title: Safety of epidural administration of Osteogenic Protein-1 (OP-1/BMP-7): behavioral and macroscopic observation.
abstract: METHODS
  To assess the safety of epidural administration of Osteogenic Protein-1 (OP-1).
  
  
  OBJECTIVE
  To examine if epidural administration of OP-1 or administration into the nucleus pulposus (NP) resulted in ectopic bone formation and/or pain-related behavior.
  
  
  BACKGROUND
  OP-1 has the potential for treatment of degenerative disc disease. However, OP-1's safety, when it is applied into the epidural space or herniated nucleus pulposus, is not well established.
  
  
  METHODS
  Forty rats were divided into 5 groups. Sham group: Left L4 and L5 nerve roots were exposed. NP group: The NP obtained from the tail was relocated onto the exposed nerve roots. NP+OP group: The NP obtained from the tail and injected with 0.2 microg of OP-1 in 1 microL of 5% lactose-buffered solution was placed on the nerve roots. GS group: A gelatin sponge was applied on the nerve roots. GS+OP group: A gelatin sponge soaked with 0.2 microg of OP-1 in 1 microL of 5% lactose-buffered solution was placed onto the nerve roots. Motor function and reflex responses to mechanical noxious stimuli were measured in all rats up to 3 weeks after surgery. Three weeks after surgery, all rats were killed for analysis of ectopic bone formation and magnitude of neural compression.
  
  
  RESULTS
  Motor paresis was not observed in any groups. Only rats in the NP group showed evidence of irreversible mechanical hyperalgesia after surgery. There were no differences in the mechanical stimuli response among all groups except the NP group. Macroscopic examination revealed no ectopic bone formation or differences in neural compression among the groups.
  
  
  CONCLUSIONS
  OP-1 application in the epidural space is safe based on behavioral measures and macroscopic observation on ectopic bone formation at 21 days after surgery.
authors.affiliation: Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama City, Wakayama, Japan. kawakami@wakayama-med.ac.jp
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kawakami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashizume
authors.forename: Takuji
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Enyo
authors.forename: Motohiro
authors.initials: M
authors.lastname: Okada
authors.forename: Munehito
authors.initials: M
authors.lastname: Yoshida
authors.forename: Susan
authors.initials: S
authors.lastname: Chubinskaya
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000473:pathology; D007268:Injections, Epidural; D007403:Intervertebral Disc / Q000187:drug effects* / Q000473:pathology*; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000473:pathology*; D008159:Lumbar Vertebrae; D008297:Male; D009043:Motor Activity; D009999:Ossification, Heterotopic / Q000473:pathology; D017288:Pain Threshold; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000473:pathology; D013623:Tail; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta