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. Author manuscript; available in PMC: 2015 Dec 1.
Published in final edited form as: Pain. 2014 Sep 19;155(12):2560–2567. doi: 10.1016/j.pain.2014.09.016

Fig. 5. Proposed schematic representation of mechanisms underlying IB-MECA’s beneficial actions on CIPN.

Fig. 5

Chemotherapy (paclitaxel)-induced neuropathic pain is associated with increased NADPH oxidase activity within the spinal cord contributing to enhanced peroxynitrite (PN) production. Due to its ability to post-translationally modify protein function, peroxynitrite could be a driver behind many of the spinal neuropathological changes underlying CIPN including 1) the nitration/inactivation of glutamate transporter 1 (GLT-1) and glutamine synthetase (GS) and 2) the activation of redox-dependent signaling pathways (NFκB and MAPK) leading to a surge in glial-associated pro-inflammatory cytokine production (TNF-α and IL-1β). Treatment with the selective A3AR agonist, IB-MECA, not only inhibits paclitaxel-induced pain and the associated spinal events, it also increases the formation of the neuroprotective/anti-inflammatory cytokine, IL-10.