Relationship between allodynia, muscle ischemia and exercise. a, compared to sham treatment HPDM lactate (mmol/μg) is increased at 2 hrs (n = 6,6,6 for sham, ipsilateral (ipsi), contralateral (contra)) and 2 days (n = 7,7,5 for sham, ipsi, contra) after hind paw IR injury, and returns to normal at 7 days (n = 7,7,5 for sham, ipsi, contra) and 14 days (n = 6,6,5 for sham, ipsi, contra) post-reperfusion (*P < 0.05). b, 2 days after hind paw IR injury, rats refusal to run results in increased running stoppages in CPIP (n = 7) compared to sham (n = 6) animals (*P < 0.05). c, 7 days after IR injury, HPDM lactate (mmol/μg) levels are significantly increased in unexercised (no run) and exercised (run) CPIP (n = 10), compared to unexercised and exercised sham rats (n = 7), respectively (*P < 0.05). While 20 min of treadmill running does not increase HPDM lactate in sham/run (n = 6) rats (p > 0.05, compared to sham/no run), exercise leads to a further increase in lactate for CPIP/run rats (†P < 0.05 compared to CPIP/no run). d, Although PWTs (g) were lower for all CPIP rats (n = 12,15 for unexercised (no run) and exercised (run)) compared to sham rats (n = 9,9 for unexercised and exercised), there is a significantly greater reduction in PWTs (g) in exercised CPIP rats compared to unexercised CPIP rats (*P < 0.05, Pre vs Post for CPIP run). No significant decrease was observed for unexercised CPIP rats tested twice (p > 0.05, Pre vs Post for CPIP no run). e, scatterplot of PWT (g) vs HPDM lactate (mmol/μg) levels in both exercised and non-exercised sham and 7 day CPIP rats shows a significant inverse linear correlation, indicating that allodynia is directly related to HPDM lactate. f, Reduced pre-drug CPIP PWTs (g) (compared to baseline (Bas)) are significantly elevated by systemic treatment with amiloride on day 2 post-reperfusion (*P < 0.05 compared to pre-drug) (n = 7 for all groups). All data expressed as mean ± s.e.m.