Effects of pentazocine and acetylsalicylic acid on pain-rating, pain-related evoked potentials and vigilance in relationship to pharmakokinetic parameters

Abstract

Achieving objective and quantitative measurement of experimental pain in human volunteers and establishing the impact of drugs remains a difficult task. This problem may be overcome by employing a method which allows the simultaneous measurement of pain ratings elicited by standardized stimulation of the nasal mucosa by carbon dioxide, together with pain-related chemo-somatosensory evoked potentials (CSSEP) and vigilance. We assessed the effect of pentazocine and acetylsalicylic acid on these parameters in 14 human volunteers and related the effects to the pharmacokinetic parameters of the drugs measured at the same time. Pentazocine was found to reduce the pain ratings as well as the amplitudes of the pain-related evoked potentials and to increase their latencies. Vigilance (measured by EEG power spectra and performance of a tracking task) was also significantly reduced. These effects were observed during the distribution phase and the first period of the terminal elimination phase of the drug. Acetylsalicylic acid had no significant effects on pain ratings, but reduced the amplitudes of the event-related potentials when compared to placebo controls. At the same time a slight, but significant, effect on vigilance (reduced performance of the tracking task) was observed. These effects could not be related to the presence of unmetabolized acetylsalicylic acid in the plasma. They appeared at later times when only salicylic acid was left. It is concluded that chemical stimuli of sufficient intensity produce pain which may be suppressed by opioid analgesics such as pentazocine. The effect of acetylsalicylic acid on this experimental pain did not reach significance for all measured parameters under the experimental conditions chosen. The changes in vigilance and in the amplitudes of pain-related chemo-somatosensory evoked potentials indicated as yet unknown CNS-effects of this non-steroidal anti-inflammatory drug.

Brain Mapping-Based Model of Δ9-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix

“…CO 2 is converted into bicarbonate and protons (Tarun et al, 2003), which have been shown to excite trigeminal nociceptors via activating TRPV1 (Reeh and Kress, 2001) or TRPA1 (Wang et al, 2010) ion channels. This pain model is well established for clinical pharmacological pain research (eg, Kobal et al, 1990;Lötsch et al, 1998Lötsch et al, , 2006 including fMRI assessments (Oertel et al, 2008).…”

Effects of flurbiprofen enantiomers on pain‐related chemo‐somatosensory evoked potentials in human subjects.

“…The subjects rated the intensity of the pain by means of a visual-analogue scale displayed on a computer monitor [22]. The intensity of the standard was defined as 100 Estimation Units (EU).…”

“…Subjects were required to perform a simple task on a video screen during the intervals between phasic stimuli [22]. Using a joystick, they had to keep a small square inside a larger one, which randomly moved around.…”

“…Using a variety of stimulation techniques, ERPs have been shown to correlate well with the ratings of pain intensity [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Furthermore, event-related potentials have been used to assess the analgesic effects of numerous drugs [15,[21][22][23][24][25][26]. For example, Kobal and co-workers established an experimental pain model based on chemo-somatosensory event-related potentials (CSSERP) in response to painful stimulation of the nasal mucosa with carbon dioxide [12,[27][28][29][30].…”

“…One of the advantages of this technique is that the method is non-invasive and the results seem negligibly influenced by non-analgesic drug effects [24,30]. So far, this model has been applied in quantifying the analgesic activity of both opioid and nonopioid analgesics [22][23][24][25]34].…”