NDLI: Involvement of Nav 1.8 sodium ion channels in the transduction of mechanical pain in a rodent model of osteoarthritis

Content Provider	Springer Nature : BioMed Central
Author	Schuelert, Niklas McDougall, Jason J
Abstract	Introduction A subgroup of voltage gated sodium channels including Nav1.8 are exclusively expressed on small diameter primary afferent neurons and are therefore believed to be integral to the neurotransmission of nociceptive pain. The present study examined whether local application of A-803467, a selective blocker of the Nav 1.8 sodium channel, can reduce nociceptive transmission from the joint in a rodent model of osteoarthritis (OA). Methods OA-like changes were induced in male Wistar rats by an intra-articular injection of 3 mg sodium monoiodoacetate (MIA). Joint nociception was measured at day 14 by recording electrophysiologically from knee joint primary afferents in response to non-noxious and noxious rotation of the joint both before and following close intra-arterial injection of A-803467. The effect of Nav1.8 blockade on joint pain perception and secondary allodynia were determined in MIA treated animals by hindlimb incapacitance and von Frey hair algesiometry respectively. Results A-803467 significantly reduced the firing rate of joint afferents during noxious rotation of the joint but had no effect during non-noxious rotation. In the pain studies, peripheral injection of A-803467 into OA knees attenuated hindlimb incapacitance and secondary allodynia. Conclusions These studies show for the first time that the Nav1.8 sodium channel is part of the molecular machinery involved in mechanotransduction of joint pain. Targeting the Nav1.8 sodium channel on joint nociceptors could therefore be useful for the treatment of OA pain, avoiding the unwanted side effects of non-selective nerve blocks.
Related Links	https://arthritis-research.biomedcentral.com/counter/pdf/10.1186/ar3553.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
ISSN	14786362
DOI	10.1186/ar3553
Journal	Arthritis Research & Therapy
Issue Number	1
Volume Number	14
Language	English
Publisher	BioMed Central
Publisher Date	2012-01-07
Access Restriction	Open
Subject Keyword	Rheumatology Orthopedics Firing Rate Saphenous Nerve Intraarticular Injection Vehicle Treated Animal Joint Afferents
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Rheumatology
Journal Impact Factor	4.4/2023
5-Year Journal Impact Factor	4.9/2023

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