Neuroplasticity related to chronic pain and its modulation by microglia

Abstract

Neuropathic pain is often chronic and can persist after overt tissue damage heals, suggesting that its underlying mechanism involves the alteration of neuronal function. Such an alteration can be a direct consequence of nerve damage or a result of neuroplasticity secondary to the damage to tissues or to neurons. Recent studies have shown that neuroplasticity is linked to causing neuropathic pain in response to nerve damage, which may occur adjacent to or remotely from the site of injury. Furthermore, studies have revealed that neuroplasticity relevant to chronic pain is modulated by microglia, resident immune cells of the central nervous system (CNS). Microglia may directly contribute to synaptic remodeling and altering pain circuits, or indirectly contribute to neuroplasticity through property changes, including the secretion of growth factors. We herein highlight the mechanisms underlying neuroplasticity that occur in the somatosensory circuit of the spinal dorsal horn, thalamus, and cortex associated with chronic pain following injury to the peripheral nervous system (PNS) or CNS. We also discuss the dynamic functions of microglia in shaping neuroplasticity related to chronic pain. We suggest further understanding of post-injury ectopic plasticity in the somatosensory circuits may shed light on the differential mechanisms underlying nociceptive, neuropathic, and nociplastic-type pain. While one of the prominent roles played by microglia appears to be the modulation of post-injury neuroplasticity. Therefore, future molecular- or genetics-based studies that address microglia-mediated post-injury neuroplasticity may contribute to the development of novel therapies for chronic pain.

Differential Expression of microRNAs in Serum of Patients with Chronic Painful Polyneuropathy and Healthy Age-Matched Controls

“…Perhaps surprisingly, both adult neurogenesis and neuroplasticity have been reported to contribute to the maintenance of long-lasting NP (i.e., chronicity) [ 52 ] and NP that may occur adjacent to or remotely from any injury site [ 53 ].…”

Metabotropic Glutamate Receptor 5 in the Dysgranular Zone of Primary Somatosensory Cortex Mediates Neuropathic Pain in Rats

“…The somatosensory cortices are located in the parietal lobe and play a pivotal role in discriminating sensory modalities and localization of sensations [ 7 , 8 ]. Although controversial [ 33 ], somatosensory cortices are known to be involved in the development and maintenance of chronic pain symptoms [ 34 ]. Multiple studies have reported changes in the somatosensory cortex following nerve injury [ 35 , 36 , 37 , 38 ].…”

“…Multiple studies have reported changes in the somatosensory cortex following nerve injury [ 35 , 36 , 37 , 38 ]. Animal studies have shown that pain induced by peripheral nerve injury alters neuronal activity and glial activation in the affected S1 region, leading to abnormal pain processing in the brain [ 3 , 34 ]. Conversely, mimicking these changes in S1 results in neuropathic pain-like symptoms [ 3 , 23 ].…”

Macrophages and glial cells: Innate immune drivers of inflammatory arthritic pain perception from peripheral joints to the central nervous system

“…Thus, it is plausible that changes in microglia phenotype might alter the neuronal function in brain regions related to pain facilitating chronic pain development. Accordingly, it has been reported that activated microglia are involved in shaping the neuroplasticity underlying chronic pain ( 178 ) and pain-associated affective disorders ( 179 ).…”