Trait perceived injustice is associated with pain intensity and pain behaviour in participants undergoing an experimental pain induction procedure

Over the past decade, numerous investigations have examined the role of justice-related appraisals as determinants of health and mental health outcomes of individuals with chronic pain conditions 40, 41. In the context of pain and pain-related disability, perceived injustice has been conceptualized as an appraisal process characterized by a tendency to construe injury or illness as a violation of justice principles, to view one's losses as severe and irreparable, and to attribute blame to others for one's suffering 39.

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Pan-Canadian estimates of chronic pain prevalence from 2000 to 2014: A Repeated Cross-Sectional Survey Analysis

The prevalence of chronic pain in Canada increased between 1996 and 2006, from 15.3% to 19.5%.20 This increase parallels changes reported in other western countries, including the United States,9,13 and is of major concern because chronic pain is associated with substantial costs to the individual and society (i.e., decreased quality of life, lost productivity, and increased health care expenses).16,14 However, since 2008, there has been a paucity of information on the prevalence of chronic pain in Canada.

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Alleviation of mechanical allodynia by 14,15-EET in a central post-stroke pain model: possible role of allopregnanolone and δGABAAR

Central post-stroke pain (CPSP) is a neuropathic pain syndrome arising after lesion of the central nervous system (CNS) due to cerebrovascular insult. This syndrome is characterised by somatosensory abnormalities including spontaneous pain, hyperalgesia and allodynia, which localized to body areas corresponding to the injured brain region.2 These conditions are constant and could impair activities of daily living, consequently undermine quality of life and rehabilitation process. However, CPSP is probably the least recognized complication of stroke and the mechanism of which has not been adequately studied to date.

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Trait mindfulness is associated with lower pain reactivity and connectivity of the default mode network

Mindfulness training reduces pain in clinical and laboratory settings.10,24,34,41,53,60 Similarly, long term meditative practice mitigates sensory17–19 and emotional8,16,37 components of pain. Several studies have shown that mindfulness attenuates pain by enhancing attentional focus on the present moment and regulating associated emotional responses.4,31,43 A growing body of work documents neural activations associated with the effects of mindfulness training on pain. Decreases in pain following mindfulness-based training are frequently associated with greater activation in brain areas associated with sensory and/or salience processing,16,32,61 alongside decreases in the prefrontal cortical regions linked to evaluative and/or emotional responses.

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Preoperative Psychosocial and Psychophysical Phenotypes as Predictors of Acute Pain Outcomes after Breast Surgery

The effective and safe management of postsurgical pain is an important clinical goal, as an estimated 240 million surgeries are performed each year worldwide.60 Despite increased recognition of acute41 and chronic34 postsurgical pain, and much excellent study of the mechanistic underpinnings of postsurgical pain,7 acute postsurgical pain remains a problem21 for a significant minority of patients. In a recent large study in a variety of surgical types, 28% of patients (of 22,000 patients studied) still experienced moderate-severe acute pain after surgery,24 and a sizable number of patients remain on long-term opioids months after orthopedic surgery.

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The Influence of Chronic Neck Pain on Explicit Sequence Learning

Publication date: December 2018

Source: Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 12

Author(s): Michael Brown, Zhengxiong Li, Baicheng Chen, Wenyao Xu, Jeanne Langan

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[Clinical Picture] Kidneys are key in secondary hypertension: a case of fibromuscular dysplasia

A 29-year-old woman was referred to our renal clinic because of pain in her right flank and severe hypertension; her blood pressure was more than 180/110 mm Hg. She was diagnosed as having treatment-resistant-hypertension because her blood pressure remained high at 157/105 mm Hg despite being treated with three antihypertensive drugs, including a diuretic, at maximum doses. 24-h ambulatory monitoring showed increased daytime and nocturnal (non-dipper pattern) blood pressures. She had no history of previous medical difficulties.

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A tired young man with a dysmorphic thumb

A 23 year old man with short stature, congenital malformation of the left thumb and both ears, and a single kidney presented with back pain, shortness of breath, fatigue, and easy bruising that had...

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Monoclonal Antibody Targeting the Matrix Metalloproteinase 9 Prevents and Reverses Paclitaxel-Induced Peripheral Neuropathy in Mice

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect associated with anticancer drugs.45 Nearly 70% of cancer patients experience neuropathic pain symptoms due to the administration of anticancer drugs such as platinum compounds, proteasomes inhibitors, and antitubulins (e.g., vinca alkaloids and taxanes).11,59 Paclitaxel is the frontline chemotherapeutic agent used to treat many solid tumors, but it is also associated with a high incidence of CIPN leading to dose reduction or termination of an otherwise potential life-saving treatment.

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Incident chronic spinal pain and depressive disorders: Data from the National Comorbidity Survey

Chronic spinal pain and depression are common conditions associated with a good deal of morbidity and healthcare utilization. In the US, low back pain, neck pain, and major depressive disorder comprise three of the top four leading causes of years lived with disability.51 The point-prevalence or past-year prevalence of chronic neck and back pain has been estimated at 8.1%-19% in large population-based studies.15,19,25,49,52 The lifetime prevalence of major depressive disorder (MDD) was 17.1% and 16.2% and dysthymic disorder (DD) was 6.4% and 6.9% in the original National Comorbidity Survey (NCS) and its replication (NCS-R), respectively.

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Activation of KCNQ channels prevents paclitaxel-induced peripheral neuropathy and associated neuropathic pain

Paclitaxel is a commonly used chemotherapeutic agent for the treatment of breast and other cancers12. Unfortunately, its use is often associated with significant neurotoxicity, especially resulting in sensory peripheral neuropathies that are often accompanied by neuropathic pain and are frequently severe and resistant to intervention. Paclitaxel-induced peripheral neuropathy (PIPN) results from damage to, or dysfunction of, peripheral nerves, including sensory, autonomic, and motor neurons. The incidence and severity of PIPN is duration- and dose-related, such that more than 60% of patients receiving paclitaxel-based chemotherapy experience peripheral neuropathy in first 3 months58.

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Long-Term Results of Surgery Compared With Nonoperative Treatment for Lumbar Degenerative Spondylolisthesis in the Spine Patient Outcomes Research Trial (SPORT)

Study Design. Randomized trial with a concurrent observational cohort study. Objective. To compare 8-year outcomes between surgery and nonoperative care and among different fusion techniques for symptomatic lumbar degenerative spondylolisthesis (DS). Summary of Background Data. Surgical treatment of DS has been shown to be more effective than nonoperative treatment out to 4 years. This study sought to further determine the long-term (8-year) outcomes. Methods. Surgical candidates with DS from 13 centers with at least 12 weeks of symptoms and confirmatory imaging were offered enrollment in a randomized controlled trial (RCT) or observational cohort study (OBS). Treatment consisted of standard decompressive laminectomy (with or without fusion) versus standard nonoperative care. Primary outcome measures were the Short Form-36 (SF-36) bodily pain and physical function scores and the modified Oswestry Disability Index at 6 weeks, 3 months, 6 months, and yearly up to 8 years. Results. Data were obtained for 69% of the randomized cohort and 57% of the observational cohort at the 8-year follow up. Intent-to-treat analyses of the randomized group were limited by high levels of nonadherence to the randomized treatment. As-treated analyses in the randomized and observational groups showed significantly greater improvement in the surgery group on all primary outcome measures at all time points through 8 years. Outcomes were similar among patients treated with uninstrumented posterolateral fusion, instrumented posterolateral fusion, and 360° fusion. Conclusion. For patients with symptomatic DS, patients who received surgery had significantly greater improvements in pain and function compared with nonoperative treatment through 8 years of follow-up. Fusion technique did not affect outcomes. Level of Evidence: 1

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Activity of Daily Living After Long Level Fusion in Adult Spinal Deformity: Compared With Over 60-Year-Old Degenerative Spine Patients Without Adult Spinal Deformity

Study Design. Prospective single center study. Objective. The aim of this study was to evaluate 1) the activity of daily living (ADL) of three categorized patients group; over 60-year-old degenerative spine patients without adult spinal deformity (ASD), nonoperative ASD patients, and operative ASD patients, 2) what kinds of activities would be impaired, and 3) how the ADL changes over time after long level fusion. Summary of Background Data. There is still debate how surgeons could decide treatment methods for old-aged adult spinal deformity, operatively or not. There was lack of information how long level fusion impacts daily activities, especially sedentary Asian lifestyle. In Asia, impaired ADL is much more important issue because of different lifestyle. Methods. Patients were categorized into three groups; Group 1 was over 60-year old aged degenerative spine disease without deformity, Group 2 was ASD patients who did not have surgery, and Group 3 was ASD patients who had surgery for deformity correction. Patients were evaluated using answer Oswestry Low Back Pain Disability Questionnaire, and Assessment activities of daily living for sedentary Asian culture (ADL-SA) questionnaire. Results. Group 1 showed nearly full functions in every activity (ADL-SA: 41.4). ADL-SA scores of Group 2 were similar to Group 1 (P = 0.452). However, get up from bottom (P < 0.001), and pick up object (P < 0.001) were impaired. After long level fusion, ADL was impaired but gradually improved by time. From postoperative 1 year, total ADL score recovered to acceptable range. However, among ADL, activities associated sedentary lifestyle (get up from bottom, wipe floor, pick up object, and sit cross-legged) were still impaired after 2 years postoperatively. Conclusion. ADL was impaired after long level fusion; however it would improve as time goes by. However, among ADL, activities associated sedentary lifestyle was still impaired. Hence give enough information to patients about limited activities before deciding operation. Level of Evidence: 3

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Predicting Factors at Skeletal Maturity for Curve Progression and Low Back Pain in Adult Patients Treated Nonoperatively for Adolescent Idiopathic Scoliosis With Thoracolumbar/Lumbar Curves: A Mean 25-year Follow-up

Study Design. A retrospective, long-term follow-up study. Objective. We aimed to clarify the predicting factors at skeletal maturity for future curve progression and low back pain (LBP) in adolescent idiopathic scoliosis (AIS) with thoracolumbar/lumbar (TL/L) curve. Summary of Background Data. TL/L curves are likely to progress after skeletal maturity and cause LBP. Methods. Of 147 patients treated nonoperatively for AIS with TL/L curve, 56 (55 females; average age at the time of survey, 39.5 ± 7.1 years; average follow-up duration after maturity, 24.9 ± 6.9 years) completed questionnaires, including the visual analogue scale (VAS) for LBP and Oswestry disability index (ODI). Forty-nine patients underwent a radiological examination, and 48 underwent lumbar magnetic resonance imaging (MRI). Results. The mean Cobb angle of the TL/L curve increased from 37.3° ± 7.5° to 47.8° ± 12.6° (0.41° ± 0.39° per year). The factors at skeletal maturity that were associated with the annual progression of the TL/L curve included a cranially located apical vertebra, and great apical vertebral translation and L3 tilt. In addition, the VAS for LBP was positively correlated with L4 tilt, and the ODI was positively correlated with L4 tilt and apical vertebral rotation. Multivariate analyses and receiver-operating characteristic curves demonstrated that L3 tilt at skeletal maturity independently predicted a curve progression ≥0.5° per year (odds ratio [OR], 1.17), while L4 tilt at skeletal maturity independently predicted a VAS ≥3 cm (OR, 1.20) and ODI ≥21% (OR, 1.25) in adulthood, with a cutoff value of approximately 16° for each factor. Moreover, lumbar disc degeneration on MRI was associated with L4 tilt at skeletal maturity and LBP in adulthood. Conclusion. Great L3 and L4 tilt at skeletal maturity, especially those >16°, are predictors of future curve progression and LBP in adulthood, respectively. For adolescent patients with these risk factors, periodic follow-ups into adulthood should be considered. Level of Evidence: 4

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The Relationship Between Fear-Avoidance and Neuromuscular Measures of Function in Patients With Adult Degenerative Scoliosis

Study Design. A prospective cohort study. Objective. To examine the relationship of fear-avoidance beliefs and neuromuscular activity during gait in adult degenerative scoliosis (ADS) patients. Summary of Background Data. Among patients with chronic spine pain, fear-avoidance beliefs are predictive of poor surgical outcomes. Fear-avoi occurs when patients perceive that movement will worsen underlying physical problems. This process leads them to restrict activity, which further heightens emotional distress. Patients with ADS have previously been shown to have an altered gait pattern. Electromyography is evolving into a useful tool to further our understanding of the pathologic manifestations of ADS during gait. Methods. Fifty ADS patients completed the Tampa Scale for Kinesiophobia (TSK) questionnaire and the Fear Avoidance Beliefs Questionnaire (FABQ). Surface electromyography electrodes were bilaterally placed on trunk and lower extremity muscles. Each patient performed a series of over-ground gait trials at a self-selected comfortable speed. Pearson Product Correlation analysis was used to determine the relationship between the self-reported fear of movement measures and the neuromuscular gait analysis biomechanical data. Results. The TSK total score and the FABQ physical were correlated with muscle onset of the External Oblique (P = 0.005), Gluteus Maximus (P = 0.018), Multifidi (P = 0.017), Erector Spinae (P = 0.014), Rectus Femoris (i = 0.008), Semitendinosus (P = 0.012), Tibilais Anterior (P = 0.012), and Medial Gastrocnemius (P = 0.010). Furthermore, the TSK total score, FABQ physical portion were correlated with muscle peak activity of Medial Gastrocnemius (P = 0.007), Multifidi (P = 0.014), and Tibilais Anterior (i = 0.050) and time to peak muscle activity of the Medial Gastrocnemius (P = 0.006) and Semitendinosus P = 0.038. Conclusion. This study demonstrates a strong correlation between neuromuscular gait parameters and fear-avoidance of movement which may reflect ADS patient experiences during ambulation. Further, it demonstrates that there are different aspects of fear-avoidance that may influence gait parameters. This study extends previous research on the role of fear-avoidance to include patients with spinal deformity. Level of Evidence: 3

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Course and Contributors to Back Pain in Middle-aged Women Over 9 Years: Data From the Australian Longitudinal Study on Women's Health

Study Design. Community-based, cohort study. Objective. Our aim was to determine the course of back pain in middle-aged women over a 9-year period, and assess whether obesity and physical inactivity are associated with more frequent back pain. Summary of Background Data. Back pain is the leading cause of disability worldwide. With minimal effective therapies and rising financial burden, identifying modifiable risk factors remains a key priority. Methods. The Australian Longitudinal Study on Women's Health is a cohort study of community-based, middle-aged women who completed questionnaires every 3 years between 2004 and 2013. Approximately, 10,530 women completed the survey in 2004 (mean age 55.5 yrs), and 9020 completed follow-up 9 years later. Self-reported data on back pain in the last 12 months and other sociodemographic factors were collected at all four surveys. ‘Frequent back pain’ was defined as back pain reported at ≥ three surveys. Results. Back pain was common and persistent, with 48% having back pain in ≥ three out of four surveys. Baseline obesity (relative risk [RR] 1.18, 95% confidence interval [CI] 1.12–1.25), lack of vigorous physical activity (RR 1.17, 95% CI 1.10–1.25), depressive symptoms (RR 1.40, 95% CI 1.33–1.47), and low-education status (RR 1.17, 95% CI 1.12–1.24), were independently associated with an increased risk of frequent back pain (all P < 0.001). Overall, 28% of the risk of frequent back pain could be attributed to these factors, equating to one extra case of frequent back pain for every five women with depressive symptoms, for every 11 obese women, for every 12 women with low-education status, and for every 13 women who do not do vigorous physical activity, at baseline. Conclusion. Obesity, depressive symptoms, low-education status, and lack of vigorous physical activity are associated with higher risk of frequent back pain over the following 9 years among women in their mid-50 s. Targeting these risk factors may lessen the burden of back pain. Level of Evidence: 2

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Influence of Abuse History on Concurrent Benzodiazepine and Opioid Use in Chronic Pain Patients

In 2016, more than 42,200 deaths in the United States involved opioids.41 The rate of opioid-related deaths has risen steadily and drastically since 1999. Although public policy has focused on curbing these high rates, the epidemic remains a public health crisis. An important predictor of opioid overdose is the co-use of benzodiazepines.12,22,36 Benzodiazepines are frequently prescribed among patients with chronic pain due to their broad clinical applications, including treatment of anxiety, sleep disorders, and seizures.

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AAPT Diagnostic Criteria for Fibromyalgia

Over many decades, there have been efforts to develop diagnostic criteria for the condition we now recognize as fibromyalgia (FM). The multiple symptoms and comorbidities associated with FM make it difficult to diagnose, and FM is still under-diagnosed and under-treated.7,34,79 The diagnosis of FM might take more than 2 years, with patients seeing an average of 3.7 different physicians during this time.34 Many health care providers, particularly in primary care, report unclear diagnostic criteria, a lack of confidence in using existing criteria for diagnosis, insufficient training or skill in diagnosing FM, and a lack of knowledge of treatment options.

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Experimental Pain Decreases Corticomuscular Coherence in a Force- But Not a Position-Control Task

Neural drive to muscles is altered in pain, but this depends on task type. Acute experimental pain reduces the discharge rate of many active motor units during gentle isometric contractions,12,51,54 but this is less pronounced in position- than force-control tasks.44 Even when tasks are identical in mechanical requirements and muscle torques, neuromotor control during position- and force-control tasks differs. Task-specific differences at the spinal cord and descending inputs are thought to explain this difference.

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Pfizer could owe NHS {pound}500m for extending pregabalin patent for pain

The UK Supreme Court has thrown out an appeal by the drug company Pfizer over its blockbuster drug pregabalin (Lyrica).The court’s ruling that Pfizer’s subsidiary Warner-Lambert was not entitled to a...

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An unusual cause of right iliac fossa pain

A 34 year old woman presented to the emergency department with a history of worsening right iliac fossa pain over several days. She described the pain as alternating dull and sharp, and had found...

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Holding out for an apology

My emotional recovery from surgical complications was unbelievably difficult. The anger became haunting, and the physical pain made it impossible to forget the trauma. It was only when I was able to...

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The Neuroscience of Pain: Biobehavioral, Developmental, and Psychosocial Mechanisms Relevant to Intervention Targets

Chronic pain is a major problem in clinical medicine and public health, affecting approximately one in five adults, and is associated with significant societal and familial burden. Early-life adversities, psychological, and biobehavioral factors are associated with an elevated risk of the subsequent development of chronic pain. In this special issue of Psychosomatic Medicine, articles address the neuroscientific, psychological, and biobehavioral processes involved in acute and chronic pain. We focus on the following themes that emerged in this special issue: (a) risk factors and early adversity as related to chronic pain; (b) the role of expectations in shaping pain perception; and (c) mechanisms of interventions targeting pain modulation. This article concludes by outlining important new targets for research, including the neurobiology of pain, important methodological challenges, and targets for personalized pain interventions.

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Unique Autonomic Responses to Pain in Yoga Practitioners

Objective Autonomic nervous system activity is associated with neurobehavioral aspects of pain. Yogis use breathing, relaxation, and mindfulness to tolerate pain, which could influence autonomic responses. To evaluate how the link between autonomic responses and pain is altered by other factors, we compared perceptual and autonomic responses to pain between yogis and controls. Methods Nineteen yogis and 15 controls rated warm and painfully hot stimuli (1-cm2 thermode on calf), with visual anticipatory cues indicating certainly painful, certainly nonpainful, or uncertainly either painful or nonpainful. Heart rate, skin conductance, respiration, and blood pressure were measured. Results At baseline, yogis breathed slower and deeper than did controls, with no differences in other autonomic measures. During the task, perceptual ratings did not differ between groups in either the certain or uncertain conditions. Nevertheless, yogis had higher phasic skin conductance responses in anticipation of and response to all stimuli, but particularly during painful heat in uncertain contexts (uncertain: 0.46 [0.34] μS; certain: 0.37 [0.28] μS; t(18) = 3.962, p = .001). Furthermore, controls showed a decrease in heart rate to warm (−2.51 [2.17] beats/min) versus painful stimuli (0.83 [1.63] beats/min; t(13) = 5.212, p < .001) and lower respiratory sinus arrhythmia during pain compared with warm trials, whereas yogis had similar reactions to painful and nonpainful stimuli. Conclusions Autonomic responses to pain differed in yogis and healthy volunteers, despite similar pain ratings. Thus, autonomic reactivity to pain may be altered by environmental and psychological factors throughout an individual's life.

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Reduced Fear-Conditioned Pain Modulation in Experienced Meditators: A Preliminary Study

Objective Mindfulness-based practice is a form of cognitive/affective training that may help reduce suffering by attenuating maladaptive anticipatory processes. This study's objective was to examine the pain modulating impact of classical fear learning in meditation practitioners. Methods The hyperalgesic effects of pain expectation and uncertainty were assessed outside formal meditation in 11 experienced meditators (>1000 hours) compared with meditation-naive controls during a Pavlovian classical fear-conditioning paradigm involving two visual stimuli (CS+/CS−), one of which (CS+) co-terminated with a noxious electrical stimulus (unconditioned stimulus) on 50% of trials. A Rescorla-Wagner/Pearce-Hall hybrid model was fitted onto the conditioned skin conductance responses using computational modeling to estimate two learning parameters: expected shock probability and associability (i.e., uncertainty). Results Using a scale ranging between 0 (no pain) and 100 (extremely painful), meditators reported less pain (M = 19.9, SE = 5.1 for meditators, M = 32.4, SE = 2.4 for controls) but had comparable spinal motor responses (nociceptive flexion reflex) to the unconditioned stimulus. Multilevel mediation analyses revealed that meditators also exhibited reduced hyperalgesic effects of fear learning on higher-order pain responses but comparable effects on the nociceptive flexion reflex. These results suggest that mindfulness affects higher-order perceptual processes to a greater extent than from descending inhibitory controls. Furthermore, meditators showed reduced hyperalgesic effects of fear conditioning with no significant group difference in conditioned learning as evidenced by discriminative anticipatory skin conductance responses and learning parameters derived from computational modeling. Conclusions These results highlight potential mechanisms underlying mindfulness-related hypoalgesia, relevant to clinical conditions in which repeated pain exposure might reinforce hyperalgesic processes through fear conditioning.

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Enhancement of Meditation Analgesia by Opioid Antagonist in Experienced Meditators

Objective Studies have consistently shown that long-term meditation practice is associated with reduced pain, but the neural mechanisms by which long-term meditation practice reduces pain remain unclear. This study tested endogenous opioid involvement in meditation analgesia associated with long-term meditation practice. Methods Electrical pain was induced with randomized, double-blind, cross-over administration of the opioid antagonist naloxone (0.15-mg/kg bolus dose, then 0.2-mg/kg per hour infusion dose) with 32 healthy, experienced meditation practitioners and a standardized open monitoring meditation. Results Under saline, pain ratings were significantly lower during meditation (pain intensity: 6.41 ± 1.32; pain unpleasantness: 3.98 ± 2.17) than at baseline (pain intensity: 6.86 ±1.04, t(31) = 2.476, p = .019, Cohen's d = 0.46; pain unpleasantness: 4.96 ±1.75, t(31) = 3.746, p = .001, Cohen's d = 0.68), confirming the presence of meditation analgesia. Comparing saline and naloxone revealed significantly lower pain intensity (t(31) = 3.12, p = .004, d = 0.56), and pain unpleasantness (t(31) = 3.47, p = .002, d = 0.62), during meditation under naloxone (pain intensity: 5.53 ± 1.54; pain unpleasantness: 2.95 ± 1.88) than under saline (pain intensity: 6.41 ± 1.32; pain unpleasantness: 3.98 ± 2.17). Naloxone not only failed to eliminate meditation analgesia but also made meditation analgesia stronger. Conclusions Long-term meditation practice does not rely on endogenous opioids to reduce pain. Naloxone's blockade of opioid receptors enhanced meditation analgesia; pain ratings during meditation were significantly lower under naloxone than under saline. Possible biological mechanisms by which naloxone-induced opioid receptor blockade enhances meditation analgesia are discussed.

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Transforming Pain With Prosocial Meaning: A Functional Magnetic Resonance Imaging Study

Objective Contextual factors can transform how we experience pain, particularly if pain is associated with other positive outcomes. Here, we test a novel meaning-based intervention. Participants were given the opportunity to choose to receive pain on behalf of their romantic partners, situating pain experience in a positive, prosocial meaning context. We predicted that the ventromedial prefrontal cortex (vmPFC), a key structure for pain regulation and generation of affective meaning, would mediate the transformation of pain experience by this prosocial interpersonal context. Methods We studied fMRI activity and behavioral responses in 29 heterosexual female participants during (1) a baseline pain challenge and (2) a task in which participants decided to accept a self-selected number of additional pain trials to reduce pain in their male romantic partners (“accept-partner-pain” condition). Results Enduring extra pain for the benefit of the romantic partner reduced pain-related unpleasantness (t = −2.54, p = .016) but not intensity, and increased positive thoughts (t = 3.60, p = .001) and pleasant feelings (t = 5.39, p < .0005). Greater willingness to accept the pain of one's partner predicted greater unpleasantness reductions (t = 3.94, p = .001) and increases in positive thoughts (r = .457, p = .013). The vmPFC showed significant increases (q < .05 FDR-corrected) in activation during accept-partner-pain, especially for women with greater willingness to relieve their partner's pain (t = 2.63, p = .014). Reductions in brain regions processing pain and aversive emotion significantly mediated reductions in pain unpleasantness (q < .05 FDR-corrected). Conclusions The vmPFC has a key role in transforming the meaning of pain, which is associated with a cascade of positive psychological and brain effects, including changes in affective meaning, value, and pain-specific neural circuits.

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From Anticipation to the Experience of Pain: The Importance of Visceral Versus Somatic Pain Modality in Neural and Behavioral Responses to Pain-Predictive Cues

Objective The aim of this study was to compare behavioral and neural anticipatory responses to cues predicting either somatic or visceral pain in an associative learning paradigm. Methods Healthy women (N = 22) underwent functional magnetic resonance imaging. During an acquisition phase, two different visual cues repeatedly signalled either experimental visceral or somatic pain. In a subsequent extinction phase, identical cues were presented without pain. Before and after each phase, cue valence and contingency awareness were assessed on visual analog scales. Results Visceral compared to somatic pain–predictive cues were rated as more unpleasant after acquisition (visceral, 32.18 ± 13.03 mm; somatic, −18.36 ± 10.36 mm; p = .021) with similarly accurate cue-pain contingencies. After extinction, cue valence returned to baseline for both modalities (visceral, 1.55 ± 9.81 mm; somatic, −18.45 ± 7.12; p = .41). During acquisition, analyses of cue-induced neural responses revealed joint neural activation engaging areas associated with attention processing and cognitive control. Enhanced deactivation of posterior insula to visceral cues was observed, which correlated with enhanced responses within the salience network (anterior cingulate cortex, anterior insula) during visceral compared to somatic pain stimulation. During extinction, both pain modalities induced anticipatory neural activation in the extinction and salience network (all pFWE values < .05). Conclusions Conditioned emotional responses to pain-predictive cues are modality specific and enhanced for the visceral modality, suggesting that pain anticipation is shaped by the salience of painful stimuli. Common but also modality-specific neural mechanisms are involved during cue-pain learning, whereas extinction of cued responses seems unaffected by modality. Future research should examine potential implications for the pathophysiology of chronic pain conditions, especially chronic visceral pain.

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