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Disease modifying and anti-nociceptive effects of the bisphosphonate, zoledronic acid in a model of bone cancer pain.
- Source :
-
Pain [Pain] 2002 Dec; Vol. 100 (3), pp. 219-229. - Publication Year :
- 2002
-
Abstract
- Inoculation of syngeneic MRMT-1 mammary tumour cells into one tibia of female rats produced tumour growth within the bone associated with a reduction in bone mineral density (BMD) and bone mineral content (BMC), severe radiological signs of bone destruction, together with the development of behavioural mechanical allodynia and hyperalgesia. Histological and radiological examination showed that chronic treatment with the bisphosphonate, zoledronic acid (30 microg/kg, s.c.), for 19 days significantly inhibited tumour proliferation and preserved the cortical and trabecular bone structure. In addition, BMD and BMC were preserved and a dramatic reduction of tartrate resistant acid phosphatase-positive polykaryocytes (osteoclasts) was observed. In behavioural tests, chronic treatment with zoledronic acid but not the significantly less effective bisphosphonate, pamidronate, or the selective COX-2 inhibitor, celebrex, attenuated mechanical allodynia and hyperalgesia in the affected hind paw. Zoledronic acid also attenuated mechanical hyperalgesia associated with chronic peripheral neuropathy and inflammation in the rat. In contrast, pamidronate or clodronate did not have any anti-hyperalgesic effect on mechanical hyperalgesia in the neuropathic and inflammatory pain models. We conclude that zoledronic acid, in addition to, or independent from, its anti-metastatic and bone preserving therapeutic effects, is an anti-nociceptive agent in a rat model of metastatic cancer pain. This unique property of zoledronic acid amongst the bisphosphonate class of compounds could make this drug a preferred choice for the treatment of painful bone metastases in the clinic.
- Subjects :
- Animals
Bone Density drug effects
Bone Neoplasms diagnostic imaging
Bone Neoplasms pathology
Clodronic Acid administration & dosage
Female
Hyperalgesia drug therapy
Hyperalgesia etiology
Hyperesthesia drug therapy
Hyperesthesia etiology
Models, Animal
Neoplasm Transplantation
Observer Variation
Pain Measurement drug effects
Pain Threshold drug effects
Pamidronate
Radiography
Rats
Rats, Sprague-Dawley
Reference Values
Reproducibility of Results
Sensitivity and Specificity
Tibia drug effects
Tibia pathology
Tibia surgery
Touch drug effects
Treatment Outcome
Zoledronic Acid
Bone Neoplasms complications
Bone Neoplasms drug therapy
Diphosphonates administration & dosage
Imidazoles administration & dosage
Pain drug therapy
Pain etiology
Subjects
Details
- Language :
- English
- ISSN :
- 0304-3959
- Volume :
- 100
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Pain
- Publication Type :
- Academic Journal
- Accession number :
- 12467993
- Full Text :
- https://doi.org/10.1016/S0304-3959(02)00040-4