and excitatory neuronal signaling in vitro, its effects on neuronal activity and central sensitization early after painful nerve root injury are unknown. This study investigated whether inhibiting spinal sPLA2 at the time of nerve root compression (NRC) modulates the pain, dorsal horn hyperexcitability, and spinal genes involved in glutamate signaling, nociception, and inflammation that are seen early after injury. Rats underwent a painful C7 NRC injury with immediate intrathecal administration of the sPLA2 inhibitor thioetheramide-phosphorlycholine. Additional groups underwent either injury alone or sham surgery. One day after injury, behavioral sensitivity, spinal neuronal excitability, and spinal cord gene expression for glutamate receptors (mGluR5 and NR1) and transporters (GLT1 and EAAC1), the neuropeptide substance P, and pro-inflammatory cytokines (TNFα, IL1α, and IL1ß) were assessed. Treatment with the sPLA2 inhibitor prevented mechanical allodynia, attenuated neuronal hyperexcitability in the spinal dorsal horn, restored the proportion of spinal neurons classified as wide dynamic range, and reduced genes for mGluR5, substance P, IL1α, and IL1ß to sham levels. These findings indicate spinal regulation of central sensitization after painful neuropathy and suggest that spinal sPLA2 is implicated in those early spinal mechanisms of neuronal excitability, perhaps via glutamate signaling, neurotransmitters, or inflammatory cascades.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spinal Nerve Roots
/
Neuroimmunomodulation
/
Genes, Regulator
/
Phospholipases A2, Secretory
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Nerve Compression Syndromes
Limits:
Animals
Language:
En
Journal:
Neuroreport
Journal subject:
NEUROLOGIA
Year:
2020
Document type:
Article