Alpha-conotoxin Vc1.1 alleviates neuropathic pain and accelerates functional recovery of injured neurones.
This paper demonstrates the capacity of the neuronal nicotinic acetylcholine receptor (nAChR) antagonist alpha-conotoxin Vc1.1 to inhibit pain responses in vivo. Vc1.1 suppressed pain behaviors when tested in two models of peripheral neuropathy of the rat sciatic nerve, the chronic constriction injury (CCI) and partial nerve ligation (PNL) models. Mechanical hyperalgesia was assessed using an Ugo Basile Analgesymeter. Vc1.1 was administered by intramuscular bolus injection near the site of injury at doses of 0.036 microg, 0.36 microg and 3.6 microg in CCI rats and at a dose of 0.36 microg in PNL rats. Vc1.1 was also administered contralaterally in CCI rats at doses of 0.36 microg and 3.6 microg. Treatment started after the development of hyperalgesia and continued for 7 days. Vc1.1 significantly attenuated mechanical hyperalgesia in both CCI and PNL rats for up to a week following cessation of treatment. Vc1.1 also accelerated functional recovery of injured neurones. A blister was raised over the footpad innervated by the peripheral terminals of the injured nerve. The ability of these terminals to mount an inflammatory vascular response upon perfusion of the blister base with substance P provided a measure of functional recovery. This study shows that alpha-conotoxin Vc1.1, a neuronal nAChR antagonist, suppressed mechanical pain responses associated with peripheral neuropathy in rats in vivo and accelerated functional recovery of the injured neurones. A role for neuronal nAChRs in the analgesic activity of Vc1.1 is proposed.
Satkunanathan
Narmatha
N
National Ageing Research Institute, University of Melbourne, Parkville Victoria, Australia.
Livett
Bruce
B
Gayler
Ken
K
Sandall
David
D
Down
John
J
Khalil
Zeinab
Z
D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D020916:Conotoxins / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D018733:Nicotinic Antagonists / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D018709:Statistics, Nonparametric
D000700:Analgesics; D020916:Conotoxins; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C507383:alpha-conotoxin Vc1.1