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Objective: The influence of unconscious emotional processes on pain remains poorly understood. The present study tested whether cues to forgotten unpleasant images might amplify pain (i.e., in the absence of conscious recall)., Methods: Seventy-two healthy female adults (19 to 34 years) performed an adapted Think/No-think paradigm (T/NT) using 72 combinations of neutral face images (cues) paired with 36 neutral and 36 unpleasant images. After completion of the T/NT task, cues associated with forgotten neutral or unpleasant images were identified. Cues to either neutral or unpleasant images from the NT condition were then presented in randomized order while participants received intermediate-level thermal pain stimulation on the left hand. Ratings of both pain intensity and unpleasantness were acquired after each trial., Results: Mean pain unpleasantness ratings were greater during presentation of cues to forgotten negative versus neutral images (5.52 [SD = 2.06] versus 5.23 [SD = 2.10]; p = .02). This pattern was also present when comparing cues to remembered negative versus neutral images (5.62 [SD = 1.94] versus 5.04 [SD = 1.90]; p < .001). Mean pain intensity ratings were higher for cues to negative versus neutral images when remembered (5.48 [SD = 1.79] versus 5.00 [SD = 1.69]; p < .001), but not when forgotten (5.27 [SD = 1.96] versus 5.16 [SD = 1.93]; p = .30)., Conclusions: Using an adapted T/NT-Pain paradigm, this study demonstrated that cues to nonrecallable (but potentially unconsciously activated) negative emotional memories amplify pain unpleasantness, similar to known effects of conscious negative emotions., (Copyright © 2024 by the American Psychosomatic Society.)

Although depression is associated with more clinical pain complaints, psychophysical data sometimes point to hypoalgesic alterations. Studying the more reflex-like facial expression of pain in patients with depression may offer a new perspective. Facial and psychophysical responses to nonpainful and painful heat stimuli were studied in 23 patients with major depressive disorder (MDD) and 23 matched control participants. As psychophysical data, pain thresholds, tolerance thresholds, and self-report were assessed. Facial responses were videotaped and subjected offline to Facial Action Coding System analysis. One of the key facial responses of pain, which is a known facial signal of negative affect (contraction of the eyebrows), was significantly increased in MDD patients. Moreover, facial expressions and pain ratings were strongly correlated in MDD patients, whereas these 2 response systems were-in line with established findings-only weakly related in healthy participants. Pain psychophysics was unaltered in MDD patients compared with healthy control participants. In conclusion, the facial expression of pain in MDD patients indicates rather hyper- than hypoalgesia, with enhanced affective pain processing. Moreover, the linkage between subjective and facial responses was much stronger in MDD patients, which may be due to a reduced influence of social display rules, which normally complicate this relationship., Perspective: The facial expression of pain in patients with depression indicates stronger affective pain processing and stronger association with self-report than in healthy individuals., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)

This study investigated electroencephalographic correlates in chronically depressed patients compared to healthy controls using intracutaneously applied electrical pain stimulus, to better understand the interaction between pain processing and depression. A close interaction between pain and depression is generally recognized although the precise mechanisms are not yet fully understood. The present study focuses on the hypothesis that effective brain connectivity in major depression patients is altered. Multifunctional interactions between brain regions represent a robust index of effective interactions within the brain, and can be quantified by network redundancy. Thus, structural network differences between 18 normal controls and 18 major depression patients before as well as during the processing of moderately painful intracutaneous electrical stimuli were investigated on the basis of network redundancy differences. In our sample, both patients and control subjects exhibit comparable network redundancies before stimulus application. Caused by the stimulus, there is a global increase of network redundancy in both groups. This increase is diminished in the group of major depression patients. We found clear differences between patients and controls during the stimulus processing, where the network redundancy in normal controls is larger in comparison to patients. The differences might be explained by the fact that major depression patients are more restricted to the affective component of the processing. The well-established biasing to affective processing might suppress the somatosensory processing resulting in a lower number of connections within the considered network. This might then lead to a reduction in network redundancy during stimulus processing.

Objective: The thermal grill illusion (TGI) in which interlacing cold and warm bars create the illusion of a painful sensation has been suggested as an experimental model for central pain states and pain processing. The aim of this study was to use this technique to gain further insights into the altered pain perception in major depressive disorder (MDD)., Methods: In 18 unmedicated patients with MDD, cold and heat pain thresholds (CPT/HPT) as well as the perception of the TGI were examined and compared with 18 matched controls., Results: CPT and HPT were significantly increased in patients (7.9°C and 47.5°C) compared with controls (15.9°C and 45.2°C, respectively; p < .05). In the range of TGI stimuli that were perceived painful by controls, the patients did not indicate painful sensations, thereby indicating a shift of the stimulus-response curve of TGI pain perception toward higher stimulus intensities, that is, greater temperature differentials between cold and warm bars (11.5°C for controls, 16.7°C for patients). The patients rated the pain intensity perceived at the respective pain thresholds (CPT and HPT) in tendency higher than did the controls, whereas they perceived the TGI less painful despite increased stimulus intensities. Unpleasantness ratings were similar between groups., Conclusions: CPT, HPT and temperature differentials for the perception of the TGI, were increased in patients with MDD as compared with controls. Pain intensity, however, was rated differently for CPT and HPT, where patients indicated higher ratings in tendency, and for the TGI stimulation, where pain was perceived less intense.

The perception and processing of pain is disturbed in many psychiatric diseases. Some diseases are known to show decreased perception of pain (e.g. borderline personality disorder), while others are associated with augmented pain perception (e.g. alcohol and drug dependence). The close relationship between psychiatric diseases and pain is most probably caused by aberrant processing of pain in brain structures, known to be involved in psychiatric disorders as well. Aberrant perception and processing of pain in patients with anorexia nervosa (AN) will be used to demonstrate this close relationship. Dysfunction within the insula has been suggested to account for many features of AN and might contribute to reduced pain perception. Moreover, it might lead to increased adrenergic descending inhibition associated with increased sympathetic modulation. Thus, pain research might be able to alter our view on autonomic regulation, which is putatively associated with increased cardiac mortality of the disease.

Stimulation of acupuncture point Pc6, located above the median nerve, has been shown to be effective in treating nausea and vomiting. It has also frequently been reported to cause a heart rate reduction. The mechanism behind this autonomic reaction has not been clarified, so far. We combined brainstem-sensitive functional magnetic resonance imaging with heart rate recording and time-resolved rating of the needling sensation to measure neuronal correlates of sensations and autonomic reactions during acupuncture. On the cortical level, needling sensation activated typical pain-related areas, of which the ventromedial and dorsolateral prefrontal cortex and perigenual anterior cingulate cortex were further involved in mediating the heart rate response. In the brainstem, needling sensation activated nuclei of the descending pain control system, in which a network of hypothalamus, periaqueductal gray, rostral ventromedial medulla, and ventrolateral medulla was identified as the source of the heart rate changes. Our findings indicate that acupuncture may be a special pain stimulus, whose autonomic concomitants could explain its non-analgesic effects and in some cases even have a therapeutic potential., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Temporal summation of C-fiber evoked responses generates an increase in action potential discharge in second-order neurons and in perceived pain intensity (wind-up). This may be related to the central serotonergic system which modulates and partly inhibits sensory input. Aim of the study was to investigate the relationship between wind-up and serotonergic activity using loudness dependence of auditory evoked potentials (LDAEP). 18 healthy subjects were compared to 18 patients with major depression, a disease with a putative serotonin deficit. They were examined with quantitative sensory testing (QST) using the protocol of the German Research Network on Neuropathic Pain (DFNS), including the wind-up ratio (WUR), LDAEP, and psychometric measurements. We found a slight positive correlation between WUR and LDAEP both in healthy controls and depressed patients combined (r=0.340, p=0.043), indicating that WUR may be modulated by serotonergic activity. It can be concluded that inhibitory control to noxious stimuli is partly associated with the central serotonergic function as indicated by LDAEP., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

In different fields of neuroscience research, illusions have successfully been used to unravel underlying mechanisms of stimulus processing. One such illusion existing for the field of pain research is the so-called thermal grill illusion. Here, painful sensations are elicited by interlacing warm and cold bars, with stimulus intensities (temperatures) of these bars being below the respective heat pain or cold pain thresholds. To date, the underlying mechanisms of this phenomenon are not completely understood. There is some agreement, however, that the sensation evoked by this stimulation is generated by central nervous interactions. Therefore, we followed two approaches in this study: firstly, we aimed at developing and validating a water-driven device which might be used in fMRI scanners in future studies - subject to minor adaptations. Secondly, we aimed to interfere with this illusion by induction of a sad mood state, a procedure which is suggested to influence central nervous structures that are also involved in pain processing. The newly developed device induced thermal grill sensations similar to those reported in the literature. Induction of sad, but not neutral mood states, resulted in higher pain and unpleasantness ratings of the painful illusion. These findings might be of importance for the understanding of pain processing in healthy volunteers, but putatively even more so in patients with major depressive disorder. Moreover, our results might indicate that central nervous structures involved in the affective domain or cognitive domain of pain processing might be involved in the perception of the illusion., (Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Patients suffering from major depressive disorder (MDD) have been shown to exhibit increased thresholds towards experimentally induced thermal pain applied to the skin. In contrast, the induction of sad mood can increase pain perception in healthy controls. Here, we aimed to test the hypothesis that heat pain thresholds are further increased after sad mood induction in depressed patients. Thermal pain thresholds were obtained from 25 female depressed patients and 25 controls before and after sad mood induction applying a modified Velten Mood Induction procedure (MIP). Valence and arousal ratings were obtained using the self-assessment manikin. The Montgomery Depression Rating Scale and the Beck Depression Inventory (BDI) were obtained at baseline from all participants. Pain thresholds at baseline did not significantly differ between groups. Pain thresholds and valence of mood significantly decreased both in patients and controls, while arousal showed an inverse time course between groups. Therefore, our hypothesis could not be confirmed. From these data, we propose that the depressed mood as seen in MDD patients influences pain experience differently as compared to the shorter-lasting mood change after MIP. A differential interaction of both affective states with brain areas of the pain matrix might be assumed. Eventually, the induction of sad mood might mirror the increased number of pain complaints in depressed patients and thus adds to the current concept of adjuvant antidepressant treatment both in depressed patients with pain complaints and in chronic pain patients., (Copyright 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

Patients with major depressive disorder have repeatedly been described to exhibit increased thresholds upon experimentally applied pain stimuli to the skin as compared to respective controls. Since the sensory-discriminative component of stimulus perception, e.g. for warmth, cold and vibration, appears to be unaltered in depression, higher central nervous centres have been assumed to cause this phenomenon. To date, hardly any attention has been paid to the efferent components of the noxious reflex loop. Here, we aimed to assess the autonomic reaction upon a painful stimulus and to examine whether this is likewise reduced in major depression. For this purpose, sympathetic skin response was obtained from 22 patients with major depression and 20 matched controls. To induce sympathetic skin responses, we applied either noxious electrical stimuli (12 and 18 mA) or innocuous acoustic stimuli (85 dB SPL). Pain intensity was rated using a numeric analogue scale. In contrast to our a priori hypothesis patients showed shorter latencies and higher amplitudes of skin potentials upon noxious stimulation, i.e. a stronger sympathetic response. Intriguingly, the noxious stimuli were still perceived less painful in the patient group. Pain perception weakly correlated with disease severity. From these data, we conclude that despite the diminished pain perception, the autonomic reflex loop following noxious stimulation is not affected in patients with major depressive disorder, and that the increase in sympathetic outflow is not directly related to the perceived pain as in controls, but might rather be attributed to the autonomic dysfunction known for the disease., (Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Objectives: Connectivity analysis was used to investigate the processing of intracutaneous stimuli and directed interactions within the pain matrix in patients with major depression (MD) and healthy controls (HCs), by means of frequency selective generalized partial directed coherence (gPDC)., Methods: Eighteen patients with MD and 18 HCs underwent stimulations consisting of moderately painful intracutaneous electrical stimuli to the right and left middle fingers. Connectivity analysis was based on nine selected EEG electrodes., Results: Stimulus-induced changes of the gPDC in a pre/post stimulus comparison and changes in the connectivity pattern in the post-stimulus condition were found. We could identify network changes correlating to the side stimulated, as well as differences between HCs and MD patients., Conclusions: These data support the suggestion that pain processing in response to noxious stimulation in MD patients is different compared to healthy controls, suggesting aberrant functional connectivity. Generalized partial directed coherence is shown to be a promising method to detect changes in connectivity in both within- and between-subject designs.

Negative affective states influence pain processing in healthy subjects in terms of augmented pain experience. Furthermore, our previous studies revealed that patients with major depressive disorder showed increased heat pain thresholds on the skin. Potential neurofunctional correlates of this finding were located within the fronto-thalamic network. The aim of the present study was to investigate the neurofunctional underpinnings of the influence of sad mood upon heat pain processing in healthy subjects. For this purpose, we used a combination of the Velten Mood Induction procedure and a piece of music to induce sad affect. Initially we assessed heat pain threshold after successful induction of sad mood outside the MR scanner in Experiment 1. We found a highly significant reduction in heat pain threshold on the left hand and a trend for the right. In Experiment 2, we applied thermal pain stimuli on the left hand (37, 42, and 45 degrees C) in an MRI scanner. Subjects were scanned twice, one group before and after sad-mood induction and another group before and after neutral-mood induction, respectively. Our main finding was a significant group x mood-induction interaction bilaterally in the ventrolateral nucleus of the thalamus indicating a BOLD signal increase after sad-mood induction and a BOLD signal decrease in the control group. We present evidence that induced sad affect leads to reduced heat pain thresholds in healthy subjects. This is probably due to altered lateral thalamic activity, which is potentially associated with changed attentional processes.

Background: To further elucidate the close interrelation of pain and depression, we investigated cerebral responses to parametrically varied thermal pain intensities in female patients suffering from major depressive disorder (MDD) (n = 13) and matched control subjects (n = 13) by means of functional magnetic resonance imaging (fMRI)., Methods: After the assessment of the individual thermal pain threshold, an fMRI-compatible thermode was used to deliver thermal painful stimuli to the right arm. All stimuli were initiated for 10 sec from a baseline resting temperature (32 degrees C) in three different conditions (37 degrees C, 42 degrees C, 45 degrees C). Statistical Parametric Mapping 2 (SPM2) software was used for image processing and statistical analyses., Results: Patients displayed significantly increased thermal pain thresholds. A comparable increase in blood oxygenation level-dependent (BOLD) signal was observed in key structures of the pain matrix in patients and control subjects. Patients displayed hyperactivation in comparison with control subjects for the painful 45 degrees C condition in the left ventrolateral thalamus, in the right ventrolateral prefrontal cortex (VLPFC) and dorsolateral prefrontal cortex (DLPFC), as well as a stronger parametric BOLD signal increase in the right VLPFC, DLPFC, and in the contralateral insula. Symptom severity correlated positively with the BOLD signal in the left ventrolateral nucleus of the thalamus., Conclusions: We present evidence that cortical structures of the pain matrix are similarly activated in depressed patients and healthy subjects. We report increased prefrontal and lateral thalamic activation during the presentation of painful stimuli, which might explain reduced thermal pain perception on the skin in depressed patients.

We recently described an increase of pain thresholds and tolerances for thermal and electrical pain in patients suffering from adjustment disorder (AD). Furthermore, we presented evidence that pain perception in major depressive disorder (MDD) depends on pain modality, with thresholds for ischemic pain being decreased compared to increased thermal and electrical pain thresholds. Here, we investigated perception of experimentally induced ischemic pain in 15 patients suffering from AD (subtype with depressive symptoms) and controls matched for age and sex in order to examine whether a similar pattern of modality dependent pain perception can be established. Thresholds and tolerances were assessed on both sides of the body. We found a significant decrease of ischemic pain thresholds in AD patients as compared to controls. Analogue findings have been reported for pain perception in MDD, therefore suggesting similarities with regards to pain perception in both disorders. This adds weight to the assumption that depressive symptomatology might alter pain sensitivity in this subtype of AD since symptoms are milder, yet comparable to MDD.

Objectives: The underlying mechanisms of reduced pain perception in anorexia nervosa (AN) are unknown. To gain more insight into the pathology, the authors investigated pain perception, autonomic function, and endocrine parameters before and during successful treatment of adolescent AN patients., Method: Heat pain perception was assessed in 15 female adolescent AN patients and matched controls. Results were correlated with autonomic and endocrine parameters (free triiodothyronine, free cortisol). Autonomic function was studied using heart rate variability and pupillary light reflex assessment. To investigate the influence of therapy on these parameters, data were obtained at three different time points., Results: Heat pain thresholds were significantly increased in the acute state and decreased after weight had been regained for 6 months. Similarly, an increased parasympathetic tone was present in the acute state only. The relative amplitude of the pupillary light reflex showed a positive correlation to pain thresholds over time and predicted disease progression. In addition, the authors found a negative correlation between increased pain thresholds and low free cortisol., Conclusion: Increased pain thresholds are associated with increased parasympathetic tone and a hypothyroid state in AN. This may either indicate common central mechanisms or suggest a causative interaction.

An altered perception of pain has been described for several psychiatric disorders. To date the influence of adjustment disorders (AD) on pain perception has not been described. Here, we investigated perception of experimentally induced pain in 15 patients suffering from AD (subtype with depressive symptoms) and controls matched for age and sex. Thresholds and tolerances were assessed for thermal and electrical pain on both sides of the body. We found an overall increase of pain thresholds and tolerances in AD patients as compared to controls, predominately on the right side of the body. Analogue findings have been reported for pain perception in major depressive disorder (MDD). Of the data obtained, only thermal pain threshold on the right arm correlated with the severity of depressive symptoms. Although the underlying pathology is elusive it is likely that the mechanisms for reduced pain sensitivity are comparable in MDD and AD.

One frequently described feature of depression is an increased vulnerability to pain complaints, and chronic pain is frequently accompanied by symptoms of depression. In contrast to this, a decreased sensitivity to experimental pain has been described in major depression. The physiological basis of this phenomenon is yet elusive. We investigated 30 patients suffering from a major depressive disorder and matched controls. Pain testing (threshold and tolerance) was performed on both sides of the body and included assessment of thermal, electrical and ischemic pain. While confirming hypoalgesia to heat and electrical pain in comparison to controls, we found hyperalgesia to ischemic muscle pain. Furthermore, thermal pain tolerance and electrical pain tolerance were significantly increased on the right hand side confirming previous results of a lateralized perception of pain in depression. Our main finding suggests that painful stimuli are processed differentially depending on the localization of pain induction in depression. This knowledge may enable us to understand and ultimately treat pain complaints more appropriately in depressed patients.

Neuroborreliosis has become the most frequently recognized tick-borne infection of the nervous system in Europe and the United States. In addition to dermatological, cardiac, articular, and neurologic manifestations, psychiatric disorders such as depression, panic attacks, and schizophrenia-like psychosis can also arise. We report on a 61-year-old woman who developed a severe pain syndrome following several tick bites. She was diagnosed with neuroborreliosis; she received various courses of antibiotics over several years, but without any clinical improvement in her condition. Her eventual admission to a psychiatric ward due to mental symptoms and neuroleptic treatment led to a dramatic improvement of her pain symptoms. However, increasing delusions disclosed a psychotic episode, which ceased over time. We discuss therapeutic difficulties and psychiatric complications in the absence of a clear-cut diagnosis of neuroborreliosis. Although this patient might have suffered from late-onset schizophrenia with painful hallucinations right from the start of her disease, the case highlights psychiatric complications that might be associated with neuroborreliosis.

Inflammatory pain is caused by sensitization of peripheral and central nociceptive neurons. Prostaglandins substantially contribute to neuronal sensitization at both sites. Prostaglandin E2 (PGE2) applied to the spinal cord causes neuronal hyperexcitability similar to peripheral inflammation. Because PGE2 can act through EP1-EP4 receptors, we addressed the role of these receptors in the spinal cord on the development of spinal hyperexcitability. Recordings were made from nociceptive dorsal horn neurons with main input from the knee joint, and responses of the neurons to noxious and innocuous stimulation of the knee, ankle, and paw were studied after spinal application of recently developed specific EP1-EP4 receptor agonists. Under normal conditions, spinal application of agonists at EP1, EP2, and EP4 receptors induced spinal hyperexcitability similar to PGE2. Interestingly, the effect of spinal EP receptor activation changed during joint inflammation. When the knee joint had been inflamed 7-11 hr before the recordings, only activation of the EP1 receptor caused additional facilitation, whereas spinal application of EP2 and EP4 receptor agonists had no effect. Additionally, an EP3alpha receptor agonist reduced responses to mechanical stimulation. The latter also attenuated spinal hyperexcitability induced by spinal PGE2. In isolated DRG neurons, the EP3alpha agonist reduced the facilitatory effect of PGE2 on TTX-resistant sodium currents. Thus pronociceptive effects of spinal PGE2 can be limited, particularly under inflammatory conditions, through activation of an inhibitory splice variant of the EP3 receptor. The latter might be an interesting target for controlling spinal hyperexcitability in inflammatory pain states.

Increased incidence of clinical pain complaints from patients with major depression, as well as increased experimental pain thresholds have been reported. The basis of this phenomenon remains unclear, as well as its relation to medication, clinical recovery, gender and lateralization of hemispheric function. We aimed to further elucidate heat pain perception in depression applying a testing battery including assessment (on both arms) of warmth perception, heat pain perception and heat pain tolerance, and the jaw opening reflex (duration of ES2 component) as a putative indicator of descending pain inhibition. The battery was applied to 20 patients and 20 age- and sex-matched controls. Patients were assessed: on admission (acutely depressed, off-medication), few days after admission (depressed, on medication), and after clinical recovery (mostly on medication), and controls at corresponding intervals. Significant elevated heat pain thresholds were found off and on medication in the acute stage (mainly in women) and after recovery on the right arm only. Elevated heat pain tolerance (on the right arm only) was seen in medicated patients in the acute and recovered stage. Significant prolongation of ES2 duration was only found in acutely depressed patients off medication. While confirming hypalgesia to heat pain in major depression, our findings demonstrate a close relation to gender and strong influence of lateralization after recovery. Altered pain processing at brain stem level might only partially be responsible for the observed finding.

The disturbance of somatosensory perception and bodily experiences, including somatosensory hallucinations, are main features of the coenaesthesia sub-syndrome of schizophrenia. We used functional MRI to study a coenaesthesia patient with rapidly fluctuating painful somatosensory hallucinatory perceptions. Transient brain activations accompanying hallucinations were similar to the pattern elicited in a control experiment (non-painful tactile stimulation). However, an area in the medial parietal cortex, including parts of the precuneus and previously characterised as a supplementary sensory area, was activated significantly stronger during hallucinations than the control condition. This finding demonstrates elevated brain activity in a somatosensory area accompanying painful somatic hallucinations.

Miriam Kunz,1 Stefanie F Bunk,2 Anna J Karmann,3 Karl-Jürgen Bär,4 Stefan Lautenbacher3 1Department of Medical Psychology and Sociology, University of Augsburg, Augsburg, Germany; 2Department of General Practice and Elderly Care Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; 3Physiological Psychology, Otto-Friedrich University Bamberg, Bamberg, Germany; 4Department of Psychosomatic Medicine and Psychotherapy, University Hospital, Jena, GermanyCorrespondence: Miriam KunzDepartment of Medical Psychology and Sociology, University of Augsburg, Augsburg, GermanyTel +49 821 598-3720Fax +49 821 598-5116Email Miriam.kunz@med.uni-augsburg.dePurpose: Conditioned pain modulation (CPM) is most often assessed using self-report of pain. However, self-report of pain is not always available (eg in individuals with cognitive impairment) and is susceptible to report bias. In comparison, the facial expression of pain is more reflex-like and represents one of the most sensitive and specific non-verbal signals of pain. The aim of the present study was to investigate whether the facial expression of pain is sensitive enough to capture endogenous pain inhibition as elicited during CPM paradigms.Patients and Methods: In total, 26 female participants took part in this study. Facial and verbal responses to phasic heat pain were assessed once while participants immersed their hand in a hot water bath and once without additional stimulation. Facial responses were analyzed using the Facial Action Coding System (FACS). Verbal responses were assessed using a Numerical Rating Scale (NRS).Results: Pain-relevant facial responses as well as pain ratings to phasic heat pain were significantly reduced when participants simultaneously immersed their hand in a hot water bath compared to baseline. Thus, CPM effects could be demonstrated both on subjective as well as on facial responses. Moreover, CPM-induced changes in pain-relevant facial responses and in NRS ratings were significantly correlated.Conclusion: The present study shows that facial expressions of pain are sensitive enough to capture CPM effects. Given the proven clinical usefulness of assessing CPM, the parallel assessment of verbal and facial CPM effects might be a promising approach with wider scope of applications. Further research in other demographic healthy participant and clinical cohorts is warranted.Keywords: pain, CPM, conditioned pain modulation, facial expression, FACS