Development of a rat model to assess the efficacy of the somatosensory-evoked potential as indicator of analgesia

Abstract

Drug-induced changes in somatosensory-evoked potentials (SEPs) are considered to reflect an altered nociceptive state. Therefore, the SEP is proposed to be a parameter of analgesic efficacy. However, at present, SEPs have not been studied in relation to animal pain. The present study aims to develop a rat model in which this relationship can be studied based on Pavlovian fear conditioning. Therefore, rats, implanted with epidural electro-encephalogram recording electrodes, were randomly assigned to either a paired or random-control group and subjected to an aversive-to-appetitive transfer paradigm. During the aversive phase, the SEP-stimulation paradigm (5 mA square wave pulses, n = 72, of 2 ms duration each, with a stimulus frequency of 0.5 Hz; total duration 144 s) was used as the unconditioned stimulus (US), while a tone (40 s, 1500 Hz, 85 dB sound pressure level) was used as the conditioned stimulus (CS). During the appetitive phase, the CS was presented paired to the presentation of a sugar pellet. When compared to the random-control group, the paired group showed significantly more freezing behavior and significantly less reward-directed behavior in response to the CS in the appetitive phase. In addition, SEPs were not significantly affected by fear conditioning. Based on these results, we conclude that the SEP-stimulation paradigm can be successfully employed as a US in fear conditioning. In future studies, fear conditioning can be carried out under different levels of an analgesic regimen to allow the changes in SEP parameters to be compared to changes in fear-induced behavior making this model potentially useful to validate SEP parameters as indicators of analgesia. D 2005 Elsevier B.V. All rights reserved.Theme: Neural basis of behavior Topic: Learning and memory: systems and functions-animals

Somatosensory-evoked potentials indicate increased unpleasantness of noxious stimuli in response to increasing stimulus intensities in the rat

“…In conclusion, the SEP components in the latency range studied in the present study are considered to be related to nociception which is in line with other studies using SEPs evoked by electrical stimulation to study nociception [7,15,35,[39][40][41][42][43].…”

“…The fear-conditioning sessions on day 1 (training session) were performed under the same conditions and using the same procedures as described previously [42,43]. In brief, after 30 min of acclimatization in the experimental room the animals were fitted in a tight fitting jacket and an electrical stimulation device (two brass electrodes of 3 mm in diameter tapered towards the end, fixed in a silicon tube, which enclosed the tail base [40]) was fixed at the left tail base and tightened by Velcro tape for maximal fixation.…”

“…The sessions to assess the CS-US association on day 2 (testing session) were performed under the same conditions and using the same procedures as described previously [42,43]. In brief, after 30 min of acclimatization in the experimental room the animals were placed in the testing box.…”

“…SEPs recorded in animals (1) are sensitive to analgesic intervention [4,18,25,35,40,41,42] and (2) a recent study in rats showed a correlation between the Vx-SEP and the unpleasantness of the noxious stimuli applied to evoke the SEP [42] [43]. This Pavlovian fear-conditioning model consists of two sessions executed on consecutive days.…”

“…On day 2 (testing session) the strength of the rat's CS-US association is investigated by determining the duration of freezing behaviour after presenting the CS without the US. The literature provides ample evidence that the duration of freezing behaviour is to be considered to reflect the unpleasantness of the noxious stimuli experienced by the animal [1,12,43]. Thus, correlating the SEPs recorded on day 1 with the duration of freezing behaviour recorded on day 2 shows whether the SEP indicates the unpleasantness of the noxious stimuli.…”