title: The inhibition of subchondral bone lesions significantly reversed the weight-bearing deficit and the overexpression of CGRP in DRG neurons, GFAP and Iba-1 in the spinal dorsal horn in the monosodium iodoacetate induced model of osteoarthritis pain.
abstract: BACKGROUND
  Chronic pain is the most prominent and disabling symptom of osteoarthritis (OA). Clinical data suggest that subchondral bone lesions contribute to the occurrence of joint pain. The present study investigated the effect of the inhibition of subchondral bone lesions on joint pain.
  
  
  METHODS
  Osteoarthritic pain was induced by an injection of monosodium iodoacetate (MIA) into the rat knee joint. Zoledronic acid (ZOL), a third generation of bisphosphonate, was used to inhibit subchondral bone lesions. Joint histomorphology was evaluated using X-ray micro computed tomography scanning and hematoxylin-eosin staining. The activity of osteoclast in subchondral bone was evaluated using tartrate-resistant acid phosphatase staining. Joint pain was evaluated using weight-bearing asymmetry, the expression of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG), and spinal glial activation status using glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) immunofluorescence. Afferent neurons in the DRGs that innervated the joints were identified using retrograde fluorogold labeling.
  
  
  RESULTS
  MIA injections induced significant histomorphological alterations and joint pain. The inhibition of subchondral bone lesions by ZOL significantly reduced the MIA-induced weight-bearing deficit and overexpression of CGRP in DRG neurons, GFAP and Iba-1 in the spinal dorsal horn at 3 and 6 weeks after MIA injection; however, joint swelling and synovial reaction were unaffected.
  
  
  CONCLUSIONS
  The inhibition of subchondral bone lesions alleviated joint pain. Subchondral bone lesions should be a key target in the management of osteoarthritic joint pain.
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Degang
authors.initials: D
authors.lastname: Yu
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Mao
authors.forename: Zhenan
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000188:drug therapy*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002135:Calcium-Binding Proteins; D059350:Chronic Pain / Q000139:chemically induced / Q000188:drug therapy*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D007461:Iodoacetates / Q000633:toxicity; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010003:Osteoarthritis / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D016474:Weight-Bearing; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: C112986:AIF1 protein, human; D000477:Alkylating Agents; D050071:Bone Density Conservation Agents; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D004164:Diphosphonates; D005904:Glial Fibrillary Acidic Protein; D007093:Imidazoles; D007461:Iodoacetates; D008840:Microfilament Proteins; D000077211:Zoledronic Acid; D015740:Calcitonin Gene-Related Peptide