TY - JOUR T1 - Neuropathic Pain Memory Is Maintained by Rac1-Regulated Dendritic Spine Remodeling after Spinal Cord Injury JF - The Journal of Neuroscience JO - J. Neurosci. SP - 13173 LP - 13183 DO - 10.1523/JNEUROSCI.3142-08.2008 VL - 28 IS - 49 AU - Andrew M. Tan AU - Severine Stamboulian AU - Yu-Wen Chang AU - Peng Zhao AU - Avis B. Hains AU - Stephen G. Waxman AU - Bryan C. Hains Y1 - 2008/12/03 UR - http://www.jneurosci.org/content/28/49/13173.abstract N2 - Localized increases in synaptic strength constitute a synaptic basis for learning and memory in the CNS and may also contribute to the maintenance of neuropathic pain after spinal cord injury (SCI) through the de novo formation or elaboration of postsynaptic dendritic structures. To determine whether SCI-induced dendritic spine remodeling contributes to neuronal hyperexcitability and neuropathic pain, we analyzed spine morphometry, localization, and functional influence in dorsal horn (DH) neurons in adult rats 1 month after sham surgery, contusion SCI, and SCI treated with a selective inhibitor of Rac1 activation, NSC23766. After SCI, DH neurons located in lamina IV–V exhibited increased spine density, redistributed spines, and mature spines compared with control neurons, which was associated with enhancement of EPSCs in computer simulations and hyperexcitable responsiveness to innocuous and noxious peripheral stimuli in unit recordings in vivo. SCI animals also exhibited symptoms of tactile allodynia and thermal hyperalgesia. Inhibition of the small GTP-binding protein Rac1 ameliorated post-SCI changes in spine morphology, attenuated injury-induced hyperexcitability of wide-dynamic range neurons, and progressively increased pain thresholds over a 3 d period. This suggests that Rac1 is an important intracellular signaling molecule involved in a spinal dendritic spine pathology associated with chronic neuropathic pain after SCI. Our report provides robust evidence for a novel conceptual bridge between learning and memory on the one hand, and neuropathic pain on the other. ER -