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.