Pain-related Brain Activity Research Articles

Region of interest determination algorithm of lensless calcium imaging datasets.

Advances in fluorescence imaging technology have been crucial to the progress of neuroscience. Whether it was specific expression of indicator proteins, detection of neurotransmitters, or miniaturization of fluorescence microscopes, fluorescence imaging has improved upon electrophysiology, the gold standard for monitoring brain activity, and enabled novel methods to sense activity in the brain. Hence, we developed a lightweight and compact implantable CMOS-based lensless Ca2+ imaging device for freely moving transgenic G-CaMP mouse experiments. However, without a lens system, determination of regions of interest (ROI) has proven challenging. Localization of fluorescence activity and separation of signal from noise are difficult. In this study, we report an ROI selection method using a series of adaptive binarizations with a gaussian method and morphological image processing. The parameters for each operation such as the kernel size, sigma and footprint size were optimized. We then validated the utility of the algorithm with simulated data and freely moving nociception experiments using the lensless devices. The device was implanted in the dorsal raphe nucleus to observe pain-related brain activity following a formalin test to stimulate pain. We observed significant increases in fluorescence activity after formalin injection compared to the control group when using the ROI determination algorithm.

Effect of parental touch on relieving acute procedural pain in neonates and parental anxiety (Petal): a multicentre, randomised controlled trial in the UK

Touch interventions such as massage and skin-to-skin contact relieve neonatal pain. The Parental touch trial (Petal) aimed to assess whether parental stroking of their baby before a clinically required heel lance, at a speed of approximately 3 cm/s to optimally activate C-tactile nerve fibres, provides effective pain relief. Petal is a multicentre, randomised, parallel-group interventional superiority trial conducted in the John Radcliffe Hospital (Oxford University Hospitals NHS Foundation Trust, Oxford, UK) and the Royal Devon and Exeter Hospital (Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK). Neonates without neurological abnormalities who were born at 35 weeks gestational age or more and required a blood test via a heel lance in the first week of life were randomly assigned (1:1) to receive parental touch for 10 s either before (intervention group) or after (control group) the clinically required heel lance. Randomisation was managed at the Oxford site using a web-based minimisation algorithm with allocation concealment. The primary outcome measure was the magnitude of noxious-evoked brain activity in response to the heel lance measured with electroencephalography (EEG). Secondary outcome measures were Premature Infant Pain Profile-Revised (PIPP-R) score, development of tachycardia, and parental anxiety score. For all outcomes, the per-protocol effect was estimated via complier average causal effect analysis on the full analysis set. The trial is registered on ISRCTN (ISRCTN14135962) and ClinicalTrials.gov (NCT04901611). Between Sept 1, 2021, and Feb 7, 2023, 159 parents were approached to participate in the study, and 112 neonates were included. 56 neonates were randomly assigned to the intervention group of parental stroking before the heel lance and 56 to the control group of parental stroking after the heel lance. The mean of the magnitude of the heel lance-evoked brain activity was 0·85 arbitrary units (a.u.; SD 0·70; n=39; a scaled magnitude of 1 a.u. represents the expected mean response to a heel lance in term-aged neonates) in the intervention group and 0·91 a.u. (SD 0·76; n=43) in the control group. Therefore, the primary outcome did not differ significantly between groups, with a mean difference of -0·11 a.u. (lower in intervention group; SD 0·77; 95% CI -0·42 to 0·20; p=0·38; n=82). No significant difference was observed across secondary outcomes. The PIPP-R difference in means was 1·10 (higher in intervention group, 95% CI -0·42 to 2·61; p=0·15; n=100); the odds ratio of becoming tachycardic was 2·08 (95% CI 0·46 to 9·46; p=0·34, n=105) in the intervention group with reference to the control group; and the difference in parental State-Trait Anxiety Inventory-State score was -0·44 (higher in control group; SD 6·85; 95% CI -2·91 to 2·02; p=0·72; n=106). One serious adverse event (desaturation) occurred in a neonate randomly assigned to the control group, which was not considered to be related to the study. Parental stroking delivered at an optimal speed to activate C-tactile fibres for a duration of 10 s before the painful procedure did not significantly change neonates' magnitude of pain-related brain activity, PIPP-R score, or development of tachycardia. The trial highlighted the challenge of translating an experimental researcher-led tactile intervention into a parent-led approach, and the value of involving parents in their baby's pain management. Wellcome Trust and Bliss.

P39 Virtual reality headset as an alternative to Entonox for intraarticular corticosteroid injection

P39 Virtual reality headset as an alternative to Entonox for intraarticular corticosteroid injection

Segmental Chiropractic Spinal Manipulation Does not Reduce Pain Amplification and the Associated Pain-Related Brain Activity in a Capsaicin-Heat Pain Model.

Musculoskeletal injuries lead to sensitization of nociceptors and primary hyperalgesia (hypersensitivity to painful stimuli). This occurs with back injuries, which are associated with acute pain and increased pain sensitivity at the site of injury. In some cases, back pain persists and leads to central sensitization and chronic pain. Thus, reducing primary hyperalgesia to prevent central sensitization may limit the transition from acute to chronic back pain. It has been shown that spinal manipulation (SM) reduces experimental and clinical pain, but the effect of SM on primary hyperalgesia and hypersensitivity to painful stimuli remains unclear. The goal of the present study was to investigate the effect of SM on pain hypersensitivity using a capsaicin-heat pain model. Laser stimulation was used to evoke heat pain and the associated brain activity, which were measured to assess their modulation by SM. Eighty healthy participants were recruited and randomly assigned to one of the four experimental groups: inert cream and no intervention; capsaicin cream and no intervention; capsaicin cream and SM at T7; capsaicin cream and placebo. Inert or capsaicin cream (1%) was applied to the T9 area. SM or placebo were performed 25 min after cream application. A series of laser stimuli were delivered on the area of cream application (1) before cream application, (2) after cream application but before SM or placebo, and (3) after SM or placebo. Capsaicin cream induced a significant increase in laser pain (p < 0.001) and laser-evoked potential amplitude (p < 0.001). However, SM did not decrease the amplification of laser pain or laser-evoked potentials by capsaicin. These results indicate that segmental SM does not reduce pain hypersensitivity and the associated pain-related brain activity in a capsaicin-heat pain model.

Chiropractic Spinal Manipulation Prevents Secondary Hyperalgesia Induced by Topical Capsaicin in Healthy Individuals.

Background and Aims: Spinal manipulation (SM) is currently recommended for the management of back pain. Experimental studies indicate that the hypoalgesic mechanisms of SM may rely on inhibition of segmental processes related to temporal summation of pain and, possibly, on central sensitization, although this remains unclear. The aim of this study was to determine whether experimental back pain, secondary hyperalgesia, and pain-related brain activity induced by capsaicin are decreased by segmental SM.Methods: Seventy-three healthy volunteers were randomly allocated to one of four experimental groups: SM at T5 vertebral level (segmental), SM at T9 vertebral level (heterosegmental), placebo intervention at T5 vertebral level, or no intervention. Topical capsaicin was applied to the area of T5 vertebra for 40 min. After 20 min, the interventions were administered. Pressure pain thresholds (PPTs) were assessed outside the area of capsaicin application at 0 and 40 min to examine secondary hyperalgesia. Capsaicin pain intensity and unpleasantness were reported every 4 min. Frontal high-gamma oscillations were also measured with electroencephalography.Results: Pain ratings and brain activity were not significantly different between groups over time (p > 0.5). However, PPTs were significantly decreased in the placebo and control groups (p < 0.01), indicative of secondary hyperalgesia, while no hyperalgesia was observed for groups receiving SM (p = 1.0). This effect was independent of expectations and greater than placebo for segmental (p < 0.01) but not heterosegmental SM (p = 1.0).Conclusions: These results indicate that segmental SM can prevent secondary hyperalgesia, independently of expectations. This has implications for the management of back pain, particularly when central sensitization is involved.

DOES FEAR OF MOVEMENT ALTER BRAIN ACTIVITY? INVESTIGATING THE NEURAL MARKERS OF KINESIOPHOBIA IN PEDIATRIC PATIENTS WITH PATELLOFEMORAL PAIN

Background:Patellofemoral pain (PFP) is a chronic knee condition that inhibits movement quality and can cascade into kinesiophobia (i.e., fear of pain/movement). Despite its high prevalence in adolescent girls, PFP etiology has remained elusive, potentially due to an incomplete understanding of how pain, motor control, and kinesiophobia interact with central nervous system (CNS) functioning. Discovering linkages between motor control, kinesiophobia, and the CNS for patients with PFP could provide novel opportunities to refine neural therapeutic strategies for enhanced, personalized treatment approaches.Hypothesis/Purpose:To identify neural markers of kinesiophobia in pediatric patients with PFP.Methods:Adolescent girls clinically diagnosed with PFP (n = 14; 14.3 ± 3.2 yrs) were positioned supine in a magnetic resonance imaging (MRI) scanner. A modified Clarke’s test (patellofemoral grind test) was administered to the left knee of patients during brain functional MRI (fMRI) acquisition. The experimenter placed a hand at the superior patellar border applying intermittent distal pressure while the patient contracted her quadriceps. Patients also completed a quadriceps contraction test without application of external pressure (control). Kinesiophobia was measured using the Tampa Scale of Kinesiophobia. fMRI analyses compared brain activation between the two tasks, and correlation analyses were performed to assess relationships between task-induced brain activity and kinesiophobia. Statistical corrections were made to account for multiple, voxel-wise comparisons.Results:Evidenced in Table 1 and Figure 1A, neuroimaging analyses revealed distinct bidirectional activation during the Clarke’s test compared to the control (all p corrected < .05, all z max > 3.1). Table 1 and Figure 1B further highlight that greater kinesiophobia was associated with increased brain activity during the Clarke’s test in two clusters (both p corrected < .05, both z max > 3.1), but no relationships between kinesiophobia and brain activity during the control test were observed (all p corrected > .05, all z max < 3.1).Conclusion:The current results indicate that the Clarke’s test induced differential pain-related brain activity relative to the control (e.g., paracingulate gyrus). The patients’ degree of kinesiophobia was also related to brain activity in regions important for sensorimotor control, attention, and pain. Collectively, these data indicate that PFP may be due to alterations in nociceptive processing throughout the CNS, providing novel complementary pathways for targeted restoration of patellofemoral joint dysfunction. Future research should consider combined mechanistic pain profiling, sensorimotor, psychometric, and CNS assessments to identify patients most susceptible to kinesiophobia to refine treatment approaches that work towards a goal of disease prevention.Tables/Figures:Figure 1: A:.Greater activation during the modified Clarke’s test compared to the control test is colored red and less activation during the Clarke’s test compared to the control test colored blue. B: Green indicates regions for which higher kinesiophobia was positively associated with increased activity during the Clarke’s test. All image slices are shown in neurological convention and identified by the respective Z coordinate in Montreal neurological institute space. Cluster and anatomical details are provided in Table 1.

Peripheral arterial stiffness during electrocutaneous stimulation is positively correlated with pain-related brain activity and subjective pain intensity: an fMRI study

Brain activity associated with pain perception has been revealed by numerous PET and fMRI studies over the past few decades. These findings helped to establish the concept of the pain matrix, which is the distributed brain networks that demonstrate pain-specific cortical activities. We previously found that peripheral arterial stiffness {beta }_{text{art}} responds to pain intensity, which is estimated from electrocardiography, continuous sphygmomanometer, and photo-plethysmography. However, it remains unclear whether and to what extent {beta }_{text{art}} aligns with pain matrix brain activity. In this fMRI study, 22 participants received different intensities of pain stimuli. We identified brain regions in which the blood oxygen level-dependent signal covaried with {beta }_{text{art}} using parametric modulation analysis. Among the identified brain regions, the lateral and medial prefrontal cortex and ventral and dorsal anterior cingulate cortex were consistent with the pain matrix. We found moderate correlations between the average activities in these regions and {beta }_{text{art}} (r = 0.47, p < 0.001). {beta }_{text{art}} was also significantly correlated with self-reported pain intensity (r = 0.44, p < 0.001) and applied pain intensity (r = 0.43, p < 0.001). Our results indicate that {beta }_{text{art}} is positively correlated with pain-related brain activity and subjective pain intensity. This study may thus represent a basis for adopting peripheral arterial stiffness as an objective pain evaluation metric.

Electrophysiological investigation of the contribution of attention to altered pain inhibition processes in patients with irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with chronic abdominal pain and altered pain processing. The aim of this study was to examine whether attentional processes contribute to altered pain inhibition processes in patients with IBS. Nine female patients with IBS and nine age-/sex-matched controls were included in a pain inhibition paradigm using counter-stimulation and distraction with electroencephalography. Patients with IBS showed no inhibition of pain-related brain activity by heterotopic noxious counter-stimulation (HNCS) or selective attention. In the control group, HNCS and selective attention decreased the N100, P260 and high-gamma oscillation power. In addition, pain-related high-gamma power in sensorimotor, anterior cingulate and left dorsolateral prefrontal cortex was decreased by HNCS and selective attention in the control group, but not in patients with IBS. These results indicate that the central pain inhibition deficit in IBS reflects interactions between several brain processes related to pain and attention.

Could Brain Decoding Machines Change Our Minds?

In a recent experiment, Zhang and colleagues designed a closed-loop brain-machine interface that learned to reduce participants' pain by decoding pain-related brain activity. In doing so, they also highlighted some of the challenges associated with coadaptive processes in brain-machine communication.

The impact of parental contact upon cortical noxious-related activity in human neonates.

BackgroundNeonates display strong behavioural, physiological and cortical responses to tissue‐damaging procedures. Parental contact can successfully regulate general behavioural and physiological reactivity of the infant, but it is not known whether it can influence noxious‐related activity in the brain. Brain activity is highly dependent upon maternal presence in animal models, and therefore this could be an important contextual factor in human infant pain‐related brain activity.MethodsGlobal topographic analysis was used to identify the presence and inter‐group differences in noxious‐related activity in three separate parental contexts. EEG was recorded during a clinically required heel lance in three age and sex‐matched groups of neonates (a) while held by a parent in skin‐to‐skin (n = 9), (b) while held by a parent with clothing (n = 9) or (c) not held at all, but in individualized care (n = 9).ResultsThe lance elicited a sequence of 4–5 event‐related potentials (ERPs), including the noxious ERP (nERP), which was smallest for infants held skin‐to‐skin and largest for infants held with clothing (p=0.016). The nERP was then followed by additional and divergent long‐latency ERPs (> 750 ms post‐lance), not previously described, in each of the groups, suggesting the engagement of different higher level cortical processes depending on parental contact.ConclusionsThese results show the importance of considering contextual factors in determining infant brain activity and reveal the powerful influence of parental contact upon noxious‐related activity across the developing human brain.SignificanceThis observational study found that the way in which the neonatal brain processes a noxious stimulus is altered by the type of contact the infant has with their mother. Specifically, being held in skin‐to‐skin reduces the magnitude of noxious‐related cortical activity. This work has also shown that different neural mechanisms are engaged depending on the mother/infant context, suggesting maternal contact can change how a baby's brain processes a noxious stimulus.

Virtual Reality to Relieve Pain in Burn Patients Undergoing Imaging and Treatment.

Pain from burn injuries is among the most excruciating encountered in clinical practice. Pharmacological methods often fail to achieve acceptable level of analgesia in these patients, especially during burn wound dressing and debridement. Virtual reality (VR) distraction is a promising analgesic technique that progressed significantly in the last decade with development of commercially available, low-cost, high-resolution, wide field-of-view, standalone VR devices that can be used in many clinical scenarios. VR has demonstrated clinical benefit as an adjunctive analgesic during burn wound dressing and other painful medical procedures. The technique has proven useful also in preparing patients for magnetic resonance imaging scans, particularly in claustrophobic patients. Modulation of pain-related brain activity at cortical and subcortical levels by VR, and its correlation with subjective improvement in various laboratory and clinical pain experiences has been demonstrated using multiple functional brain imaging studies including functional magnetic resonance imaging and brain perfusion single photon emission computed tomography.

Aberrant Salience? Brain Hyperactivation in Response to Pain Onset and Offset in Fibromyalgia.

While much brain research on fibromyalgia (FM) focuses on the study of hyperresponsiveness to painful stimuli, some studies suggest that the increased pain-related brain activity often reported in FM studies may be partially explained by stronger responses to salient aspects of the stimulation rather than, or in addition to, the stimulation's painfulness. Therefore, this study was undertaken to test our hypothesis that FM patients would demonstrate elevated brain responses to both pain onset and offset-2 salient sensory events of opposing valences. Thirty-eight FM patients (mean ± SD age 46.1 ± 13.4 years; 33 women) and 15 healthy controls (mean ± SD age 45.5 ± 12.4; 10 women) received a moderately painful pressure stimulus to the leg during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Stimulus onset and offset transients were analyzed using a general linear model as stick functions. During pain onset, higher BOLD signal response was observed in FM patients compared to healthy controls in dorsolateral and ventrolateral prefrontal cortices (DLPFC and VLPFC, respectively), orbitofrontal cortex (OFC), frontal pole, and precentral gyrus (PrCG). During pain offset, higher and more widespread BOLD signal response was demonstrated in FM patients compared to controls in frontal regions significantly hyperactivated in response to onset. In FM patients, some of these responses were positively correlated with pain unpleasantness ratings (VLPFC, onset; r = 0.35, P = 0.03), pain catastrophizing scores (DLPFC, offset; r = 0.33, P = 0.04), or negatively correlated with stimulus intensity (OFC, offset; r = -0.35, P = 0.03) (PrCG, offset; r = -0.39, P = 0.02). Our results suggest that the increased sensitivity exhibited by FM patients in response to the onset and offset of painful stimuli may reflect a more generalized hypersensitivity to salient sensory events, and that brain hyperactivation may be a mechanism potentially involved in the generalized hypervigilance to salient stimuli in FM.

Strategy-dependent modulation of cortical pain circuits for the attenuation of pain

The effectiveness of cognitive strategies to attenuate pain has been reported in various behavioural studies, however the underlying neuronal mechanisms are only now beginning to be understood. Using a 7 T fMRI, we investigated three different pain attenuation strategies in 20 healthy subjects via: (a) non-imaginal distraction by counting backwards in steps of seven; (b) imaginal distraction by imagining a safe place; and (c) reinterpretation of the pain valence (reappraisal).Although we found considerable variability in the performances, all strategies exhibited a significant relief of pain compared to an unmodulated pain condition. Our finding argues against a subject's potential predisposition for a certain attenuation approach, as some of the subjects performed well on all attenuation tasks yet others performed low on all attenuation tasks. We further investigated the variability of performance within-subjects and explored the cortical regions that contribute to successful single attempts of pain attenuation at trial level. For each of the three tasks, we found a different pattern of brain activity that reflects the performance of pain attenuation. The more successful trials are related to reduced activity of different parts of the insular cortex.Behavioural data suggest that distraction is the preferable cognitive strategy to modulate pain perception. For three different cognitive strategies we revealed brain regions that are suggested to reliably modulate the perception of pain. The findings could be of utmost benefit for future attempts to integrate neuroscientific techniques into the treatment of pain. Further studies are necessary to investigate whether the present results are transferable to patients as an essential part of the multimodal therapy for chronic pain. These patients may also benefit from additional neurofeedback techniques by combining the strategies with the cortical feedback in order to modulate pain-related brain activity.

Evidence for decreased Neurologic Pain Signature activation following thoracic spinal manipulation in healthy volunteers and participants with neck pain.

Spinal manipulation (SM) is a common treatment for neck and back pain, theorized to mechanically affect the spine leading to therapeutic mechanical changes. The link between specific mechanical effects and clinical improvement is not well supported. SM's therapeutic action may instead be partially mediated within the central nervous system. To introduce brain-based models of pain for spinal pain and manual therapy research, characterize the distributed central mechanisms of SM, and advance the preliminary validation of brain-based models as potential clinical biomarkers of pain. Secondary analysis of two functional magnetic resonance imaging studies investigating the effect of thoracic SM on pain-related brain activity: A non-controlled, non-blinded study in healthy volunteers (Study 1, n = 10, 5 females, and mean age = 31.2 ± 10.0 years) and a randomized controlled study in participants with acute to subacute neck pain (Study 2, n = 24, 16 females, mean age = 38.0 ± 15.1 years). Functional magnetic resonance imaging was performed during noxious mechanical stimulation of the right index finger cuticle pre- and post-intervention. The effect of SM on pain-related activity was studied within brain regions defined by the Neurologic Pain Signature (NPS) that are predictive of physical pain. In Study 1, evoked mechanical pain (p < 0.001) and NPS activation (p = 0.010) decreased following SM, and the changes in evoked pain and NPS activation were correlated (rRM2 = 0.418, p = 0.016). Activation within the NPS subregions of the dorsal anterior cingulate cortex (dACC, p = 0.012) and right secondary somatosensory cortex/operculum (rS2_Op, p = 0.045) also decreased following SM, and evoked pain was correlated with dACC activity (rRM2 = 0.477, p = 0.019). In Study 2, neck pain (p = 0.046) and NPS (p = 0.033) activation decreased following verum but not sham SM. Associations between evoked pain, neck pain, and NPS activation, were not significant and less clear, possibly due to inadequate power, methodological limitations, or other confounding factors. The findings provide preliminary evidence that SM may alter the processing of pain-related brain activity within specific pain-related brain regions and support the use of brain-based models as clinical biomarkers of pain.

The influence of the descending pain modulatory system on infant pain-related brain activity.

The descending pain modulatory system (DPMS) constitutes a network of widely distributed brain regions whose integrated function is essential for effective modulation of sensory input to the central nervous system and behavioural responses to pain. Animal studies demonstrate that young rodents have an immature DPMS, but comparable studies have not been conducted in human infants. In Goksan et al. (2015) we used functional MRI (fMRI) to show that pain-related brain activity in newborn infants is similar to that observed in adults. Here, we investigated whether the functional network connectivity strength across the infant DPMS influences the magnitude of this brain activity. FMRI scans were collected while mild mechanical noxious stimulation was applied to the infant's foot. Greater pre-stimulus functional network connectivity across the DPMS was significantly associated with lower noxious-evoked brain activity (p = 0.0004, r = -0.86, n = 13), suggesting that in newborn infants the DPMS may regulate the magnitude of noxious-evoked brain activity.

Functional Connectivity Alterations: Novel Therapy and Future Implications in Chronic Pain Management

Background: Chronic pain is a major public health problem resulting in physical and emotional pain for individuals and families, loss of productivity, and an annual cost of billions of dollars. The lack of objective measures available to aid in diagnosis and evaluation of therapies for chronic pain continues to be a challenge for the clinician. Objectives: Functional magnetic resonance imaging (fMRI) is an imaging technique that can establish regional areas of interest and examine synchronous neuronal activity in functionally related but anatomically distinct regions of the brain, known as functional connectivity. Study Design: The present investigation examines changes in functional connectivity in 4 common pain syndromes: chronic back pain (CBP), fibromyalgia, diabetic neuropathy, and complex regional pain syndrome (CRPS). Setting: This is a review of the current understanding of functional connectivity. Methods: Utilizing functional imaging, patients with these conditions have been shown to have significant structural and functional differences when compared to healthy controls. Results: Functional connectivity, therefore, has the potential to assist in diagnostic classification of different pain conditions, predict individual responses to specific therapeutic interventions, and serve as a gateway for personalized medicine. Indirect activation of brain activity can be seen by the blood flow to the brain at specific sites, with chronic pain patients having increased brain activity. Limitations: The present investigation is limited in that few studies have examined this relatively new modality. Conclusions: Knowing and observing the brain’s activity as related to pain gives pain patients an opportunity to decrease pain-related brain activity and decrease severe chronic pain. This modality can be used along with interventional pain management techniques in order to provide optimum pain relief. Key words: Functional connectivity, fMRI, chronic pain, chronic back pain, fibromyalgia, diabetic neuropathy, chronic regional pain syndrome

Determining Brain Mechanisms that Underpin Analgesia Induced by the Use of Pain Coping Skills.

Cognitive behavioral therapies decrease pain and improve mood and function in people with osteoarthritis. This study assessed the effects of coping strategies on the central processing of knee pain in people with osteoarthritis of the knees. Mechanical pressure was applied to exacerbate knee pain in 28 people with osteoarthritis of the knee. Reports of pain intensity and functional magnetic resonance imaging measures of pain-related brain activity were recorded with and without the concurrent use of pain coping skills. Coping skills led to a significant reduction in pain report (Coping = 2.64 ± 0.17, Not Coping = 3.28 ± 0.15, P < 0.001). These strategies were associated with increased activation in pain modulatory regions of the brain (medial prefrontal and rostral anterior cingulate cortices, Pcorrected < 0.05) and decreased pain-related activation in regions that process noxious input (midcingulate cortex, supplementary motor area, secondary somatosensory cortex, and anterior parietal lobule, Pcorrected < 0.05). The magnitude of the decrease in pain report during the use of pain coping strategies was found to be proportional to the decrease in pain-related activation in brain regions that code the aversive/emotional dimension of pain (anterior insula, inferior frontal gyrus, orbitofrontal cortex, Pcorrected < 0.05) but did not differ between groups with and without training in coping skills. However, training in coping skills reduced the extent to which brain responses to noxious input were influenced by anxiety. The results of this study support previous reports of pain modulation by cognitive pain coping strategies and contribute to the current understanding of how analgesia associated with the use of pain coping strategies is represented in the brain.

Inhibition of Pain and Pain-Related Brain Activity by Heterotopic Noxious Counter-Stimulation and Selective Attention in Chronic Non-Specific Low Back Pain

The aim of the present study was to assess inhibition of pain and somatosensory-evoked potentials (SEPs) by heterotopic noxious counter-stimulation (HNCS) and by selective attention in patients with chronic non-specific LBP. Seventeen patients and age/sex-matched controls were recruited (10 men, 7 women; mean age ± SD: 43.3 ± 10.4 and 42.7 ± 11.1, respectively). On average, patients with LBP reported pain duration of 7.6 ± 6.5 years, light to moderate disability (19.3 ± 5.7/100) and low clinical pain intensity (21.8 ± 1.5/100), while pain catastrophizing, state and trait anxiety and depressive symptoms were not significantly different between groups (all p’s >0.05). HNCS and selective attention had differential inhibitory effects on pain and SEP, but no difference was observed between groups. Across both groups, HNCS decreased pain (p = 0.06) as well as the N100 and the N150 components of SEP (p’s <0.001), while selective attention only decreased pain (p < 0.01) and the N100 (p<0.001). In contrast, the P260 was decreased by HNCS only when attention was directed toward the HNCS stimulus (p<0.01). This indicates that patients with the characteristics described above do not show altered pain inhibitory mechanisms involved in HNCS and selective attention. Importantly, this experiment was carefully designed to control for non-specific effects associated with the repetition of the test stimulus and the effect of an innocuous counter-stimulation. It remains to be determined if these results hold for patients with severe LBP and psychological symptoms or whether symptom severity may be associated with pain inhibition deficits.

Common functional pain syndromes

### Key points When a patient presents with pain of no obvious organic origin, they are often labelled as having ‘functional’ pain. The exact diagnosis is derived from the organ system displaying the predominant symptoms e.g. musculoskeletal pain in fibromyalgia (FM) or visceral pain in irritable bowel syndrome (IBS). The worldwide prevalence of all functional pain syndromes (FPS) is 15–20%. World Health Organization (WHO) surveys reveal that ∼10% of primary care patients develop a chronic pain condition within 12 months of initial registration. Of these, at least 50% continue to have symptoms beyond 1 yr. FPS cause enormous economic burden on society with concurrent ramifications for the individual's family in particular and society in general. FM alone has been estimated to cost around £4000 per patient per year. There has been a paradigm shift in the understanding of FPS. The old model of multiple discrete chronic pain conditions is being replaced by a more overarching, although no less complex, state of central sensitivity syndrome (CSS). Evidence is being accrued that FPS represent the phenotypic output of a complex interplay between genetic susceptibility, gene–environment interactions, and environmental triggers. Four common FPS will be reviewed in this article: FM, IBS, temporomandibular dysfunction (TMD), and chronic cardiac chest pain (CCCP). The pathophysiology and management of each will be examined and the case presented for a shared underlying mechanism called CSS. Once this new mechanism is adopted more widely, it will allow for future novel management options to be …

Increased Pain Communication following Multiple Group Memberships Salience Leads to a Relative Reduction in Pain-Related Brain Activity.

Pain is a fundamental human experience that triggers a range of social and psychological responses. In this study, we present behavioral and fMRI data to examine the effect of multiple group memberships salience on reported and neural indices of pain. We found that participants expressed higher levels of pain when more social group memberships were salient. This is consistent with the notion that pain itself motivates people to communicate their pain, and more so when multiple psychological resources are salient. In addition, fMRI results reveal an interesting twist: when participants increased their pain reporting as group memberships increased (from one group to four), there was a corresponding relative reduction in dorsal anterior cingulate cortex and anterior insula activation. These results provide evidence for an adaptive response to pain: the more people make use of the social resources at their disposal when experiencing pain, the less pain areas are activated.