Dendritic spine dysgenesis in superficial dorsal horn sensory neurons after spinal cord injury.
Neuropathic pain is a major complication of spinal cord injury, and despite aggressive efforts, this type of pain is refractory to available clinical treatment. Our previous work has demonstrated a structure-function link between dendritic spine dysgenesis on nociceptive sensory neurons in the intermediate zone, laminae IV/V, and chronic pain in central nervous system and peripheral nervous system injury models of neuropathic pain. To extend these findings, we performed a follow-up structural analysis to assess whether dendritic spine remodeling occurs on superficial dorsal horn neurons located in lamina II after spinal cord injury. Lamina II neurons are responsible for relaying deep, delocalized, often thermally associated pain commonly experienced in spinal cord injury pathologies. We analyzed dendritic spine morphometry and localization in tissue obtained from adult rats exhibiting neuropathic pain one-month following spinal cord injury. Although the total density of dendritic spines on lamina II neurons did not change after spinal cord injury, we observed an inverse relationship between the densities of thin- and mushroom-shaped spines: thin-spine density decreased while mushroom-spine density increased. These structural changes were specifically noted along dendritic branches within 150 µm from the soma, suggesting a possible adverse contribution to nociceptive circuit function. Intrathecal treatment with NSC23766, a Rac1-GTPase inhibitor, significantly reduced spinal cord injury-induced changes in both thin- and mushroom-shaped dendritic spines. Overall, these observations demonstrate that dendritic spine remodeling occurs in lamina II, regulated in part by the Rac1-signaling pathway, and suggests that structural abnormalities in this spinal cord region may also contribute to abnormal nociception after spinal cord injury.
1 Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA.|2 Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
Xiaoyu C
XC
Cao
1 Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA.|2 Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
Laura W
LW
Pappalardo
1 Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA.|2 Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
Stephen G
SG
Waxman
1 Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA.|2 Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
Andrew M
AM
Tan
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure*; D004195:Disease Models, Animal; D008297:Male; D015739:Nocodazole / Q000494:pharmacology / Q000627:therapeutic use; D020671:Posterior Horn Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016622:Silver Staining; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology*
D000970:Antineoplastic Agents; D015739:Nocodazole
central sensitization; dendritic spines; lamina II; pain; spinal cord injury; superficial dorsal horn