title: Omega-conotoxins as experimental tools and therapeutics in pain management.
abstract: Neuropathic pain afflicts a large percentage of the global population. This form of chronic, intractable pain arises when the peripheral or central nervous systems are damaged, either directly by lesion or indirectly through disease. The comorbidity of neuropathic pain with other diseases, including diabetes, cancer, and AIDS, contributes to a complex pathogenesis and symptom profile. Because most patients present with neuropathic pain refractory to current first-line therapeutics, pharmaceuticals with greater efficacy in pain management are highly desired. In this review we discuss the growing application of ω-conotoxins, small peptides isolated from Conus species, in the management of neuropathic pain. These toxins are synthesized by predatory cone snails as a component of paralytic venoms. The potency and selectivity with which ω-conotoxins inhibit their molecular targets, voltage-gated Ca2+ channels, is advantageous in the treatment of neuropathic pain states, in which Ca2+ channel activity is characteristically aberrant. Although ω-conotoxins demonstrate analgesic efficacy in animal models of neuropathic pain and in human clinical trials, there remains a critical need to improve the convenience of peptide drug delivery methods, and reduce the number and severity of adverse effects associated with ω-conotoxin-based therapies.
authors.affiliation: Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, USA. hannonhe@msu.edu
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Hannon
authors.forename: William D
authors.initials: WD
authors.lastname: Atchison
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D052078:Conus Snail / Q000378:metabolism*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D058990:Molecular Targeted Therapy; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D020960:omega-Conotoxins / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D015220:Calcium Channels; D020960:omega-Conotoxins