Article Figures & Data
Figures
- Fig. 1.
Mechanical allodynia induced by SNL is attenuated by the systemic inhibition of TNF and the intrathecal inhibition of p38. A, Treatment with the TNF antagonist etanercept (▴) starting 2 d before SNL (d-2) attenuates mechanical allodynia induced by SNL.B, Treatment with etanercept started 1 d after SNL (▴) has no effect on mechanical thresholds, even when the etanercept dose is doubled (dark shaded bar).C, Treatment with etanercept started 7 d after SNL has no effect. D, Treatment with the p38 inhibitor SB203580 (d-2) but not treatment starting 7 d after SNL attenuates mechanical allodynia induced by SNL. *p < 0.05, **p < 0.005, ***p < 0.001 versus vehicle-treated rats;n = 6–12 per treatment group.
- Fig. 2.
SNL induces transient p38 activation in DRG neurons and spinal cord. A, Time course of p38 phosphorylation in DRG neurons after SNL. Phospho-p38 (p-p38) is transiently increased 5 hr after SNL.B, Time course of p38 phosphorylation in lumbar spinal cord after SNL; phospho-p38 is increased between 5 hr and 3 d after SNL. *p < 0.05, **p < 0.005 versus control; n = 6 per time point.
- Fig. 3.
Phospho-p38 (p-p38) is activated in small, presumably nociceptive DRG neurons and not in activated satellite cells. A–C, p38 phosphorylation is increased in DRG neurons (arrows) 5 hr after SNL.D, Serial staining of phospho-p38 (red) with PGP 9.5 (green), a marker for neuronal cells, in DRG neurons indicates that p38 is predominantly activated in neuronal cells (arrows). E, Serial staining of phospho-p38 (red) with GFAP (green, open arrow), a marker for activated satellite cells, indicates that p38 (arrows) is not phosphorylated in activated satellite cells 5 hr after SNL.F, Double staining demonstrates colocalization (arrows) of phospho-p38 (red) with IB4 (green) in DRG neurons after SNL, suggesting p38 activation in small, presumably nociceptive DRG neurons. Scale bars, 30 μm. n = 4 per time point.
- Fig. 4.
TNF induces p38 activation in DRG after SNL.A, Phospho-p38 (p-p38,red) is colocalized with TNF (green) in small DRG neurons after SNL (arrows). Scale bar, 30 μm. B, Systemic anti-TNF treatment with etanercept (Eta, 1 mg/rat, i.p.) suppresses the SNL-induced increase in phospho-p38 in DRG 5 hr after SNL. C, Systemic etanercept does not suppress the increase of phospho-p38 in lumbar spinal cord after SNL. *p < 0.05, **p < 0.005 versus control; n = 6 per group.
