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.
Highlights
Neuropathic pain is a chronic neurologic condition afflicting more than 15% of the population in the United States
Numerous classes of ion channels and receptors participate in the propagation and processing of pain signals. Among these are voltage-gated Ca2+ channels (VGCCs) [17]
The rapid infusion resulted in a 30%–53% reduction of pain, according to the Visual Analogue Scale of Pain Intensity, in ziconotide-treated patients with chronic non-malignant, or cancer- or AIDS-related pain
Summary
Neuropathic pain is a chronic neurologic condition afflicting more than 15% of the population in the United States. Antidepressants and anticonvulsants are employed [5,6] These drugs are not universally effective in pain-afflicted patients; it is estimated that oral administration of current first-line medications fails to provide adequate and sustained pain relief in up to 30% of patients with neuropathic pain [7]. This may be due, in part, to the fact that efficacy of these medications is often limited by the development of tolerance. With a better understanding of the pathogenesis of neuropathic pain, drug targets with greater specificity for the pathologic condition will be identified [10]
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