directly influenced. BC168687 siRNA caused upregulation of glial fibrillary acidic

protein on the satellite glial cells present in the dorsal root ganglion. As a result, the

upregulated nitric oxide associated with the nociception of rats was also inhibited

(Liu et al. 2017).

In another pain model, the 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. This effect was then

attempted for reproducibility in another model for neuropathic chronic pain (Dorn

et al. 2004). Microglia homing peptide molecules are promising delivery candidates

for siRNA because of their potent knockdown efficacy. Interferon regulatory factor-

1 is situated in the microglia. MG1 is the most commonly utilized homing peptide

for the siRNA-interferon regulatory factor-1 complex. This delivery system is

successful in suppressing hyperalgesia-associated spinal nerve injury in comparison

with other peptide molecules or even naked siRNA. The study highlights siRNA

delivery devices as a plausible therapeutic in relieving neuropathic pain (Terashima

et al. 2018). Sensory neurons which show expression of calcitonin gene-related

peptide situated in the trigeminal ganglion or dorsal root ganglion are known to

influence nociception in afferent input of transmission. The activation of the primary

afferent neuron preceded by the sensory axon reflex releases the calcitonin gene-

related peptide in the spinal cord. There is an enhancement in the glutamate release

in the presynaptic membrane. Activated NMDA receptors increase the entry of

calcium in the cell which acts as a trigger for the intercellular calcium stores.

Enhanced calcium concentration activates many protein kinases which contribute

to the pathology of neuropathic pain (Lipp and Reither 2011). Inflammatory pain

response prevails. siRNA delivery device alleviates neuropathic pain by inhibition of

excitation transmission due to the P2X3 receptor in the dorsal root ganglion as well

as inhibition of expressed calcitonin gene-related peptide in the spinal cord (Xiong

et al. 2017). Glial cells induce the release of various inflammatory cytokines which

activate the kinase-activated cascade situated in the sensory neuron cytokine

receptors. siRNA therapeutics inhibit this activation and hence eradicate the mani-

festation of neuropathic pain (Gonçalves dos Santos et al. 2020).

A rat chronic constriction injury model investigated the importance of TLR4 and

the plausible implication of siRNA-associated inhibition through TLR4 mRNA

block. On injecting siRNA-TLR4, inhibition of allodynia, hyperalgesia, TNF-α,

and IL-1β was seen. Moreover, these observations were seen to be isochronous

and efficient in neuropathy pain (Wu et al. 2010). In a rat model of chronic

constriction injury, lentivirus containing siRNA was administered into the spinal

cord through the intrathecal route. The results indicated a reduction in nociception

due to the consequent inhibition of mRNA and expressed protein GluN2B.

The lentiviral delivery device showed success in transfecting to the dorsal horn

where the GluN2B resides and thus reducing pain (Wu et al. 2014). Figure 20.2

shows the molecular mechanism of siRNA-based nanocarriers in relieving neuro-

pathic pain.

20

siRNA-Encapsulated Nanoparticles for Targeting Dorsal Root Ganglion (DRG). . .

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