Effects of TrkA inhibitory peptide on cancer-induced pain in a mouse melanoma model.

Purpose: Tropomyosin receptor kinase (Trk) A, a high-affinity receptor of nerve growth factor, is a therapeutic target for both noxious and neuropathic pain. The present study examined the effects of an inhibitory peptide of Trk activity (IPTRK) 3 that inhibits TrkA activity on cancer-induced pain in a mouse melanoma model.

Methods: The hind paws of mice were inoculated with B16-F1 mouse melanoma cells on day 0. We administered IPTRK3 (20 mg/kg i.p.) repetitively on days 5, 6, 7, 8, and 9, and evaluated pain-related behaviors on days 0, 5, 10, 15, and 20 after tumor inoculation.

Results: Following inoculation, mice demonstrated mechanical allodynia and thermal hyperalgesia with an increased number of flinches, and paw volume increased gradually. However, an intraperitoneal injection of IPTRK3 significantly inhibited mechanical allodynia on day 15 and suppressed the number of flinches on day 20. The increased paw volume was significantly suppressed on day 20 after tumor inoculation. IPTRK3, however, showed no significant effect on thermal hyperalgesia.

Conclusions: These results suggest that TrkA inhibitory peptide likely suppress melanoma-induced pain with concomitant reduction in the increased paw volume in a mouse skin cancer pain model.