Journal
NEUROSCIENCE
Volume 291, Issue -, Pages 93-105Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2015.02.011
Keywords
cancer-induced bone pain; P2X7R antagonism; analgesia; neuronal responses; pain behavior
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Funding
- Advokat Bent Thorbergs Fond og Fonden til laegevidenskabens fremme v/A.P.
- Moller og Hustru and Chastine Mc-Kinney Mollers Fond til almene Formeal
- Wellcome Trust
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Pain is a common and debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of molecular events, including mechanisms observed in inflammatory and neuropathic pain states, but also changes unique for cancer-induced bone pain. The P2X7 receptor (P2X7R) is involved in a variety of cellular functions and has been linked to both inflammatory and neuropathic pain. Here we study the analgesic potential of P2X7R antagonism in a rat model of cancer-induced bone pain. In cancer-bearing animals, the P2X7R antagonist A839977 attenuated dorsal horn neuronal responses in a modality and intensity-specific way. Spinal application of 0.4-mg/kg and 1.2-mg/kg A839977 significantly reduced the evoked responses to high-intensity mechanical and thermal stimulation, whereas no effect was seen in response to low-intensity or electrical stimulation. In contrast, A839977 had no effect on the tested parameters in naive or sham animals. In awake animals, 40-mg/kg A839977 (i.p.) significantly reduced both early-and late-stage pain behavior. In contrast, no effect was observed in sham or vehicle-treated animals. The results suggest that the P2X7R is involved in the mechanisms of cancer-induced bone pain, and that P2X7R antagonism might be a useful analgesic target. No effect was observed in sham or naive animals, indicating that the P2X7R-mediated effect is state-dependent, and might therefore be an advantageous target compared to traditional analgesics. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
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