Activation of glial glutamate transporter via MAPK p38 prevents enhanced and long-lasting non-evoked resting pain after surgical incision in rats
Pain after surgery has recently become a major issue not only due to lack of treatment success in the acute phase; even more alarming is the large number of patients developing prolonged pain after surgery. Because spinal glutamate as well as spinal glia plays a major role in acute incisional pain,...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
23 February 2016
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| In: |
Neuropharmacology
Year: 2016, Volume: 105, Pages: 607-617 |
| ISSN: | 1873-7064 |
| DOI: | 10.1016/j.neuropharm.2016.02.024 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.neuropharm.2016.02.024 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0028390816300594 
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| Author Notes: | Sylvia Reichl, Daniel Segelcke, Viktor Keller, Robin Jonas, Armin Boecker, Manuel Wenk, Dagmar Evers, Peter K. Zahn, Esther M. Pogatzki-Zahn |
| Summary: | Pain after surgery has recently become a major issue not only due to lack of treatment success in the acute phase; even more alarming is the large number of patients developing prolonged pain after surgery. Because spinal glutamate as well as spinal glia plays a major role in acute incisional pain, we investigated the role of the spinal glial glutamate transporters (GT), GLAST, GLT-1, for acute and prolonged pain and hyperalgesia caused by an incision. Spinal administration of the GT-inhibitor DL-TBOA increased non-evoked pain but not evoked pain behavior (hyperalgesia) up to 2 weeks after incision. In accordance, spinal GLAST (and to a lesser degree GLT-1) were upregulated after incision for several days. Long-term incision induced GT upregulation was prevented by long-lasting p38-inhibitor administration but not by long-lasting ERK1/2-inhibition after incision. In accordance, daily treatment with the p38-inhibitor (but not the ERK1/2 inhibitor) prolonged non-evoked but not evoked pain behavior after incision. In electrophysiological experiments, spontaneous activity of high threshold (HT) (but not wide dynamic range (WDR)) neurons known to transmit incision induced non-evoked pain was increased after prolonged treatment with the p38-inhibitor. In conclusion, our findings indicate a new spinal pathway by which non-evoked pain behavior after incision is modulated. The pathway is modality (non-evoked pain) and neuron (HT) specific and disturbance contributes to prolonged long-term pain after surgical incision. This may have therapeutic implications for the treatment of acute and - even more relevant - for prevention of chronic pain after surgery in patients. |
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| Item Description: | Gesehen am 25.06.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1873-7064 |
| DOI: | 10.1016/j.neuropharm.2016.02.024 |