Vertex-recorded, rather than primary somatosensory cortex-recorded, somatosensory-evoked potentials signal unpleasantness of noxious stimuli in the rat

Abstract

In the present study, we investigated in the rat whether vertex-or primary somatosensory cortex-recorded somatosensory-evoked potentials (Vx-SEP/SI-SEP, respectively) signal unpleasantness of noxious stimuli. Therefore, initially we characterised fentanyl effects (0, 20, 40 or 50 g/kg/h) on somatosensory and auditory processing by recording Vx-/SI-SEPs and vertex-and primary auditory cortex-recorded auditory-evoked potentials (Vx-/AI-AEPs, respectively). Subsequently, in a separate experiment, the animals were subjected to a Pavlovian fear-conditioning paradigm. The noxious stimuli applied to evoke Vx-/SI-SEPs (unconditioned stimulus (US)) were paired to a tone (conditioned stimulus (CS)) under 'steady state' conditions of 0, 20, 40 or 50 g/kg/h fentanyl. Vx-/SI-SEPs were recorded simultaneously during these trials. After CS-US presentation, CS-induced fear-conditioned behaviour was analysed in relation to the SEPs recorded during CS-US presentation and the AEPs recorded in the first experiment. While the SI-SEP and AI-AEP were minimally but significantly affected, fentanyl dose-dependently decreased the Vx-SEP and Vx-AEP. The decrease of the Vx-SEP and Vx-AEP was parallelled by the dose-dependent decrease of the amount of CS-induced fear-conditioned behaviour. These results suggest that the dose-dependent decrease of the Vx-SEP amplitude, rather than of the SI-SEP, indicates that the US was experienced as less unpleasant. Next to an altered US processing, altered CS processing contributed to the decrease of the amount of CS-induced fear-conditioned behaviour as indicated by the dose-dependent decrease of the Vx-AEP.

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

“…Therefore, the relation between the Vx-SEP and the unpleasantness of the noxious stimuli, found in the previous study [42], might be confounded by the use of fentanyl. Although the possible co-influences of fentanyl were argued to be of little importance in the previous study [42], the present study further investigated the relation between both the Vx-SEP and the SI-SEP and the unpleasantness of the noxious stimuli. To this aim, we used the SEP fear-conditioning model while modulating the US unpleasantness by using different stimulus intensities instead of a pharmacological intervention.…”

“…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.…”

“…However, analgesic drugs can influence the outcome of Pavlovian fear-conditioning tasks by other mechanisms than analgesic actions alone [10,31,45]. Therefore, the relation between the Vx-SEP and the unpleasantness of the noxious stimuli, found in the previous study [42], might be confounded by the use of fentanyl. Although the possible co-influences of fentanyl were argued to be of little importance in the previous study [42], the present study further investigated the relation between both the Vx-SEP and the SI-SEP and the unpleasantness of the noxious stimuli.…”

“…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.…”

“…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. In a previous study, using this model in combination with the -opioid analgesic fentanyl applied to modulate the unpleasantness of the US, it was shown that SEPs recorded from vertex (Vx-SEP) did signal the unpleasantness of noxious stimuli whereas SEPs recorded from the primary somatosensory cortex (SI) (SI-SEP) did not [42]. However, analgesic drugs can influence the outcome of Pavlovian fear-conditioning tasks by other mechanisms than analgesic actions alone [10,31,45].…”