alpha-conotoxin-vc1.1 and Pain

alpha-conotoxin-vc1.1 has been researched along with Pain* in 5 studies

Reviews

1 review(s) available for alpha-conotoxin-vc1.1 and Pain

ArticleYear
Conotoxin Interactions with α9α10-nAChRs: Is the α9α10-Nicotinic Acetylcholine Receptor an Important Therapeutic Target for Pain Management?
    Toxins, 2015, Sep-28, Volume: 7, Issue:10

    The α9α10-nicotinic acetylcholine receptor (nAChR) has been implicated in pain and has been proposed to be a novel target for analgesics. However, the evidence to support the involvement of the α9α10-nAChR in pain is conflicted. This receptor was first implicated in pain with the characterisation of conotoxin Vc1.1, which is highly selective for α9α10-nAChRs and is an efficacious analgesic in chronic pain models with restorative capacities and no reported side effects. Numerous other analgesic conotoxin and non-conotoxin molecules have been subsequently characterised that also inhibit α9α10-nAChRs. However, there is evidence that α9α10-nAChR inhibition is neither necessary nor sufficient for analgesia. α9α10-nAChR-inhibiting analogues of Vc1.1 have no analgesic effects. Genetically-modified α9-nAChR knockout mice have a phenotype that is markedly different from the analgesic profile of Vc1.1 and similar conotoxins, suggesting that the conotoxin effects are largely independent of α9α10-nAChRs. Furthermore, an alternative mechanism of analgesia by Vc1.1 and other similar conotoxins involving non-canonical coupling of GABAB receptors to voltage-gated calcium channels is known. Additional incongruities regarding α9α10-nAChRs in analgesia are discussed. A more comprehensive characterisation of the role of α9α10-nAChRs in pain is crucial for understanding the analgesic action of conotoxins and for improved drug design.

    Topics: Analgesics; Animals; Conotoxins; Disease Models, Animal; Humans; Mice, Knockout; Nicotinic Antagonists; Pain; Rats; Receptors, Nicotinic

2015

Other Studies

4 other study(ies) available for alpha-conotoxin-vc1.1 and Pain

ArticleYear
α9α10 nicotinic acetylcholine receptors regulate murine bone marrow granulocyte functions.
    Immunobiology, 2021, Volume: 226, Issue:1

    Polymorphonuclear neutrophilic granulocytes (PMNs) are extremely important in defense of the organism against infections and in inflammatory processes including neuroinflammation and pain sensation. Different subtypes of nicotinic acetylcholine receptors (nAChRs) are involved in modulation of PMN activities. Earlier we determined expression of α2-7, α9, β3, β4 subunits and regulatory role of α7 and α3β2 nAChR subtypes in functions of inflammatory PMNs. Other authors detected mRNA of α9 subunit in bone marrow neutrophils (BM-PMNs). Murine BM-PMNs coming out from the bone marrow, where they develop, to blood were characterized as mature. There was no data for α10 and for the presence of functionally active α9α10 nAChRs in BM-PMNs. Here we detected for the first time mRNA expression of the α10 nAChR subunit in BM-PMNs and confirmed the expression of mRNA for α9 nAChR. With the help of α-conotoxins RgIA and Vc1.1, highly selective antagonists of α9α10 nAChRs, we have revealed participation of α9 and/or α9α10 nAChRs in regulation of cytosolic Ca

    Topics: Animals; Bone Marrow Cells; Calcium Signaling; Cell Adhesion; Cells, Cultured; Conotoxins; Cytotoxicity, Immunologic; Granulocytes; Mice; Mice, Inbred BALB C; Neurogenic Inflammation; Pain; Reactive Oxygen Species; Receptors, Nicotinic; RNA, Messenger; Sensation

2021
Structure-Activity Studies Reveal the Molecular Basis for GABA
    ACS chemical biology, 2018, 06-15, Volume: 13, Issue:6

    α-Conotoxins are disulfide-bonded peptides from cone snail venoms and are characterized by their affinity for nicotinic acetylcholine receptors (nAChR). Several α-conotoxins with distinct selectivity for nAChR subtypes have been identified as potent analgesics in animal models of chronic pain. However, a number of α-conotoxins have been shown to inhibit N-type calcium channel currents in rodent dissociated dorsal root ganglion (DRG) neurons via activation of G protein-coupled GABA

    Topics: Analgesics; Animals; Calcium Channel Blockers; Calcium Channels, N-Type; Conotoxins; Male; Mice, Inbred C57BL; Molecular Structure; Nicotinic Antagonists; Pain; Rats, Wistar; Receptors, GABA-B; Receptors, Nicotinic; Structure-Activity Relationship; Xenopus laevis

2018
Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors.
    Proceedings of the National Academy of Sciences of the United States of America, 2006, Nov-21, Volume: 103, Issue:47

    alpha9alpha10 nicotinic acetylcholine receptors (nAChRs) have been identified in a variety of tissues including lymphocytes and dorsal root ganglia; except in the case of the auditory system, the function of alpha9alpha10 nAChRs is not known. Here we show that selective block (rather than stimulation) of alpha9alpha10 nAChRs is analgesic in an animal model of nerve injury pain. In addition, blockade of this nAChR subtype reduces the number of choline acetyltransferase-positive cells, macrophages, and lymphocytes at the site of injury. Chronic neuropathic pain is estimated to affect up to 8% of the world's population; the numerous analgesic compounds currently available are largely ineffective and act through a small number of pharmacological mechanisms. Our findings not only suggest a molecular mechanism for the treatment of neuropathic pain but also demonstrate the involvement of alpha9alpha10 nAChRs in the pathophysiology of peripheral nerve injury.

    Topics: Analgesia; Analgesics; Animals; Behavior, Animal; Conotoxins; Electrophysiology; Humans; Male; Nicotinic Antagonists; Pain; Protein Subunits; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic; Sciatic Nerve

2006
Alpha-conotoxin Vc1.1 alleviates neuropathic pain and accelerates functional recovery of injured neurones.
    Brain research, 2005, Oct-19, Volume: 1059, Issue:2

    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.

    Topics: Analgesics; Animals; Conotoxins; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Nicotinic Antagonists; Pain; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic; Recovery of Function; Sciatic Neuropathy; Statistics, Nonparametric

2005