Fig. 1.

Hindpaw nociceptive and vascular changes in 7 cohorts of rats; 1) controls (Controls, n = 25), 2) a tibia fracture with 4 weeks cast immobilization (Fx + cast 4 wk, n = 28), 3) hindlimb cast immobilization for 4 weeks (Cast 4 wk, n = 39), 4) cast immobilization for 4 weeks treated with the substance P (SP) neurokinin 1 (NK1) receptor antagonist LY303870 once prior to testing (Cast 4 wk + LY, n = 14), 5) tibia fracture treated with intramedullary pinning for 1 week (Fx + pin 1 wk, n = 18), 6) tibia fracture treated with intramedullary pinning for 4 weeks (Fx + pin 4 wk, n = 28), 7) tibia fracture treated with intramedullary pinning and casting for 4 weeks (Fx + pin + cast 4 wk, n = 19). Fx+cast and Cast only treatments both resulted in significant hindpaw allodynia (A), unweighting (B), warmth (C) and edema (D) after 4 weeks. Cast rats treated with a single dose of SP NK1 antagonist had reduced hindpaw allodynia, unweighting and edema, but no change in warmth. Fx + pin treatment caused allodynia and unweighting at 1 week, but not at 4 weeks, and had no effect on hindpaw temperature or thickness. Fx + pin + cast caused hindpaw allodynia and unweighting, but no significant warmth or edema. Measurements for withdrawal thresholds (A), temperature (C), and paw thickness (D) represent the difference between the treatment side and the contralateral paw, thus a positive value represents an increase in temperature or thickness on the fracture side; a negative value represents a decrease in mechanical nociceptive thresholds on the affected side. Measurements for (B) represent weight-bearing on the fracture hindlimb as a ratio to 50% of bilateral hindlimb loading, thus a percentage lower than 100% represents hindpaw unweighting. *P<0.05, **P<0.01, ***P<0.001 vs. control values; ## P<0.01, ### P<0.001 vs. FX + cast; &&& P<0.001 Cast 4 wk + LY vs. Cast 4 wk.