Osteogenic protein-1 (osteogenic protein-1/bone morphogenetic protein-7) inhibits degeneration and pain-related behavior induced by chronically compressed nucleus pulposus in the rat.
METHODS
To study the therapeutic efficacy of intradiscal injection of osteogenic protein-1 (OP-1) to reduce degeneration and associated discogenic pain.


OBJECTIVE
To evaluate if intradiscal injection of OP-1 can reverse disc degeneration and reduce hyperalgesia, a pain-related behavior.


BACKGROUND
We showed that induction of hyperalgesia was higher in rats exposed to compressed nucleus pulposus (NP). It has been reported that intradiscal injection of OP-1 stimulates synthesis of proteoglycans and collagen in normal intervertebral discs.


METHODS
Rats were divided into several groups. In the sham group, the rings of an Ilizarov-type apparatus were only applied to the tail without compression. In the compressed NP group, the apparatus was used to apply chronically compression to the tail. Four weeks after surgery, the NP group was subdivided into 3 groups: saline-treated and OP-1-treated, which was divided into 2 groups (i.e., the continuous compression OP-1 [COP-1] group, in which compression was continuously applied to the tail for 4 weeks after OP-1 treatment and the release compression OP-1 [ROP-1] group, in which compression was released at treatment. Either physiologic saline or OP-1 was injected into the instrumented NP. The treated NP was harvested and applied to the left lumbar nerve roots 4 weeks after injection. Hyperalgesia was measured up to 3 weeks after surgery. The degree of disc degeneration and the appearance of the extracellular matrix in the intervertebral discs were evaluated by histology.


RESULTS
Mechanical hyperalgesia was observed in the sham and saline groups, but not in the OP-1 treated group. In the saline group, NP cells became spindle-shaped. In the OP-1 group, the NP cells became swollen with vacuolated cytoplasm, and the content of the extracellular matrix was markedly increased.


CONCLUSIONS
OP-1 injection into degenerative intervertebral disc resulted in the enhancement of the extracellular matrix and the inhibition of pain-related behavior.
Kawakami
Mamoru
M
Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, Japan. kawakami@wakayama-med.ac.jp
Matsumoto
Takuji
T
Hashizume
Hiroshi
H
Kuribayashi
Koichi
K
Chubinskaya
Susan
S
Yoshida
Munehito
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007278:Injections, Spinal; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010146:Pain / Q000209:etiology / Q000523:psychology*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013122:Spinal Diseases / Q000517:prevention & control*; D013623:Tail; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000494:pharmacology
C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta