title: Calpain inhibitor reduces cancer-induced bone pain possibly through inhibition of osteoclastogenesis in rat cancer-induced bone pain model.
abstract: BACKGROUND
  Calpain, a calcium-dependent cysteine protease, has been demonstrated to regulate osteoclastogenesis, which is considered one of the major reasons for cancer-induced bone pain (CIBP). In the present study, calpain inhibitor was applied in a rat CIBP model to determine whether it could reduce CIBP through regulation of osteoclastogenesis activity.
  
  
  METHODS
  A rat CIBP model was established with intratibial injection of Walker 256 cells. Then, the efficacy of intraperitoneal administered calpain inhibitor III (MDL28170, 1 mg/kg) on mechanical withdrawal threshold (MWT) of bilateral hind paws was examined on postoperative days (PODs) 2, 5, 8, 11, and 14. On POD 14, the calpain inhibitor's effect on tumor bone tartrate-resistant acid phosphatase (TRAP) stain and radiology was also carefully investigated.
  
  
  RESULTS
  Pain behavioral tests in rats showed that the calpain inhibitor effectively attenuated MWTs of both the surgical side and contralateral side hind paws on POD 5, 8, and 11 (P < 0.05). TRAP-positive cell count of the surgical side bone was significantly decreased in the calpain inhibitor group compared with the vehicle group (P < 0.05). However, bone resorption and destruction measured by radiographs showed no difference between the two groups.
  
  
  CONCLUSIONS
  Calpain inhibitor can effectively reduce CIBP of both the surgical side and nonsurgical side after tumor injection in a rat CIBP model. It may be due to the inhibition of receptor activator of nuclear factor-kappa B ligand-induced osteoclastogenesis. Whether a calpain inhibitor could be a novel therapeutic target to treat CIBP needs further investigation.
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: Huang
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D004151:Dipeptides / Q000627:therapeutic use; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006023:Glycoproteins / Q000627:therapeutic use*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004151:Dipeptides; D006023:Glycoproteins; C039304:calpain inhibitors; C058076:calpain inhibitor III