Alpha9 nicotinic acetylcholine receptors and the treatment of pain

J. Michael McIntosh, Nathan Absalom, Mary Chebib, Ana Belén Elgoyhen, Michelle Vincler

Research output: Contribution to journalArticle

Abstract

Chronic pain is a vexing worldwide problem that causes substantial disability and consumes significant medical resources. Although there are numerous analgesic medications, these work through a small set of molecular mechanisms. Even when these medications are used in combination, substantial amounts of pain often remain. It is therefore highly desirable to develop treatments that work through distinct mechanisms of action. While agonists of nicotinic acetylcholine receptors (nAChRs) have been intensively studied, new data suggest a role for selective antagonists of nAChRs. α-Conotoxins are small peptides used offensively by carnivorous marine snails known as Conus. A subset of these peptides known as α-conotoxins RgIA and Vc1.1 produces both acute and long lasting analgesia. In addition, these peptides appear to accelerate the recovery of function after nerve injury, possibly through immune mediated mechanisms. Pharmacological analysis indicates that RgIA and Vc1.1 are selective antagonists of α9α10 nAChRs. A recent study also reported that these α9α10 antagonists are also potent GABA-B agonists. In the current study, we were unable to detect RgIA or Vc1.1 binding to or action on cloned GABA-B receptors expressed in HEK cells or Xenopus oocytes. We review the background, findings and implications of use of compounds that act on α9* nAChRs.11* indicates the possible presence of additional subunits.

Original languageEnglish (US)
Pages (from-to)693-702
Number of pages10
JournalBiochemical Pharmacology
Volume78
Issue number7
DOIs
StatePublished - Oct 1 2009
Externally publishedYes

Fingerprint

Nicotinic Receptors
Conotoxins
Pain
Peptides
GABA-B Receptor Agonists
GABA-B Receptors
Recovery of Function
Snails
Xenopus
Chronic Pain
Analgesia
Oocytes
Analgesics
Therapeutics
Pharmacology
Recovery
Wounds and Injuries

Keywords

  • α-Conotoxin Vc1.1
  • α-Contoxin RgIA
  • Alpha9 nicotinic
  • GABA-B
  • Pain

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Cite this

McIntosh, J. M., Absalom, N., Chebib, M., Elgoyhen, A. B., & Vincler, M. (2009). Alpha9 nicotinic acetylcholine receptors and the treatment of pain. Biochemical Pharmacology, 78(7), 693-702. https://doi.org/10.1016/j.bcp.2009.05.020

Alpha9 nicotinic acetylcholine receptors and the treatment of pain. / McIntosh, J. Michael; Absalom, Nathan; Chebib, Mary; Elgoyhen, Ana Belén; Vincler, Michelle.

In: Biochemical Pharmacology, Vol. 78, No. 7, 01.10.2009, p. 693-702.

Research output: Contribution to journalArticle

McIntosh, JM, Absalom, N, Chebib, M, Elgoyhen, AB & Vincler, M 2009, 'Alpha9 nicotinic acetylcholine receptors and the treatment of pain', Biochemical Pharmacology, vol. 78, no. 7, pp. 693-702. https://doi.org/10.1016/j.bcp.2009.05.020
McIntosh JM, Absalom N, Chebib M, Elgoyhen AB, Vincler M. Alpha9 nicotinic acetylcholine receptors and the treatment of pain. Biochemical Pharmacology. 2009 Oct 1;78(7):693-702. https://doi.org/10.1016/j.bcp.2009.05.020
McIntosh, J. Michael ; Absalom, Nathan ; Chebib, Mary ; Elgoyhen, Ana Belén ; Vincler, Michelle. / Alpha9 nicotinic acetylcholine receptors and the treatment of pain. In: Biochemical Pharmacology. 2009 ; Vol. 78, No. 7. pp. 693-702.
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