SiRNA-Encapsulated Nanoparticles for Targeting Dorsal Root Ganglion (DRG) in Diabetic Neuropathic Pain

Abstract

AbstractDiabetic neuropathy is the most established complication of diabetes. Typically, diabetic neuropathy involves the distal foot and toes but eventually advances to include the lower part of the legs. The toxic effects of hyperglycemia are accepted to be a major factor in the emergence of this complication. In the dorsal root ganglion, upregulation of voltage-gated sodium channels due to hyperglycemia was commonly seen in models of neuropathic pain. To increase intracellular sodium ion levels, DRG increases its opening frequency, which in turn may lead to increased calcium channel opening that further triggers other pathways that lead to DPN. Relief from pain due to diabetic neuropathy has been seen with the use of antidepressants, GABA analogues, opioids, and topical agents that are recommended in clinical guidelines. Currently available medications provide adequate pain relief for approximately half of the affected patients, and their use is also restricted due to unwanted adverse reactions like somnolence, dizziness, and multiple daily doses reduce patient compliance. siRNA showed behavior-associated inhibition in allodynia as well as hyperalgesia which was correlated with the downregulated P2X3 receptor in the dorsal root ganglion and spinal cord. siRNA is very unstable under normal physiology in the blood wherein it undergoes digestion by nuclease enzymes. Thus, the development of drug delivery systems that can enhance site-specific delivery of siRNA therapeutics for aiding relief from disease is important. siRNA encapsulated in nanoparticle delivery devices can be utilized as a plausible therapeutic in relieving neuropathic pain.KeywordsDiabetic neuropathic pain (DNP)Dorsal root ganglion (DRG)siRNA