title: Modulation of nociceptive ion channels and receptors via protein-protein interactions: implications for pain relief.
abstract: In the last 2 decades biomedical research has provided great insights into the molecular signatures underlying painful conditions. However, chronic pain still imposes substantial challenges to researchers, clinicians and patients alike. Under pathological conditions, pain therapeutics often lack efficacy and exhibit only minimal safety profiles, which can be largely attributed to the targeting of molecules with key physiological functions throughout the body. In light of these difficulties, the identification of molecules and associated protein complexes specifically involved in chronic pain states is of paramount importance for designing selective interventions. Ion channels and receptors represent primary targets, as they critically shape nociceptive signaling from the periphery to the brain. Moreover, their function requires tight control, which is usually implemented by protein-protein interactions (PPIs). Indeed, manipulation of such PPIs entails the modulation of ion channel activity with widespread implications for influencing nociceptive signaling in a more specific way. In this review, we highlight recent advances in modulating ion channels and receptors via their PPI networks in the pursuit of relieving chronic pain. Moreover, we critically discuss the potential of targeting PPIs for developing novel pain therapies exhibiting higher efficacy and improved safety profiles.
authors.affiliation: a Max Planck Institute for Experimental Medicine. Somatosensory Signaling Group ; Goettingen , Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Rouwette
authors.forename: Luca
authors.initials: L
authors.lastname: Avenali
authors.forename: Julia
authors.initials: J
authors.lastname: Sondermann
authors.forename: Pratibha
authors.initials: P
authors.lastname: Narayanan
authors.forename: David
authors.initials: D
authors.lastname: Gomez-Varela
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D059350:Chronic Pain / Q000503:physiopathology* / Q000517:prevention & control; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D060066:Protein Interaction Maps / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000700:Analgesics; D007473:Ion Channels
keywords: inflammatory pain; ion channels; neuropathic pain; pain; protein complexes; protein-protein interactions; receptors