Subcutaneous ω-Conotoxins Alleviate Mechanical Pain in Rodent Models of Acute Peripheral Neuropathy
Open Access
- 11 February 2021
- journal article
- research article
- Published by MDPI AG in Marine Drugs
- Vol. 19 (2), 106
- https://doi.org/10.3390/md19020106
Abstract
The peripheral effects of ω-conotoxins, selective blockers of N-type voltage-gated calcium channels (CaV2.2), have not been characterised across different clinically relevant pain models. This study examines the effects of locally administered ω-conotoxin MVIIA, GVIA, and CVIF on mechanical and thermal paw withdrawal threshold (PWT) in postsurgical pain (PSP), cisplatin-induced neuropathy (CisIPN), and oxaliplatin-induced neuropathy (OIPN) rodent models. Intraplantar injection of 300, 100 and 30 nM MVIIA significantly (p < 0.0001, p < 0.0001, and p < 0.05, respectively) alleviated mechanical allodynia of mice in PSP model compared to vehicle control group. Similarly, intraplantar injection of 300, 100, and 30 nM MVIIA (p < 0.0001, p < 0.01, and p < 0.05, respectively), and 300 nM and 100 nM GVIA (p < 0.0001 and p < 0.05, respectively) significantly increased mechanical thresholds of mice in OIPN model. The ED50 of GVIA and MVIIA in OIPN was found to be 1.8 pmol/paw and 0.8 pmol/paw, respectively. However, none of the ω-conotoxins were effective in a mouse model of CisIPN. The intraplantar administration of 300 nM GVIA, MVIIA, and CVIF did not cause any locomotor side effects. The intraplantar administration of MVIIA can alleviate incision-induced mechanical allodynia, and GVIA and MVIIA effectively reduce OIPN associated mechanical pain, without locomotor side effects, in rodent models. In contrast, CVIF was inactive in these pain models, suggesting it is unable to block a subset of N-type voltage-gated calcium channels associated with nociceptors in the skin.Keywords
Funding Information
- National Health and Medical Research Council (APP1072113, APP1119056)
This publication has 74 references indexed in Scilit:
- TRPV1, but not TRPA1, in Primary Sensory Neurons Contributes to Cutaneous Incision-Mediated HypersensitivityMolecular Pain, 2013
- Novel ω-Conotoxins from C. Catus Reverse Signs of Mouse Inflammatory Pain after Systemic AdministrationMolecular Pain, 2013
- Conus Venom Peptide PharmacologyPharmacological Reviews, 2012
- Differential Effect of Capsaicin Treatment on Pain-Related Behaviors After Plantar IncisionThe Journal of Pain, 2009
- Comparison of Oxaliplatin- and Cisplatin-Induced Painful Peripheral Neuropathy in the RatThe Journal of Pain, 2009
- ω-Conotoxin GVIA Alters Gating Charge Movement of N-Type (CaV2.2) Calcium ChannelsJournal of Neurophysiology, 2009
- The prevalence of postoperative pain in a sample of 1490 surgical inpatientsEuropean Journal of Anaesthesiology, 2008
- Neurite Outgrowth andIn VivoSensory Innervation Mediated by a CaV2.2–Laminin β2 Stop SignalJournal of Neuroscience, 2008
- Structural determinants of the blockade of N-type calcium channels by a peptide neurotoxinNature, 1994
- Alkylating agents and platinumCurrent Opinion in Oncology, 1991