Dendritic spine dysgenesis in neuropathic pain

Abstract

Neuropathic pain is a significant unmet medical need in patients with variety of injury or disease insults to the nervous system. Neuropathic pain often presents as a painful sensation described as electrical, burning, or tingling. Currently available treatments have limited effectiveness and narrow therapeutic windows for safety. More powerful analgesics, e.g., opioids, carry a high risk for chemical dependence. Thus, a major challenge for pain research is the elucidation of the mechanisms that underlie neuropathic pain and developing targeted strategies to alleviate pathological pain. The mechanistic link between dendritic spine structure and circuit function could explain why neuropathic pain is difficult to treat, since nociceptive processing pathways are adversely "hard-wired" through the reorganization of dendritic spines. Several studies in animal models of neuropathic pain have begun to reveal the functional contribution of dendritic spine dysgenesis in neuropathic pain. Previous reports have demonstrated three primary changes in dendritic spine structure on nociceptive dorsal horn neurons following injury or disease, which accompany chronic intractable pain: (I) increased density of dendritic spines, particularly mature mushroom-spine spines, (II) redistribution of spines toward dendritic branch locations close to the cell body, and (III) enlargement of the spine head diameter, which generally presents as a mushroom-shaped spine. Given the important functional implications of spine distribution, density, and shape for synaptic and neuronal function, the study of dendritic spine abnormality may provide a new perspective for investigating pain, and the identification of specific molecular players that regulate spine morphology may guide the development of more effective and long-lasting therapies.

Keywords: Dendritic spine; Diabetes; Nerve injury; Neuropathic pain; Nociception; Plasticity; Rac1; SCI; Spinal cord.