Dendritic spine dysgenesis in neuropathic pain.
The failure of neuropathic pain to abate even years after trauma suggests that adverse changes to synaptic function must exist in a chronic pathological state in nociceptive pathways. The chronicity of neuropathic pain therefore underscores the importance of understanding the contribution of dendritic spines--micron-sized postsynaptic structures that represent modifiable sites of synaptic contact. Historically, dendritic spines have been of great interest to the learning and memory field. More recent evidence points to the exciting implication that abnormal dendritic spine structure following disease or injury may represent a "molecular memory" for maintaining chronic pain. Dendritic spine dysgenesis in dorsal horn neurons contributes to nociceptive hyperexcitability associated with neuropathic pain, as demonstrated in multiple pain models, i.e., spinal cord injury, peripheral nerve injury, diabetic neuropathy, and thermal burn injury. Because of the relationship between dendritic spine structure and neuronal function, a thorough investigation of dendritic spine behavior in the spinal cord is a unique opportunity to better understand the mechanisms of sensory dysfunction after injury or disease. At a conceptual level, a spinal memory mechanism that engages dendritic spine remodeling would also contribute to a broad range of intractable neurological conditions. Molecules involved in regulating dendritic spine plasticity may offer novel targets for the development of effective and durable therapies for neurological disease.
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut, USA; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA; Hopkins School, New Haven, Connecticut, USA. Electronic address: Andrew.Tan@yale.edu.
Andrew Michael
AM
Tan
D000818:Animals; D002056:Burns / Q000473:pathology; D049229:Dendritic Spines / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000473:pathology; D006801:Humans; D009437:Neuralgia / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000473:pathology; D013569:Synapses / Q000473:pathology
Dendritic spine; Diabetes; LTP; Memory; Neuropathic pain; Nociception; Pain; Peripheral nerve injury; Rac1; Spinal cord injury; Synaptic plasticity