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Objective: Cancer pain severely affects patients’ overall quality of life; its management is challenging.Because Chinese herbal medicine has been widely used for cancer pain, its efficacy and mechanisms warrant the study.We explored the effects and spinal mechanisms of a seven-herb compound, Long-Teng-Tong-Luo(LTTL) gel, on bone cancer pain.Methods: Walker 256 cells(3.5×105 in 6 μL of vehicle) were injected into the tibias of female Sprague-Dawley rats to produce a bone cancer pain model.Six sets of experiments were carried out:(1) the effect of LTTL on cancer-induced pain was assessed with mechanical allodynia and thermal hyperalgesia;(2) cancer and LTTL modulation of transient receptor potential cation channel(TRP) subfamily members V1, A1, and V4 in lumbar dorsal root ganglia(DRG) were detected with immunofluorescence staining;(3) cancer and LTTL modulation of spinal interleukin-17A(IL-17A) were measured with real time-polymerase chain reaction and enzyme-linked immunosorbent assay;(4) the effects of intrathecal(i.t.) TRPV1, TRPA1, and TRPV4 antagonists on cancer-induced pain;(5) i.t.antibodies against IL-17A on cancerinduced pain, and(6) TRP channel antagonists on spinal IL-17A were determined.LTTL or inert gel, 0.5 g/(cm2·d), was applied to the skin of the rats’ tumor-bearing tibias for 21 d, starting a day after the injection.Results: LTTL significantly(P<0.01) increased mechanical threshold and hind paw withdrawal latency compared to the vehicle, demonstrating that the gel inhibited cancer-induced mechanical allodynia and thermal hyperalgesia, and it suppressed cancer-enhanced expression of spinal IL-17A, TRPV1, TRPV4, and TRPA1 in lumbar DRG.TRP antagonists at 10 μg significantly attenuated mechanical allodynia, thermal hyperalgesia, and IL-17A expression, indicating that TRP channels facilitate spinal IL-17 expression and cancer pain; IL-17A antibodies inhibited cancer pain, suggesting that IL-17A promotes the pain.Conclusion: We concluded that the gel inhibits cancer pain by decreasing DRG TRP and spinal IL-17A action.
Objective: Cancer pain severely affects patients’ overall quality of life; its management is challenging.Because Chinese herbal medicine has been widely used for cancer pain, its efficacy and mechanisms warrant the study. We explored the effects and spinal mechanisms of a seven-herb compound, Long-Teng-Tong-Luo (LTTL) gel, on bone cancer pain. Methods: Walker 256 cells (3.5 x 105 in 6 μL of vehicle) were injected into the tibias of female Sprague-Dawley rats to produce a bone cancer pain model. Six sets of experiments were carried out: (1) the effect of LTTL on cancer-induced pain was assessed with mechanical allodynia and thermal hyperalgesia; (2) cancer and LTTL modulation of transient receptor potential cation channel (TRP) subfamily members V1, A1, and V4 in lumbar dorsal root ganglia (DRG) were detected with immunofluorescence staining; (3) cancer and LTTL modulation of spinal interleukin-17A (IL- 17A) were measured with real time-polymerase chain reaction and enzyme- linked immunosorbent assa (4) the effects of intrathecal (it) TRPV1, TRPA1, and TRPV4 antagonists on cancer-induced pain; (5) itantibodies against IL- 17A on cancer induced pain, and (6) TRP channel antagonists on spinal IL- 17A were applied to the skin of the rats’ tumor-bearing tibias for 21 d, starting a day after the injection. Results: LTTL significantly (P <0.01) increased mechanical threshold and hind paw withdrawal latency compared to the vehicle, demonstrating that the gel inhibited cancer-induced mechanical allodynia and thermal hyperalgesia, and suppressed pravastatin-enhanced expression of spinal IL-17A, TRPV1, TRPV4, and TRPA1 in lumbar DRG. TRP antagonists at 10 μg significantly attenuated mechanical allodynia, thermal hyperalgesia, and IL-17A expression, indicating that TRP channels for facilitating spinal IL-17 expression and cancer pain; IL-17A antibodies inhibited cancer pain, suggesting that IL-17A promotes the pain. Conclusion: We said that the gel inhibits cancer pain by increasing DRG TRP and spinal IL-17A action.