Rats with chronic post-ischemia pain exhibit an analgesic sensitivity profile similar to human patients with complex regional pain syndrome--type I

Abstract

Chronic post-ischemia pain was induced in anesthetized rats by placing a tourniquet at the ankle joint for 3 h, and removing it to allow reperfusion. The effectiveness of standard analgesic drugs to attenuate mechanical allodynia was assessed 2 and 7 days after ischemia/reperfusion. Only high doses of morphine, dexamethasone and pregabalin partially reduced mechanical allodynia 2 days post-ischemia/reperfusion, while other treatments (ibuprofen, acetaminophen, amitriptyline) were not effective. Furthermore, only the highest dose of pregabalin reduced mechanical allodynia 7 days post-ischemia/reperfusion. These results are consistent with findings that complex region pain syndrome-I pain is refractory to most standard analgesic treatments.

Fig. 1

Mechanical (von Frey) thresholds (grams) were assessed on the ipsilateral hind paw prior to ischemia/reperfusion injury (Bas), pre-drug treatment (Pre) and at various times post-drug treatment, 2 or 7 days after the ischemia/reperfusion-injury (left and right panels, respectively). Animals received (A) saline or acetaminophen (1, 2 and 3 = 100, 200 and 400 mg/kg, respectively), (B) saline or ibuprofen (1, 2 and 3 = 50, 100 and 200 mg/kg, respectively), (C) saline or dexamethasone (1, 2 and 3 = 1, 5 and 10 mg/kg, respectively). The δAUC (inset histograms) were calculated relative to the mechanical threshold measured pre-treatment (Pre) over the full period of observation. N = 6 to 9/group (t: vs. Pre, corrected P-value P<0.05, repeated measures Bonferroni/Dunn test; *: vs. saline, δAUC, P<0.05, Fisher’s PLSD).

Fig. 2

Mechanical (von Frey) thresholds (grams) were assessed on the ipsilateral paw prior to ischemia/reperfusion (Bas), pre-drug treatment (Pre) and at various times post-drug treatment, 2 or 7 days after ischemia/reperfusion-injury (left and right panels, respectively). Animals received (A) saline or morphine (1, 2 and 3 = 0.3, 1 and 3 mg/kg, respectively), (B) saline or amitriptyline (1, 2 and 3 = 3, 10 and 30 mg/kg, respectively), (C) saline or pregabalin (1, 2 and 3 = 25, 50 and 100 mg/kg, respectively). The δAUC (inset histograms) were calculated relative to the mechanical threshold measured pre-treatment (Pre) over the full period of observation. N = 6 to 9/ group. (°: vs. Pre P<0.01, t: vs. Pre, P<0.05 (repeated measure Bonferroni/Dunn test); *: P<0.05, τ (trend): vs. saline δAUC, Fisher’s PLSD).