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Multisensory hypersensitivity (MSH), which refers to persistent discomfort across sensory modalities, is a risk factor for chronic pain. Developing a better understanding of the neural contributions of disparate sensory systems to MSH may clarify its role in the development of chronic pain. We recruited a cohort of women ( =147) enriched with participants with menstrual pain at risk for developing chronic pain. Visual sensitivity was measured using a periodic pattern-reversal stimulus during EEG. Self-reported visual unpleasantness ratings were also recorded. Bladder pain sensitivity was evaluated with an experimental bladder-filling task associated with early clinical symptoms of chronic pelvic pain. Visual stimulation induced unpleasantness was associated with bladder pain and evoked primary visual cortex excitation; however, the relationship between unpleasantness and cortical excitation was moderated by bladder pain. Thus, future studies aimed at reversing the progression of MSH into chronic pain should prioritize targeting of cortical mechanisms responsible for maladaptive sensory input integration.
Learn More >The vast majority of individuals who come to the emergency department (ED) for care after a motor vehicle collision (MVC) are diagnosed with musculoskeletal strain only and are discharged to home. A significant subset of this population will still develop persistent pain and posttraumatic psychological sequelae may play an important role in pain persistence.
Learn More >The genetic background of pain is becoming increasingly well understood, which opens up possibilities for predicting the individual risk of persistent pain and the use of tailored therapies adapted to the variant pattern of the patient's pain-relevant genes. The individual variant pattern of pain-relevant genes is accessible via next-generation sequencing, although the analysis of all "pain genes" would be expensive. Here, we report on the development of a cost-effective next generation sequencing-based pain-genotyping assay comprising the development of a customized AmpliSeq™ panel and bioinformatics approaches that condensate the genetic information of pain by identifying the most representative genes. The panel includes 29 key genes that have been shown to cover 70% of the biological functions exerted by a list of 540 so-called "pain genes" derived from transgenic mice experiments. These were supplemented by 43 additional genes that had been independently proposed as relevant for persistent pain. The functional genomics covered by the resulting 72 genes is particularly represented by mitogen-activated protein kinase of extracellular signal-regulated kinase and cytokine production and secretion. The present genotyping assay was established in 61 subjects of Caucasian ethnicity and investigates the functional role of the selected genes in the context of the known genetic architecture of pain without seeking functional associations for pain. The assay identified a total of 691 genetic variants, of which many have reports for a clinical relevance for pain or in another context. The assay is applicable for small to large-scale experimental setups at contemporary genotyping costs.
Learn More >Virtual reality (VR) has been shown to produce analgesic effects during different experimental and clinical pain states. Despite this, the top-down mechanisms are still poorly understood. In this study, we examined the influence of both a real and sham (i.e. the same images in 2D) immersive arctic VR environment on conditioned pain modulation (CPM) and in a human surrogate model of central sensitisation in 38 healthy volunteers. CPM and acute heat pain thresholds (HPT) were assessed before and during VR/sham exposure in the absence of any sensitisation. In a follow-on study, we used the cutaneous high frequency stimulation (HFS) model of central sensitisation and measured changes in mechanical pain sensitivity (MPS) in an area of heterotopic sensitisation before and during VR/sham exposure. There was an increase in CPM efficiency during the VR condition compared to baseline (P<0.01). In the sham condition, there was a decrease in CPM efficiency compared to baseline (P<0.01) and the real VR condition (P<0.001). Neither real nor sham VR had any effect on pain ratings reported during the conditioning period or on HPT. There was also an attenuation of MPS during the VR condition indicating a lower sensitivity compared to sham (P<0.05). We conclude that exposure to an immersive VR environment has no effect over acute pain thresholds but can modulate dynamic CPM responses and mechanical hypersensitivity in healthy volunteers. Perspective: This study has demonstrated that exposure to an immersive virtual reality environment can modulate perceptual correlates of endogenous pain modulation and secondary hyperalgesia in a human surrogate pain model. These results suggest that virtual reality could provide a novel mechanism-driven analgesic strategy in patients with altered central pain processing.
Learn More >C tactile (CT) fibres, responsible for the so-called "affective" touch (AT), have drawn a fair amount of attention within the scientific community for their marked social dimension. However, while the pain-relieving potential of discriminative touch (DT) has been documented, proofs of the analgesic properties of AT are still scarce. Additionally, no study has so far tested its possible pain-relieving effect on a clinically-relevant model. Temporal summation of second pain (TSSP), otherwise referred to as 'wind-up', relies on repetitive stimulation of C-nociceptors and it is thought to reflect central sensitization, a process linked to many chronic pain conditions. In the present experimental, within participants, design we induced TSSP trough trains of ascending and descending repetitive heat stimulation. Forty-two healthy participants' pain was measured during two different tactile stimulations (stroking velocities AT: 10 cm/s; DT: 0.3 cm/s) or without concomitant tactile input. Since measures of pleasantness of the tactile stimulation have been found to strongly correlate with C-tactile fibres' firing rate, these, together with participants' body awareness, were also taken into account. Our results show that AT brought about a decrease of our participants' pain as opposed to both DT and no touch, while DT did not produce any significant pain reduction. Thus, only AT successfully modulated wind-up. As expected, AT was perceived more pleasant than DT, while a clear relationship between body awareness and pain was found only during DT. Targeting CT fibres could pave the way to new treatments for chronic pain conditions whose aetiology depend on abnormal C-nociceptors' physiology.
Learn More >The present study investigated pain trajectories of husbands and wives over their mid-later years, the grouping of these trajectories, and differences in baseline biopsychosocial profiles and health and well-being outcomes in later years across the pain trajectory groups.
Learn More >Persistent post-mastectomy pain (PPMP) is a significant negative outcome occurring after breast surgery, and understanding which individual women are most at risk is essential to targeting of preventive efforts. The biopsychosocial model of pain suggests that factors from many domains may importantly modulate pain processing and predict the progression to pain persistence.
Learn More >The current study used data from a clinical trial to identify variables that are associated with and/or mediate the beneficial effects of four psychological chronic pain treatments: one teaching patients self-hypnosis to reduce pain intensity (HYP), one teaching self-hypnosis to change thoughts about pain (hypnotic cognitive therapy, or HYP-CT), one teaching cognitive restructuring skills to change thoughts about pain (cognitive therapy, or CT), and one providing education about pain (ED; included as an active control condition). Of 17 possible mechanism variables examined, and with alpha not corrected for multiple comparisons, significant between-group differences were observed for three. Two of these (changes in beliefs about control over pain and number of days of skill practice) were supported as mediators of the beneficial effects of HYP, CT, or HYP-CT, relative to ED. Six mechanism variables evidenced significant pre- to post-treatment changes in the sample as a whole, without showing significant between-group differences. Pre- to post-treatment changes in all six were associated with improvements in pain interference, pain intensity, or both. In addition, participant ratings of therapeutic alliance at post-treatment were associated significantly with improvements in both pain intensity and pain interference in the sample as a whole. Thus, of the 17 possible mediators examined, there were relatively few that serve as mediators for the beneficial effects of specific treatments; a larger number of variables predicted treatment outcome overall. The extent to which these variables are treatment mediators (i.e., are responsible for, rather than merely associated with, treatment-related improvements) will require further research.
Learn More >The study evaluated if chronic musculoskeletal (MSK) pain predicts the severity of insomnia, and whether the effect is moderated by age, gender, and number of comorbid diseases in older people. An 18-month prospective study was performed within the framework of a community health program in Hong Kong. A total of 498 older people aged ≥ 60 with multimorbidity were recruited. The predictors included the presence of chronic MSK pain, pain measured by the Brief Pain Inventory (BPI), insomnia measured by baseline Insomnia Severity Index (ISI), and number of co-morbid diseases, age, and gender. The outcome was ISI repeated at 18 months. The moderators included age, gender, and number of comorbid diseases. Multivariate linear regression and moderation analysis were conducted. We found that the presence of chronic MSK pain (β = 1.725; 95% CI, 0.607-2.842; P < 0.01) predicted the severity of ISI, after controlling for age, gender, BMI, and the number of comorbid diseases. Participants with chronic MSK pain throughout the period had worse trend of improvement in ISI compared to those who were "pain-free" (β = 2.597; 95% CI, 1.311-3.882; P < 0.001). Age, gender, and number of comorbid diseases did not moderate the longitudinal relationship. We propose that pain management should prioritized in the prevention of insomnia.
Learn More >Disrupted connectivity within visual, attentional and salience networks in the visual snow syndrome.
Here we investigate brain functional connectivity in patients with visual snow syndrome (VSS). Our main objective was to understand more about the underlying pathophysiology of this neurological syndrome. Twenty-four patients with VSS and an equal number of gender and age-matched healthy volunteers attended MRI sessions in which whole-brain maps of functional connectivity were acquired under two conditions: at rest while watching a blank screen and during a visual paradigm consisting of a visual-snow like stimulus. Eight unilateral seed regions were selected a priori based on previous observations and hypotheses; four seeds were placed in key anatomical areas of the visual pathways and the remaining were derived from a pre-existing functional analysis. The between-group analysis showed that patients with VSS had hyper and hypoconnectivity between key visual areas and the rest of the brain, both in the resting state and during a visual stimulation, compared with controls. We found altered connectivity internally within the visual network; between the thalamus/basal ganglia and the lingual gyrus; between the visual motion network and both the default mode and attentional networks. Further, patients with VSS presented decreased connectivity during external sensory input within the salience network, and between V5 and precuneus. Our results suggest that VSS is characterised by a widespread disturbance in the functional connectivity of several brain systems. This dysfunction involves the pre-cortical and cortical visual pathways, the visual motion network, the attentional networks and finally the salience network; further, it represents evidence of ongoing alterations both at rest and during visual stimulus processing.
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