Abstract
Spinal cord injury (SCI) and associated pain and inflammation caused by trauma or infection
are serious health care issues world-wide. The various inflammatory, redox-sensitive and
apoptotic events are contributing factors, but altered neuronal function, axonal degeneration, activated
microglia, endothelial cells, astrocytes, fibroblasts, pericytes, Schwann cells, and meningeal
cells are major players in its pathogenesis. Further, monocytes and neutrophil infiltration get recruited
and facilitate the release of chemokines, cytokines, and other mediators of inflammation.
This event leads to the production of different amino acids, neuropeptides kinin, prostaglandins,
prostacyclin, thromboxane, leukotrienes, bradykinin, histamine, matrix metal proteinases, and serotonin
that stimulate nerve endings and manifest the inflammation and pain processes, etc. Arachidonic
acid (AA), NF-kB, NLRP3 inflammasome, and nitric oxide pathways along with P2X7 receptor
and ion channel transient receptor potential (TRP) vanilloid are some of the recently explored
targets for modulation of pain and inflammation in SCI. Till now, NSAIDs, opioids, antidepressants,
anticonvulsants, NMDA antagonists, α2-adrenergic agonists, and GABA-receptor agonists
are used for the management of these pathological conditions. However, these drugs are associated
with various side effects. Additionally, the number of available animal models for SCI has enhanced
the understanding of the complex pathological mechanisms involved in the generation of
chronic inflammatory pain in SCI. These findings enable us to identify and validate several potent
natural analgesic-anti-inflammatory drug candidates with minimal side effects. However, these
compounds have been studied in preclinical models and shown promising results, but no clinical
studies have been performed. Therefore, a detailed exploration of these natural compounds is important
for bringing them from bench to bedside.