Data on Possible Bone Cancer Pain Treatment Released

September 3, 2010

Preclinical in vivo results for a P2X3 receptor antagonist demonstrate positive results in preventing and reversing bone cancer pain behavior.

Preclinical in vivo results for a P2X3 receptor antagonist demonstrate positive results in preventing and reversing bone cancer pain behavior.

The antagonist was developed by Afferent Pharmaceuticals. The new data expands on earlier findings and reveals that a “marked reduction in apparent bone cancer pain occurs following oral administration of the propriety P2X3 antagonist,” according to a press release. The findings were presented in a poster session at the 13th World Congress on Pain, in Montreal, Canada.

The study, “P2X3 and P2x2/3 Antagonist as a Novel Bone Cancer Pain Treatment — In Vivo and In Vitro Mechanistic Insights,” was co-authored by Anthony Ford, PhD, founder and chief scientific officer of Afferent Pharmaceuticals. The study showed that P2X3 antagonist reduced bone cancer pain behavior by dampening down dorsal horn neuronal activity. It also reduced activation of extracellular-signal regulated kinase (ERK) in dorsal root ganglion (DRG) neurons.

“The results of this study capture some of the mechanistic elements that may support the use of P2X3 antagonists to treat bone cancer pain,” said Dr. Ford, in a press release. "P2X3 receptors are preclinically well-validated targets, highly specific to unmyelinated, C fiber afferent nerves that have dense innervations in visceral organs, skin and joints. These small diameter fibers transmit sensations of pain and irritation via mechanisms that include ATP signaling. ATP released from cancer cells appears capable of driving peripheral sensitization, while P2X3 signaling in the dorsal horn is clearly adding central sensitization, and together these give rise to chronic cancer pain.”

“P2X3 receptors have limited distribution beyond sensory nerves and no significant expression in the higher centers of the brain. A highly specific and targeted approach to chronic pain therapy, including bone cancer pain, is expected to provide patients with a safer and more effective alternative to current treatments. Clinical treatments of bone cancer pain remain limited and often result in significant adverse side effects."