Skip to main content
. 2015 Apr 24;156(10):1852–1863. doi: 10.1097/j.pain.0000000000000204

Figure 6.

Figure 6

Substance P–deficient (SP KO) and CGRP RAMP1 receptor–deficient (RAMP1 KO) fracture (FX) mice failed to develop exaggerated spinal neuropeptide signaling and inflammatory mediator expression at 3 weeks after fracture, measured by real-time polymerase chain reaction. Similar to the changes observed in 4-week postfracture rats (Figs. 1 and 3), in wild-type (WT) fracture (FX) mice, there was increased gene expression of (A) SP (TAC1), (B) SP NK1 receptor (TACR1), (C, D) CGRP (CALCA and CALCB), (E) CGRP CRLR receptor (CALCRL), (F) CGRP RAMP1 receptor (RAMP1), (G) TNF-α, (H) IL-1β, (I) IL-6, (J) CCL2, and (K) nerve growth factor (NGF), compared with WT mice with no fracture (WT control). Substance P–deficient fracture (SP KO FX) mice had attenuated postfracture spinal cord changes compared with WT FX mice, and there was no increase in the expression of (D) CALCB, (E) CALCRL, (F) RAMP1, (H) IL1β, and (K) CCL2 in the SP KO FX mice, compared with WT control mice. CGRP RAMP1 receptor–deficient fracture (RAMP1 KO FX) mice also exhibited attenuated postfracture spinal cord changes, compared with WT FX mice, and there was no increase in (B) TACR1, (D) CALCB, (E) CALCRL, (H) IL-1β, (I) IL-6, and (J) NGF mRNA levels, compared with WT controls. (A) TAC1 mRNA was not detected in the TAC1-deficient mice, and (F) RAMP1 mRNA was not measurable in the RAMP1 receptor–deficient mice. Values are mean ± SE, n = 8 per cohort. One-way analysis of variance (P < 0.01 for graph E, P < 0.001 for all other graphs), with Bonferroni post hoc testing *P < 0.05, **P < 0.01, and ***P < 0.001 for WT FX, SP KO FX, or RAMP1 KO FX vs WT control, #P < 0.05, ##P < 0.01, and ###P < 0.001 for SP KO FX, or RAMP1 KO FX vs WT FX.