Modulation of Thalamocingulate Nociceptive Transmission and Glutamate Secretion by Targeting P2x7 Receptor

Academia Sinica (NPAS), Taipei, Taiwan, </n>Department of Organismal Biology & Anatomy, University of Chicago, Chicago, Illinois Abstract: The complexity and diversity of pain signaling have led to obstacles for prominent treatments due to mechanisms that are not yet fully understood. Among adenosine triphosphate (ATP) receptors, P2x7 differs in many respects from P2x1-6, it plays a significant role in various inflammatory pain, but whether it plays a role in noninflammatory pain has not been widely discussed. In this study, we utilized major neuropharmacological methods to record the effects of manipulating P2x7 during nociceptive signal transmission in the thalamocingulate circuits. Our results show that regardless of the specific cell type distribution of P2x7 in the central nervous system (CNS), it participates directly in the generated nociceptive transmission, which indicates its apparent functional existence in the major pain transmission path, the thalamo-cingulate circuits. Activation of P2x7 may facilitate transmission velocity along the thalamo-cingulate projection as well as neuron firings and synaptic vesicle release in anterior cingulate cortical neurons. Targeting thalamic P2x7 affects glutamate and ATP secretion during nociceptive signal transmission.Perspective: The observations in this study provide evidence that the ATP receptor P2x7 presents in the central ascending pain path and plays a modulatory role during nociceptive transmission, which could contribute new insights for many antinociceptive applications.(c) Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc