title: Innovative Opioid Peptides and Biased Agonism: Novel Avenues for More Effective and Safer Analgesics to Treat Chronic Pain.
abstract: BACKGROUND
  Chronic pain states are clinically relevant and yet unsolved conditions impacting on quality of life and representing an important social and economic burden; these diseases are poorly treated with the currently available drugs, being urgent the need of innovative analgesics. In this frame, novel analogues of endomorphin-1 and dermorphin emerge as promising starting points to develop innovative, more effective analgesics to treat neuropathic pain.
  
  
  METHODS
  An extensive and structured search of bibliographic databases for peer-reviewed research literature was undertaken using focused review questions; all the retrieved papers were published on prestigious international journals by the experts of the field and were carefully analyzed to collect all the information and data necessary to the conceptual framework of this review.
  
  
  RESULTS
  One hundred papers were included in this review; forty-one defined the up-to-date findings on neuropathic pain etiopathogenesis and its currently available treatment options. Thirty-five papers described all the advantages and drawbacks of using endomorphin-1 (23) or dermorphin (12) in the frame of neuropathic pain and outlined the most relevant advances in developing endomorphin-1 and dermorphin analogs useful as potential, innovative analgesics. Twenty-four papers provided the latest insights into exploiting biased agonism at opioid receptor as an innovative strategy to develop more effective and safer analgesics.
  
  
  CONCLUSIONS
  This review reports that innovative opioid peptides will be of great help in better understanding the multifaceted scenario of neuropathic pain treatment, providing very interesting opportunities for the identification of novel and more effective opioid analgesics to be employed as medications.
authors.affiliation: Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bedini
authors.affiliation: Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Bologna, Italy.
authors.forename: Santi
authors.initials: S
authors.lastname: Spampinato
mesh_terms: D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008024:Ligands; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D009842:Oligopeptides / Q000737:chemistry / Q000627:therapeutic use*; D018847:Opioid Peptides / Q000737:chemistry / Q000627:therapeutic use*; D011957:Receptors, Opioid / Q000819:agonists* / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D008024:Ligands; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; C105293:endomorphin 1; C030058:dermorphin
keywords: Mu opioid receptor; biased
  agonism; delta opioid receptor; dermorphin; endomorphin; innovative analgesics.; kappa opioid receptor.