Alpha-conotoxin Vc1.1 alleviates neuropathic pain + accelerates functional rec

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Brain Res. 2005 Sep 20

Alpha-conotoxin Vc1.1 alleviates neuropathic pain and accelerates

functional recovery of injured neurones.

Satkunanathan N, Livett B, Gayler K, Sandall D, Down J, Khalil Z.

National Ageing Research Institute, University of Melbourne, PO Box

31, Parkville 3052, Australia.

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 mug, 0.36

mug and 3.6 mug in CCI rats and at a dose of 0.36 mug in PNL rats.

Vc1.1 was also administered contralaterally in CCI rats at doses of

0.36 mug and 3.6 mug. 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.