Phasic and tonic pain serve distinct functions during adaptive behaviour

Reviewer #1 (Public review):

Summary:

This article presents a study consisting of two experiments, which aim to dissociate and quantify the distinct motivational functions of phasic and tonic pain within a naturalistic and immersive VR setting. Specifically, the authors test two hypotheses: (i) that phasic pain acts as a punishment signal that drives avoidance learning; (ii) that tonic pain reduces motivational vigor, promoting energy conservation and recuperation. In both experiments, participants performed a free-operant foraging task, where they collected virtual pineapples to earn points.

In Experiment 1, phasic pain was delivered as a brief electric shock to the grasping hand when picking up green pineapples. As phasic pain intensity increased, participants were less likely to choose painful fruits. A reinforcement learning model that incorporated reward, pain cost, and effort cost was able to successfully capture behavior.

Experiment 2 combined the effects of phasic and tonic pain. Tonic pain was induced by a pressure cuff on the non-dominant arm, simulating sustained discomfort. Interestingly, tonic pain did not affect the perceived intensity or avoidance of phasic pain. However, it significantly reduced movement velocity and pineapple collection rate, interpreted as a reduction of motivational vigor. A temporal decision model incorporating vigor cost successfully captured these effects.

Concomitant EEG recordings showed that tonic pain was associated with reduced alpha and beta power in parietal and temporal areas. Phasic pain ratings and decision values distinctively correlated with skin conductance responses.

Overall, these findings indicate that phasic and tonic pain have distinct and dissociable motivational effects.

Strengths:

This is an ambitious study that provides a quantitative dissociation of the roles of phasic and tonic pain in adaptive behavior, by integrating ecological neuroscience, motivational theory, and computational modeling. The use of immersive VR combined with a free-operant foraging task offers a more ecologically valid context to study pain-related behavior compared to traditional paradigms. Furthermore, the study employs a multimodal approach by combining behavioral data, computational frameworks, physiological signals, and EEG. In particular, one of the main strengths of the study is the use of sophisticated computational modeling to capture phasic and tonic pain effects. The experiment codes are available on GitHub, increasing reproducibility.

Weaknesses:

The main limitations of this article are that it provides insufficient detail on VR implementation. The design of the VR environment is, at this stage, under-described. Crucial information is missing, such as the number of pineapples per block, timing precision, details on how motion is mapped to the virtual movement, etc. This aspect strongly limits the reproducibility of the experiments. A second limitation lies in the lack of clarity regarding the study hypotheses. Although two overarching hypotheses can be inferred, they are not explicitly formulated. To this end, it is unclear which analyses were merely exploratory, especially for physiological and EEG outcomes.

In Experiment 2, the reduction in vigor during tonic pain could plausibly reflect attentional load rather than pain per se. As recognized by the authors, there is no control condition involving an innocuous salient stimulus to rule out non-specific effects of distraction. Perhaps a tonic non-painful but salient somatosensory stimulus (e.g., a strong vibrotactile stimulus applied on the same arm) could have been used as a control stimulus.

Reviewer #2 (Public review):

Summary:

The study investigated the distinct roles of phasic and tonic pain in adaptive behavior. Phasic pain was proposed to function as a teaching signal, promoting avoidance of further injury, while tonic pain was hypothesized to support recuperative behavior by reducing motivational vigor. This hypothesis was tested using an immersive virtual reality (VR) EEG foraging task, in which participants harvested fruit in a forest environment. Some fruits triggered brief phasic pain to the grasping hand, which in turn reduced the likelihood of choosing those fruits. Concurrently, tonic pressure pain applied to the contralateral upper arm was associated with reduced action velocities. The authors employed a free-operant computational framework to quantify how phasic and tonic pain modulate motivational vigor and decision value. Importantly, model parameters were found to correlate with EEG responses, providing neurophysiological support for the hypothesized functional distinctions.

Strengths:

Overall, this study aims to address an important topic and is generally well written.

Weaknesses:

Two critical issues require clarification or justification.

First, phasic pain was induced using electrical stimulation, which typically elicits somatosensory evoked potentials (SEPs). These responses may not reflect pain-specific processes and thus complicate interpretation. This issue bears directly on the study's conclusions, especially when discussing interactions between phasic and tonic pain. For example, tonic pain is known to reduce perceived intensity or cortical responses to phasic pain stimuli delivered elsewhere on the body - an effect not expected for SEPs elicited by electrical stimuli.

Second, additional control experiments are necessary to rule out alternative explanations. For instance, the authors are suggested to deliver phasic pain to the contralateral arm (e.g., at 1-2 Hz), which might also reduce action velocity. Similarly, tonic pain applied to the grasping hand should be tested to disentangle hand-specific effects.

Reviewer #3 (Public review):

Summary:

This study investigates how phasic and tonic pain modulate behaviour in a free-operant foraging paradigm. The authors apply a computational modeling approach to the behavioural data to quantify the decision value of phasic pain, as well as the degree to which tonic pain reduces motivational vigour. EEG assessments showed, e.g., reduced signal power at alpha and beta frequencies in tonic pain conditions compared to no-tonic-pain conditions, but no association between these neural measures and motivational vigour. The authors conclude that tonic and phasic pain serve different motivational functions, with phasic pain acting as a punishment signal promoting avoidance and tonic pain reducing motivational vigour.

Strengths:

The experimental paradigm is highly innovative. Assessing human behaviour in a naturalistic yet highly controlled setting represents a promising approach to pain research. Notably, assessing pain magnitude implicitly, via its motivational value, offers insights about the overall pain experience that are not usually accessible via common pain ratings.

Weaknesses:

Despite these strengths, the manuscript would benefit significantly from more precise definitions of key concepts and an overall clearer, more coherent presentation of its main arguments. The writing, in its current form, often presents claims that are too vague or insufficiently connected with the experimental findings. Moreover, certain aspects of the computational modeling and statistical analysis appear flawed or inadequately justified.

Author response:

Reviewer #1 (Public review):

The main limitations of this article are that it provides insufficient detail on VR implementation. The design of the VR environment is, at this stage, under-described. Crucial information is missing, such as the number of pineapples per block, timing precision, details on how motion is mapped to the virtual movement, etc. This aspect strongly limits the reproducibility of the experiments. A second limitation lies in the lack of clarity regarding the study hypotheses. Although two overarching hypotheses can be inferred, they are not explicitly formulated. To this end, it is unclear which analyses were merely exploratory, especially for physiological and EEG outcomes.

In Experiment 2, the reduction in vigor during tonic pain could plausibly reflect attentional load rather than pain per se. As recognized by the authors, there is no control condition involving an innocuous salient stimulus to rule out non-specific effects of distraction. Perhaps a tonic non-painful but salient somatosensory stimulus (e.g., a strong vibrotactile stimulus applied on the same arm) could have been used as a control stimulus.

We appreciate the reviewer's comments regarding the insufficient implementation details. We hope the newly uploaded software for reproducing the experiment can improve the reader's understanding of the task. In addition to making the software available, we will expand the Methods section in the revised manuscript to include greater detail on the task description.

The hypothesised functions of phasic and tonic pain, and their collaborative interaction, are both broad and deep topics. In the revised manuscript, we will more explicitly formulate our hypotheses and clarify the distinction between a priori predictions and exploratory analyses, particularly concerning the extent to which our evidence supports these hypotheses.

We agree that examining the potential role of attentional load on the interaction between tonic and phasic pain is an important area of future investigation. Addition of additional control conditions matched for attentional salience with additional experiments is possible but introduces other confounds related to their different qualities (e.g. a salient vibrotactile stimulus might invigorate behaviour): however more fundamentally, attentional processes are a core part of pain function, and should not necessarily be viewed as a confound (i.e. the way that pain mediates some of its core functional effects may directly be through its salient attentional nature) . This view is formalised in Wall and Melzack’s classical tripartite model of pain, and distinguishes pain from purely sensory systems such as somatosensation, vision and so on..

Reviewer #2 (Public review):

Two critical issues require clarification or justification. First, phasic pain was induced using electrical stimulation, which typically elicits somatosensory evoked potentials (SEPs). These responses may not reflect pain-specific processes and thus complicate interpretation. This issue bears directly on the study's conclusions, especially when discussing interactions between phasic and tonic pain. For example, tonic pain is known to reduce perceived intensity or cortical responses to phasic pain stimuli delivered elsewhere on the body - an effect not expected for SEPs elicited by electrical stimuli.

We acknowledge the reviewer’s concern regarding the specificity of evoked potentials elicited by electrical stimulation. We agree that traditional SEPs—particularly those evoked by large surface electrodes—primarily reflect activation of non-nociceptive A-beta fibres and thus may not reliably index pain-specific processes or be modulated by tonic pain via descending nociceptive control. However, we would like to clarify that phasic pain was administered in the present study using small-diameter concentric ‘Wasp’ electrodes. These are comparable to intraepidermal electrodes shown to preferentially activate nociceptive A-delta fibres, thereby eliciting ERPs more closely associated with nociceptive processing rather than mixed somatosensory input [1, 2]. Accordingly, our ERP results demonstrated a reliable increase in N1-P2 amplitude with higher phasic pain intensity, suggesting that the evoked responses captured stimulus-evoked nociceptive processing.

We acknowledge that these ERPs may still reflect mixed sensory processing and thus may not be fully modulated by tonic pain. Previous studies have shown that ERPs elicited by nociceptive electrical stimulation can be attenuated during tonic pain using cold-water immersion in CPM paradigms [3, 4]. However, these studies typically employ passive tasks, whereas our paradigm involved continuous voluntary behaviour during sustained tonic pressure pain. This difference in task context may engage distinct modulatory systems, possibly prioritising behavioural adaptation over sensory gating.

We will revise the manuscript to acknowledge these factors and to encourage a more nuanced interpretation of the ERP findings in light of this literature.

Second, additional control experiments are necessary to rule out alternative explanations. For instance, the authors are suggested to deliver phasic pain to the contralateral arm (e.g., at 1-2 Hz), which might also reduce action velocity. Similarly, tonic pain applied to the grasping hand should be tested to disentangle hand-specific effects.

We are grateful to the reviewer for this suggestion. In the current study, phasic pain was delivered to the grasping hand to generate a coherent, spatially congruent representation of virtual stimuli (painful fruit) and behavioural consequences (pain upon grasp). Delivering phasic pain stimuli to the contralateral hand would be incongruent with the task design and may alter the interpretation of the learning signal, which was central to our computational modelling framework. Similarly, tonic pain was not applied to the grasping hand to avoid interfering with motor control. Applying tonic pain to the grasping hand would make it extremely difficult for participants to effectively grasp the hand controller, thereby complicating the interpretation of behavioural and neural measures. We will discuss these issues in the revision. Therefore, while we agree that such manipulations could be informative for future studies, they were not the focus of the current investigation.

Reviewer #3 (Public review):

Despite these strengths, the manuscript would benefit significantly from more precise definitions of key concepts and an overall clearer, more coherent presentation of its main arguments. The writing, in its current form, often presents claims that are too vague or insufficiently connected with the experimental findings. Moreover, certain aspects of the computational modeling and statistical analysis appear flawed or inadequately justified.

We thank the reviewer for highlighting the need for clearer definitions and a more coherent presentation. In the revised manuscript, we will refine our definitions of key concepts and improve the presentation of hypothesised functions of phasic and tonic pain. As stated previously, we will clarify the extent to which our evidence supports these hypotheses. We also appreciate the feedback on our statistical analysis and computational modelling. We will address these points and provide the necessary clarifications and justifications in the revised manuscript.