Dendritic spine dysgenesis in spinal cord injury: A structural contributor to pain and spasticity

Abstract

Pain and spasticity are common consequences of spinal cord injury (SCI) that profoundly diminish quality of life. Although pain arises from sensory pathways and spasticity from motor pathways, both reflect post-injury mechanisms that renders spinal circuits hyperexcitable. Dendritic spines—specialized protrusions on neuronal dendrites that mediate excitatory synaptic transmission—undergo striking structural remodeling after SCI. Abnormal spine morphology has been documented in both the superficial and deeper laminae of the dorsal horn, correlating with pain, and on motor neurons in the lumbar spinal cord after, correlating with spasticity. These abnormalities include: (i) increased spine density, (ii) redistribution of spines closer to the soma, and (iii) enlargement of spine heads. A growing body of evidence implicates dysregulation of the Rac1-PAK1 signaling pathway in driving these changes, and pharmacologic inhibition of this pathway can reverse these dendritic spine dysgeneses and attenuate circuit hyperexcitability in preclinical models. This review examines dendritic spine pathology as a shared mechanistic substrate linking pain and spasticity after SCI and highlights dendritic spines and their regulatory pathways a promising therapeutic target for intervention.