Spinal Cord Stimulation Paradigms and Pain Relief:A Preclinical Systematic Review on Modulation of the Central Inflammatory Response in Neuropathic Pain

OBJECTIVES: Spinal cord stimulation (SCS) is a last-resort treatment for patients with chronic neuropathic pain. The mechanism underlying SCS and pain relief is not yet fully understood. Because the inflammatory balance between pro- and anti-inflammatory molecules in the spinal nociceptive network is pivotal in the development and maintenance of neuropathic pain, the working mechanism of SCS is suggested to be related to the modulation of this balance. The aim of this systematic review is to summarize and understand the effects of different SCS paradigms on the central inflammatory balance in the spinal cord.MATERIALS AND METHODS: A systematic literature search was conducted using MEDLINE, Embase, and PubMed. All articles studying the effects of SCS on inflammatory or glial markers in neuropathic pain models were included. A quality assessment was performed on predetermined entities of bias.RESULTS: A total of 11 articles were eligible for this systematic review. In general, induction of neuropathic pain in rats results in a proinflammatory state and at the same time an increased activity/expression of microglial and astroglial cells in the spinal cord dorsal horn. Conventional SCS seems to further enhance this proinflammatory state and increase the messenger RNA expression of microglial markers, but it also results in a decrease in microglial protein marker levels. High-frequency and especially differential targeted multiplexed SCS can not only restore the balance between pro- and anti-inflammatory molecules but also minimize the overexpression/activation of glial cells. Quality assessment and risk of bias analysis of the studies included make it clear that the results of these preclinical studies must be interpreted with caution.CONCLUSIONS: In summary, the preclinical findings tend to indicate that there is a distinct SCS paradigm-related effect in the modulation of the central inflammatory balance of the spinal dorsal horn.