Immediate Inhibition of Spinal Secretory Phospholipase A(2) Prevents the Pain and Elevated Spinal Neuronal Hyperexcitability & Neuroimmune Regulatory Genes that Develop with Nerve Root Compression
| Autor: | Julia C. Quindlen‐Hotek, Beth A. Winkelstein, Sonia Kartha |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Neuroimmunomodulation Neuropeptide Pain Inflammation Substance P Pharmacology Article Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genes Regulator Medicine Premovement neuronal activity Animals Phospholipases A2 Secretory Radiculopathy Injections Spinal business.industry Metabotropic glutamate receptor 5 General Neuroscience Nerve Compression Syndromes Glutamate receptor Peripheral Nervous System Diseases Spinal cord Rats 030104 developmental biology medicine.anatomical_structure Nociception nervous system chemistry Phosphatidylcholines medicine.symptom business Spinal Nerve Roots 030217 neurology & neurosurgery |
| Zdroj: | Neuroreport |
| Popis: | Cervical nerve root injury induces a host of inflammatory mediators in the spinal cord that initiate and maintain neuronal hyperexcitability and pain. Secretory phospholipase A(2) (sPLA(2)) is an enzyme that has been implicated as a mediator of pain onset and maintenance in inflammation and neural injury. Although sPLA(2) 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 sPLA(2) at the time of nerve root compression 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 nerve root compression injury with immediate intrathecal administration of the sPLA(2) inhibitor thioetheramide-PC (TEA-PC). Additional groups underwent either injury alone or a sham surgery. One day after injury, behavioral sensitivity, spinal neuronal excitability, and spinal cord gene expression for glutamate receptors (mGluR5, NR1) and transporters (GLT1, EAAC1), the neuropeptide substance P, and pro-inflammatory cytokines (TNFα, IL1α, IL1β) were assessed. Treatment with the sPLA(2) 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 IL1β to sham levels. These findings indicate spinal regulation of central sensitization after painful neuropathy and suggest that spinal sPLA(2) is implicated in those early spinal mechanisms of neuronal, perhaps via glutamate signaling, neurotransmitters, and/or inflammatory cascades. |
| Databáze: | OpenAIRE |
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