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Cytokine Expression Profiles and Electrophysiological Recordings of Dorsal Root Ganglion Cells in an In Vitro Model of Chronic Pain
Author(s) -
Staunton Caroline,
BarrettJolley Richard,
Djouhri Laiche,
Thippeswamy Thimmasettappa
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.838.1
Subject(s) - dorsal root ganglion , neuropathic pain , nociceptor , medicine , tumor necrosis factor alpha , electrophysiology , cytokine , peripheral nerve injury , nerve injury , microglia , patch clamp , neuroscience , pharmacology , in vitro , endocrinology , chemistry , anesthesia , inflammation , nociception , dorsum , receptor , biology , anatomy , biochemistry , sciatic nerve
Chronic neuropathic pain (CNP) affects ∼116m adults in the US alone. Frequently it results from nerve dysfunction and involves a wide range of responses, including the upregulation of inflammatory markers. In this study we used an in vitro model of CNP to analyse the effects of a TNFα treatment on cultured dorsal root ganglion (DRG) and glial cells. Using ELISA, aspirated cell culture media was examined from control DRG, TNFα treated DRG and from DRG treated with medium from TNF‐a stimulated glial cultures. IL1α, IL4, IL6, and IFN‐γ expression was decreased post‐TNFα treatment compared to control(n=4,p<0.05). DRG challenged with media from TNFα stimulated glial cultures had elevated IL1α, IL6, IFN‐γ and CCL5 compared to both control and TNFα treated DRG(n=4,p<0.05). This highlights the importance of glial cells and shows DRG properties change in their presence. Whole‐cell patch clamp electrophysiology was also used to investigate functional DRG changes post‐TNFα treatment. Voltage step protocols were carried out at 22, 30, 37 and 45 o C and steady state current recorded. Under control conditions, elevated temperatures decreased reversal potential however, whole cell conductance remained stable. TNFα caused similar effects to elevated temperature. These data suggest that cytokines may act on multiple DRG ion channels. Cytokines are known to alter ion channel activity and sensitise nociceptors and so further work will explore if interventions could prevent neuronal hyperexcitability. Funded by Pain Relief Foundation & University of Liverpool.