title: Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity.
abstract: Cancer patients often suffer from pain and most will be prescribed μ-opioids. μ-opioids are not satisfactory in treating cancer pain and are associated with multiple debilitating side effects. Recent studies show that μ and δ opioid receptors are separately expressed on IB4 (-) and IB4 (+) neurons, which control thermal and mechanical pain, respectively. In this study we investigated IB4 (+) and IB4 (-) neurons in mechanical and thermal hypersensitivity in an orthotopic mouse oral cancer model. We used a δ opioid receptor agonist and a P2X(3) antagonist to target IB4 (+) neurons and to demonstrate that this subset plays a key role in cancer-induced mechanical allodynia, but not in thermal hyperalgesia. Moreover, selective removal of IB4 (+) neurons using IB4-saporin impacts cancer-induced mechanical but not thermal hypersensitivity. Our results demonstrate that peripherally administered pharmacological agents targeting IB4 (+) neurons, such as a selective δ-opioid receptor agonist or P2X(3) antagonist, might be useful in treating oral cancer pain.
  
  
  CONCLUSIONS
  To clarify the mechanisms of oral cancer pain, we examined the differential role of IB4 (+) and IB4 (-) neurons. Characterization of these 2 subsets of putative nociceptors is important for further development of effective clinical cancer pain relief.
authors.affiliation: Bluestone Center for Clinic Research, New York University, New York, NY, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ye
authors.forename: Dongmin
authors.initials: D
authors.lastname: Dang
authors.forename: Chi T
authors.initials: CT
authors.lastname: Viet
authors.forename: John C
authors.initials: JC
authors.lastname: Dolan
authors.forename: Brian L
authors.initials: BL
authors.lastname: Schmidt
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000150:complications; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D037102:Lectins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009062:Mouth Neoplasms / Q000150:complications; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D059225:Nociception / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000378:metabolism
chemical_list: D000700:Analgesics; D037102:Lectins; D017450:Receptors, Opioid, mu