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BackgroundCortical reorganization and its potential pathological significance is increasingly studied in chronic low back pain (CLBP) patients. Yet, detailed cortical maps of the healthy human back are lacking. To better understand cortical changes during the development and maintenance of CLBP, a detailed baseline characterization resulting from sensory thoracolumbar afferent input is needed. To this end, a novel pneumatic vibrotactile stimulation method was used to stimulate paraspinal sensory afferents while studying their cortical representations in unprecedented detail.MethodsIn 30 young healthy participants, vibrotactile stimulations at 20Hz and 80Hz were applied bilaterally at nine locations along the thoracolumbar axis while functional magnetic resonance imaging (fMRI) was performed. A whole-brain searchlight representational similarity analysis (RSA) in combination with different experimental models of paraspinal afferent input was used to investigate the representational organization of the respective neuronal activation patterns.ResultsFor 80Hz, the organizational structure of the neuronal activation patterns yielded the best fit for a model based on segmental distances between the stimulated paraspinal locations, located bilaterally in the primary (S1) and secondary somatosensory (S2) cortices. For 20Hz, this observation was restricted to the right S1.ConclusionsfMRI during paraspinal vibrotactile stimulation in combination with RSA is a powerful tool that can be used to establish highly detailed cortical maps of the human back. The current findings constitute a promising basis to further explore cortical reorganization and its potential pathological meaning in CLBP patients.FundingPrimary funding (as part of a project grant to MLM): Swiss National Science Foundation, Bern, Switzerland (ID 320030 185123).

Fear-avoidance beliefs, particularly the fear of lifting with a flexed spine, are associated with reduced spinal motion during object lifting. Low back pain patients thereby also showed potentially clinically relevant changes in the spatial distribution of back muscle activity, but it remains unknown whether such associations are also present in pain-free individuals. This cross-sectional observational study investigated the relationship between fear-avoidance beliefs and the spatial distribution of lumbar paraspinal muscle activity in pain-free individuals during a repetitive lifting task. Thirty participants completed two pain-related fear questionnaires and performed 25 repetitions of lifting a 5 kg-box from a lower to an upper shelf and back, while multi-channel electromyographic signals were recorded bilaterally from the lumbar erector spinae muscles. Changes in spatial distribution were defined as the differences in vertical position of the weighted centroids of muscle activity (centroid shift) between the first and last few repetitions. Linear regression analyses were performed to examine the relationships between centroid shift and fear-avoidance belief scores. Fear of lifting an object with a flexed spine was negatively associated with erector spinae activity centroid shift (R

Fear-avoidance beliefs, particularly the fear of lifting an object with a flexed spine, were shown to be associated with reduced spinal motion during object lifting in both individuals with and without low back pain (LBP). LBP patients thereby also showed potentially clinically relevant changes in the spatial distribution of back muscle activity, but it remains unknown whether such associations are also present in pain-free individuals. The aim of this study was therefore to investigate the relationship between fear-avoidance beliefs and the change in spatial distribution of lumbar paraspinal muscle activity in pain-free individuals during a repetitive object lifting task. Thirty participants completed two pain-related fear questionnaires and performed 25 repetitions of lifting a 5kg-box from a lower to an upper shelf and back, while multi-channel electromyographic signals were recorded bilaterally from the lumbar erector spinae muscles. Changes in spatial distribution were determined by calculating the differences in vertical position of the weighted centroids of muscle activity (centroid shift) between the first and last few repetitions. Multiple linear regression analyses were performed to examine the relationship between the centroid shift and fear-avoidance belief scores. The analyses showed that the fear of lifting an object with a flexed spine was negatively associated with erector spinae activity centroid shift (R2 adj. = 0.1832; p = 0.045), which might be an expression of behavioral alterations in order to prevent the back from possible harm.

Musculoskeletal models have the potential to improve diagnosis and optimize clinical treatment by predicting accurate outcomes on an individual basis. However, the subject-specific modeling of spinal alignment is often strongly simplified or is based on radiographic assessments, exposing subjects to unnecessary radiation. We therefore developed and introduced a novel skin marker-based approach for modeling subject-specific spinal alignment and evaluated its feasibility by comparing the predicted L1/L2 spinal loads during various functional activities with the loads predicted by the generically scaled models as well as with in vivo measured data obtained from the OrthoLoad database. Spinal loading simulations resulted in considerably higher compressive forces for both scaling approaches over all simulated activities, and AP shear forces that were closer or similar to the in vivo data for the subject-specific approach during upright standing activities and for the generic approach during activities that involved large flexions. These results underline the feasibility of the proposed method and associated workflow for inter- and intra-subject investigations using musculoskeletal simulations. When implemented into standard model scaling workflows, it is expected to improve the accuracy of muscle activity and joint loading simulations, which is crucial for investigations of treatment effects or pathology-dependent deviations., Journal of Biomechanics, 137, ISSN:0021-9290, ISSN:1873-2380

Pain-related fear is associated with less lumbar flexion during lifting in pain-free adults, indicating a protective movement strategy in the absence of low back pain., There is a long-held belief that physical activities such as lifting with a flexed spine is generally harmful for the back and can cause low back pain (LBP), potentially reinforcing fear-avoidance beliefs underlying pain-related fear. In patients with chronic LBP, pain-related fear has been shown to be associated with reduced lumbar range of motion during lifting, suggesting a protective response to pain. However, despite short-term beneficial effects for tissue health, recent evidence suggests that maintaining a protective trunk movement strategy may also pose a risk for (persistent) LBP due to possible pronociceptive consequences of altered spinal motion, potentially leading to increased loading on lumbar tissues. Yet, it is unknown if similar protective movement strategies already exist in pain-free individuals, which would yield potential insights into the role of fear-avoidance beliefs in motor behavior in the absence of pain. Therefore, the aim of this study is to test whether fear-avoidance beliefs influence spinal motion during lifting in a healthy cohort of pain-free adults without a history of chronic pain. The study subjects (N = 57) filled out several pain-related fear questionnaires and were asked to perform a lifting task (5kg-box). High-resolution spinal kinematics were assessed using an optical motion capturing system. Time-sensitive analyses were performed based on statistical parametric mapping. The results demonstrated time-specific and negative relationships between self-report measures of pain-related fear and lumbar spine flexion angles during lifting, indicating potential unfavorable interactions between psychological factors and spinal motion during lifting in pain-free subjects.

There is a long-held belief that physical activities such as lifting with a flexed spine is generally harmful for the back and can cause low back pain (LBP), potentially nurturing fear avoidance beliefs underlying pain-related fear. In chronic LBP patients, pain-related fear has been shown to be associated with reduced lumbar range of motion during lifting, indicating distinct and probably protective psychomotor responses to pain. However, despite short term beneficial effects for tissue health, recent evidence suggests that maintaining a protective trunk movement strategy may also pose a risk for (persistent) LBP due to possible pro-nociceptive consequences of altered spinal kinematics, reflected by increased loading on lumbar tissues and persistent muscle tension. Yet, it is unknown if similar psychomotor interactions already exist in pain-free individuals which would yield potential insights into how a person might react when they experience LBP. Therefore, the aim of this study is to test the impact of pain-related fear on spinal kinematics in a healthy cohort of pain-free adults without a history of chronic pain. The study subjects (N=57) filled out several pain-related fear questionnaires and were asked to perform a lifting task (5kg-box). High-resolution spinal kinematics were assessed using an optical motion capturing system. Time-sensitive analyses were performed based on statistical parametric mapping. The results demonstrated time-specific and negative relationships between self-report measures of pain-related fear and lumbar spine flexion angles during lifting, yielding important implications regarding unfavorable psychomotor interactions that might become relevant in a future LBP incident.

Motor control, which relies on constant communication between motor and sensory systems, is crucial for spine posture, stability and movement. Adaptions of motor control occur in low back pain (LBP) while different motor adaption strategies exist across individuals, probably to reduce LBP and risk of injury. However, in some individuals with LBP, adapted motor control strategies might have long-term consequences, such as increased spinal loading that has been linked with degeneration of intervertebral discs and other tissues, potentially maintaining recurrent or chronic LBP. Factors contributing to motor control adaptations in LBP have been extensively studied on the motor output side, but less attention has been paid to changes in sensory input, specifically proprioception. Furthermore, motor cortex reorganization has been linked with chronic and recurrent LBP, but underlying factors are poorly understood. Here, we review current research on behavioral and neural effects of motor control adaptions in LBP. We conclude that back pain-induced disrupted or reduced proprioceptive signaling likely plays a pivotal role in driving long-term changes in the top-down control of the motor system via motor and sensory cortical reorganization. In the outlook of this review, we explore whether motor control adaptations are also important for other (musculoskeletal) pain conditions.

BACKGROUND Quantification of dentin hypersensitivity (DH) is challenging and requires standardised, graded stimulation by natural-like stimuli. OBJECTIVE The present study aimed at identifying DH subjects and longitudinally monitoring their pain thresholds by cold air quantitative sensory testing (QST). METHODS Subject recruitment started with an online DH questionnaire. Respondents were screened by dental air stimulation. Sensitising and habituating subjects were excluded. A recently developed stimulation device was employed for cold air QST. Single tooth DH was verified by applying an equi-intense stimulus to a control tooth. Descriptive statistics were applied for subject characteristics. Mean values were calculated for the stimulation parameters temperature and air flow. Reliability of temperatures for detecting pain and for evoking moderate pain over multiple time points within a 3-week period was analysed by two-way random single- and average-measure intra-class correlation coefficients. RESULTS A total of 353 persons completed the online DH questionnaire of which 117 were screened. Forty-four passed the screening, yet 15 were excluded for various reasons. Twenty-nine subjects were monitored by QST across 3 weeks. Results revealed a high intra-individual stability of the temperature inducing moderate to strong pain intensity (MPI) (single-measure ICC of T 0.83, P

Non-specific chronic low back pain (NSCLBP) is a major health problem, affecting about one fifth of the population worldwide. To avoid further pain or injury, patients with NSCLBP seem to adopt a stiffer movement pattern during everyday living activities. However, it remains unknown how NSCLBP affects the lumbar lordosis angle (LLA) during repetitive activities such as walking or running. This pilot study therefore aimed at exploring possible NSCLBP-related alterations in LLAs during walking and running by focusing on discrete parameters as well as continuous data. Thirteen patients with NSCLBP and 20 healthy pain-free controls were enrolled and underwent a full-body movement analysis involving various everyday living activities such as standing, walking and running. LLAs were derived from markers placed on the spinous processes of the vertebrae L1-L5 and S1. Possible group differences in discrete (average and range of motion (ROM)) and continuous LLAs were analyzed descriptively using mean differences with confidence intervals ranging from 95% to 75%. Patients with NSCLBP indicated reduced average LLAs during standing, walking and running and a tendency for lower LLA-ROM during walking. Analyses of continuous data indicated the largest group differences occurring around 25% and 70% of the walking and 25% and 75% of the running cycle. Furthermore, patients indicated a reversed movement pattern during running, with increasing instead of a decreasing LLAs after foot strike. This study provides preliminary evidence that NSCLBP might affect LLAs during walking and running. These results can be used as a basis for future large-scale investigations involving hypothesis testing., Comment: This is the accepted manuscript version of an article published in the Journal of Biomechanics (https://doi.org/10.1016/j.jbiomech.2020.109883)

Fear of pain demonstrates significant prognostic value regarding the development of persistent musculoskeletal pain and disability. Its assessment often relies on self-report measures of pain-related fear by a variety of questionnaires. However, based either on “fear of movement/(re)injury/kinesiophobia”, “fear avoidance beliefs” or “pain anxiety”, pain-related fear constructs seemingly differ while the potential overlap of the questionnaires is unclear. Furthermore, the relationship to other anxiety measures such as state or trait anxiety remains ambiguous. Because the neural bases of fearful and anxious states are well described, advances in neuroimaging such as machine learning on brain activity patterns recorded by functional magnetic resonance imaging might help to dissect commonalities or differences across pain-related fear constructs. We applied a pattern regression approach in 20 non-specific chronic low back pain patients to reveal predictive relationships between fear-related neural information and different pain-related fear questionnaires. More specifically, the applied Multiple Kernel Learning approach allowed generating models to predict the questionnaire scores based on a hierarchical ranking of fear-related neural patterns induced by viewing videos of potentially harmful activities for the back. We sought to find evidence for or against overlapping pain-related fear constructs by comparing the questionnaire prediction models according to their predictive abilities and associated neural contributors. The results underpin the diversity of pain-related fear constructs by demonstrating evidence of non-overlapping neural predictors within fear processing regions. This neuroscientific approach might ultimately help to further understand and dissect psychological pain-related fear constructs.SignificancePain-related fear, often assessed through self-reports such as questionnaires, has shown prognostic value and clinical utility for a variety of musculoskeletal pain disorders. However, it remains difficult to determine a common underlying construct of pain-related fear due to several proposed constructs among questionnaires. The current study describes a novel neuroscientific approach using machine learning of neural patterns within the fear circuit of chronic low back pain patients that has the potential to identify neural commonalities or differences among the various pain-related fear constructs. Ultimately, this approach might afford a deeper understanding of the suggested constructs and might be also applied to other domains where ambiguity exists between different psychological constructs.

Fear of pain demonstrates significant prognostic value regarding the development of persistent musculoskeletal pain and disability. Its assessment often relies on self-report measures of pain-related fear by a variety of questionnaires. However, based either on “fear of movement/(re)injury/kinesiophobia,” “fear avoidance beliefs,” or “pain anxiety,” pain-related fear constructs plausibly differ while it is unclear how specific the questionnaires are in assessing these different constructs. Furthermore, the relationship of pain-related fear to other anxiety measures such as state or trait anxiety remains ambiguous. Advances in neuroimaging such as machine learning on brain activity patterns recorded by functional magnetic resonance imaging might help to dissect commonalities or differences across pain-related fear constructs. We applied a pattern regression approach in 20 human patients with nonspecific chronic low back pain to reveal predictive relationships between fear-related neural pattern information and different pain-related fear questionnaires. More specifically, the applied multiple kernel learning approach allowed the generation of models to predict the questionnaire scores based on a hierarchical ranking of fear-related neural patterns induced by viewing videos of activities potentially harmful for the back. We sought to find evidence for or against overlapping pain-related fear constructs by comparing the questionnaire prediction models according to their predictive abilities and associated neural contributors. By demonstrating evidence of nonoverlapping neural predictors within fear-processing regions, the results underpin the diversity of pain-related fear constructs. This neuroscientific approach might ultimately help to further understand and dissect psychological pain-related fear constructs.

Supplemental Digital Content is Available in the Text., Introduction: Pain-related fear plays a substantial role in chronic low back pain (LBP) by amplifying the experienced disability. Related dysfunctional emotions and cognitions may also affect sensory aspects of pain through a modulatory pathway in which the periaqueductal gray (PAG) and the amygdala play key roles. Objectives: We therefore hypothesized a differential amygdala-PAG functional connectivity (FC) in patients with chronic LBP that is modulated by the degree of pain-related fear. Methods: We used data of a previously reported fMRI study where 20 chronic LBP patients (7 females, mean age = 39.35) and 20 healthy controls (12 females, mean age = 32.10) were asked to observe video clips showing potentially harmful and neutral activities for the back. Pain-related fear was assessed using the Tampa Scale of kinesiophobia (TSK) and Fear Avoidance Beliefs questionnaires (FABQ). Generalized psychophysiological interactions were used to reveal task-based FC. Results: Compared to controls, patients exhibited a significant decrease in amygdala-PAG-FC (P = 0.022) during observation of harmful activities, but not of neutral activities. Furthermore, amygdala-PAG-FC correlated negatively with Tampa Scale of kinesiophobia scores in patients (R2 = 0.28, P = 0.01) but not with Fear Avoidance Beliefs questionnaires scores. Discussion: Our findings might indicate a maladaptive psychobiological interaction in chronic LBP patients characterized by a disrupted amygdala-PAG-FC that is modulated by the degree of pain-related fear. These results shed new light on brain mechanisms underlying psychological factors that may have pronociceptive effects in chronic LBP.

Eight decades after Penfield's discovery of the homunculus only sparse evidence exists on the cortical representation of the lumbar spine. The aim of our investigation was the description of the lumbar spine's cortical representation in healthy subjects during the application of measured manual pressure. Twenty participants in the prone position were investigated during functional magnetic resonance imaging (fMRI). An experienced manual therapist applied non‐painful, posterior‐to‐anterior (PA) pressure on three lumbar spinous processes (L1, L3, and L5). The pressure (30 N) was monitored and controlled by sensors. The randomized stimulation protocol consisted of 68 pressure stimuli of 5 s duration. Blood oxygenation level dependent (BOLD) responses were analyzed in relation to the lumbar stimulations. The results demonstrate that controlled PA pressure on the lumbar spine induced significant activation patterns. The major new finding was a strong and consistent activation bilaterally in the somatosensory cortices (S1 and S2). In addition, bilateral activation was located medially in the anterior cerebellum. The activation pattern also included other cortical areas probably related to anticipatory postural adjustments. These revealed stable somatosensory maps of the lumbar spine in healthy subjects can subsequently be used as a baseline to investigate cortical and subcortical reorganization in low back pain patients. Hum Brain Mapp 35:3962–3971, 2014. © 2014 Wiley Periodicals, Inc.

In this study we investigated sensorimotor processing of painful pressure stimulation on the lower back of patients with chronic lower back pain (CLBP) by using functional near-infrared spectroscopy (fNIRS) to measure changes in cerebral hemodynamics and oxygenation. The main objectives were whether patients with CLBP show different relative changes in oxy- and deoxyhemoglobin ([O2Hb] and [HHb]) in the supplementary motor area (SMA) and primary somatosensory cortex (S1) compared to healthy controls (HC). Twelve patients with CLBP (32 ± 6.1 years; range: 24–44 years; nine women) and 20 HCs (33.5 ± 10.7 years; range 22–61 years; eight women) participated in the study. Painful and non-painful pressure stimulation was exerted with a thumb grip perpendicularly to the spinous process of the lumbar spine. A force sensor was attached at the spinous process in order to control pressure forces. Tactile stimulation was realized by a one-finger brushing. Hemodynamic changes in the SMA and S1 were measured bilaterally using a multi-channel continuous wave fNIRS imaging system and a multi-distant probe array. Patients with CLBP showed significant stimulus-evoked hemodynamic responses in [O2Hb] only in the right S1, while the HC exhibited significant [O2Hb] changes bilaterally in both, SMA and S1. However, the group comparisons revealed no significant different hemodynamic responses in [O2Hb] and [HHb] in the SMA and S1 after both pressure stimulations. This non-significant result might be driven by the high inter-subject variability of hemodynamic responses that has been observed within the patients group. In conclusion, we could not find different stimulus-evoked hemodynamic responses in patients with CLBP compared to HCs. This indicates that neither S1 nor the SMA show a specificity for CLBP during pressure stimulation on the lower back. However, the results point to a potential subgrouping regarding task-related cortical activity within the CLBP group; a finding worth further research., Frontiers in Human Neuroscience, 10, ISSN:1662-5161

Background and Objectives This study aimed at investigating the feasibility of functional near‐infrared spectroscopy (fNIRS) to measure changes in cerebral hemodynamics and oxygenation evoked by painful and nonpainful mechanosensory stimulation on the lower back. The main objectives were to investigate whether cortical activity can be (1) detected using functional fNIRS, and (2) if it is possible to distinguish between painful and nonpainful pressure as well as a tactile brushing stimulus based on relative changes in oxy‐ and deoxyhemoglobin ([O2Hb] and [HHb]). Methods Twenty right‐handed subjects (33.5 ± 10.7 years; range 20–61 years; 8 women) participated in the study. Painful and nonpainful pressure stimulation was exerted with a thumb grip perpendicularly to the spinous process of the lumbar spine. Tactile stimulation was realized by a one‐finger brushing. The supplementary motor area (SMA) and primary somatosensory cortex (S1) were measured bilaterally using a multichannel continuous‐wave fNIRS imaging system. Results Characteristic relative changes in [O2Hb] in the SMA and S1 after both pressure stimulations (corrected for multiple comparison) were observed. [HHb] showed only much weaker changes (uncorrected). The brushing stimulus did not reveal any significant changes in [O2Hb] or [HHb]. Conclusion The results indicate that fNIRS is sensitive enough to detect varying hemodynamic responses to different types of mechanosensory stimulation. The acquired data will serve as a foundation for further investigations in patients with chronic lower back pain. The future aim is to disentangle possible maladaptive neuroplastic changes in sensorimotor areas during painful and nonpainful lower back stimulations based on fNIRS neuroimaging., Brain and Behavior, 6 (12), ISSN:2162-3279

Converging lines of evidence indicate that the pain experience emerges from distributed cortical nodes that share nociceptive information. While the theory of a single pain center is still not falsifiable by current neuroimaging technology, the validation of distinct brain mechanisms for acute pain and its relief is ongoing and strongly dependent on the employed experimental design. In the current study including a total of 28 subjects, a recently presented, innovative experimental approach was adopted that is able to clearly differentiate painful from non-pain perceptions without changing stimulus strength and while recording brain activity using functional magnetic resonance imaging (fMRI). Namely, we applied a repetitive and purely nociceptive stimulus to the tooth pulp with subsequent suppression of the nociceptive barrage via a regional nerve block. The study aims were 1) to replicate previous findings of acute pain demonstrating a fundamental role of the operculo-insular region and 2) to explore its functional connectivity during pain and subsequent relief. The brain activity reduction in the posterior insula (pINS) due to pain extinction was confirmed. In addition, the posterior S2 region (OP1) showed a similar activity pattern, thus confirming the relevance of the operculo-insular cortex in acute pain processing. Furthermore, the functional connectivity analysis yielded an enhanced positive coupling of the pINS with the cerebellar culmen during pain relief, whereas the OP1 demonstrated a positive coupling with the posterior midcingulate cortex during pain. The current results support the conceptual synthesis of localized specialization of pain processing with interactions across distributed neural targets.

The advent of neuroimaging in dental research provides exciting opportunities for relating excitation of trigeminal neurons to human somatosensory perceptions. Cold air sensitivity is one of the most frequent causes of dental discomfort or pain. Up to date, devices capable of delivering controlled cold air in an MR-environment are unavailable for quantitative sensory testing. This study therefore aimed at constructing and evaluating a novel MR-compatible, computer-controlled cold air stimulation apparatus (CASA) that produces graded air puffs. CASA consisted of a multi-injector air jet delivery system (AJS), a cold exchanger, a cooling agent, and a stimulus application construction. Its feasibility was tested by performing an fMRI stimulation experiment on a single subject experiencing dentine cold sensitivity. The novel device delivered repetitive, stable air stimuli ranging from room temperature (24.5°C ± 2°C) to −35°C, at flow rates between 5 and 17 liters per minute (l/min). These cold air puffs evoked perceptions similar to natural stimuli. Single-subject fMRI-analysis yielded brain activations typically associated with acute pain processing including thalamus, insular and cingulate cortices, somatosensory, cerebellar, and frontal brain regions. Thus, the novel CASA allowed for controlled, repetitive quantitative sensory testing by using air stimuli at graded temperatures (room temperature down to −35°C) while simultaneously recording brain responses. No MR-compatible stimulation device currently exists that is capable of providing non-contact natural-like stimuli at a wide temperature range to tissues in spatially restricted areas such as the mouth. The physical characteristics of this novel device thus holds promise for advancing the field of trigeminal and spinal somatosensory research, namely with respect to comparing therapeutic interventions for dentine hypersensitivity.

STUDY DESIGN: A cross-sectional comparative study between chronic low back pain (CLBP) patients and healthy control subjects. OBJECTIVE: The aim of this study was to investigate reorganization in the sensory cortex by comparing cortical activity due to mechanosensory stimulation of the lumbar spine in CLBP patients versus a control group by using functional magnetic resonance imaging (fMRI). SUMMARY OF BACKGROUND DATA: LBP is now the number 1 condition across the world in terms of years living with a disability. There is growing evidence that maladaptive changes in the processing of sensory input by the central nervous system are central to understanding chronic (back) pain. METHODS: Nonpainful, posterior-anterior (PA) movement pressure was applied manually to lumbar vertebrae at L1, L3, and L5 in 13 healthy subjects and 13 CLBP patients. The manual pressure (30 N) was monitored and controlled using sensors. A randomized stimulation protocol was used consisting of 51 pressure stimuli of 5 seconds duration. fMRI data analysis was performed for the group activation within the primary and secondary sensory cortices (S1 and S2, respectively) and the representation of the individual vertebrae was extracted and statistically analyzed. RESULTS: Nonpainful PA pressure revealed no cortical reorganization in S1. In contrast, the extent of S2 activation in the CLBP group was significantly reduced in both hemispheres. In the control group, a somatotopy was identified for the lumbar vertebrae between L1 and L3, respectively, and L5 in S2 of the right hemisphere. Most importantly, a blurring of the somatotopic representation of the lumbar spine in S2 was observed in the patient group. CONCLUSION: Together, these maladaptive changes suggest a reorganization of higher-order processing for sensory information in CLBP patients that might have implications for a decreased sensory acuity, also related to body perception and subsequent altered functioning of the lumbar spine. LEVEL OF EVIDENCE: 2.

Drug effects of loco-regional anesthetics are commonly measured by unidimensional pain rating scales. These scales require subjects to transform their perceptual correlates of stimulus intensities onto a visual, verbal, or numerical construct that uses a unitless cognitive reference frame. The conceptual understanding and execution of this magnitude estimation task may vary among individuals and populations. To circumvent inherent shortcomings of conventional experimental pain scales, this study used a novel perceptual reference approach to track subjective sensory perceptions during onset of an analgesic nerve block. In 34 male subjects, nociceptive electric stimuli of 1-ms duration were repetitively applied to left (target) and right (reference) mandibular canines every 5 s for 600 s, with a side latency of 1 ms. Stimulus strength to the target canine was programmed to evoke a tolerable pain intensity perception and remained constant at this level throughout the experiment. A dose of 0.6 ml of articaine 4% was submucosally injected at the left mental foramen. Subjects then reported drug effects by adjusting the stimulus strength (in milliamperes) to the reference tooth, so that the perceived intensity in the reference tooth was equi-intense to the target tooth. Pain and stimulus perception offsets were indicated by subjects. Thus, the current approach for matching the sensory experience in one anatomic location after regional anesthesia allows detailed tracking of evolving perceptual changes in another location. This novel perceptual reference approach facilitates direct and accurate quantification of analgesic effects with high temporal resolution. We propose using this method for future experimental investigations of analgesic/anesthetic drug efficacy.

Identification of brain regions that differentially respond to pain intensity may improve our understanding of trigeminally mediated nociception. This report analyzed cortical responses to painless and painful electrical stimulation of a right human maxillary canine tooth. Functional magnetic resonance images were obtained during the application of five graded stimulus strengths, from below, at, and above the individually determined pain thresholds. Study participants reported each stimulus on a visual rating scale with respect to evoked sensation. Based on hemodynamic responses of all pooled stimuli, a cerebral network was identified that largely corresponds to the known lateral and medial nociceptive system. Further analysis of the five graded stimulus strengths revealed positive linear correlations for the anterior insula bilaterally, the contralateral (left) anterior mid-cingulate, as well as contralateral (left) pregenual cingulate cortices. Cerebral toothache intensity coding on a group level can thus be attributed to specific subregions within the cortical pain network.

Local anesthesia has made dental treatment more comfortable since 1884, but little is known about associated brain mechanisms. Functional magnetic resonance imaging is a modern neuroimaging tool widely used for investigating human brain activity related to sensory perceptions, including pain. Most brain regions that respond to experimental noxious stimuli have recently been found to react not only to nociception alone, but also to visual, auditory, and other stimuli. Thus, presumed functional attributions have come under scrutiny regarding selective pain processing in the brain. Evidently, innovative approaches are warranted to identify cerebral regions that are nociceptive specific. In this study, we aimed at circumventing known methodological confounders by applying a novel paradigm in 14 volunteers: rather than varying the intensity and thus the salience of painful stimuli, we applied repetitive noxious dental stimuli at constant intensity to the left mandibular canine. During the functional magnetic resonance imaging paradigm, we suppressed the nociceptive barrage by a mental nerve block. Brain activity before and after injection of 4% articaine was compared intraindividually on a group level. Dental pain extinction was observed to correspond to activity reduction in a discrete region of the left posterior insular cortex. These results confirm previous reports demonstrating that direct electrical stimulation of this brain region—but not of others—evokes bodily pain sensations. Hence, our investigation adds further evidence to the notion that the posterior insula plays a unique role in nociceptive processing.

The collapse of the World Trade Center (WTC) buildings #2 (South Tower), #1 (North Tower), and #7 created an enormous collapse pile which emitted intense plumes of acrid smoke and dust until roughly mid-December, when the last spontaneous surface fire occurred. We collected particles by size (8 modes, ≈12 to 0.09 micrometers diameter) and time (typical resolution of 1 to 3 h) from October 2 until late December at the EML 201 Varick Street site roughly 1.8 km NNE of the collapse site and 50 m above ground level. Here we show some of the 70,000 mass and elemental data from the time period October 2 through October 30. Identification of a WTC collapse pile source for aerosols seen at the receptor site were based upon the simultaneous presence of finely powdered concrete, gypsum, and glass with intense very fine combustion mode mass episodes concurrent with winds from the southwest quadrant. The results, derived from seven independent beam-based analytical techniques, showed that while PM10 and PM2.5 24 h val...

The aim was to investigate the effect of mechanical pain stimulation at the lower back on hemodynamic and oxygenation changes in the prefrontal cortex (PFC) assessed by functional near-infrared spectroscopy (fNIRS) and on the partial pressure of end-tidal carbon dioxide ( PetCO 2) measured by capnography. 13 healthy subjects underwent three measurements (M) during pain stimulation using pressure pain threshold (PPT) at three locations, i.e., the processus spinosus at the level of L4 (M1) and the lumbar paravertebral muscles at the level of L1 on the left (M2) and the right (M3) side. Results showed that only in the M2 condition the pain stimulation elicited characteristic patterns consisting of (1) a fNIRS-derived decrease in oxy- and total hemoglobin concentration and tissue oxygen saturation, an increase in deoxy-hemoglobin concentration, (2) a decrease in the PetCO 2 response and (3) a decrease in coherence between fNIRS parameters and PetCO 2 responses in the respiratory frequency band (0.2-0.5 Hz). We discuss the comparison between M2 vs. M1 and M3, suggesting that the non-significant findings in the two latter measurements were most likely subject to effects of the different stimulated tissues, the stimulated locations and the stimulation order. We highlight that PetCO 2 is a crucial parameter for proper interpretation of fNIRS data in experimental protocols involving pain stimulation. Together, our data suggest that the combined fNIRS-capnography approach has potential for further development as pain monitoring method, such as for evaluating clinical pain treatment.

Objective The purpose of this study was to develop and test a clinically relevant method to mechanically stimulate lumbar functional spinal units while recording brain activity by means of functional magnetic resonance imaging (MRI). Methods Subjects were investigated in the prone position with their face lying on a modified stabilization pillow. To minimize head motion, the pillow was fixed to the MRI headrest, and supporting straps were attached around the shoulders. An experienced manual therapist applied controlled, nonpainful pressure stimuli to 10 healthy subjects at 3 different lumbar vertebrae (L1, L3, and L5). Pressure applied to the thumb was used as a control. The stimulation consisted of posterior to anterior (PA) pressure movement. The therapist followed a randomized stimulation protocol projected onto a screen in the MRI room. Blood oxygenation level–dependent responses were analyzed in relation to the lumbar and the thumb stimulations. The study was conducted by the Chiropractic Department, Faculty of Medicine, University of Zurich, Switzerland. Results No participant reported any discomfort due to the prone-lying position or use of the pillow. Importantly, PA-induced pressure produced only minimal head movements. Stimulation of the lumbar spinous processes revealed bilateral neural responses in medial parts of the postcentral gyrus (S1). Additional activity was observed in the secondary somatosensory cortex (S2), posterior parts of the insular cortex, different parts of the cingulate cortex, and the cerebellum. Thumb stimulations revealed activation only in lateral parts of the contralateral S1. Conclusion The current study demonstrates the feasibility of the application of PA pressure on lumbar spinous processes in an MRI environment. This approach may serve as a promising tool for further investigations regarding neuroplastic changes in chronic low back pain subjects.

AIM: Dentine hypersensitivity (DH) is characterized by a short, sharp pain arising from exposed dentin. Most published literature reports on peripheral neural aspects of this pain condition. The current investigation focused on differential cerebral activity elicited by stimulation of sensitive and insensitive teeth by means of natural air stimuli. MATERIALS AND METHODS: Five graded stimulus strengths were randomly applied by means of a multi-injector air jet delivery system, each followed by an individual rating of perceived stimulus intensity. Brain activity was analysed by functional magnetic resonance imaging (fMRI). RESULTS: Stimulation of sensitive teeth induced significant activation in the thalamus, somatosensory cortices (SI & SII), anterior, middle and posterior insular cortices, anterior mid cingulate cortex, perigenual anterior cingulate cortex and frontal regions (BA10 and BA46). Differential responses to DH and painless perceptions were observed in the anterior insula and anterior midcingulate cortex. CONCLUSION: For the first time, this fMRI study demonstrates the feasibility of investigating cerebral processes related to DH evoked by natural (air) stimuli. Our neuroimaging data additionally provide evidence that differential activity in the anterior Insula (aIC) and anterior midcingulate cortex (aMCC) may represent clinically relevant pain experienced by DH patients.

To evaluate whether induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex after stimulation of the right maxillary canine and to examine whether these metabolic changes and the subjective pain intensity perception correlate. Ten male volunteers were included in the pain group and compared with a control group of 10 other healthy volunteers. The pain group received a total of 87–92 electrically induced pain stimuli over 15 min to the right maxillary canine tooth. Contemporaneously, they evaluated the subjective pain intensity of every stimulus using an analogue scale. Neurotransmitter changes within the left insular cortex were evaluated by MR spectroscopy. Significant metabolic changes in glutamine (+55.1%), glutamine/glutamate (+16.4%) and myo-inositol (−9.7%) were documented during pain stimulation. Furthermore, there was a significant negative correlation between the subjective pain intensity perception and the metabolic levels of Glx, Gln, glutamate and N-acetyl aspartate. The insular cortex is a metabolically active region in the processing of acute dental pain. Induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex resulting in significant alterations in metabolites. Negative correlation between subjective pain intensity rating and specific metabolites could be observed.

The current fMRI study investigated cortical processing of electrically induced painful tooth stimulation of both maxillary canines and central incisors in 21 healthy, right-handed volunteers. A constant current, 150% above tooth specific pain perception thresholds was applied and corresponding online ratings of perceived pain intensity were recorded with a computerized visual analog scale during fMRI measurements. Lateralization of cortical activations was investigated by a region of interest analysis. A wide cortical network distributed over several areas, typically described as the pain or nociceptive matrix, was activated on a conservative significance level. Distinct lateralization patterns of analyzed structures allow functional classification of the dental pain processing system. Namely, certain parts are activated independent of the stimulation site, and hence are interpreted to reflect cognitive emotional aspects. Other parts represent somatotopic processing and therefore reflect discriminative perceptive analysis. Of particular interest is the observed amygdala activity depending on the stimulated tooth that might indicate a role in somatotopic encoding., Frontiers in Human Neuroscience, ISSN:1662-5161

Chronic low back pain (chronic LBP) is both debilitating for patients but also a major burden on the health care system. Previous studies reported various maladaptive structural and functional changes among chronic LBP patients on spine- and supraspinal levels including behavioral alterations. However, evidence for cortical reorganization in the sensorimotor system of chronic LBP patients is scarce. Motor Imagery (MI) is suitable for investigating the cortical sensorimotor network as it serves as a proxy for motor execution. Our aim was to investigate differential MI-driven cortical processing in chronic LBP compared to healthy controls (HC) by means of functional magnetic resonance imaging (fMRI). Twenty-nine subjects (15 chronic LBP patients, 14 HC) were included in the current study. MI stimuli consisted of randomly presented video clips showing every-day activities involving different whole-body movements as well as walking on even ground and walking downstairs and upstairs. Guided by the video clips, subjects had to perform MI of these activities, subsequently rating the vividness of their MI performance. Brain activity analysis revealed that chronic LBP patients exhibited significantly reduced activity compared to HC subjects in MI-related brain regions, namely the left supplementary motor area and right superior temporal sulcus. Furthermore, psycho-physiological-interaction analysis yielded significantly enhanced functional connectivity (FC) between various MI-associated brain regions in chronic LBP patients indicating diffuse and non-specific changes in FC. Current results demonstrate initial findings about differences in MI-driven cortical processing in chronic LBP pointing towards reorganization processes in the sensorimotor network., PLoS ONE, 10 (11), ISSN:1932-6203

For 26 days in mid-June and July 2000, a research group comprised of U.S. Navy, NASA, and university scientists conducted the Puerto Rico Dust Experiment (PRIDE). In this paper we give a brief overview of mean meteorological conditions during the study. We focus on findings on African dust transported into the Caribbean utilizing Navajo aircraft and AERONET Sun photometer data. During the study midvisible aerosol optical thickness (AOT) in Puerto Rico averaged 0.25, with a maximum less than 0.5 and with clean marine periods of _0.08. Dust AOTs near the coast of Africa (Cape Verde Islands and Dakar) averaged _0.4, 30% less than previous years. By analyzing dust vertical profiles in addition to supplemental meteorology and MPLNET lidar data we found that dust transport cannot be easily categorized into any particular conceptual model. Toward the end of the study period, the vertical distribution of dust was similar to the commonly assumed Saharan Air Layer (SAL) transport. During the early periods of the study, dust had the highest concentrations in the marine and convective boundary layers with only a, weak dust layer in the SAL being present, a state usually associated with wintertime transport patterns. We corroborate the findings of Maring et al. that in most cases, there was an unexpected lack of vertical stratification of dust particle size. We systematically analyze processes which may impact dust vertical distribution and determine and speculate that dust vertical distribution predominately influenced by flow patterns over Africa and differential advection couple with mixing by easterly waves and regional subsidence.

We analyzed the postmortem blood of a total of 100 fatal cases for beta-hydroxybutyric acid (BHBA). In 25 cases of sudden and unexpected death of alcoholics we found pathologically increased levels of BHBA of 1260 to 47200 (median 8000) micromol/L. This led us to the diagnosis of an alcoholic ketoacidosis (AKA) as cause of death in these cases. The control group of 69 postmortem cases revealed that BHBA concentrations below 500 can be regarded as normal, and values up to 2500 micromol/L as elevated. Our study shows that BHBA values over 2500 micromol/L could lead to death, if no medical attention is sought. During storage we did not find any indication of postmortem formation or decomposition of BHBA in blood in vitro or in the corpses. In our opinion, BHBA should be considered the diagnostic marker of choice for the postmortem determination of alcoholic ketoacidosis (AKA) as the cause of death. The classical indications of such deaths are: unexpected death of a chronic alcoholic; none or only traces of ethanol in the blood; increased acetone blood concentration; and neither autopsy, histology, microbiology, nor toxicology reveal the cause of death. In six further cases a diabetic ketoacidosis (DKA) was diagnosed as the cause of death.