Functional neurological disorder: a comparative analysis of experience of Czech, Slovak, and Italian neurologists.

AIM OF STUDY: We aimed to compare knowledge, opinions, and clinical experiences among Czech, Slovak, and Italian neurologists to identify potential educational gaps and unify understanding. CLINICAL RATIONALE FOR STUDY: Functional neurological disorder (FND) is a disabling condition characterised by motor, sensory, or cognitive symptoms which are incompatible with other neurological disorders. Novel diagnostic and treatment approaches have improved FND management. However, the extent of their adoption, and any differences or similarities across European communities, remain to be established. MATERIAL AND METHODS: Members of the Czech and Slovak Neurological Societies were invited via e-mail to participate in a 14- -item web-based survey investigating their approach to FND. This data was compared to results from a previous study involving 492 Italian neurologists. RESULTS: 232 questionnaires were completed by Czech and Slovak neurologists (CZ-SK). Similarities were found between CZ- -SK and Italian neurologists in their preference for the term 'FND' over other psychological-related terms and in explaining symptoms as due to abnormal functioning of the nervous system rather than attributing them to mental illness. However, only fewer than 5% in both groups thought that simulation was highly unlikely. Both groups reported relying on positive signs (e.g. inconsistency, distractibility) according to the current diagnostic criteria, but also a tendency to perform additional tests to exclude other causes. However, some differences were observed: Italian neurologists placed a greater emphasis on psychological factors including litigation. CZ-SK neurologists were more likely to suggest physiotherapy as a treatment option and to provide educational intervention for patients and their relatives. CONCLUSIONS: Overall, our findings suggest that although Czech, Slovak, and Italian neurologists have adopted some new developments in the field of FND, significant gaps still exist in their understanding and common practices regarding conceptualisation, diagnosis, and treatment. CLINICAL IMPLICATIONS: Our results suggest that promoting knowledge through postgraduate curricula and teaching courses for neurologists is necessary to optimise patient management in various European countries.

How Does Postural Control in Patients with Functional Motor Disorders Adapt to Multitasking-Based Immersive Virtual Reality?

BACKGROUND: Motor symptoms in functional motor disorders (FMDs) refer to involuntary, but learned, altered movement patterns associated with aberrant self-focus, sense of agency, and belief/expectations. These conditions commonly lead to impaired posture control, raising the likelihood of falls and disability. Utilizing visual and cognitive tasks to manipulate attentional focus, virtual reality (VR) integrated with posturography is a promising tool for exploring postural control disorders. OBJECTIVES: To investigate whether postural control can be adapted by manipulating attentional focus in a 3D immersive VR environment. METHODS: We compared postural parameters in 17 FMDs patients and 19 age-matched healthy controls over a single session under four increasingly more complex and attention-demanding conditions: simple fixation task (1) in the real room and (2) in 3D VR room-like condition; complex fixation task in a 3D VR city-like condition (3) avoiding distractors and (4) counting them. Dual-task effect (DTE) measured the relative change in performance induced by the different attention-demanding conditions on postural parameters. RESULTS: Patients reduced sway area and mediolateral center of pressure displacement velocity DTE compared to controls (all, P < 0.049), but only under condition 4. They also showed a significant reduction in the sway area DTE under condition 4 compared to condition 3 (P = 0.025). CONCLUSIONS: This study provides novel preliminary evidence for the value of a 3D immersive VR environment combined with different attention-demanding conditions in adapting postural control in patients with FMDs. As supported by quantitative and objective posturographic measures, our findings may inform interventions to explore FMDs pathophysiology.

Preserving the placebo effect after disclosure: A new perspective on non-deceptive placebos.

The present study explores whether a particular style of placebo disclosure could serve as a tool to foster a renewed trust in one's own inherent resources and elicit a meaningful placebo effect. In a motor performance task, two placebo groups received inert transcutaneous electrical nerve stimulation (TENS) in each of four sessions along with information on its force-enhancing properties. Before the final session, one of the placebo groups was informed about the placebo, which was portrayed as a means to unleash an inherent potential. Along with force, we systematically monitored task-specific self-efficacy to test whether this variable would be differentially modulated in the two placebo groups. Compared to two control groups, placebo groups showed higher force and self-efficacy in the last session. No differences in self-efficacy were observed in the placebo groups even after revealing the placebo procedure, suggesting that the disclosure was effective in 'safeguarding' individuals' self-efficacy. These findings may have important implications, paving the way for the use of placebos that not only are ethically permissible but also support individuals' self-efficacy.

Trait-related neural basis of attentional bias to emotions: a tDCS study.

Negative emotional stimuli can strongly bias attention, particularly in individuals with high levels of dispositional negative affect (NA). The current study investigated whether the prefrontal cortex (PFC), a brain region involved in the top-down regulation of emotional processing, plays a different role in controlling attention to emotions, depending on the individual NA. Sham and anodal transcranial direct current stimulation (tDCS) was delivered over the right or left PFC while assessing attentional bias (AB) to emotions (happy, angry, sad faces) in individuals with higher and lower trait NA. When tDCS was inactive (sham), individuals with higher trait NA showed AB toward angry and away from sad faces, while individuals with lower trait NA presented with no AB. Right anodal-tDCS abolished the AB toward angry faces and induced an AB toward sad faces in individuals with higher trait NA, while no effect was found in individuals with lower trait NA. Left anodal-tDCS abolished any AB in individuals with higher trait NA and induced an AB away from happy faces in individuals with lower trait NA. These findings confirm a critical role of trait NA in AB to emotions and demonstrate a different involvement of PFC in emotional processing based on dispositional affect.

Psychiatrists' attitudes towards functional neurological disorders: results from a national survey.

Introduction: Functional neurological disorder (FND) presents motor, sensory, and cognitive symptoms characterized by clinical signs incongruent with known neurological disease. Together with other health professionals, like neurologists, psychiatrists can play an essential role in diagnosing and managing these disorders. Hence, understanding their opinion and clinical experience with FND is of utmost importance to catch potential educational needs and improve healthcare services for patients. This study aims at assessing the knowledge, opinion, and clinical approach of Italian psychiatrists to FND. Methods: Members of the Italian Society of Psychiatry completed a 14-item web-based survey investigating their approach to FND. Results. Overall, 174 questionnaires were completed. Our main findings suggest that Italian psychiatrists have a psychogenetic conceptualization of FND. "Conversion disorders", in fact, is the term most frequently used by Italian psychiatrists to refer to FND, thus implying a psychological etiology of these disorders. Congruently with this view, psychotherapy associated with pharmacological therapy is considered the most appropriate treatment by psychiatrists, while physiotherapy is an under-recognized treatment option for FND. Discussion: The present study highlights that a psychogenetic view of FND dominates among Italian psychiatrists. This could be due to out-of-date knowledge about the pathophysiology of this group of disorders. Promoting education about novel approaches to FND would be of crucial importance to improving care for patients suffering from this condition.

Placebo effect on gait: a way to reduce the dual-task cost in older adults.

The ability to perform two tasks simultaneously is essential for daily activities. In older adults, this ability is markedly reduced, as evidenced by the dual-task cost on gait. Preliminary evidences indicate that the dual-task cost can be influenced by different types of manipulations. Here, we explored the effectiveness of a new approach to reduce the dual-task cost, based on the placebo effect, a psychobiological phenomenon whereby a positive outcome follows the administration of an inert device thought to be effective. Thirty-five healthy older adults were asked to walk on a sensorized carpet (single-task condition) and to walk while counting backward (dual-task condition) in two sessions (pre-test and post-test). A placebo group, randomly selected, underwent sham transcranial direct current stimulation over the supraorbital areas between sessions, along with information about its positive effects on concentration and attention. A control group did not receive any intervention between sessions. The dual-task cost was significantly reduced in the placebo group at the post-test session compared to the pre-test for several gait parameters (Cohen's d > 1.43). At the post-test session, the dual-task cost was also lower in the placebo group than in the control group (d > 0.73). Cognitive (number of subtractions and number of errors) and subjective (perceived mental fatigability) variables remained stable across sessions. The reduced dual-task cost in the placebo group could indicate the ability to re-establish the allocation of attentional resources between tasks. These findings could contribute to the development of cognitive strategies that leverage positive expectations to boost motor control in older adults.

Dual tasking affects gait performance but not automaticity in functional gait disorders: A new diagnostic biomarker.

INTRODUCTION: Functional gait disorders (FGDs) are disabling symptoms of Functional Motor Disorders. Clinical observations show improvement with distraction suggesting an association with higher-level control mechanisms. Dual tasking is a valuable tool for exploring the interplay between gait and cognition. Our research question was: how do different dual task paradigms shape spatio-temporal gait parameters in FGDs?. METHODS: In all, 29 patients with FGDs (age 43.48 ± 15.42 years; female 75%) and 49 healthy controls (age 43.33 ± 15.41 years; female 62%) underwent spatio-temporal gait analysis during a single task and during performance on a motor, a cognitive, and a visual-fixation dual-task. The dual-task effect was a measure of interference of the concurrent task on gait speed, stride length (a measure of gait performance), and stride time variability (a measure of automaticity and steadiness). RESULTS: Overall lower gait speed, shorter stride length, and higher stride time variability were noted in FGDs compared to healthy controls (for all, p < 0.019). The was a significant effect of group and Task × Group interaction for the dual-task effect on gait speed (p = 0.023) and stride length (p = 0.01) but not for stride time variability. CONCLUSION: Poorer gait performance and less automaticity and steadiness were noted in FGDs. However, dual tasking affected gait performance but, unlike different neurological diseases, not automaticity and steadiness compared to controls. Our findings shed light on higher-level gait control mechanisms in FGDs and suggest stride time variability could be a diagnostic and prognostic biomarker.

Performance validity tests in nonlitigant patients with functional motor disorder.

BACKGROUND AND PURPOSE: Performance validity tests (PVTs) are used in neuropsychological assessments to detect patterns of performance suggesting that the broader evaluation may be an invalid reflection of an individual's abilities. Data on functional motor disorder (FMD) are currently poor and conflicting. We aimed to examine the rate of failure on three different PVTs of nonlitigant, non-compensation-seeking FMD patients, and we compared their performance to that of healthy controls and controls asked to simulate malingering (healthy simulators). METHODS: We enrolled 29 nonlitigant, non-compensation-seeking patients with a clinical diagnosis of FMD, 29 healthy controls, and 29 healthy simulators. Three PVTs, the Coin in the Hand Test (CIH), the Rey 15-Item Test (REY), and the Finger Tapping Test (FTT), were employed. RESULTS: Functional motor disorder patients showed low rates of failure on the CIH and REY (7% and 10%, respectively) and slightly higher rates on the FTT (15%, n = 26), which implies a motor task. Their performance was statistically comparable to that of healthy controls but statistically different from that of healthy simulators (p < 0.001). Ninety-three percent of FMD patients, 7% of healthy simulators, and 100% of healthy controls passed at least two of the three tests. CONCLUSIONS: Performance validity test performance of nonlitigant, non-compensation-seeking patients with FMD ranged from 7% to 15%. Patients' performance was comparable to that of controls and significantly differed from that of simulators. This simple battery of three PVTs could be of practical utility and routinely used in clinical practice.

The placebo effect shortens movement time in goal-directed movements.

The placebo effect is a powerful psychobiological phenomenon whereby a positive outcome follows the administration of an inert treatment thought to be effective. Growing evidence shows that the placebo effect extends beyond the healing context, affecting also motor performance. Here we explored the placebo effect on the control of goal-directed movement, a fundamental function in many daily activities. Twenty-four healthy volunteers performed upper-limb movements toward a target at different indexes of difficulty in two conditions: in the placebo condition, an electrical device (inert) was applied to the right forearm together with verbal information about its positive effects in improving movement precision; in the control condition, the same device was applied along with verbal information about its neutral effects on performance. Interestingly, we found shorter movement time in the placebo compared to the control condition. Moreover, subjective perception of fatigability was reduced in the placebo compared to the control condition. These findings indicate that the placebo effect can improve the execution of goal-directed movements, thus adding new evidence to the placebo effect in the motor domain. This study could inspire future applications to improve upper-limb movements or in clinical settings for patients with motor deficits.

Functional neurological disorder and placebo and nocebo effects: shared mechanisms.

Functional neurological disorder (FND) is characterized by neurological symptoms that cannot be explained by a structural neurological cause. Among the different aetiological models that have been proposed for FND, of note is the Bayesian predictive coding model, which posits that perception relies on top-down cortical predictions (priors) to infer the source of incoming sensory information. This model can also apply to non-pathological experiences, such as placebo and nocebo effects, wherein sensory information is shaped by prior expectations and learning. To date, most studies of the relationship between placebo and nocebo effects and FND have focused on the use of placebos for diagnosis and treatment of FND. Here, we propose that this relationship might go beyond diagnosis and therapy. We develop a framework in which shared cognitive, personality and neuroanatomical factors justify the consideration of a deeper link between FND and placebo and nocebo effects. This new perspective might offer guidance for clarification of the pathogenesis of FND and for the identification of potential biomarkers and therapeutic targets.

Unpleasant olfactory and gustatory stimuli increase pain unpleasantness in patients with chronic oral burning pain: An exploratory study.

BACKGROUND: Despite mounting evidence for the powerful influence of smell and taste substances in experimental pain, our knowledge of their effects in the clinical context is scarce, especially for patients with chronic oral burning pain. To fill this gap, we investigated the effect of olfactory and gustatory stimuli on pain perception in patients with chronic oral burning pain, a disabling condition that is difficult to manage and treat. METHODS: Twenty-two patients with chronic oral burning pain underwent testing with a variety of olfactory and gustatory substances (pleasant, neutral, unpleasant) in multisensory interaction. The order of testing was randomized. Perception of pain intensity and unpleasantness was evaluated on a numerical rating scale at baseline and immediately after each test trial. RESULTS: Pain unpleasantness but not pain intensity was found to be modulated by chemosensory stimuli. Unpleasant olfactory and gustatory stimuli increased the perception of pain unpleasantness compared to pleasant and neutral stimuli. Pain unpleasantness after unpleasant olfactory and gustatory stimuli correlated with psychological questionnaire subscale scores for distress (CORE-OM) and emotional awareness (TAS-20). CONCLUSIONS: Our findings suggest a role of unpleasant chemosensory stimuli in increasing the perception of pain unpleasantness in patients with chronic oral burning. The lack of an effect on pain intensity indicates a dissociation between sensory and affective pain components. Future research is needed to further study the association between chemosensory stimuli and emotional and subjective aspects in modulating chronic oral burning pain. SIGNIFICANCE: This exploratory work suggests that unpleasant smell and taste stimuli may have an adverse effect on the affective component of chronic oral burning pain. Future comprehensive large-scale research, also applying brain imaging investigations as well as full psychological analysis, is required to better understand the role of smell and taste stimuli on this chronic and disabling pain condition.

Attentional bias to emotions after prolonged endurance exercise is modulated by age.

Physical exercise has an impact in biasing attention to positive or negative emotional stimuli. While attentional shift to emotions varies with age, evidence is lacking on the effect of prolonged endurance exercise on age-related attentional bias to emotions. This study aims at filling this knowledge gap, by applying a dot-probe task to measure attentional bias to emotions before and after a half-marathon in healthy participants of different ages (age range 21-65 years). State anxiety, positive and negative affect were also assessed. Younger adults showed attentional bias towards anger and away from sadness after the race, supporting the hypothesis of the congruency between the high-arousing task and the associated emotion (anger) in the modulation of attention. Conversely, older adults showed a bias away from anger, likely representing an attempt to maintain an optimal emotional level after the competition. This study sheds new light on how age impacts on emotional mechanisms involved in prolonged endurance exercise and suggests that regulatory processes in response to stress may be involved differently, depending on age.

Opinion, knowledge, and clinical experience with functional neurological disorders among Italian neurologists: results from an online survey.

BACKGROUND: Functional neurological disorders (FND) are disabling medical conditions commonly seen in neurological practice. Neurologists play an essential role in managing FND, from establishing a diagnosis to coordination of multidisciplinary team-based treatment for patients. With this study, we investigated the knowledge and the clinical experience of Italian neurologists in managing patients with FND. METHODS: Members of the Italian Society of Neurology were invited via e-mail to participate in this ad hoc online survey; 492 questionnaires were returned completed. RESULTS: The term "Functional neurological disorders" in reference to FND was used more frequently than other psychological (e.g., psychogenic or conversion), or descriptive terms (e.g., non-organic or stress-related). When speaking with patients, the respondents stated that they preferred explaining symptoms based on abnormal functioning of the nervous system than discussing mental illness and that they would refer their patient to a psychologist rather than to a psychiatrist. Few considered that physiotherapy and psychiatric interventions are useful approaches to treating FND. Some believed that patients simulate their symptoms. CONCLUSIONS: Overall, the responses suggest that knowledge about scientific advances in FND is somewhat sparse. A psychiatric-centered view of FND opens the way to an approach in which neurobiological and psychological aspects constitute essential factors of the condition. In this context, professional education could improve understanding of FND and optimize patient management.

The Role of Expectation and Beliefs on the Effects of Non-Invasive Brain Stimulation.

Non-invasive brain stimulation (NIBS) techniques are used in clinical and cognitive neuroscience to induce a mild magnetic or electric field in the brain to modulate behavior and cortical activation. Despite the great body of literature demonstrating promising results, unexpected or even paradoxical outcomes are sometimes observed. This might be due either to technical and methodological issues (e.g., stimulation parameters, stimulated brain area), or to participants' expectations and beliefs before and during the stimulation sessions. In this narrative review, we present some studies showing that placebo and nocebo effects, associated with positive and negative expectations, respectively, could be present in NIBS trials, both in experimental and in clinical settings. The lack of systematic evaluation of subjective expectations and beliefs before and after stimulation could represent a caveat that overshadows the potential contribution of placebo and nocebo effects in the outcome of NIBS trials.

Corrigendum: Major Stress-Related Symptoms During the Lockdown: A Study by the Italian Society of Psychophysiology and Cognitive Neuroscience.

[This corrects the article DOI: 10.3389/fpubh.2021.636089.].

Bodily self-perception during voluntary actions: The causal contribution of premotor cortex and cerebellum.

Voluntary actions are accompanied by the experience of controlling one's own movements (sense of agency) and the feeling that the moving body part belongs to one's self (sense of body ownership). So far, agency and body ownership have been investigated separately, leaving the neural underpinnings of the relation between the two largely unexplored. The aim of this study was to explore the causal role of two multisensory brain regions, that is the premotor cortex (PMc) and the cerebellum, in agency and body ownership concurrently on the same behavioral task, i.e., the moving Rubber Hand Illusion (mRHI). Participants watched a rubber hand while moving their hidden hand. The type of movement (active or passive) and posture of the rubber hand (congruent or incongruent) differed in three conditions (active congruent, passive congruent, active incongruent), so that agency and ownership could be elicited either separately or concurrently. Agency and ownership were measured by subjective report and proprioceptive drift. Sham and anodal transcranial direct current stimulation (tDCS) were delivered to the PMc (Experiment 1) or the cerebellum (Experiment 2) prior to the mRHI task. Independent of the site or type of tDCS, subjective reports revealed that both agency and ownership were evoked in the active congruent condition, ownership but not agency in the passive congruent condition, and agency but not ownership in the active incongruent condition. The proprioceptive drift was evoked in the active congruent and the passive congruent condition. Anodal tDCS over the PMc reduced the feeling of agency in the active congruent condition, while it enhanced proprioceptive drift when applied over the cerebellum. These findings suggest a specific causal contribution of the PMc and the cerebellum to bodily self-perception during voluntary movement, with the PMc mainly involved in awareness of action and the cerebellum in proprioceptive adaptation of body position in space.

Motor dual task with eyes closed improves postural control in patients with functional motor disorders: A posturographic study.

BACKGROUND: Functional motor disorders (FMD) are highly disabling neurological conditions in which postural control deficits increase the risk of falls and disability in performing daily living activities. Scattered evidence suggests that such disturbances may depend on abnormal attentional focus and might improve with distraction. RESEARCH QUESTION: How do motor and cognitive dual tasks performed under two different sensory conditions shape postural control in patients with FMD. METHODS: This posturographic study involved 30 patients with FMD (age, 45.20 ± 14.57 years) and 30 healthy controls (age, 41.20 ± 16.50 years). Postural parameters were measured with eyes open, and eyes closed in quiet stance (single task) and on a motor dual task (m-DT) and a calculation (cognitive) dual task (c-DT). The dual task effect (DTE, expressed in percentage) on motor and cognitive performance was calculated for sway area, length of Center of Pressure (CoP), and velocity of CoP displacement. RESULTS: There was a statistically significant three-way interaction between task, condition, and group for the DTE on sway area (p = 0.03). The mean sway area DTE on the motor task in the eyes-closed condition was increased by 70.4 % in the healthy controls, while it was decreased by 1% in the patient group (p = 0.003). No significant three-way interaction was observed for the DTE on length of CoP and velocity of CoP displacement. SIGNIFICANCE: This study provides novel preliminary evidence for the benefit of a simple motor dual task in the eyes closed condition as a way to improve postural control in patients with FMD. These findings are relevant for the management of postural control disorders in patients with FMD.

Major Stress-Related Symptoms During the Lockdown: A Study by the Italian Society of Psychophysiology and Cognitive Neuroscience.

The clinical effects of the Covid-19 pandemic are now the subject of numerous studies worldwide. But what are the effects of the quarantine imposed by the states that implemented the measures of lockdown? The present research aims to explore, in a preliminary way, the major stress-related symptoms during the lockdown, due to Covid-19, in the Italian population. Subjects were asked to fill out a survey, that traced a line identifying the most relevant psychophysiological symptoms that took into account factors such as perceived stress, body perception, perceived pain, quality of sleep, perceptive variations (i.e., olfactory, gustatory, visual, acoustic, and haptic perception). A network approach formulating a hypothesis-generating exploratory analysis was adopted. Main results of the network analysis showed that the beliefs of having had the Covid-19 was related to individual variables (i.e., gender, working in presence, sleep quality, anxiety symptoms), while the familiarity of Covid-19 disease was related to contextual factors (e.g., number of recorded cases in the Region, working in presence). The self-perception of olfactory and perceptive alterations highlighted a great sensorial cross-modality, additionally, the olfactory impairment was related to the belief of having had the Covid-19. Compared to general network data, BAI, perceived stress, anxiety and chronic pain were in relation to daily sleep disturbance. Main study's results show how the management of the Covid-19 stressful representation, in its cognitive aspects, can modulate the psychophysiological responses.

Movement perception of the tonic vibration reflex is abnormal in functional limb weakness.

INTRODUCTION: We tested the hypothesis that functional limb weakness is associated with possible dysfunction of the central processing of proprioceptive information, by evaluating the amount of tonic vibration reflex (TVR) and the perception of the TVR movement. METHODS: The study sample was 20 patients with functional weakness of the lower and/or the upper limbs and 25 healthy controls; delivery of 92-Hz transcutaneous vibration of the biceps brachii tendon of the unrestrained arm stimulated predominantly the muscle spindle afferent and elicited elbow flexion (tonic vibration reflex, TVR). Blindfolded participants had to match the final position of the vibrated arm with their contralateral tracking arm. The TVR and perception of the TVR movement were measured as angle movements of the vibrated arm and the tracking arm, respectively. RESULTS: The magnitude of the TVR of the vibrated arm and movement perception of the TVR of the tracking arm were significantly reduced in the patients compared to the controls. No correlation was found between magnitude of the TVR and perception of the TVR movement, suggesting that the abnormalities were independent of each other. Moreover, the abnormalities did not differ between the patients with/without bilateral upper limb involvement or between the affected and the unaffected side in patients with unilateral impairment, suggesting that the observed deficits are independent of motor impairment. CONCLUSIONS: Proprioceptive dysfunction may underlie alterations in body movement and in sense of agency in such patients and may play a role in the pathophysiology of functional limb weakness.

Pain, Smell, and Taste in Adults: A Narrative Review of Multisensory Perception and Interaction.

Every day our sensory systems perceive and integrate a variety of stimuli containing information vital for our survival. Pain acts as a protective warning system, eliciting a response to remove harmful stimuli; it may also be a symptom of an illness or present as a disease itself. There is a growing need for additional pain-relieving therapies involving the multisensory integration of smell and taste in pain modulation, an approach that may provide new strategies for the treatment and management of pain. While pain, smell, and taste share common features and are strongly linked to emotion and cognition, their interaction has been poorly explored. In this review, we provide an overview of the literature on pain modulation by olfactory and gustatory substances. It includes adult human studies investigating measures of pain threshold, tolerance, intensity, and/or unpleasantness. Due to the limited number of studies currently available, we have structured this review as a narrative in which we comment on experimentally induced and clinical pain separately on pain-smell and pain-taste interaction. Inconsistent study findings notwithstanding, pain, smell, and taste seem to interact at both the behavioral and the neural levels. Pain intensity and unpleasantness seem to be affected more by olfactory substances, whereas pain threshold and tolerance are influenced by gustatory substances. Few pilot studies to date have investigated these effects in clinical populations. While the current results are promising for the future, more evidence is needed to elucidate the link between the chemical senses and pain. Doing so has the potential to improve and develop novel options for pain treatment.