Biology subjects

Luedtke, K.

Publications and source records attributed to Luedtke, K..

10 recordsLinked to original sources

bioRxiv2026

Interaction of attentional tuning and localisation of pain maxima shift the balance between lateral inhibition and spatial facilitation in nociceptive processing

Spatial interactions among noxious inputs can enhance or suppress pain, but the conditions determining whether spatially organized nociceptive processing is dominated by facilitation or inhibition remain unclear. The present study examined whether attentional tuning and localization of pain maxima regulate the balance between lateral inhibition (LI) and spatial summation of pain (SSP). Thirty healthy participants completed a within-participant psychophysical experiment with electrocutaneous stimulation across LI, sham-control, diffuse noxious inhibitory control, and SSP trials. The spatial configuration of noxious input was manipulated by varying the number and arrangement of activated electrodes. Depending on the attentional instruction, participants continuously rated either pain intensity attributed to a target electrode or overall pain from all activated electrodes using an electronic visual analogue scale. Secondary measures assessed target-pain extraction, attentional focus, and localization of the pain maximum. Rather than observing the predicted inhibitory profile, pain ratings increased suggesting a predominance of facilitatory spatial interactions that were strongly modulated by attention and the perceived location of the pain maximum. When the pain maximum was localized outside the target electrode, facilitation was absent and overall pain intensity was lower. Bilateral stimulation of homologous sites elicited SSP, indicating integration of noxious input across body sides. These findings suggest that LI and spatial facilitation are not fixed consequences of stimulus geometry. Instead, their expression depends on the interaction between top-down attentional selection and spatial attribution of the most intense component of pain.

neuroscience↗

bioRxiv2025

Temporal contrast enhancement generalizes across pain and auditory modalities

Temporal contrast enhancement (TCE), also termed offset analgesia, describes a temporal filtering mechanism whereby a small decrease in stimulus intensity produces a disproportionately large reduction in perceived pain. Although TCE is considered a robust marker of endogenous pain modulation, its underlying mechanisms remain unresolved. It is unclear whether TCE reflects a nociceptive-specific modulatory process or a supramodal temporal filtering mechanism that generalizes to non-painful but aversive sensory stimulation. In this study, healthy and pain-free participants were enrolled in two experiments: a behavioral study (n=33) or a neurophysiological study (n=29). Continuous pain-ratings, electroencephalography (EEG) and pupillometry data were collected. A conventional TCE paradigm was applied using either noxious heat delivered via a thermal contact stimulator or unpleasant auditory stimulation delivered through over-ear headphones. Both noxious heat and unpleasant sounds induced behavioral TCE-effects (p<0.01), indicating a supramodal mechanism with modality-specific temporal dynamics, which was further supported by the absence of a significant correlation of TCE-effects across modalities (p>0.05). In the second experiment, noxious heat - but not unpleasant sound - resulted in decreased power of neural alpha oscillations ([~]10 Hz, p<0.05) and increased pupil size (p<0.05) potentially indicating bottom-up modulation of the autonomic nervous system and a release of neural inhibition, respectively. However, subjectively experienced TCE-effects were not reflected in neurophysiological correlates. These findings support the view of TCE as a supramodal temporal filtering mechanism characterized by modality-specific temporal dynamics, for which no corresponding signatures are found in EEG or pupillometry.

neuroscience↗

bioRxiv2025

Perception of first and second pain during offset analgesia

IntroductionOffset analgesia (OA) is defined as a disproportionate reduction in pain perception following a small decrease in noxious stimulation. However, the mechanisms underlying this phenomenon remain unclear, with ongoing debate on peripheral versus central contributions. ObjectivesThis experimental study aimed to differentiate first and second pain perception during the OA paradigm, thereby assessing fiber-specific influences on OA. MethodsThirty-two healthy participants were asked to distinguish a double pain sensation (first and second pain), to assess pain quality descriptors related to A-{delta} and C-fibers, and to indicate response times to brief noxious heat stimuli. This procedure was repeated while implementing heat pulses in an OA paradigm. ResultsNo significant differences were found between offset and constant trials in the reported double pain sensation or the fiber specific pain descriptors (p > 0.05). Nevertheless, significant differences in response times were observed depending on the type of trial and the timing of the stimulus. Response time to noxious stimuli was delayed after prolonged stimulation in both offset and constant trials (p < 0.05). ConclusionsThe findings suggest that A-{delta} and C-fiber response characteristics were unaffected during the OA paradigm; however, higher stimulation intensities or prolonged pain induce a notable response delay. This indicates a negligible role of specific peripheral nerve fibers in OA, emphasizing the predominance of central mechanisms, particularly those related to attention and cognitive resources, which merit further investigation.

neuroscience↗

bioRxiv2024

Pain distribution can be determined by classical conditioning

ABSTRACTChronic widespread pain (CWP) - as many other clinical presentations - manifests in ongoing pain without identifiable structural cause, with pain that spreads over multiple body areas. The development and maintenance of symptoms may involve learning mechanisms. Ninety-four healthy volunteers participated in this study and were randomly distributed to four groups. In the classical conditioning combined with verbal suggestion group, US-(small pain distribution) and US+ (large pain distribution) were paired with visual stimuli (CS+ and CS-) and participants were told about this association. In the verbal suggestion group, the conditioning was not performed, whereas in classical conditioning only group, learning was not combined with suggestion. In the control group, conditioning and suggestion did not take place. Ratings of perceived pain distribution (PD) were collected after each trial and ratings of pain intensity after each block of trials. During the testing phase, participants were exposed to electrocutaneous stimuli corresponding to only the small (US-) pain distribution. Results showed significant differences between CS+ and CS-pain distribution ratings across the experimental groups: conditioning + verbal suggestion (p<0.01), conditioning only group (p<0.05) and verbal suggestion only group (p<0.05), but not in the control group (p>0.05). Furthermore, significant differences in the perceived pain distribution were found between the control group and all experimental groups. This result supports our main hypothesis that the perceived pain distribution can be influenced by classical conditioning as well as verbal suggestion, although the effect is stronger when both are combined.

physiology↗

bioRxiv2024

Experimentally induced pain and paresthesia respond differently to cuff-based compression

Neuropathic pain is a significant therapeutic challenge due to the co-occurrence with other neurological symptoms such as paresthesia. Human-based models such as cuff algometry can enhance our understanding of pain-paresthesia relationships. This experiment aimed to characterize (psychophysically) pain and paresthesia evoked by stimuli of different temporal and intensity parameters and to demonstrate the reliability of experimental induction of these two symptoms using cuff algometry. Forty participants, aged 18-35, were exposed to mechanical pressure stimuli at three intensities (100, 150, 200 mmHg) and three durations (90, 120, 150s). Skin Conductance (SC) was continuously monitored, and participants rated pain and paresthesia in real-time using a computerized visual analog scale. The General Linear Model analysis revealed significant differences in paresthesia across all durations (p<0.01), but not all intensities, as paresthesia did not increase from 150 to 200 mmHg (p>0.05). Conversely, pain responses showed significant differences across all pressure intensities (p<0.05) but not durations, as pain did not increase from 90 to 120 and from 120 to 150s (p>0.05). No interaction effects were found for either symptom. SC analysis showed no significant main or interaction effects. Intraclass correlation coefficients (ICCs) indicated moderate to good reliability for pain and paresthesia induction across different durations and intensities (ICC: 0.52-0.90), while SC showed poor to moderate reliability (ICC: 0.21-0.73). In conclusion, computerized cuff algometry seems to be an effective and reliable method for simultaneously inducing and assessing pain and paresthesia, revealing that these symptoms follow different patterns based on pressure duration and intensity.

physiology↗

bioRxiv2022

Reproducibility of spatial summation of pain effect during COVID-19 pandemic

The purpose of this study was to reproduce the previously observed spatial summation of pain effect (SSp) using non-laboratory procedures and commercial equipment. An additional aim was to explore the association between expectations and SSp. The Cold Pressor Task (CPT) was used to induce SSp. Healthy participants (N=68) immersed their non-dominant hands (divided into 5 segments) into cold water (CPT). Two conditions were used 1) gradual hand immersion (ascending condition) and 2) gradual hand withdrawal (descending condition). Pain intensity was measured on a Visual Analogue Scale (VAS). Psychological factors, such as the participants expectations of pain intensity were also measured on a VAS. Results showed significant SSp (X2(4) = 116.90, p < 0.001), reproduced with non-laboratory equipment in a home-based set-up. Furthermore, two novel findings were observed: i) there was a significant correlation between expectations and perceived pain, indicating a link between pain expectations and SSp, ii) spatial summation increased with the increase in duration exposure to the noxious stimulus (Wald X2(8) = 80.80, p < 0.001). This study suggests that SSp is associated with pain expectations and can be formed by a mixture of excitatory and inhibitory mechanisms potentially driven by temporal characteristics of neural excitation. Moreover, this study proposes a new feasible way to induce SSp using a home-based set-up.

physiology↗

bioRxiv2022

Psychological mechanisms of offset analgesia: The effect of expectancy manipulation

A frequently used paradigm to quantify endogenous pain modulation is offset analgesia, which is defined as a disproportionate large reduction in pain following a small decrease in a heat stimulus. The aim of this study was to determine whether suggestion influences the magnitude of offset analgesia in healthy participants. A total of 97 participants were randomized into three groups (hypoalgesic group, hyperalgesic group, control group). All participants received four heat stimuli (two constant trials and two offset trials) to the ventral, non-dominant forearm while they were asked to rate their perceived pain using a computerized visual analogue scale. In addition, electrodermal activity was measured during each heat stimulus. Participants in both intervention groups were given a visual and verbal suggestion about the expected pain response in an hypoalgesic and hyperalgesic manner. The control group received no suggestion. In all groups, significant offset analgesia was provoked, indicated by reduced pain ratings (p < 0.001) and enhanced electrodermal activity level (p < 0.01). A significant group difference in the magnitude of offset analgesia was found between the three groups (F[2,94] = 4.81, p < 0.05). Participants in the hyperalgesic group perceived significantly more pain than the hypoalgesic group (p = 0.031) and the control group (p < 0.05). However, the electrodermal activity data did not replicate this trend (p > 0.05). The results of this study indicate that suggestion can be effective to reduce but not increase endogenous pain modulation quantified by offset analgesia in healthy participants.

neuroscience↗

bioRxiv2022

Spatial tuning in nociceptive processing is driven by attention

When the source of nociception expands across a body area, the experience of pain increases due to the spatial integration of nociceptive information. This well-established effect is called spatial summation of pain (SSp) and has been the subject of multiple investigations. Here, we used cold-induced SSp to investigate the effect of attention on the spatial tuning of nociceptive processing. Forty pain-free volunteers (N=40, 20 females) participated in this experiment. They took part in an SSp paradigm based on three hand immersions into cold water (5{degrees}C): Participants either immersed the ulnar segment ("a"), radial segment ("b") or both hand segments ("a+b") and provided overall pain ratings. In some trials based on "a+b" immersions, they were also asked to provide divided (i.e., first pain in "a" then in "b"; or reversed) and directed attention ratings (i.e., pain only in "a" or "b"). Results confirmed a clear SSp effect in which reported pain during immersions of "a" or "b" was less intense than pain during immersions of "a+b" (p<0.001). Data also confirmed that spatial tuning was altered. SSp was fully abolished when participants provided two ratings in a divided fashion (p<0.001). Furthermore, pain was significantly lower when attention was directed only to one segment ("a" OR "b") during "a+b" immersion (p<0.001). We conclude that spatial tuning is dynamically driven by attention as reflected in abolished SSp. Directed attention was sufficient to focus spatial tuning and abolish SSp. Results support the role of cognitive processes such as attention in spatial tuning. PerspectiveThis article presents experimental investigation of spatial tuning in pain and offers mechanistic insights of contiguous spatial summation of pain in healthy volunteers. Depending on how pain is evaluated in terms of attentional derivative (overall pain, directed, divided attention) the pain is reduced and spatial summation abolished.

neuroscience↗

bioRxiv2021

Temporal properties of painful contrast enhancement using repetitive stimulation

Offset analgesia is characterized by a disproportionately large reduction in pain following a small decrease in a heat stimulus and is based on the phenomenon of temporal pain contrast enhancement (TPCE). The aim of this study is to investigate whether this phenomenon can also be induced by repetitive stimulation, i.e., by stimuli that are clearly separated in time. With this aim, the repetitive TPCE paradigm was induced in healthy, pain-free subjects (n=33) at the volar non-dominant forearm using heat stimuli. This paradigm was performed applying three different interstimulus intervals (ISIs): 5, 15, and 25 seconds. All paradigms were contrasted with a control paradigm without temperature change. Participants continuously rated the perceived pain intensity. In addition, electrodermal activity was recorded as a surrogate measure of autonomic arousal. Temporal pain contrast enhancement was confirmed for both ISI 5 seconds (p < 0.001) and ISI 15 seconds (p = 0.005), but not for ISI 25 seconds (p = 0.07), however the magnitude of TPCE did not differ between ISIs (p = 0.11). Electrodermal activity was consistent previous pain ratings, but showing significantly higher autonomic activity being measured. Thus, the phenomenon of temporal contrast enhancement of pain can also be induced by repetitive stimulation. Both the involvement of the autonomic nervous system and the involvement of habituation processes are conceivable, which consequently points to both central and peripheral mechanisms of TPCE. SummaryThe temporal contrast enhancement of pain and electrodermal activity can be provoked by stimuli that are clearly separated in time.

neuroscience↗

bioRxiv2020

Spatial summation of pain increases logarithmically

Pain intensity is difficult to predict. Mostly, because of modulatory processes underlying its formation. For example, when nociceptive stimulation occupies a larger body area, pain increases disproportionally. This modulation is called spatial summation of pain (SSp) and is responsible for coding pain intensity. To predict pain based on spatial variables, a profound understanding of the SSp effect is crucial. The aim of this study was i) to describe the SSp effect as a function of the size (or distance) of a stimulated area(s), ii) to investigate the effect of pain intensity on SSp and iii) to evaluate the influence of the SS type on the magnitude of SSp. Thirty-one healthy participants took part in a within-subject experiment. Participants were exposed to area- and distanced based SSp. In the former, electrocutaneous noxious stimuli were applied by up to 5 electrodes (5 areas) forming a line-like pattern at the ulnar side of the hand, while in the latter the same position and lengths of stimuli were used but only two electrodes were stimulated (5 separations). Each paradigm was repeated using pain of low, moderate and high intensity in a random and counterbalanced order. Each stimulus was assessed on a 0-100 scale. It was found that the pattern of increase in pain followed a logarithmic rather than a linear function. The dynamics of the pain increase were statistically different across pain intensities, with more summation occurring, if stimuli were calibrated to eliciting "high" pain. SSp was resistant to saturation in the area-based but not in the distance- based SSp, where 0.8cm separation between two electrodes produced a similar pain intensity as 1.6cm and 2.4cm. Results indicate that area-based SSp is more painful than distance-based SSp when low and moderate but not when high pain intensity is induced. Presented findings have important implications for all studies, in which the spatial dimension of pain is measured. When the area or separation between nociceptive stimulation increases, pain does not increase linearly. Furthermore, the pattern of the pain increase depends on i) intensity and ii) the number of sites of nociception. In conclusion, a logarithmic function should be considered when predicting the size of a nociceptive source. This pattern is indicative for inhibitory processes underlying SSp.

physiology↗