Related Experiment Video
Updated: Oct 8, 2025
08:16
Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
6.7K
α-Conotoxin RgIA and oligoarginine R8 in the mice model alleviate long-term oxaliplatin induced neuropathy
I A Dyachenko1, Yu A Palikova1, V A Palikov1
1Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki Avenue, 142290, Pushchino, Moscow, Russia.
Biochimie
|January 3, 2022
Summary
Octaoligoarginine R8 and α-conotoxin RgIA show similar efficacy in alleviating chemotherapy-induced peripheral neuropathy in mice. R8 demonstrates potential as a drug candidate for neuropathic pain by targeting nicotinic acetylcholine receptors.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Nicotinic acetylcholine receptors (nAChRs), particularly the α9/α10 subtype, are implicated in neuropathic pain.
- α-conotoxin RgIA and its analogs are known inhibitors of α9/α10 nAChR and are explored for pain management.
- Oligoarginines, including octaoligoarginine R8, have emerged as a novel class of nAChR inhibitors.
Purpose of the Study:
- To compare the efficacy of octaoligoarginine R8 with α-conotoxin RgIA in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN).
- To investigate the potential drug targets of R8, specifically α9/α10 nAChR, TRPV1, and TRPA1 receptors.
Main Methods:
- Assessment of neuropathic pain using behavioral tests: cold allodynia, hot plate, Von Frey, and grip strength analysis.
- Histological examination of dorsal root ganglia to evaluate neuronal morphology.
- In vitro analysis of R8's inhibitory activity against rat TRPV1 and TRPA1 receptors.
Main Results:
- Both R8 and α-conotoxin RgIA demonstrated significant positive effects on CIPN symptoms, most notably after two weeks of administration.
- Histological analysis revealed a similar partial amelioration of neuronal nuclear morphology changes in the dorsal root ganglia for both R8 and RgIA.
- R8 showed no inhibition against rat TRPV1 but exhibited an IC50 of approximately 20 μM against rat TRPA1, while possessing a high affinity for α9/α10 nAChR (44 nM).
Conclusions:
- Octaoligoarginine R8 exhibits comparable therapeutic effects to α-conotoxin RgIA in mitigating chemotherapy-induced peripheral neuropathy.
- The α9/α10 nAChR appears to be the primary target for R8's analgesic effects, although TRPA1 involvement cannot be entirely ruled out.
- Easily synthesized R8 represents a promising candidate for further drug design and development in the treatment of neuropathic pain.
