Time Course of Inflammation in Dorsal Root Ganglia Correlates with Differential Reversibility of Mechanical Allodynia. (21st January 2020)

• Record Type: Journal Article
• Authors: Noh, Myung-chul; Mikler, Benjamin; Joy, Twinkle; Smith, Peter A.
• Is Part Of: Neuroscience. Volume 428(2020)
• Page Start: 199
• Page End: 216
• Publication Date: 2020-01-21
• Subjects: CCI chronic constriction injury -- CSF1 colony stimulating factor 1 -- DRG dorsal root ganglia -- GFAP glial fibrillary acidic protein -- IHC immunohistochemistry -- IL-1β interleukin1 β -- PFA paraformaldehyde -- rt-qPCR real time quantitative polymerase chain reaction -- SGC satellite glial cell -- SNI spared nerve injury; colony stimulating factor 1 -- neuropathic pain -- allodynia -- interleukin 1 beta -- chronic constriction injury -- spared nerves injury; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.12.040
• Languages: English
• ISSNs: 0306-4522

Abstract

Graphical abstract: Highlights: The process of transition between acute and chronic pain is poorly understood. In rats, sciatic chronic constriction injury produces reversible allodynia. Spared nerve injury produces persistent allodynia. This may reflect differences in neuroinflammatory responses in dorsal root ganglia. Neuroinflammation involves interleukin 1β and colony stimulating factor 1. Abstract: Some individuals recover from the pain of nerve trauma within 12 months or less whereas others experience life-long intractable pain. This transition between reversible pain and the establishment of chronic neuropathic pain is poorly understood. We examined the role of persistent inflammation in the dorsal root ganglia (DRG) in the long-term maintenance of mechanical allodynia; an index of neuropathic pain. Male Sprague-Dawley rats underwent chronic constriction injury (CCI), spared nerve injury (SNI) or sham surgery. Both CCI and SNI animals displayed robust mechanical allodynia in the ipsilateral paw at 7 d post-surgery; however, only SNI animals maintained mechanical allodynia at 42 d post-surgery. DRGs were extracted at 7 d or 42 d post-surgery to assess inflammation via rt-qPCR or immunohistochemistry to measure colony stimulating factor 1 (CSF1) expression, satellite glial cell (SGC) activation, presence of Iba1 positive macrophages and interleukin1 β (IL-1β) mRNA levels. Whereas DRGs from SNI animals continued to display inflammatory markers at 42 d, those from CCI animals did not. Moreover, the level of allodynia displayed by each individual animal correlated with the extent of DRG inflammation. These data support the hypothesis that the amount of CSF1 immunoreactivity and the persistence of inflammation in ipsilateral DRGs contribute to the difference between transient and persistent mechanical allodynia observed in the CCI and SNI models. We also suggest that feedback loops involving cytokines and neurotransmitters may contribute to increased DRG activity in chronic neuropathic pain. Consequently, targeting persistent CSF1 production and peripheral neuroinflammation may be an effective approach to the management of chronic neuropathic pain.