activity (Taylor et al. 2007). Alpha2δ-1 is an auxiliary subunit of voltage-gated

calcium channels, and pregabalin binding to this subunit is responsible for pain

attenuation. When this drug binds to the alpha2δ-1 subunits, it leads to inhibition of

nerve injury-induced accumulation of alpha1 pore that forms calcium channel units

from the cytoplasm to the plasma membrane of sensory neurons of the dorsal root

ganglion (DRG) (Kukkar et al. 2013). Gabapentin administration leads to inhibition

of axoplasmic transport of alpha2δ-1 subunits from DRG to dorsal horn neurons

(Kukkar et al. 2013).

20.2.3.3 Opioids

The use of opioids for the treatment of pain has increased significantly in recent

years. However, long-term use can lead to abuse and hyperalgesia (Bril et al. 2011).

As a result, using opioids in the DPN setting is controversial. These drugs can be

used as monotherapy only in situations where other medications have failed to offer

pain relief (Lindsay et al. 2010). In the spinal cord as well as in the brain, unique

opioid receptors for opioid-like endogenous compounds were identified. Prescrip-

tion for oxycodone and morphine sulfate is popular among other opioids (Cohen

et al. 2015).

20.2.3.4 Topical Medications

Capsaicin is known to decrease the sensitivity of sensory nerves and has shown pain

relief effects in DPN (Chong and Hester 2007). But it still offers some adverse

effects in some patients like erythema (Zin et al. 2008). In a study, a single capsaicin

formulation of 8% for patch therapy in patients with DPN provided relief from

severe pain throughout 12 weeks, and no relief is seen in patients treated with a

placebo patch (Simpson et al. 2017). In July 2020, the FDA approval is given to a

new capsaicin formulation for the treatment of neuropathy pain in diabetes (Cohen

et al. 2015). Studies to determine the most potent drugs or formulations for PDN

treatment are increasingly required to optimize pain relief and to enhance the quality

of life of patients.

20.2.4 Challenges With Current Treatment of Diabetic

Neuropathic Pain

With recent progress in identifying pain-generating processes and adopting

evidence-based treatments, patients suffering from DPN are still difficult to cure

(Tölle 2010). The latest treatments do not provide adequate pain relief for about half

of the patients and also offer many non-desired side effects such as somnolence and

dizziness, as well as the requirement of a complex dose regimen to reduce patient

compliance. Standard agents for topical administration are there for the treatment of

DNP, such as capsaicin cream, without any side effects but have low efficiency, and

complex multiple administration is required, which can cause discomfort, and also

the chances of contamination of sensitive body areas are also there, both of which

can lead to poor patient compliance (Tölle 2010). Ultimately, more understanding of

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