PURPOSE: TNFα is an inflammatory mediator related to neuropathic pain including sciatica. Much basic research suggests that anti-TNFα therapy may be useful for the treatment of sciatica. The purpose of this study was to clarify the effects of etanercept in a dorsal root ganglion (DRG) compression model. METHODS: Adult male Sprague-Dawley rats (200-250 g, n = 60) were used. An L-shaped stainless rod was used to compress the left L5 DRG in the saline and etanercept groups. No rod was used in the sham group. In the etanercept group, 1 mg of etanercept was applied locally onto the DRG at the end of surgery. Saline was applied in the saline and sham groups. On day 3 and day 7 after surgery, the number of ED1-immunoreactive (IR) cells (macrophages) in the DRG was calculated by immunohistochemical methods (n = 6). In addition, double-immunofluorescence labeling for ED1 and TNFα was performed. Behavioral testing with von Frey filaments and a heat stimulator was performed (n = 12). RESULTS: ED1-IR cells in the DRG significantly increased in the control group compared with the sham group (p < 0.05). Some ED1-IR cells were co-labeled for TNFα. In the etanercept group, decrease in mechanical threshold was significantly inhibited compared with the saline group (p < 0.05). Thermal hyperalgesia was observed in the control group, but in neither the sham nor etanercept group (p < 0.05). CONCLUSION: Etanercept attenuated the pain-related behavior induced by DRG compression. These findings suggest that mechanical effects on the DRG might be reduced by etanercept in addition to the effects on nucleus pulposus in lumbar disc herniation.
PURPOSE: TNFα is an inflammatory mediator related to neuropathic pain including sciatica. Much basic research suggests that anti-TNFα therapy may be useful for the treatment of sciatica. The purpose of this study was to clarify the effects of etanercept in a dorsal root ganglion (DRG) compression model. METHODS: Adult male Sprague-Dawley rats (200-250 g, n = 60) were used. An L-shaped stainless rod was used to compress the left L5 DRG in the saline and etanercept groups. No rod was used in the sham group. In the etanercept group, 1 mg of etanercept was applied locally onto the DRG at the end of surgery. Saline was applied in the saline and sham groups. On day 3 and day 7 after surgery, the number of ED1-immunoreactive (IR) cells (macrophages) in the DRG was calculated by immunohistochemical methods (n = 6). In addition, double-immunofluorescence labeling for ED1 and TNFα was performed. Behavioral testing with von Frey filaments and a heat stimulator was performed (n = 12). RESULTS: ED1-IR cells in the DRG significantly increased in the control group compared with the sham group (p < 0.05). Some ED1-IR cells were co-labeled for TNFα. In the etanercept group, decrease in mechanical threshold was significantly inhibited compared with the saline group (p < 0.05). Thermal hyperalgesia was observed in the control group, but in neither the sham nor etanercept group (p < 0.05). CONCLUSION: Etanercept attenuated the pain-related behavior induced by DRG compression. These findings suggest that mechanical effects on the DRG might be reduced by etanercept in addition to the effects on nucleus pulposus in lumbar disc herniation.
Authors: Tracey A Ignatowski; Robert N Spengler; Krishnan M Dhandapani; Hedy Folkersma; Roger F Butterworth; Edward Tobinick Journal: CNS Drugs Date: 2014-08 Impact factor: 5.749