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Representations of the body and peripersonal space can be distorted for people with some chronic pain conditions. Experimental pain induction can give rise to similar, but transient distortions in healthy individuals. However, spatial and bodily representations are dynamic, and constantly update as we interact with objects in our environment. It is unclear whether induced pain disrupts the mechanisms involved in updating these representations. In the present study, we sought to investigate the effect of induced pain on the updating of peripersonal space and body representations during and following tool-use. We compared performance under three conditions (pain, active placebo, neutral) on a visuotactile crossmodal congruency task and a tactile distance judgement task to measure updating of peripersonal space and body representations, respectively. Consistent with previous findings, the difference in crossmodal interference from visual distractors in the same compared to opposite visual field to the tactile target was less when tools were crossed than uncrossed. This suggests an extension of peripersonal space to incorporate the tips of the tools. Also consistent with previous findings, estimates of the felt tactile distance judgements decreased after active tool-use. In contrast to our predictions, however, we found no evidence that pain interfered with performance on either task when compared to the control conditions. Our findings suggest that the updating of peripersonal space and body representations is not disrupted by induced pain. That is, experiencing acute pain does not give rise to distorted representations of the body and peripersonal space that can be present in people with chronic pain conditions.
Learn More >Voltage-gated sodium channel Nav1.9 is a threshold channel that regulates action potential firing. Nav1.9 is preferentially expressed in myenteric neurons, and small-diameter dorsal root ganglion (DRG) and trigeminal ganglion neurons including nociceptors. Recent studies have demonstrated a monogenic Mendelian link of Nav1.9 to human pain disorders. Gain-of-function variants in Nav1.9, which cause smaller depolarizations of RMP, have been identified in patients with familial episodic pain type 3 (FEPS3) and the more common pain disorder small fiber neuropathy. To explore the phenotypic spectrum of Nav1.9 channelopathy, here we report a new Nav1.9 mutation, N816K, in a child with early-onset episodic pain in both legs, episodic abdominal pain, and chronic constipation. Sequencing of further selected pain genes was normal. N816K alters a residue at the N-terminus of loop 2, proximal to the cytoplasmic terminus of transmembrane segment 6 in domain II. Voltage-clamp recordings demonstrate that Nav1.9-N816K significantly increases current density and hyperpolarizes voltage-dependence of activation by 10 mV, enabling a larger window current. Current-clamp recordings in DRG neurons shows that N816K channels depolarize RMP of small DRG neurons by 7 mV, reduce current threshold of firing an action potential and render DRG neurons hyperexcitable. Taken together these data demonstrate gain-of-function attributes of the newly described N816K mutation at the channel and cellular levels, which are consistent with a pain phenotype in the carrier of this mutation.
Learn More >Evidence supports the benefits of resilience among older adults with chronic pain. While numerous factors confer resilience, research has largely examined these measures in isolation, despite evidence of their synergistic effects. Conceptualizing resilience from a multisystem perspective may provide a deeper understanding of adaptive functioning in pain. Sixty adults (ages 60+ years) with chronic low back pain completed measures of physical function, pain intensity, disability, and a performance-based task assessing back-related physical functioning and movement-evoked pain (MEP). Depressive symptoms, quality of life, and general resilience were also evaluated. To examine multisystem resiliency, principal components analysis (PCA) was conducted to create composite domains for psychological (positive affect, hope, positive well-being, optimism), health (waist-hip ratio, body mass index, medical comorbidities), and social (emotional, instrumental, informational support) functioning measures, followed by cluster analysis to identify participant subgroups based upon composites. Results yielded four clusters: Cluster 1 (high levels of functioning across psychological, health, and social support domains); Cluster 2 (optimal health and low psychosocial functioning); Cluster 3 (high psychological function, moderate-to-high social support, and poorer health); and Cluster 4 (low levels of functioning across the three domains). Controlling for sociodemographic characteristics, individuals with a more resilient phenotype (Cluster 1) exhibited lower levels of disability, higher quality of life and psychological functioning, and greater functional performance when compared to those with a lower degree of personal resources (Cluster 4). No significant cluster differences emerged in self-reported pain intensity or MEP. These findings signify the presence of resiliency profiles based upon psychological, social, and health-related functioning. Further examination of the additive effects of multiple adaptive behaviors and resources may improve our understanding of resilience in the context of pain, informing novel interventions for older adults.
Learn More >Fabry disease belongs to lysosomal storage disorders and can be successfully treated today. On the contrary, the correct diagnostic classification of its symptoms can be challenging and most patients suffer from pain for years, until they are diagnosed correctly. The aim of this project was to characterize patients with unclassified extremity pain and to present a simple algorithm for a retrospective stratification approach.
Learn More >Increasing evidence for the efficacy of analgesic placebo effects in laboratory studies with healthy persons raises the question whether placebos could be used to improve the treatment of pain patients. Expectancies play a central role in shaping analgesic placebo but also nocebo effects.
Learn More >Whiplash injury is a common consequence of motor vehicle crashes (MVC), yet it is also one of the most poorly understood. While more than 50% of those injured should expect to rapidly recover, others are not as fortunate with approximately 25% of those exposed to and injured in an MVC transitioning from acute to chronic pain and disability. The purpose of this prospective study was to determine if the severity and direction of collisions involving participants enrolled in a longitudinal study of recovery from whiplash are able to differentiate between different recovery groups based on the neck disability index (NDI) percentage scores at 3-months, and if these crash specific parameters are associated with known risk factors for recovery. Here, we examined objective collision data, repair invoices, and characteristics of the crash for 37 acutely injured participants consented and enrolled at their emergency department visit and further assessed at three time points; < 1 week, 2-weeks, and 3-months post MVC. Collision data were used to reconstruct and estimate the severity of the crash and determine if they aligned with the heterogeneity of whiplash injury recovery. Wilcoxon rank sum tests were used to determine if % scores on the Neck Disability Index (NDI) at 3-months post MVC were associated with the following variables: sex, head turned at time of impact, seatbelt use, whether or not airbags deployed, if the vehicle was struck while stopped or while turning, or the principle direction of force (PDOF). Spearman's correlation coefficients were used to determine if NDI at 3-months post MVC was associated with age, Body Mass Index, pain-related disability at baseline, signs of post-traumatic distress, intrusion/hyperarousal, negative affect, pain intensity, estimated speed change from the impact, and damage estimates (in US$). There was a significant positive association between self-reported neck disability at 3-months post MVC, post-traumatic distress, negative affect and uncontrolled pain. There was no direct effect of participant characteristics, arousal, intrusion/hyperarousal sub-score, damage, PDOF, speed change, or other crash characteristics. Established crash parameters were not associated with the heterogeneity of whiplash injury recovery in a small sample of injured participants.
Learn More >Parental behavior can influence how well adolescents cope with chronic pain. Previous research has largely focused on how parents negatively impact adolescent functioning. Yet more recent work suggests that parents – and particularly parental psychological flexibility – can foster better adolescent pain-related functioning. In this study we examined if parental protective responses and instructions to engage in activities in the presence of pain mediate the impact of parental psychological flexibility and acceptance of adolescent pain on adolescents' daily pain-related behavior.
Learn More >To investigate the required sample size for and feasibility of a full-scale randomized controlled trial examining the impact of the "dose" effect of acupuncture in treating sciatica.
Learn More >Pain in sickle cell disease (SCD) is severe, variable, and inadequately comprehended. The β2-adrenergic receptor () is critical in mediating neurotransmitter response in the sympathetic nervous system. In this association study, we examined 16 single nucleotide polymorphisms (SNPs) covering 5'-UTR and coding regions of for pain variability in SCD. Subjects recorded their non-crisis, baseline pain experience on a computerized tool from which we obtained chronic pain measurement score- composite pain index (CPI). Regression models yielded significant associations between chronic pain and seven SNPs. Non-synonymous SNP rs1042713 A allele (Arg16) caused a 5.73-fold decrease in CPI ( = 0.002). Allele A of rs12654778 and T of rs17778257 reduced CPI by a fold of 4.52 ( = 0.019), and 4.39 ( = 0.032), respectively. Whereas, in the 5' UTR, allele C of rs1042711, G of rs11168070, C of rs11959427, and C of rs1801704 increased CPI by a fold of 10.86 ( = 0.00049), 5.99 ( = 0.016), 5.69 ( = 0.023), and 5.26 ( = 0.031), respectively. Together, these SNPs accounted for 2-15% of CPI variance after adjusting for covariates. Moreover, these SNPs were in high linkage disequilibrium (LD) showing three LD blocks in our cohort. A 10-marker haplotype increased CPI by 11.5-fold ( = 0.000407). Thus, polymorphisms might contribute to chronic pain severity and heterogeneity in SCD.
Learn More >Placebo effects benefit a wide range of clinical practice, which can be profoundly influenced by expectancy level and personal characteristics. However, research on the issue of whether these factors independently or interdependently affect the placebo effects is still in its infancy. Here, we adopted a 3-day between-subject placebo analgesia paradigm (2-day conditioning and 1-day test) to investigate the influence of expectancy levels (i.e., No, Low, and High) and personal characteristics (i.e., gender, dispositional optimism, and anxiety state) on placebo effects in 120 healthy participants (60 females). Our results showed that the reduction of pain intensity in the test phase was influenced by the interaction between expectancy and gender, as mainly reflected by greater reductions of pain intensity in females at Low expectancy level than females at No/High expectancy levels, and greater reductions of pain intensity in males than in females at High expectancy level. Additionally, the reduction of pain unpleasantness was not only modulated by the interaction between expectancy and gender, but also by the interaction between expectancy and dispositional optimism, as well as the interaction between expectancy and anxiety state. Specifically, participants who were more optimistic in Low expectancy group, or those who were less anxious in High expectancy group showed greater reductions of pain unpleasantness. To sum up, we emphasized on regulating the expectancy level individually based on the assessment of personal characteristics to maximize placebo effects in clinical conditions.
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