A Decrease in Anandamide Signaling Contributes to the Maintenance of Cutaneous Mechanical Hyperalgesia in a Model of Bone Cancer Pain

• DOI: 10.1523/jneurosci.2847-08.2008
• Publication Date: 2008-10-29T20:34:35Z
• Authors: Iryna A. Khasabova; Sergey G. Khasabov; Catherine Harding...; Lia G. Coicou; Bryan A. Seybold; Amy E. Lindberg; Christopher D. St...; Donald A. Simone; Virginia S. Seybold
• Keywords: Anandamide; Bone cancer

Tumors in bone are associated with pain humans. Data generated a murine model of cancer suggest that disturbance local endocannabinoid signaling contributes to the pain. When tumors formed after injection osteolytic fibrosarcoma cells into calcaneus mice, cutaneous mechanical hyperalgesia was decrease level anandamide (AEA) plantar paw skin ipsilateral tumors. The AEA occurred conjunction increased degradation by fatty acid amide hydrolase (FAAH). Intraplantar reduced hyperalgesia, and intraplantar URB597, an inhibitor FAAH, also hyperalgesia. An increase FAAH mRNA enzyme activity dorsal root ganglia (DRG) L3–L5 affected suggests DRG neurons contribute tumor-bearing mice. Importantly, anti-hyperalgesic effects URB597 were blocked CB1 receptor antagonist. Increased expression receptors limbs may effect elevated levels. Furthermore, protein-immunoreactivity as well inhibitory on depolarization-evoked Ca 2+ transient small cocultured indicating sufficient evoke phenotypic changes neurons. Together, data provide evidence manipulation peripheral is promising strategy for management