On the therapeutic targets and pharmacological treatments for pain relief following spinal cord injury: A mechanistic review

Spinal cord injury (SCI) is globally considered as one of the most debilitating disorders, which interferes with daily activities and life of the affected patients. Despite many developments in related recognizing and treating procedures, post-SCI neuropathic pain (NP) is still a clinical challenge for clinicians with no distinct treatments. Accordingly, a comprehensive search was conducted in PubMed, Medline, Scopus, Web of Science, and national database (SID and Irandoc). The relevant articles regarding signaling pathways, therapeutic targets and pharmacotherapy of post-SCI pain were also reviewed. Data were collected with no time limitation until November 2020. The present study provides the findings on molecular mechanisms and therapeutic targets, as well as developing the critical signaling pathways to introduce novel neuroprotective treatments of post-SCI pain. From the pathophysiological mechanistic point of view, post-SCI inflammation activates the innate immune system, in which the immune cells elicit secondary injuries. So, targeting the critical signaling pathways for pain management in the SCI population has significant importance in providing new treatments. Indeed, several receptors, ion channels, excitatory neurotransmitters, enzymes, and key signaling pathways could be used as therapeutic targets, with a pivotal role of n-methyl-D-aspartate, gamma-aminobutyric acid, and inflammatory mediators. The current review focuses on conventional therapies, as well as crucial signaling pathways and promising therapeutic targets for post-SCI pain to provide new insights into the clinical treatment of post-SCI pain. The need to develop innovative delivery systems to treat SCI is also considered. • To combat post-SCI NP, multi-target therapies, as well as novel pharmaceutical formulations are needed. • Several receptors, ion channels, neurotransmitters, and signaling pathways are involved in post-SCI NP. • Inflammatory mediators, apoptosis and oxidative stress are critical targets in combating post-SCI NP. • GABA/NMDA/opioid receptors and Na + /K + /Ca 2+ channels are upstream orchestrate of SCI associated NP.