Role of p38 mitogen activated protein kinase in a model of osteosarcoma-induced pain.
The focus of this work was to examine the potential role of p38 mitogen activated protein kinase (p38) in a mouse model of bone cancer (osteosarcoma) pain. To generate osteosarcoma and sham animals, osteosarcoma cells or medium were injected into the medullary canal of the femur. Initially, ipsilateral tactile allodynia was observed in both groups, but by 12 days post-surgery, thresholds in the sham group returned towards baseline while hypersensitivity in the osteosarcoma group lasted throughout the study. An increase in phosphorylated p38 was detected by western blotting in dorsal root ganglia (DRG) and spinal cord day 14 after surgery. Immunohistochemistry showed that p38 was phosphorylated in DRG and spinal dorsal horn neurons at this time point. Two doses of a selective p38 inhibitor, SCIO-469, were administered in the chow starting 5 days post-surgery and continued throughout the study. Treatment with SCIO-469 led to a decrease in osteosarcoma-induced clinical score but had no effect on the allodynia. Bone erosion and tumor growth were also examined but no significant reduction of bone erosion or tumor growth was observed in the SCIO-469 treated mice. These data suggest that the p38 signaling pathway does not play a major role in bone cancer-mediated pain.
Svensson
Camilla I
CI
Department of Anesthesiology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0818, USA. csvensson@ucsd.edu
Medicherla
Satyanarayana
S
Malkmus
Shelle
S
Jiang
Yebin
Y
Ma
Jing Y
JY
Kerr
Irena
I
Brainin-Mattos
Josue
J
Powell
Harry C
HC
Luo
Z David
ZD
Chakravarty
Sarvajit
S
Dugar
Sundeep
S
Higgins
Linda S
LS
Protter
Andrew A
AA
Yaksh
Tony L
TL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000502:physiology; D001859:Bone Neoplasms / Q000150:complications* / Q000201:enzymology*; D045744:Cell Line, Tumor; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005727:Ganglia, Spinal / Q000201:enzymology; D007150:Immunohistochemistry; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000150:complications* / Q000201:enzymology*; D010146:Pain / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D012684:Sensory Thresholds / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D014828:Vocalization, Animal / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D007211:Indoles; C499748:SCIO-469; D048051:p38 Mitogen-Activated Protein Kinases