Breaking barriers to novel analgesic drug development

Abstract

Acute and chronic pain complaints, while very common, are generally poorly served by existing therapies. The unmet clinical need reflects the failure in developing novel classes of analgesics with superior efficacy, diminished adverse effects and a lower abuse liability than those currently available. Reasons for this include the heterogeneity of clinical pain conditions, the complexity and diversity of underlying pathophysiological mechanisms coupled with the unreliability of some preclinical pain models. However, recent advances in our understanding of the neurobiology of pain are beginning to offer opportunities to develop new therapeutic strategies and revisit existing targets, including modulating ion channels, enzymes and GPCRs.

Heterogeneous‐Backbone Foldamer Mimics of a Computationally Designed, Disulfide‐Rich Miniprotein

“…[29] The approach we demonstrate here adds to the arsenal of methods for tuning the properties of disulfide-rich sequences through chemical alteration. [11] Importantly, sequence-guided backbone modification of the type described is fully complementary to existing approaches such as disulfide replacement and cyclization.…”

Pathophysiology of chronic pain in cerebral palsy: implications for pharmacological treatment and research

“…Selective small‐molecule inhibitors of Nav1.7 and Nav1.8 channels have been found. While the only reported clinical test of a Nav1.8‐selective inhibitor resulted in a terminated trial on dental pain, clinical trials of several Nav1.7‐selective compounds are underway …”

Spinal α2‐adrenoceptors and neuropathic pain modulation; therapeutic target

“…It has been shown that i.t. injection of tizanidine can produce dose-dependent analgesic effects in neuropathy rats (Ou-Yang et al, 2008;Yekkirala, Roberson, Bean, & Woolf, 2017). Semenchuk and Sherman (2000) in an open-label study assessed the effectiveness and tolerability of tizanidine in neuropathy patients.…”