Decrypting the multifaceted peripheral neuropathy based on molecular pathology and therapeutics: a comprehensive review

Abstract

Context

Peripheral neuropathy (PN) is a multifaceted complication characterized by nerve damage due to oxidative stress, inflammatory mediators, and dysregulated metabolic processes. Early PN manifests as sensory changes that develop progressively in a “stocking and glove” pattern.

Methods and mechanisms

A thorough review of literature has been done to find the molecular pathology, clinical trials that have been conducted to screen the effects of different drugs, current treatments and novel approaches used in PN therapy. Diabetic neuropathy occurs due to altered protein kinase C activity, elevated polyol pathway activity in neurons, and Schwann cells-induced hyperglycemia. Other causes involve chemotherapy exposure, autoimmune ailments, and chronic ethanol intake.

Conclusion

Symptomatic treatments for neuropathic pain include use of tricyclic antidepressants, anticonvulsants, and acetyl-L-carnitine. Patients will have new hope if clinicians focus on novel therapies including gene therapy, neuromodulation techniques, and cannabidiol as an alternative to traditional medications, as management is still not ideal.

Keywords:

• Peripheral neuropathy
• diabetes
• autoimmune
• neuromodulation
• ethanol

Disclosure statement

No potential conflict of interest was reported by the author(s).

Abbreviation (as per the description sequence)

PN- Peripheral neuropathy, DRG- dorsal root ganglion, IL- interleukin, TNF- tumour necrosis factor, GDNF- glial-derived neurotrophic factor, NGF- nerve growth factor, NT- neurotrophin, BDNF- brain-derived neurotrophic factor, GABABR- gamma-aminobutyric acid receptor, CCL2- CC chemokine ligand, EMG- electromyography, NCS- nerve conduction studies, CSF- cerebrospinal fluid, CDC- centres for disease control and prevention, DNP- Diabetic neuropathy, ROS- reactive oxygen species, CIPN- chemotherapy-induced peripheral neuropathy, TRP- Transient receptor potential cation channel, SARS-Cov-2- severe acute respiratory syndrome coronavirus 2, SFN- small-fibre neuropathy, GBS- Guillain-Barre syndrome, ADIP- Acute inflammatory demyelinating polyneuropathy, AMAN- Acute motor axonal neuropathy, AMSAN- Acute motor sensory axonal neuropathy, MFS- Miller-Fisher syndrome, RA- Rheumatoid arthritis, ALN- alcohol-related peripheral neuropathy, INF- intraneural facilitation, TCAs- Tricyclic antidepressants, SNRI- serotonin and norepinephrine reuptake inhibitors, ALC- Acetyl-L-carnitine, CBD- Cannabidiol, HGF– hepatocyte growth factor, NINM- Non-invasive Neuromodulation, rTMS- repetitive transcranial magnetic stimulation, TENS- transcutaneous electrical nerve stimulation, MCS- Motor cortex stimulation, tDCS- Transcranial direct current stimulation

Reference for clinical trials

https://classic.clinicaltrials.gov/ct2/show/NCT03272919

https://classic.clinicaltrials.gov/ct2/show/NCT03450200

https://classic.clinicaltrials.gov/ct2/show/NCT03492047

https://classic.clinicaltrials.gov/ct2/show/NCT04820426

https://classic.clinicaltrials.gov/ct2/show/NCT02271893

Data availability statement

The authors confirm that the data supporting the finding of this study are available within the article [and/or] its supplementary materials.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.