Alpha-Conotoxin RgIA and oligoarginine R8 in the mice model alleviate long-term oxaliplatin induced neuropathy

Authors
IA Dyachenko, YA Palikova, VA Palikov et al

Lab
Russian Academy of Sciences, Moscow, Russia

Journal
Biochimie

Abstract
_ligoarginines were recently discovered (Lebedev et al., 2019 Nov) as a novel class of nicotinic acetylcholine receptors (nAChRs) inhibitors, octaoligoarginine R8 showing a relatively high affinity (44 nM) for the alpha9/alpha10 nAChR. Since the inhibition of alpha9/ alpha 10 nAChR by alpha-conotoxin RgIA and its analogs is a possible way to drugs against neuropathic pain, here in a mice model we compared R8 with alpha-conotoxin RgIA in the effects on the chemotherapy-induced peripheral neuropathy (CIPN), namely on the long-term oxaliplatin induced neuropathy. Tests of cold allodynia, hot plate, Von Frey and grip strength analysis revealed for R8 and alpha-conotoxin RgIA similar positive effects, expressed most prominently after two weeks of administration. Histological analysis of the dorsal root ganglia sections showed for R8 and RgIA a similar partial correction of changes in the nuclear morphology of neurons. Since alpha9/ alpha 10 nAChR might be not the only drug target for R8, we analyzed the R8 action on rat TRPV1 and TRPA1, well-known nociceptive receptors. Against rTRPV1 at 25 microM there was no inhibition, while for rTRPA1 IC50 was about 20 microM. Thus, involvement of rTRPA1 cannot be excluded, but in view of the R8 much higher affinity for alpha 9/ alpha 10 nAChR the latter seems to be the main target and the easily synthesized R8 can be considered as a potential candidate for a drug design.

BIOSEB Instruments Used:
Electronic Von Frey 5 with embedded camera (BIO-EVF5),Electronic Von Frey 4 (BIO-EVF4)