Activation of glial glutamate transporter via MAPK p38 prevents enhanced and long-lasting non-evoked resting pain after surgical incision in rats. (June 2016)

• Record Type: Journal Article
• Authors: Reichl, Sylvia; Segelcke, Daniel; Keller, Viktor; Jonas, Robin; Boecker, Armin; Wenk, Manuel; Evers, Dagmar; Zahn, Peter K.; Pogatzki-Zahn, Esther M.
• Is Part Of: Neuropharmacology. Volume 105(2016)
• Page Start: 607
• Page End: 617
• Publication Date: 2016-06
• Subjects: Neurotransmitter -- Glutamate transporter -- Glia interaction -- Postoperative pain -- Incision model; SB203580 (PubChem CID 176155) -- PD98059 (PubChem CID 4713) -- DL-TBOA (PubChem CID 5311218); Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2016.02.024
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: 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. Highlights: Glial glutamate transporters (e.g. GLAST) are functional involved in non-evoked pain behavior after incision. Upregulation of GLAST expression reduces and prevents selectively non-evoked pain behavior after incision. GLAST expression is regulated by the MAPK p38 after incision. Deep high threshold neurons transmitting non-evoked pain behavior after incision. Inhibition of glutamate transporter upregulation produce an increase of spontaneous activity high threshold neurons.