Involvement of microglia in chronic neuropathic pain associated with spinal cord injury – a systematic review

In recent decade microglia have been found to have a central role in the development of chronic neuropathic pain after injury to the peripheral nervous system. It is widely accepted that peripheral nerve injury triggers microglial activation in the spinal cord, which contributes to heightened pain sensation and eventually chronic pain states. The contribution of microglia to chronic pain arising after injury to the central nervous system, such as spinal cord injury (SCI), has been less studied, but there is evidence supporting microglial contribution to central neuropathic pain. In this systematic review, we focused on post-SCI microglial activation and how it is linked to emergence and maintenance of chronic neuropathic pain arising after SCI. We found that the number of studies using animal SCI models addressing microglial activity is still small, compared with the ones using peripheral nerve injury models. We have collected 20 studies for full inclusion in this review. Many mechanisms and cellular interactions are yet to be fully understood, although several studies report an increase of density and activity of microglia in the spinal cord, both in the vicinity of the injury and in the spared spinal tissue, as well as in the brain. Changes in microglial activity come with several molecular changes, including expression of receptors and activation of signalling pathways. As with peripheral neuropathic pain, microglia seem to be important players and might become a therapeutic target in the future.