siRNA-Encapsulated Nanoparticles

for Targeting Dorsal Root Ganglion (DRG)

in Diabetic Neuropathic Pain

20

Ranjana Bhandari, Priya Badyal, Garima Khanna, and Anurag Kuhad

Abstract

Diabetic 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, dizzi-

ness, 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 therapeu-

tics for aiding relief from disease is important. siRNA encapsulated in nanoparti-

cle delivery devices can be utilized as a plausible therapeutic in relieving

neuropathic pain.

R. Bhandari (*) · P. Badyal · G. Khanna · A. Kuhad

University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab

University, Chandigarh, India

e-mail: akb10in@yahoo.co.uk

# The Author(s), under exclusive license to Springer Nature Singapore Pte

Ltd. 2022

R. C. Sobti, N. S. Dhalla (eds.), Biomedical Translational Research,

https://doi.org/10.1007/978-981-16-9232-1_20

369