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 regional pain syndrome-I pain is refractory to most standard analgesic treatments.

Role of NFκB in an Animal Model of Complex Regional Pain Syndrome–type I (CRPS-I)

“…However, because of serious immunological consequences, there may be safety issues associated with targeting NFkB in human patients, 52 and current therapeutic indications have been restricted to oncology. On the other hand, some nonspecific modulators of NFkB activity, including N-acetylcysteine 14,43 and corticosteroids, 19,27,41 have already been demonstrated to be beneficial in attenuating CRPS in animal models as well as in human trials. Currently, these drugs are not applied generally for CRPS treatment, but these new mechanistic insights warrant further clinical studies to establish their clinical benefits.…”

“…Moreover, CPIP rats express sympathetically maintained pain, 55 a phenomenon that in the past has been considered almost pathognomic for CRPS, although currently it is acknowledged to be present in only a subset of CRPS patients. Similar to CRPS-I patients, CPIP rats receive poor pain relief from classical anti-inflammatory and anti-neuropathic pain treatments, 41 but respond well to treatment with free radical scavengers. 14 The major advantage of the CPIP model above others is that the CRPSresembling features occur after a physical (not chemical) injury without microscopic evidence of direct nerve injury.…”

“…In support of this possibility, contralateral allodynia has been found in the CPIP rats in the past, 14 although not consistently in all studies. 41 It may be that contralateral allodynia depends on spinal sensitization which may be mediated by NFkB that is increased in the contralateral spinal cord dorsal horn.…”

Effect of Different Doses of Pregabalin on Erythrocyte Deformability in Rats with Lower Limb Ischemia Reperfusion Injury

“…Besides these clinical indications, it has some new properties that we need to focus on. Pregabalin has been used to protect against IR injury in many organs [1,7,8].…”

“…As reperfusion progresses generally systemic inflammatory response syndrome and multiple organ failure (kidney, respiratory and circulatory system, etc.) follow local edema and muscle necrosis [1][2][3][4][5].…”