Induced oscillatory signaling in the beta frequency of top-down pain modulation

Background: Induced synchronized brain activity, particularly in the beta-frequency range, has rarely been investigated in human electrophysiological studies of attentional modulation of the perception of nociceptive stimuli. Methods: We measured time-resolved brain responses to nociceptive stimuli in healthy subjects (final data set: n 5 17) using magnetoencephalography (MEG). In addition to investigating evoked responses as previous studies, we tested whether synchronized beta activity induced by nociceptive stimuli differs between 2 attentional conditions. Subjects were presented simultaneously with 2 stimulus modalities (pain-producing intraepidermal electrical stimuli and visual stimuli) in 2 different experimental conditions, ie, “attention to pain” and “attention to color.” Pain ratings between conditions were compared using a 2- sided paired-sample t test; MEG data were analyzed with Brainstorm. Results: Pain ratings were significantly higher in the “attention to pain” compared with the “attention to color” condition. Peak amplitudes of the evoked responses were significantly larger in the “attention to pain” condition bilaterally in the insula and secondary somatosensory cortex, and in the primary somatosensory cortex (SI) contralateral to stimulation. Induced responses to painful stimuli were significantly stronger in contralateral SI in the beta-frequency range in the “attention to pain” condition. Conclusions: This study replicates previous reports w.r.t. the attentional modulation of evoked responses and suggests a functional role of induced oscillatory activity in the beta frequency in top-down modulation of nociceptive stimuli

Contralateral hyperalgesia and allodynia following intradermal capsaicin injection in man

Objectives. Contralateral responses to unilateral stimuli have been well described in animal models. These range from central sensitization to peripheral inflammatory responses. Our aim was to test for contralateral responses following unilateral intradermal capsaicin injection in man

Treatment of chronic back pain by sensory discrimination training. A Phase I RCT of a novel device (FairMed) vs. TENS

Background: The causes of chronic low back pain (CLBP) remain obscure and effective treatment of symptoms remains elusive. A mechanism of relieving chronic pain based on the consequences of conflicting unpleasant sensory inputs to the central nervous system has been hypothesised. As a result a device was generated to deliver sensory discrimination training (FairMed), and this randomised controlled trial compared therapeutic effects with a comparable treatment modality, TENS. Methods: 60 patients with CLBP were recruited from physiotherapy referrals to a single-blinded, randomised controlled, non-inferiority trial. They were randomised to receive either FairMed or TENS and asked to use the allocated device for 30 minutes, twice a day, for 3 weeks. The primary outcome variable measured at 0 and 3 weeks was pain intensity measured using a visual analogue scale averaged over 7 days. Secondary outcome measures were Oswestry Disability Index, 3 timed physical tests, 4 questionnaires assessing different aspects of emotional coping and a global measure of patient rating of change. Data were analysed for the difference in change of scores between groups using one-way ANOVA. Results: Baseline characteristics of the two groups were comparable. The primary outcome, change in pain intensity (VAS) at 3 weeks showed a mean difference between groups of -0.1, (non significant p = 0.82). The mean difference in change in ODI scores was 0.4; (non significant p = 0.85). Differences in change of physical functioning showed that no significant difference in change of scores for any of these test (p = 0.58 – 0.90). Changes in scores of aspects of emotional coping also demonstrated no significant difference in change scores between the groups (p = 0.14 – 0.94). Conclusion: FairMed was not inferior to TENS treatment. The findings have implications for further research on current chronic pain theories and treatments. Further work to explore these mechanisms is important to expand our understanding of chronic pain and the role of neuro-modulation

The Relationship between Amygdala Activation and Passive Exposure Time to an Aversive Cue during a Continuous Performance Task

The allocation of attention modulates negative emotional processing in the amygdala. However, the role of passive exposure time to emotional signals in the modulation of amygdala activity during active task performance has not been examined. In two functional Magnetic Resonance Imaging (fMRI) experiments conducted in two different groups of healthy human subjects, we examined activation in the amygdala due to cued anticipation of painful stimuli while subjects performed a simple continuous performance task (CPT) with either a fixed or a parametrically varied trial duration. In the first experiment (N = 16), engagement in the CPT during a task with fixed trial duration produced the expected attenuation of amygdala activation, but close analysis suggested that the attenuation occurred during the period of active engagement in CPT, and that amygdala activity increased proportionately during the remainder of each trial, when subjects were passively exposed to the pain cue. In the second experiment (N = 12), the duration of each trial was parametrically varied, and we found that amygdala activation was linearly related to the time of passive exposure to the anticipatory cue. We suggest that amygdala activation during negative anticipatory processing depends directly on the passive exposure time to the negative cue

Spreading of complex regional pain syndrome: not a random process

Complex regional pain syndrome (CRPS) generally remains restricted to one limb but occasionally may spread to other limbs. Knowledge of the spreading pattern of CRPS may lead to hypotheses about underlying mechanisms but to date little is known about this process. The objective is to study patterns of spread of CRPS from a first to a second limb and the factors associated with this process. One hundred and eighty-five CRPS patients were retrospectively evaluated. Cox’s proportional hazards model was used to evaluate factors that influenced spread of CRPS symptoms. Eighty-nine patients exhibited CRPS in multiple limbs. In 72 patients spread from a first to a second limb occurred showing a contralateral pattern in 49%, ipsilateral pattern in 30% and diagonal pattern in 14%. A trauma preceded the onset in the second limb in 37, 44 and 91%, respectively. The hazard of spread of CRPS increased with the number of limbs affected. Compared to patients with CRPS in one limb, patients with CRPS in multiple limbs were on average 7 years younger and more often had movement disorders. In patients with CRPS in multiple limbs, spontaneous spread of symptoms generally follows a contralateral or ipsilateral pattern whereas diagonal spread is rare and generally preceded by a new trauma. Spread is associated with a younger age at onset and a more severely affected phenotype. We argue that processes in the spinal cord as well as supraspinal changes are responsible for spontaneous spread in CRPS

Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour

To facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. From 30 screened F-3 sibling groups, where each was derived from an individual ethyl-nitrosurea mutagenized F-0 fish, two showed increased or decreased nicotine preference. Out of 25 inactivating mutations carried by the F-3 fish, one in the slit3 gene segregated with increased nicotine preference in heterozygous individuals. Focussed SNP analysis of the human SLIT3 locus in cohorts from UK (n=863) and Finland (n=1715) identified two variants associated with cigarette consumption and likelihood of cessation. Characterisation of slit3 mutant larvae and adult fish revealed decreased sensitivity to the dopaminergic and serotonergic antagonist amisulpride, known to affect startle reflex that is correlated with addiction in humans, and increased htr1aa mRNA expression in mutant larvae. No effect on neuronal pathfinding was detected. These findings reveal a role for SLIT3 in development of pathways affecting responses to nicotine in zebrafish and smoking in humans.Peer reviewe

Influence of Body Position on Cortical Pain-Related Somatosensory Processing: An ERP Study

Background: Despite the consistent information available on the physiological changes induced by head down bed rest, a condition which simulates space microgravity, our knowledge on the possible perceptual-cortical alterations is still poor. The present study investigated the effects of 2-h head-down bed rest on subjective and cortical responses elicited by electrical, pain-related somatosensory stimulation. Methodology/Principal Findings: Twenty male subjects were randomly assigned to two groups, head-down bed rest (BR) or sitting control condition. Starting from individual electrical thresholds, Somatosensory Evoked Potentials were elicited by electrical stimuli administered randomly to the left wrist and divided into four conditions: control painless condition, electrical pain threshold, 30 % above pain threshold, 30 % below pain threshold. Subjective pain ratings collected during the EEG session showed significantly reduced pain perception in BR compared to Control group. Statistical analysis on four electrode clusters and sLORETA source analysis revealed, in sitting controls, a P1 component (40–50 ms) in the right somatosensory cortex, whereas it was bilateral and differently located in BR group. Controls ’ N1 (80–90 ms) had widespread right hemisphere activation, involving also anterior cingulate, whereas BR group showed primary somatosensory cortex activation. The P2 (190–220 ms) was larger in left-central locations of Controls compared with BR group. Conclusions/Significance: Head-down bed rest was associated to an overall decrease of pain sensitivity and an altered pai

Attention to pain! A neurocognitive perspective on attentional modulation of pain in neuroimaging studies

Several studies have used neuroimaging techniques to investigate brain correlates of the attentional modulation of pain. Although these studies have advanced the knowledge in the field, important confounding factors such as imprecise theoretical definitions of attention, incomplete operationalization of the construct under exam, and limitations of techniques relying on measuring regional changes in cerebral blood flow have hampered the potential relevance of the conclusions. Here, we first provide an overview of the major theories of attention and of attention in the study of pain to bridge theory and experimental results. We conclude that load and motivational/affective theories are particularly relevant to study the attentional modulation of pain and should be carefully integrated in functional neuroimaging studies. Then, we summarize previous findings and discuss the possible neural correlates of the attentional modulation of pain. We discuss whether classical functional neuroimaging techniques are suitable to measure the effect of a fluctuating process like attention, and in which circumstances functional neuroimaging can be reliably used to measure the attentional modulation of pain. Finally, we argue that the analysis of brain networks and spontaneous oscillations may be a crucial future development in the study of attentional modulation of pain, and why the interplay between attention and pain, as examined so far, may rely on neural mechanisms shared with other sensory modalities