Past Journal Clubs
Wednesday, May 25, 2022, 9:30 am EST
Title: A multivariate model for classifying and predicting different pain conditions in the UK Biobank
Presented by: Dr. Etienne Vachon-Presseau, Assistant Professor, Pain and Neuroscience, Faculty of Dental Medicine and Oral Health Sciences, McGill University, Canada
Abstract: Predictive modeling is becoming increasingly popular in the quest of personalized medicine. Previous studies have suggested that chronic pain conditions can be determined from the interactions between physiological, psychological, social, cognitive, affective, and behavioral factors. Despite its popularity, the elements composing the biopsychosocial model for chronic pain remain hard to define due to the difficulties of simultaneously measuring multidimensional factors in large groups of pain patients. More importantly, the evidence that the framework is useful to forecast chronic pain conditions remains to be demonstrated. Recent accessibility to large cohorts of chronic pain patients provides unprecedented opportunities to tackle these problems. Here, we used machine learning on a curated series of 99 features selected in the UK Biobank and derived a model that predicted the number of co-existing pain sites, classified chronic pain conditions, and forecasted individual differences in the spreading of chronic pain nine years later. Our model generalized to secondary outcomes such as general health, disability, opioid use, and a wide range of non-cancer illnesses. A risk score derived from the model was associated with three pre-selected biological factors available in the biobank, namely, an inflammatory blood marker, a polygenic risk score computed for the number of pain sites, and a neuroimaging-based marker for sustained pain. Overall, our results provide empirical evidence that a multivariate framework trained on pain-agnostic features can predict different chronic pain conditions in out-of-sample patients.
Wednesday, April 20, 2022, 10 am EST
Title: Modulatory Capacity: Neural and behavioural markers of resilience and vulnerability to pain
Presented by: Dr. Tim V. Salomons, Assistant Professor, Pain, Affect and Cognition Lab, Department of Psychology, Queen's University, Canada
Abstract: One of the great mysteries of pain science is why, given seemingly similar levels of peripheral pathology, some individuals are able to successfully cope with pain and achieve successful outcomes, while others fall into a negative cycle of negative affect and chronic pain. To examine these individual differences, we have developed an assessment battery for "modulatory capacity": an individual's tendency towards central mediated facilitation or inhibition of pain. We have been examining whether a combination of neuroimaging markers, quantitative sensory tests, and psychometric measures of affective style can together characterize individuals at high risk for maladaptive pain outcomes. I will present preliminary results from this work, including findings in 68 participants showing that over four separate sessions of painful thermal stimulation, individuals display a stable pattern of habituation or sensitisation, and that this characteristic response pattern is associated with changes over time in pain-evoked responses in the hippocampus and amygdala.
Thursday, April 14, 2022, 10 am EST
Title: Limits of decoding mental states with fMRI
Presented by: Dr. Apkar Vania Apkarian, Professor of Neuroscience, Anesthesiology and Physical Medicine and Rehabilitation, Center for Translational Pain Research, Northwestern University, United States
Abstract: A growing number of studies claim to decode mental states using multi-voxel decoders of brain activity. It has been proposed that the fixed, fine-grained, multi-voxel patterns in these decoders are necessary for discriminating between and identifying mental states. Here, we present evidence that the efficacy of these decoders might be overstated. Across various tasks, decoder patterns were spatially imprecise, as decoder performance was unaffected by spatial smoothing; 90% redundant, as selecting a random 10% of a decoder's constituent voxels recovered full decoder performance; and performed similarly to brain activity maps used as decoders. We distinguish decoder performance in discriminating between mental states from performance in identifying a given mental state, and show that even when discrimination performance is adequate, identification can be poor. Finally, we demonstrate that simple and intuitive similarity metrics explain 91% and 62% of discrimination performance within- and across-subjects, respectively. These findings indicate that currently used across-subject decoders of mental states are superfluous and inappropriate for decision-making.
Tuesday, February 24, 2022, 10 am EST
Title: Learning the statistics of pain: computational and neural mechanisms
Presented by: Dr. Flavia Mancini, MRC Research fellow, Department of Engineering, University of Cambridge, United Kingdom
Abstract: Pain invariably changes over time, and these temporal fluctuations are riddled with uncertainty about body safety. In theory, statistical regularities of pain through time contain useful information that can be learned, allowing the brain to generate expectations and inform behaviour. To investigate this, we exposed healthy participants to probabilistic sequences of low and high-intensity electrical stimuli to the left hand, containing sudden changes in stimulus frequencies. We demonstrate that humans can learn to extract these regularities, and explicitly predict the likelihood of forthcoming pain intensities in a manner consistent with optimal Bayesian models with dynamic update of beliefs. We studied brain activity using functional MRI whilst subjects performed the task, which allowed us to dissect the underlying neural correlates of these statistical inferences from their uncertainty and update. We found that the inferred frequency (posterior probability) of high intensity pain correlated with activity in bilateral sensorimotor cortex, secondary somatosensory cortex and right caudate. The uncertainty of statistical inferences of pain was encoded in the right superior parietal cortex. An intrinsic part of this hierarchical Bayesian model is the way that unexpected changes in frequency lead to shift beliefs and update the internal model. This is reflected by the KL divergence between consecutive posterior distributions and associated with brain responses in the premotor cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. In conclusion, this study extends what is conventionally considered a sensory pain pathway dedicated to process pain intensity, to include the generation of Bayesian internal models of temporal statistics of pain intensity levels in sensorimotor regions, which are updated dynamically through the engagement of premotor, prefrontal and parietal regions.
Relevant paper: https://www.biorxiv.org/content/10.1101/2021.10.21.465270v1
Tuesday, February 8, 2022, 5 pm EST
Title: Brainstem mechanisms of pain modulation: a within-subjects 7T fMRI study of Placebo Analgesic and Nocebo Hyperalgesic Responses
Presented by: Lewis Crawford PhD Student, Henderson Lab, University of Syndey, Australia
Abstract: Pain perception can be powerfully influenced by an individual’s expectations and beliefs. Whilst the cortical circuitry responsible for pain modulation has been thoroughly investigated, the brainstem pathways involved in the modulatory phenomena of placebo analgesia and nocebo hyperalgesia remain to be directly addressed. This study employed ultra-high field 7 Tesla functional MRI (fMRI) to accurately resolve differences in brainstem circuitry present during the generation of placebo analgesia and nocebo hyperalgesia in healthy human participants (N = 25; 12 Male). Over two successive days, through blinded application of altered thermal stimuli, participants were deceptively conditioned to believe that two inert creams labelled ‘lidocaine’ (placebo) and ‘capsaicin’ (nocebo) were acting to modulate their pain relative to a third ‘Vaseline’ (control) cream. In a subsequent test phase, fMRI image sets were collected whilst participants were given identical noxious stimuli to all three cream sites. Pain intensity ratings were collected and placebo and nocebo responses determined. Brainstem-specific fMRI analysis revealed altered activity in key pain-modulatory nuclei, including a disparate recruitment of the periaqueductal gray (PAG) – rostral ventromedial medulla (RVM) pathway when both greater placebo and nocebo effects were observed. Additionally, we found that placebo and nocebo responses differentially activated the parabrachial nucleus but overlapped in their engagement of the substantia nigra and locus coeruleus. These data reveal that placebo and nocebo effects are generated through differential engagement of the PAG-RVM pathway, which in concert with other brainstem sites likely influence the experience of pain by modulating activity at the level of the dorsal horn.
Tuesday, January 25, 2022, 2 pm EST
Title: Pain Reprocessing Therapy for Chronic Back Pain
Presented by: Yoni Ashar, Postdoctoral Fellow Wager Lab, University of Colorado, Boulder, USA
Abstract:Psychological treatments for chronic pain typically aim to improve functioning and quality of life, rather than targeting pain intensity directly. Here, we developed and tested Pain Reprocessing Therapy (PRT), a psychological treatment aiming to reduce or eliminate pain. PRT aims to help patients reconceptualize pain as non-dangerous and due to brain plasticity rather than bodily injury. In a randomized clinical trial of N = 151 primary chronic back pain patients, we compared PRT to placebo injection and usual care control conditions. 66% of participants randomized to PRT reported being pain-free or nearly so at post-treatment, as compared to less than 20% of controls. Treatment effects were largely maintained at 1-year follow-up. Effects of PRT were mediated by reductions in fearful beliefs that pain indicates injury and pain-related fear and avoidance. Longitudinal fMRI showed (1) reduced responses to evoked back pain in the anterior midcingulate and the anterior prefrontal cortex for PRT vs placebo; (2) reduced responses in the anterior insula for PRT vs usual care; (3) increased resting connectivity from the anterior prefrontal cortex and the anterior insula to the primary somatosensory cortex for PRT vs both control groups; and (4) increased connectivity from the anterior midcingulate to the precuneus for PRT vs usual care. We conclude that psychological treatment centered on changing patients’ beliefs about the causes and threat value of pain may provide substantial and durable pain relief for a substantial portion of people with primary CBP.
Tuesday, December 7, 2021, 12 noon EST
Title: Neuroimmune signatures in human chronic pain
Presented by: Marco Loggia, Associate Professor of Radiology, Harvard Medical School and Co-Director, Center for Integrative Pain NeuroImaging (CiPNI), Pain and Neuroinflammation Imaging Laboratory, Departments of Radiology and Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, A. A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA
Abstract:Despite the plethora of preclinical studies demonstrating a role for activated microglia and astrocytes in the establishment and/or maintenance of persistent pain, our understanding of the role of neuroinflammation in human pain remains limited. This has so far prevented the translation of important preclinical observations into novel glia-targeted treatments for pain. In this talk, I will present results of a series of studies which suggest the presence of elevated levels of the 18kDa translocator protein (TSPO) in the central nervous system of patients with various chronic pain disorders. Because TSPO upregulation is highly co-localized with activated glia, our results suggest that neuroinflammation might indeed occur, and in fact may be a pervasive phenomenon that can be observed across multiple, etiologically heterogeneous human pain disorders, although in a disorder-specific spatial distribution. Identifying the role of glia in the development and maintenance of persistent pain and pain-related disability in humans will have important practical implications, and provide crucial human evidence contributing to rationale for the development of tailored interventions focused on glial modulation.
Wednesday, December 1, 2021, 11 am EST
Title: Beyond Sharing Unpleasant Affect—Evidence for Pain-Specific Opioidergic Modulation of Empathy for Pain
Presented by: Markus Rütgen, Postdoctoral Fellow (Lamm Lab), Social, Cognitive and Affective Neuroscience Unit, Department of Cognition, Emotion, and Methods in Psychology, University of Vienna, Austria.
Abstract: It is not known how specific the neural mechanisms underpinning empathy for different domains are. In the present study, we set out to test whether shared neural representations between first-hand pain and empathy for pain are pain-specific or extend to empathy for unpleasant affective touch as well. Using functional magnetic resonance imaging and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them with the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiates the role of shared representations in empathy.
Relevant Article: https://academic.oup.com/cercor/article/31/6/2773/6102670?login=true
Monday, October 25, 2021, 1 pm EST
Title: Classifying chronic pain using multidimensional pain-agnostic symptom assessments and clustering analysis
Presented by: Gadi Gilam, Postdoctoral Fellow (Mackey Lab), Anesthesiology, Perioperative and Pain Medicine, Stanford University, CA, USA.
Abstract: Chronic pain conditions present in various forms, yet all feature symptomatic impairments in physical, mental, and social domains. Rather than assessing symptoms as manifestations of illness, we used them to develop a chronic pain classification system. A cohort of real-world treatment-seeking patients completed a multidimensional patient-reported registry as part of a routine initial evaluation in a multidisciplinary academic pain clinic. We applied hierarchical clustering on a training subset of 11448 patients using nine pain-agnostic symptoms. We then validated a three-cluster solution reflecting a graded scale of severity across all symptoms and eight independent pain-specific measures in additional subsets of 3817 and 1273 patients. Negative affect-related factors were key determinants of cluster assignment. The smallest subset included follow-up assessments that were predicted based on baseline cluster assignment. Findings provide a cost-effective classification system that promises to improve clinical care and alleviate suffering by providing putative markers for personalized diagnosis and prognosis.
Relevant Paper: https://www.science.org/doi/10.1126/sciadv.abj0320
Friday, October 15, 2021, 11 am EST
Title: Characterising sensorimotor adaptation in Complex Regional Pain Syndrome
Presented by: Janet Bultitude, Senior Lecturer (Associate Professor),Psychology Department and Centre for Pain Research, University of Bath, UK.
Abstract: It has been suggested that sensorimotor conflict contributes to the maintenance of some pathological pain conditions, implying that there are problems with the adaptation processes that normally resolve such conflict. We tested whether sensorimotor adaptation is impaired in people with Complex Regional Pain Syndrome (CRPS) by characterising their adaption to lateral prismatic shifts in vision. People with unilateral upper-limb CRPS Type I (n = 17), and pain-free individuals (n = 18; matched for age, sex, and handedness) completed prism adaptation with their affected/non-dominant and non-affected/dominant arms. We examined 1) the rate at which participants compensated for the optical shift during prism exposure (i.e., strategic recalibration), 2) endpoint errors made directly after prism adaptation (sensorimotor realignment) and the retention of these errors, and 3) kinematic markers associated with strategic control. Direct comparisons between people with CRPS and controls revealed no evidence of any differences in strategic recalibration, including no evidence for differences in a kinematic marker associated with trial-by-trial changes in movement plans during prism exposure. All participants made significant endpoint errors after prism adaptation exposure, indicative of sensorimotor realignment. Overall, the magnitude of this realignment did not differ between people with CRPS and pain-free controls. However, when endpoint errors were considered separately for each hand, people with CRPS made greater errors (indicating more rather than less realignment) when using their affected hand than their non-affected hand. No such difference was seen in controls. Taken together, these findings provide no evidence of impaired strategic control or sensorimotor realignment in people with CRPS. In contrast, they provide some indication that there could be a greater propensity for sensorimotor realignment in the CRPS-affected arm, consistent with more flexible representations of the body and peripersonal space. Our study challenges an implicit assumption of the theory that sensorimotor conflict might underlie some pathological pain conditions.
Wednesday, September 22, 2021, 12 noon EST
Title: Can acute pain tolerance be measured remotely? Experiences from an online trial conducted during COVID-19 social distancing
Presented by: Katherine O’Connell, Ph.D. Candidate, Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington DC, USA
Abstract: Large and supportive social environments have emerged as a potential protective factor against pain. In particular, social support has been linked to increased pain tolerance and reduced opioid use after surgery. Social support exhibits the capacity to be enhanced through some forms of meditation; however, it is unknown whether such an enhancement may correspond to improved acute pain experience in healthy adults. Working in the context of COVID-19 social distancing, two acute pain assays were designed to be safe, remote, and highly accessible for a U.S. sample and included a wall sit test and an ice cube holding test. We assessed pain tolerance and social support over online video chat before and after a social meditation training or active control. Trial results will be discussed as well as the strengths and limitations of remote, acute pain research.
Thursday, September 16, 2021, 10 am EST
Title: Hippocampal circuits and chronic pain
Presented by: A. Vania Apkarian, Director, Center for Translational Pain Research, Professor of Physiology, Anesthesiology and Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, USA.
Abstract: Over about 10 years we have been studying the involvement of hippocampal circuits in chronic pain. In this lecture I will present this evidence and discuss theoretical concepts that have driven this effort. Our human and rodent model studies complimentarily indicate that 1) hippocampal properties impart risk for the transition from acute to chronic pain; 2) hippocampal adult neurogenesis is involved in the transition to chronic pain; and 3) hippocampal circuitry reorganizes with the transition to chronic pain. Some of this reorganization is female specific, and manipulating state of excitability of the dorsal hippocampus shows its causal engagement in chronic pain as such manipulation are sufficient to reverse chronic pain-like behaviors in rodent models. I will review this body of knowledge and discuss implications from the viewpoint of what is pain and also regarding clinical implications.
Friday, July 23 2021, 12 noon EST
Title: Brain plasticity for alternative hand control: From phantoms to supernumerary robotic fingers
Presented by: Dr. Tamar Makin, Institute of Cognitive Neuroscience, UCL, London, UK
Abstract: Following arm-amputation, brain areas that previously operated the hand will be freed-up, and could potentially be “recruited” to work for other body parts. This process, termed brain plasticity, is widely held to result in the experience of phantom limb pain (pain that is perceived to be arising from the missing hand), and is therefore considered to be maladaptive. I will present evidence to challenge the proposed link between brain plasticity and phantom pain, and instead demonstrate that brain representation of the missing hand persists decades after amputation. I will next explore the idea the idea that brain plasticity can be harnessed to support adaptive behaviour. I will demonstrate hand-like representation of the toes of foot painters, born with missing upper limbs. Finally, I will present some recent studies looking at how able-bodied participants learn to use a robotic Third Thumb to provide a first glimpse into brain plasticity for motor augmentation. I will argue that brain plasticity is best driven by meaningful inputs, and could be exploited for improving rehabilitation, with exciting opportunities for substitution and augmentation devices. A more nuanced understanding of brain plasticity is needed in order to clarify the neural basis of phantom limb pain.
Tuesday, July 6, 2021, 8:30 am EST
Title: A Neuroimaging Biomarker for Sustained Experimental and Clinical Pain
Presented by: Choog-Wan (Wani) Woo, Assistant Professor, IBS Center for Neuroscience Imaging Research, Department of Biomedical Engineering, Sungkyunkwan University, Korea
Abstract: Sustained pain is a major characteristic of clinical pain disorders, but it is difficult to assess in isolation from co-occurring cognitive and emotional features in patients. In this study, we developed a functional magnetic resonance imaging signature based on whole-brain functional connectivity that tracks experimentally induced tonic pain intensity and tested its sensitivity, specificity and generalizability to clinical pain across six studies (total n = 334). The signature displayed high sensitivity and specificity to tonic pain across three independent studies of orofacial tonic pain and aversive taste. It also predicted clinical pain severity and classified patients versus controls in two independent studies of clinical low back pain. Tonic and clinical pain showed similar network-level representations, particularly in somatomotor, frontoparietal and dorsal attention networks. These patterns were distinct from representations of experimental phasic pain. This study identified a brain biomarker for sustained pain with high potential for clinical translation.
Relevant paper: https://www.nature.com/articles/s41591-020-1142-7?proof=t
Wednesday, June 23, 2021, 11 am EST
Title: The role of network interactions in opioid analgesia
Presented by: Dr. Alexandra Tinnermann, Postdoctoral Fellow (Büchel Lab), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Abstract: Opioids are potent and widely prescribed analgesic drugs with widespread cortical and subcortical targets. In particular, several brain regions such as the thalamus, the insula, the anterior cingulate cortex as well as the descending modulatory pain system including the spinal cord exhibit high µ-opioid receptor density and are thus crucial for opioid analgesia. Given the high degree of functional integration within these systems, we followed a network systems approach and investigated the entire pain system with a particular emphasis on the role of functional interactions underlying opioid analgesia. Male participants either received the rapid-acting µ-opioid receptor agonist remifentanil or saline while undergoing heat pain stimulation. In order to study the entire central pain system, we employed cortico-spinal fMRI which allows measuring BOLD responses simultaneously in the brain, brainstem and spinal cord and therefore enables investigating how opioids modulate interactions across the entire central pain system. Remifentanil reduced activity in several pain-related brain regions such as the insula, operculum and thalamus, but also in the spinal cord dorsal horn. In contrast, activity in the prefrontal cortex was higher during opioid treatment resulting from the absence of a pain-related deactivation. Importantly, activation in many of these regions correlated with individually perceived analgesia. Finally, functional interactions along the descending pain system, i.e. between the prefrontal cortex, periaqueductal gray and spinal cord were differentially modulated by remifentanil, indicating that coupling between the prefrontal cortex, brainstem and the spinal cord is a key mechanism of opioid analgesia..
Relevant paper (Preprint): https://www.biorxiv.org/content/10.1101/2021.05.11.443635v1.abstract
Monday, June 14, 2021, 12 pm EST
Title: Endogenous opioids contribute to the feeling of pain relief in humans
Presented by: Laura Sirucek, PhD Student (Becker and Schweinhardt Labs), Balgrist University, Switzerland
Abstract: Endogenous opioids mediate the pleasurable responses to positively reinforcing stimuli such as palatable food. Yet, the reduction or omission of a negative experience can also be rewarding (negative reinforcement). As such, pain relief leads to negative reinforcement and evokes a pleasant feeling in humans. While it has been shown that the feeling of pleasure associated with positive reinforcement is at least partly mediated via endogenous opioids, it is currently unknown if similar neurochemical mechanisms are involved in the pleasant feeling evoked by pain relief. In the present study, 27 healthy participants completed two identical experimental sessions, one with placebo and one with naltrexone, an endogenous opioid antagonist. Pain relief was induced by superficial cooling after heat stimulation of capsaicin-sensitized skin. Participants rated the relief and pleasantness in response to the cooling. Endogenous opioid blockade by naltrexone decreased relief and pleasantness ratings compared to placebo (p=0.0027). This study provides evidence that endogenous opioids play a role in mediating the pleasant feeling of pain relief in humans. Clinically, the rewarding nature of pain relief and its underlying mechanisms require consideration because of their potential reinforcing effects on behaviors that might be beneficial short-term but maladaptive long-term.
Friday, June 4, 2021, 11 am EST
Title: Pain-related modulations of ongoing oscillations recorded from the human insula using intracerebral EEG
Presented by: Dr. Giulia Liberati, Principal Investigator at the Institute of Neuroscience, UCLouvain, Belgium
Abstract: Pain is a very common experience in everyday life, as it enables us to develop adaptive behavior that is critical for survival. However, to this date, the exact mechanisms through which pain arises from brain activity are still debated. The complexity of studying pain is due to the fact that it is a highly flexible phenomenon that needs to continuously adjust to behavioral demands. This adjustment is evident, for instance, when a circumstance that would generally cause excruciating pain is barely noticed, such as when a soldier is wounded during a battle but keeps fighting, or in a case of an athlete during an important competition. To this end, pain might be better understood by focusing on dynamic features of pain-related activities.My main hypothesis is that pain arises from the modulation of spontaneous and dynamically fluctuating ongoing neural oscillations. To test this hypothesis, I rely on the recording of intracerebral electroencephalography (iEEG) acquired on patients undergoing a presurgical evaluation of focal epilepsy, and on a novel frequency analysis method, frequency tagging of ongoing oscillations (FT-OO).
Wednesday, May 26, 2021, 12 pm EST
Title: Observation of others’ painful heat stimulation involves responses in the spinal cord
Presented by: Dr. Jan Haaker, Research Group Leader, Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf
Abstract: Observing others’ aversive experiences is central to know what is dangerous for ourselves. Hence, observation often elicits behavioral and physiological responses comparable to first-hand aversive experiences. However, it is unresolved if first-hand aversive experiences involves neural processes that are similar when we merely observe aversive stimulation in others. I will outline neural and neuropharmacological pathways that are involved in observation of others painful stimulation and overlap with neural systems that process first-hand aversive experiences. This includes responses in the brain, as well as neural responses in the spinal cord. Beside this common cerebro-spinal network, I will further propose a distinct processing of self and others’ pain that is based on activity in the spinal cord.
Relevant Paper: https://advances.sciencemag.org/content/7/14/eabe8444.abstract
Tuesday, May 11, 2021, 1 pm EST
Title: Physiological and Chemical Properties of C-Tactile Afferents in Man and Their Distribution Across the Body
Presented by: Dr. Line Löken, Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden
Abstract: Since the discovery that the skin of man is innervated with unmyelinated tactile (CT) afferents that convey social and emotional aspects of touch, extensive explorations of the physiology and function of these afferents have been made. In spite of this, aspects of the properties of CT afferents as well as their prevalence and density in different areas of the human body have remained elusive. Numerous microneurography studies in the human peroneal nerve, without reports of CT afferents, suggested that these afferents are lacking in the more distal parts of the limbs. Here we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal, lateral antebrachial and radial nerves. The most distal receptive fields were located on the proximal phalanx of the third finger for the superficial branch of the radial nerve, and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regards to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, was similar in CT units across the antebrachial, radial and peroneal nerves. Lastly, we explored the chemical sensitivity of these afferents and found that CT afferents were not activated by either the pruritogen histamine or the cooling agent menthol. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, including a lack of responsiveness to capsaicin, these findings add to the growing body of research suggesting that CT afferents constitute a unique sense organ with highly specialized mechanisms for transducing stimuli relevant to affective touch sensation.
Tuesday, April 20, 2021, 3 pm EST
Title: A picture is worth a thousand words: linking fibromyalgia pain widespreadness from digital pain drawings with pain catastrophizing and brain cross-network connectivity
Presented by: Dr. Vitaly Napadow, Professor in Radiology, Harvard Medical School, USA
Abstract: Pain catastrophizing is prominent in chronic pain conditions such as fibromyalgia, and has been proposed to contribute to the development of pain widespreadness. However, the brain mechanisms responsible for this association are unknown. We hypothesized that increased resting Salience Network (SLN) connectivity to nodes of the Default Mode Network (DMN), representing previously reported pain-linked cross-network enmeshment, would be associated with increased pain catastrophizing and widespreadness across body sites.We applied functional Magnetic Resonance Imaging (fMRI) and digital pain drawings (free-hand drawing over a body outline, analyzed using conventional software for multivoxel fMRI analysis) to investigate precisely-quantified measures of pain widespreadness and the associations between pain catastrophizing (Pain Catastrophizing Scale, PCS), resting brain network connectivity (Dual-regression Independent Component Analysis, 6-minute multiband accelerated fMRI), and pain widespreadness in fibromyalgia patients (N=79).Fibromyalgia patients reported pain in multiple body areas (most frequently the spinal region, from the lower back to the neck), with moderately high pain widespreadness (mean±SD: 26.1±24.1 percent of total body area), and high PCS scores (27.0±21.9, scale range: 0-52), which were positively correlated (r=0.26,p=0.02). A whole-brain regression analysis focused on SLN connectivity indicated that pain widespreadness was also positively associated with SLN connectivity to the Posterior Cingulate Cortex (PCC), a key node of the DMN. Moreover, we found that SLN-PCC connectivity statistically mediated the association between pain catastrophizing and pain widespreadness (p=0.01).In conclusion, we identified a putative brain mechanism underpinning the association between greater pain catastrophizing and a larger spatial extent of body pain in fibromyalgia, implicating a role for brain SLN-DMN cross-network enmeshment in mediating this association.
Relevant Paper: https://pubmed.ncbi.nlm.nih.gov/33230008/
Tuesday, March 30, 2021, 1 pm EST
Title: Forced choices reveal a trade-off between cognitive effort and physical pain
Presented by: Todd Vogel, PhD Candidate (PI: Dr. Mathieu Roy), Department of Psychology, McGill University, Montréal, Canada
Abstract: Cognitive effort is described as aversive, and people will generally avoid it when possible. This aversion to effort is believed to arise from a cost–benefit analysis of the actions available. The comparison of cognitive effort against other primary aversive experiences, however, remains relatively unexplored. Here, we offered participants choices between performing a cognitively demanding task or experiencing thermal pain. We found that cognitive effort can be traded off for physical pain and that people generally avoid exerting high levels of cognitive effort. We also used computational modelling to examine the aversive subjective value of effort and its effects on response behaviours. Applying this model to decision times revealed asymmetric effects of effort and pain, suggesting that cognitive effort may not share the same basic influences on avoidance behaviour as more primary aversive stimuli such as physical pain.
Relevant Paper: https://elifesciences.org/articles/59410
Wednesday, March 16, 2021
Title: Touch inhibits touch: sanshool-induced paradoxical tingling reveals perceptual interaction between somatosensory submodalities.
Presented by: Professor Patrick Haggard, Action & Body Group Leader, Institute of Cognitive Neuroscience, UCL, London, UK
Abstract: Human perception of touch is mediated by inputs from multiple channels. Classical theories postulate independent contributions of each channel to each tactile feature, with little or no interaction between channels. In contrast to this view, we show that inputs from two sub-modalities of mechanical input channels interact to determine tactile perception. The flutter-range vibration channel was activated anomalously using hydroxy-α-sanshool , a bioactive compound of Szechuan pepper, which chemically induces vibration-like tingling sensations. We tested whether this tingling sensation on the lips was modulated by sustained mechanical pressure. Across four experiments, we show that sustained touch inhibits sanshool tingling sensations in a location-specific, pressure-level and time-dependent manner. Additional experiments ruled out the mediation of this interaction by nociceptive or affective (C-tactile) channels. These results reveal novel inhibitory influence from steady pressure onto flutter-range tactile perceptual channels, consistent with early-stage interactions between mechanoreceptor inputs within the somatosensory pathway.
Relevant Paper: https://royalsocietypublishing.org/doi/10.1098/rspb.2020.2914
Wednesday, March 3, 2021
Title: Confidence in subjective pain is predicted by reaction time during decision making
Presented by: Troy Dildine, PhD Candidate (Atlas Lab), NCCIH/NIH and Karolinska Institute
Abstract: Self-report is the gold standard for measuring pain. However, decisions about pain can vary substantially within and between individuals. We measured whether self-reported pain is accompanied by metacognition and variations in confidence, similar to perceptual decision-making in other modalities. Eighty healthy volunteers underwent acute thermal pain and provided pain ratings followed by confidence judgments on continuous visual analogue scales. We investigated whether eye fixations and reaction time during pain rating might serve as implicit markers of confidence. Confidence varied across trials and increased confidence was associated with faster pain rating reaction times. The association between confidence and fixations varied across individuals as a function of the reliability of individuals’ association between temperature and pain. Taken together, this work indicates that individuals can provide metacognitive judgments of pain and extends research on confidence in perceptual decision-making to pain.
Relevant Paper: https://www.nature.com/articles/s41598-020-77864-8
Wednesday, February 17, 2021
Title: Chronic pain precedes disrupted eating behavior in back pain patients
Presented by: Dr. Paul Geha, Assistant Professor, University of Rochester, USA
Abstract: Chronic low-back pain (CLBP) and obesity are interrelated, but the mechanisms of this interaction are still poorly understood. We have previously shown that patients with CLBP exhibit blunted hedonic response to highly palatable fat-rich food and disrupted satiety signals. This observation is consistent with the reorganization of the nucleus accumbens observed in CLBP patients, and the role of this striatal area in the hedonic perception of highly palatable foods. Here we asked how eating behavior would be affected in back pain patients before and after they transition to chronic pain or recover from it, and how does hedonic perception of fat-rich food relate to the properties of the nucleus accumbens in this patients’ population. Therefore, we tested sub-acute back pain patients and healthy controls at baseline when back pain was 6-12 weeks old, and at approximately one-year follow-up using behavioral assays and structural brain imaging. Likewise, we tested a cohort of CLBP patients at one time point. CLBP patients and, surprisingly, sub-acute back pain patients who recovered at follow-up (SBPr) showed disrupted eating behavior while sub-acute back pain patients who persisted in having pain at follow-up (SBPp) had an intact eating behavior. However, only SBPp patients at baseline and follow-up, and CLBP patients, showed a direct relationship between hedonic perception of fat-rich food and nucleus accumbens volume. Our data reproduces our previous findings and suggest that disrupted eating behavior sets in after pain chronification and is directly related to the properties of nucleus accumbens.
Meeting ID: 834 7571 0509
Wednesday, January 27, 2021
Title: Sex differences in brain modular organization in chronic pain
Presented by: Dr. Camille Fauchon, Postdoctoral Fellow (PI: Karen Davis), Krembil Brain Institute, University Health Network, Canada
Abstract: Men and women can exhibit different pain sensitivities and many chronic pain conditions are more prevalent in one sex. Although there is evidence of sex differences in the brain, it is not known whether there are sex differences in the organization of large-scale functional brain networks in chronic pain. Here, we used graph theory with modular analysis and machine-learning of resting-state (RS)-fMRI data from 220 participants; 155 healthy controls and 65 individuals with chronic low back pain due to ankylosing spondylitis (AS), a form of arthritis.We found an extensive overlap in the graph partitions with the major brain intrinsic systems (i.e., default mode, central, visual and sensorimotor modules), but also sex-specific network topological characteristics in healthy people and those with chronic pain. People with chronic pain exhibited higher cross-network connectivity, and sex-specific nodal graph properties changes (i.e., Hubs disruption), some of which were associated with the severity of the chronic pain condition. Females exhibited atypically higher functional segregation in the mid- and subgenual cingulate cortex and lower connectivity in the network with the default mode and fronto-parietal modules; whereas males exhibited stronger connectivity with the sensorimotor module. Classification models on nodal graph metrics could classify an individuals' sex and whether they have chronic pain with high accuracies (77-92%). These findings highlight the organizational abnormalities of RS-brain networks in people with chronic pain and provide a framework to consider sex-specific pain therapeutics.
Wednesday, December 16, 2020
Title: Reward enhances pain discrimination in humans
Presented by: Dr. Susanne Becker, Research Group Leader, Integrative Spinal Research, Department of Chiropratic Research, University of Zurich, Switzerland
Abstract: The notion that reward inhibits pain is a well-supported observation in both humans and animals, allowing suppression of pain reflexes to acquired rewarding stimuli. However, a blanket inhibition of pain by reward would also impair pain discrimination. In contrast, early counterconditioning experiments implied that reward might actually spare pain discrimination. To test this hypothesis, we investigated whether discriminative performance was enhanced or inhibited by reward. We found in adult human volunteers (N = 25) that pain-based discriminative ability is actually enhanced by reward, especially when reward is directly contingent on discriminative performance. Drift-diffusion modeling shows that this relates to an augmentation of the underlying sensory signal strength and is not merely an effect of decision bias. This enhancement of sensory-discriminative pain-information processing suggests that whereas reward can promote reward-acquiring behavior by inhibition of pain in some circumstances, it can also facilitate important discriminative information of the sensory input when necessary.
Relevant Paper: CLICK HERE
Monday, November 23, 2020
Title: Striatal hypofunction as a neural correlate of mood alterations in chronic pain patients
Presented by: Ellie Minhae Kim, Senior Clinical Research Coordinator, Pain and Neuroinflammation Imaging Lab (Dr. Marco Loggia), A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA
Abstract: Chronic pain and mood disorders share common neuroanatomical substrates involving disruption of the reward system. Although increase in negative affect (NA) and decrease in positive affect (PA) are well-known factors complicating the clinical presentation of chronic pain patients, our understanding of the mechanisms underlying the interaction between pain and PA/NA remains limited. Here, we used a validated task probing behavioral and neural responses to monetary rewards and losses in conjunction with functional magnetic reso- nance imaging (fMRI) to test the hypothesis that dysfunction of the striatum, a key mesolimbic structure involved in the encoding of motivational salience, relates to mood alterations comorbid with chronic pain. Twenty-eight chronic musculoskeletal pain patients (chronic low back pain, n1⁄415; fibromyalgia, n1⁄413) and 18 healthy controls underwent fMRI while performing the Monetary Incentive Delay (MID) task. Behavioral and neural responses were compared across groups and correlated against measures of depression (Beck Depression Inventory) and hedonic capacity (Snaith-Hamilton Pleasure Scale). Compared to controls, patients demonstrated higher anhedonia and depression scores, and a dampening of striatal activation and incentive-related behavioral facilitation (reduction in reaction times) during reward and loss trials of the MID task (ps < 0.05). In all participants, lower activation of the right striatum during reward trials was correlated with lower incentive-related behavioral facilitation and higher anhedonia scores (ps < 0.05). Finally, among patients, lower bilateral striatal activation during loss trials was correlated with higher depression scores (ps < 0.05). In chronic pain, PA reduction and NA increase are accompanied by striatal hypofunction as measured by the MID task.
Thursday, October 22, 2020
Title: The Distributed Nociceptive System: A Framework for Understanding Pain
Presented by: Dr. Robert C. Coghill, Director, Center for Understanding Pediatric Pain (CUPP), Professor of Pediatrics Behavioral Medicine and Clinical Psychology, Cincinnati Children’s Hospital Medical Center
Abstract: Chronic pain remains challenging to both diagnose and treat. These challenges, in part, arise from limited systems-level understanding of the basic mechanisms that process nociceptive information and ultimately instantiate a subjectively available experience of pain. Here, I provide a framework, the distributed nociceptive system, for understanding nociceptive mechanisms at a systems level by integrat- ing the concepts of neural population coding with distributed processing. Within this framework, wide-spread engagement of populations of neurons produces representations of nociceptive information that are highly resilient to disruption. The distributed nociceptive system provides a foundation for understanding complex spatial aspects of chronic pain and provides an impetus for nonpharmacological cognitive and physical therapies that can effectively target the highly distributed system that gives rise to an experience of pain.
Relevant Paper: https://doi.org/10.1016/j.tins.2020.07.004
Wednesday, September 23, 2020
Title: Using fMRI hyperscanning to investigate the patient-clinician relationship in chronic pain: The role of therapeutic alliance, behavioral mirroring, and brain-to-brain concordance in therapeutic pain relief
Presented by: Dr. Dan-Mikael Ellingsen, Postdoctoral research fellow (Napadow Lab), Harvard Medical School and Martinos Center for Biomedical imaging, Boston, USA.
Abstract: The patient-clinician interaction can powerfully shape treatment outcomes such as pain, but is often considered an intangible “art-of-medicine”, and has largely eluded scientific inquiry. Although brain correlates of social processes such as em- pathy and theory-of-mind have been studied using single-subject designs, the spe- cific behavioral and neural mechanisms underpinning the patient-clinician interac- tion are unknown. Using a two-person interactive design, we simultaneously rec- orded functional MRI (i.e. hyperscanning) in patient-clinician dyads, who interacted via live video while clinicians treated evoked pain in chronic pain patients. Our re- sults show that patient analgesia is mediated by patient-clinician nonverbal behav- ioral mirroring and brain-to-brain concordance in circuitry implicated in theory-of- mind and social mirroring. Dyad-based analyses showed extensive dynamic cou- pling of these brain nodes with the partners’ brain activity, yet only in dyads where clinical rapport had been established prior to the interaction. These findings point to a putatively key brain-behavioral mechanism for therapeutic alliance and psycho- social analgesia.
Relevant Paper: https://www.biorxiv.org/content/10.1101/2020.08.05.237511v1
Thursday, August 6/11 2020
We have an outstanding lineup of trainees who will present at the DataBlitz.
We had 31 submissions (!!) that will be presented in three sessions. The first two sessions will be held in parallel on August 6 at 3pm EST and the third session will be held on August 11 at 6:30pm EST. All presenters have been contacted and assigned their timeslots. All trainees will get feedback on their presentations.
An overview of the DataBlitz, including instructions, judges panel, and timings is available here.
The Abstracts and Order of Presentations for each of the DataBlitz events can be found here:
DataBlitz 1 - Room 1
Prizes will be announced on August 15, 2020.
Prizes sponsored by:
Thursday, July 16, 2020
Title: “But for pain words are lacking”: using language features to predict placebo analgesia in chronic pain. (New Data; Unpublished work)
Presented by: Dr. Paulo Branco, Postdoctoral Fellow at Apkarian Pain and Passions lab, Northwestern University, Chicago, USA.
Abstract: “But for pain words are lacking”, writes Virginia Woolf in her Magnum Opus, The Waves. And indeed, even though language is rich in meaning and is seen as “a window to the soul”, the discourse of patients with chronic illness and pain – like Woolf herself – have long been neglected. Natural language processing (NLP) is a relatively popular technique that extracts languages features out of discourse reflecting the person’s personality, behavior and mood. In this study, we hypothesize that chronic back pain patients who respond to placebo will show specific language patterns that can be picked up, quantified, and used to classify and infer the extent of analgesia after placebo pill ingestion. We were able to classify placebo responders with high accuracy (79% cross-validated). Further, with just three language features (semantic proximity to stigma, identity, and text tags associated with achievement) we were able to explain 50% of the variance in the reported pain after treatment. Predictive language features were also associated with personality traits and are not explained by treatment effects alone. Together, these show high promise to the use of quantitative language features to study placebo analgesia and have important implications for both the design of clinical trials and, conceivably, for identifying subjects that can benefit from placebo as a treatment option for chronic pain.
Thursday, July 9, 2020
PANEL DISCUSSION: WHAT HAS IMAGING ADDED TO OUR UNDERSTANDING OF PAIN
A recent editorial in the journal Brain (https://academic.oup.com/brain/article-abstract/143/4/1045/5823483?redirectedFrom=fulltext) criticized brain imaging (in particular fMRI) and stated that it has offered little to our understanding of brain-based disease, and has little (if any) clinical utility.
I thought it would be a good exercise to have a discussion about fMRI/sMRI papers that have had a meaningful impact on our mechanistic understanding of pain, or that have had meaningful clinical impact. This is a useful exercise for us to pull back and to think about the work we do.
Several faculty members have offered to participate, including:
David A. Seminowicz, Associate Professor, University of Maryland School of Dentistry, USA
Flavia Mancini, MRC Career Development Fellow, Cambridge University, UK
Markus Ploner, Heisenberg Professor of Human Pain Research, TUM, Germany
Irene Tracey, Nuffield Chair in Anesthetic Science, Oxford University, UK
Marco Loggia, Associate Professor of Radiology, Harvard Medical School, USA
Ulrike Bingel, Professor in Clinical Neuroscience, University Hospital Essen, Germany
Tor Wager, Diana L. Taylor Distinguished Professor, Dartmouth, USA
Javeria Hashmi, Canada Research Chair (CRC) Tier II (Pain), Dalhousie University, Canada
Marina Lopez-Sola, Serra Hunter Lecturer Prof, University of Barcelona, Spain
DETAILS TO FOLLOW
Thursday, July 2, 2020
SYMPOSIUM: PAIN AND EMOTION—BRAIN, BODY, AND BEYOND
Pain and emotion are tightly linked, but are traditionally studied and treated separately. This symposium highlights conceptual, psychological, and neural intersections between these two constructs, emphasizing opportunity for collaborations across the pain and affective science research and clinical communities. Our diverse panel of speakers combine innovative experimental methodologies and conceptual models, from basic animal and human research, to clinical research in chronic pain patients
Gadi Gilam, email@example.com
Gregory Corder, firstname.lastname@example.org
Siri Leknes, email@example.com
Rachel Aaron, firstname.lastname@example.org
Thursday, June 18, 2020
Title: Multiple Brain Networks Mediating Stimulus-Pain Relationships in Humans.
Presented by: Prof. Tor Wager, Diana L. Taylor Distinguished Professor, Dartmouth, USA
Geuter et al. Multiple Brain Networks Mediating Stimulus-Pain Relationships in Humans. Cerebral Cortex 30(7): 4204–4219
Thursday, June 4, 2020
Guo et al. Ultralow-frequency neural entrainment to pain. PLoS Biology. 18(4): e3000491. https://doi.org/10.1371/journal.pbio.3000491
Presented by: Dr. Yifei Guo and Dr. Rory Bufacchi, Postdoctoral Fellow, Iannetti Lab, Italian Institute of Technology, Rome, Italy
Thursday, May 21, 2020
Title: "Mindfulness engages a novel pain modulatory neural pathway" - Preprint Talk
Presented by: Dr. Fadel Zeidan, Assistant Professor, Department of Anesthesiology, UCSD, USA
(This is new work from Fadel's lab)
Thursday, May 7, 2020
Makari et al. Loss of nucleus accumbens low-frequency fluctuations is a signature of chronic pain. Proceedings of the National Academy of Sciences, in press. DOI: 10.1073/pnas.1918682117
Presented by: Dr. Paul Geha, Assistant Professor, University of Rochester, USA
Thursday, May 21, 2020
Lim et al. Threat Prediction from Schemas as a Source of Bias in Pain Perception. Journal of Neuroscience 40 (7): 1538-1548, 2020.
Presented by: Dr. Javeria Hashmi, Canada Research Chair (CRC) Tier II (Pain), Department of Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, Canada
Thursday, April 16, 2020
Lettieri et al. Emotionotopy in the human right temporo-parietal cortex. Nature Communications 10: 5568 (2019).
Presented by: Massieh Moayedi, Assistant Professor and Co-Director of the Centre for Sensorimotor and Pain Research, University of Toronto, Canada
Furman et al. Sensorimotor peak alpha frequency is a reliable biomarker of pain sensitivity. BiorXiv (preprint).
Presented by: Andrew Furman, PhD Candidate, Seminowicz Lab, University of Maryland, USA
Thursday, April 2, 2020