Behavioral and sensory changes after direct ischemia‐reperfusion injury in rats

Abstract

Complex regional pain syndromes (CRPS) are disabling pain syndromes that can develop after trauma or minor tissue injury affecting a limb. Characteristics of CRPS are sensory signs and symptoms, autonomic abnormalities, trophic changes and an impaired motor function. Pathophysiological mechanisms for the development of CRPS are still a matter of investigation. Based on clinical data and investigations of CRPS patients it is hypothesized that tissue hypoxia and inflammation are important for the development of CRPS. The aim of the current study was therefore to examine if direct ischemia-reperfusion injury can induce behavior in rats with symptoms present in patients with CRPS. After baseline behavior measurements the femoral artery of Wistar rats was ligated for 3h with consecutive reperfusion. Sham-operated rats underwent the same preparation except ligation of the artery. Subsequent behavioral testing (observations of spontaneous pain behavior, paw withdrawal to mechanical, noxious mechanical, cold and heat stimuli) was performed up to two months after surgery. Both in rats that underwent ischemia and in sham-operated rats no obvious changes of hindpaw tissue were observed after ischemia-reperfusion injury (trophic changes, edema, differences in skin color or temperature). In behavioral tests only minor changes were observed, these being not different between postischemic rats and sham-operated rats. Using Wistar rats, our data do not support the idea that an ischemia-reperfusion injury can play a major role in the development of CRPS.

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

“…Unlike previous studies (Coderre et al, 2004;Ludwig et al, 2006), in the present study we did not observe mechanical allodynia in the contralateral hind paw. This observation could be due to the fact we always tested the contralateral hind paw prior to the ipsilateral hind paw and may have avoided acute spinal sensitization following mechanical stimulation of the hypersensitive hind paw.…”

“…Coderre et al (2004) showed that a 3 h-ischemia/ reperfusion of the hind paw induced long-term (4 weeks) mechanical and cold hypersensitivity (known as chronic post-ischemia pain), which was reduced by free radical scavengers. Mechanical hypersensitivity is also observed after 3 h-occlusion of the femoral artery (Ludwig et al, 2006), although sham rats were also affected.…”

Development of animal model for vasculatic neuropathy: Induction by ischemic-reperfusion in the rat femoral artery

“…In the present study the peripheral nerve has been targeted for induction of vasculatic neuropathy in rats by the process of femoral artery I/R. The event of femoral artery I/R process has been well documented for the induction of the neuro-inflammation, neuronal excitability and enhancement of pain sensation (Ludwig et al, 2007). The production of reactive oxygen species and reactive nitrogen species (ROS/RNS) in severe oxidative stress conditions leads to loss of membrane integrity and structural or functional changes (Gholami et al, 2007).…”

Interaction of Hyperalgesia and Sensory Loss in Complex Regional Pain Syndrome Type I (CRPS I)

“…Conspicuously, CRPS sensory abnormalities may spread in a hemisensory manner [3] or even contralaterally [4]. No generally accepted animal model of CRPS I exists, but very recently an ischemia-reperfusion injury model reproduced some changes observed in humans [5] (but see [6]). …”