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Heterotopic noxious counter-stimulation (HNCS) inhibits pain and pain processes through cerebral and cerebrospinal mechanisms. However, it is unclear whether HNCS inhibits non-nociceptive processes, which needs to be clarified for a better understanding of HNCS analgesia. The aim of this study was to examine the effects of HNCS on perception and scalp somatosensory evoked potentials (SEPs). Seventeen healthy volunteers participated in two counter-balanced sessions, including non-nociceptive (selective Aβ-fibre activation) or nociceptive electrical stimulation, combined with HNCS. HNCS was produced by a 20-min cold pressor test (left hand) adjusted individually to produce moderate pain (mean ± SEM: 42.5 ± 5.3 on a 0-100 scale, where 0 is no pain and 100 the worst pain imaginable). Non-nociceptive electrical stimulation was adjusted individually at 80% of pain threshold and produced a tactile sensation in every subject. Nociceptive electrical stimulation was adjusted individually at 120% of RIII-reflex threshold and produced moderate pain (45.3 ± 4.5). Shock sensation was significantly decreased by HNCS compared with baseline for non-nociceptive (P < 0.001) and nociceptive (P < 0.001) stimulation. SEP peak-to-peak amplitude at Cz was significantly decreased by HNCS for non-nociceptive (P < 0.01) and nociceptive (P < 0.05) stimulation. These results indicate that perception and brain activity related to Aβ-fibre activation are inhibited by HNCS. The mechanisms of this effect remain to be investigated to clarify whether it involves inhibition of spinal wide-dynamic-range neurons by diffuse noxious inhibitory controls, supraspinal processes or both., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

We present a new approach, based on Richards-Wolf formalism, to rigorously model nonparaxial focusing of radially and azimuthally polarized electromagnetic beams by axisymmetric systems without a single-point focus. Our approach is based on a combined method that uses ray tracing and diffraction integrals. Our method is validated by comparing known results obtained with a parabolic mirror. Our integral representation of the focused beams, compliant with diffraction theory, is thoroughly discussed and solved for various conics that, so far, have not been treated analytically. The extension of the method to other polarization states is straightforward.

Objective: To determine whether there are differences in the anatomical cleft measurements between patients with isolated cleft palate (CP) with or without Pierre Robin sequence (PR) and those with cleft lip and palate (CLP)., Design: Prospective case series., Setting: Tertiary care university-based medical center., Patients: From 1993 to 2012, CP and CLP patients were prospectively enrolled in a database., Main Outcome Measures: Several anatomical cleft parameters were recorded with precise measurements at the time of palatoplasty under general anesthesia., Results: One hundred twenty-five patients were included in our study: 50 patients in the CP without PR group, 87 patients in the CP with or without PR (CPPR) group, and 38 patients in the CLP group. Patients in the CLP group had increased values for the following parameters compared to patients with CP and patients with CPPR: nasopharyngeal depth (P = .02 and P = .01, respectively); cleft width at posterior hard palate border (P < .001 and P < .001); width of the dental arch (P < .001 and P < .001); and total cleft length (P < 01 and P < .001). For cleft width at the soft palate level, there was a significant difference between the CP and CLP groups (P = .005). We found no statistically significant differences between the groups (CLP versus CP and CPPR, respectively) for the length of the soft palate (P = .74, P = .21) or for the length of the hard palate (P = .19, P = .08)., Conclusion: There are significant differences in cleft and palate measurements between CLP and CP patients that may be useful to predict the occurrence of velopharyngeal insufficiency or other complications.

Erbium-doped mode-locked fiber lasers with repetition rates comparable to those of solid-state lasers and generating nJ pulses are required for many applications. Our goal was to design a fiber laser that would meet such requirements, that could be built at relatively low cost and that would be reliable and robust. We thus developed a high-fundamental-repetition-rate erbium-doped all-fiber laser operating in the amplifier similariton regime. Experimental characterization shows that this laser, which is mode-locked by nonlinear polarization evolution, emits 76-fs pulses with an energy of 1.17 nJ at a repetition rate of 100 MHz. Numerical simulations support the interpretation of self-similar evolution of the pulse in the gain fiber. More specifically we introduce the concept of vector similariton in fiber lasers. The coupled x- and y- polarization components of such a pulse have a pulse profile with a linear chirp and their combined power profile evolves self-similarly when the nonlinear asymptotic regime is reached in the gain fiber.

This article presents, for the first time to our knowledge, an all-fiber amplifier similariton laser based on a fiber Bragg grating filter. The laser emits 2.9 nJ pulses at a wavelength of 1554 nm with a repetition rate of 31 MHz. The dechirped pulses have a duration of 89 fs. The characteristic features of the pulse profile and spectrum along with the dynamics of the laser are highlighted in representative simulations. These simulations also address the effect of the filter shape and detuning with respect to the gain spectral peak.

The pulvinar is the largest extrageniculate thalamic visual nucleus in mammals. It establishes reciprocal connections with virtually all visual cortexes and likely plays a role in transthalamic cortico-cortical communication. In cats, the lateral posterior nucleus (LP) of the LP-pulvinar complex can be subdivided in two subregions, the lateral (LPl) and medial (LPm) parts, which receive a predominant input from the striate cortex and the superior colliculus, respectively. Here, we revisit the receptive field structure of LPl and LPm cells in anesthetized cats by determining their first-order spatiotemporal profiles through reverse correlation analysis following sparse noise stimulation. Our data reveal the existence of previously unidentified receptive field profiles in the LP nucleus both in space and time domains. While some cells responded to only one stimulus polarity, the majority of neurons had receptive fields comprised of bright and dark responsive subfields. For these neurons, dark subfields' size was larger than that of bright subfields. A variety of receptive field spatial organization types were identified, ranging from totally overlapped to segregated bright and dark subfields. In the time domain, a large spectrum of activity overlap was found, from cells with temporally coinciding subfield activity to neurons with distinct, time-dissociated subfield peak activity windows. We also found LP neurons with space-time inseparable receptive fields and neurons with multiple activity periods. Finally, a substantial degree of homology was found between LPl and LPm first-order receptive field spatiotemporal profiles, suggesting a high integration of cortical and subcortical inputs within the LP-pulvinar complex., (Copyright © 2015 the American Physiological Society.)

This study examines the effect of normal aging on temporal summation (TS) of pain and the nociceptive flexion reflex (RIII). Two groups of healthy volunteers, young and elderly, received transcutaneous electrical stimulation applied to the right sural nerve to assess pain and the nociceptive flexion reflex (RIII-reflex). Stimulus intensity was adjusted individually to 120% of RIII-reflex threshold, and shocks were delivered as a single stimulus or as a series of 5 stimuli to assess TS at 5 different frequencies (0.17, 0.33, 0.66, 1, and 2 Hz). This study shows that robust TS of pain and RIII-reflex is observable in individuals aged between 18 and 75 years and indicates that these effects are comparable between young and older individuals. These results contrast with some previous findings and imply that at least some pain regulatory processes, including TS, may not be affected by normal aging, although this may vary depending on the method.

The development of a novel broadband and tunable optical parametric generator (OPG) is presented. The OPG properties are studied numerically and experimentally in order to optimize the generator's use in a broadband spectroscopic LIDAR operating in the short and mid-infrared. This paper discusses trade-offs to be made on the properties of the pump, crystal, and seeding signal in order to optimize the pulse spectral density and divergence while enabling energy scaling. A seed with a large spectral bandwidth is shown to enhance the pulse-to-pulse stability and optimize the pulse spectral density. A numerical model shows excellent agreement with output power measurements; the model predicts that a pump having a large number of longitudinal modes improves conversion efficiency and pulse stability.

A strategy to align a mode-locked fiber laser with nonlinear polarization rotation is presented. This strategy is based on measurements of the output polarization state. It is shown that, as the angle of a motorized polarization controller inside the cavity is swept, the laser eventually reaches a mode-locked regime and the values of the Stokes parameters undergo an abrupt change. The sensing of this sudden variation is thus used to detect the mode-locking condition and a feedback mechanism drives the alignment of the polarization controller to force mode locking.

Background: In anesthetized rats and conscious humans, a gentle touch using a soft disc covered with microcones (with a texture similar to that of a finger), but not with a flat disc, inhibits nociceptive somatocardiac reflexes. Such an inhibitory effect is most reliably evoked when touch is applied to the skin ipsilateral and closest to nociceptive inputs. However, the mechanism of this inhibition is not completely elucidated. We aimed to clarify the types of cutaneous afferent fibers and spinal opioid receptors that contribute to antinociceptive effects of microcone touch., Results: The present study comprised two experiments with urethane-anesthetized rats. In the first experiment, unitary activity of skin afferent fibers was recorded from the saphenous nerve, and responses to a 10-min touch using a microcone disc and a flat disc (control) were compared. Greater discharge rate during microcone touch was observed in low-threshold mechanoreceptive Aδ and C afferent units, whereas many Aβ afferents responded similarly to the two types of touch. In the second experiment, the effect of an intrathecal injection of opioid receptor antagonists on the inhibitory effects of microcone touch on heart rate responses to noxious heat stimulation was examined. The magnitude of the heart rate response was significantly reduced by microcone touch in rats that received saline or naltrindole (δ-opioid receptor antagonist) injections. However, such an inhibition was not observed in rats that received naloxone (non-selective opioid receptor antagonist) or Phe-Cys-Tyr-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; μ-opioid receptor antagonist) injections., Conclusions: Microcone touch induced greater responses of low-threshold mechanoreceptive Aδ and C afferent units than control touch. The antinociceptive effect of microcone touch was abolished by intrathecal injection of μ-opioid receptor antagonist. These results suggest that excitation of low-threshold mechanoreceptive Aδ and C afferents produces the release of endogenous μ-opioid ligands in the spinal cord, resulting in the inhibition of nociceptive transmission that contributes to somatocardiac reflexes.

The anatomy of the somatosensory system allows both serial and parallel information flow but the conditions involving each mode of processing is a matter of debate. In this functional magnetic resonance imaging (fMRI) study, cutaneous electrical stimulation was applied to human volunteers at three intensities (low-innocuous, moderate-noxious and high-noxious) to investigate interactions between contralateral primary and secondary somatosensory cortices (S1c and S2c), and between contralateral and ipsilateral S2 (S2c and S2i), using dynamic causal modeling (DCM). Our results are consistent with serial processing with a key role of the direct input to S1c for all three intensity levels. The more intense stimulus also induced significantly more interactions between S2i and S2c, consistent with an increase in inter-hemispheric integration associated with the additional recruitment of nociceptive inputs. However, stronger pain reports were also associated with reduced information flow from S1c to S2c at both the moderate (r=-0.81, p=0.004) and the high stimulation level (r=-0.63, p=0.037). These findings suggest that the connectivity pattern driven by innocuous inputs is modified by the additional activation of nociceptive afferents., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Patients with chronic low back pain exhibit characteristics such as clinical pain, psychological symptoms and neuromuscular adaptations. The purpose of this study was to determine the independent contribution of clinical pain, psychological factors and neuromuscular adaptations to disability in patients with chronic low back pain. Clinical pain intensity, pain catastrophizing, fear-avoidance beliefs, anxiety, neuromuscular adaptations to chronic pain and neuromuscular responses to experimental pain were assessed in 52 patients with chronic low back pain. Lumbar muscle electromyographic activity was assessed during a flexion-extension task (flexion relaxation phenomenon) to assess both chronic neuromuscular adaptations and neuromuscular responses to experimental pain during the task. Multiple regressions showed that independent predictors of disability included neuromuscular adaptations to chronic pain (β=0.25, p=0.006, sr(2)=0.06), neuromuscular responses to experimental pain (β=-0.24, p=0.011, sr(2)=0.05), clinical pain intensity (β=0.28, p=0.002, sr(2)=0.08) and psychological factors (β=0.58, p<0.001, sr(2)=0.32). Together, these predictors accounted for 65% of variance in disability (R(2)=0.65 p<0.001). The current investigation revealed that neuromuscular adaptations are independent from clinical pain intensity and psychological factors, and contribute to inter-individual differences in patients' disability. This suggests that disability, in chronic low back pain patients, is determined by a combination of factors, including clinical pain, psychological factors and neuromuscular adaptations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The effects of non-noxious skin stimulation on nerve growth factor (NGF) secretion in the parietal cortex were examined in anesthetized rats. Innocuous skin stimulation was delivered to the left hindlimb with a soft-hair brush. Extracellular NGF in the right parietal cortex was collected by microdialysis methods using a protein-permeable probe and was measured using an enzyme-linked immune-sorbent assay. Brushing produced a significant increase in extracellular NGF levels. This NGF response was not observed in rats pretreated with a nicotinic ACh receptor (nAChR) antagonist mecamylamine. We further examined whether brushing could activate the basal forebrain nucleus (nucleus basalis of Meynert, NBM), which is the main source of cholinergic fibers in the cerebral cortex, by means of functional MRI. The blood oxygen level-dependent signal in the right NBM was significantly higher during brushing compared to baseline. The results suggest that non-noxious skin stimulation activates NBM and promotes NGF secretion in the parietal cortex via nAChRs.

The aim of this study was to investigate the association between the magnitude of anti-nociceptive effects induced by heterotopic noxious counter-stimulation (HNCS) and the basal μ-opioid receptor availability in the amygdala. In 8 healthy volunteers (4 females and 4 males), transcutaneous electrical stimulation was applied to the right sural nerve to produce the nociceptive flexion reflex (RIII-reflex), moderate pain, and scalp somatosensory evoked potentials (SEPs). Immersion of the left hand in cold water for 20min was used as HNCS. In a separate session, basal μ-opioid receptor availability was measured using positron emission tomography with the radiotracer [(11)C]carfentanil. HNCS produced a reduction of the P260 amplitude (p<0.05), a late component of SEP that reflects activity in the anterior cingulate cortex. This reduction was associated with higher basal μ-opioid receptor availability in the amygdala on the right (R(2)=0.55, p=0.03) with a similar trend on the left (R(2)=0.24, p=0.22). Besides, HNCS did not induce significant changes in pain and RIII-reflex amplitude (p>0.05). These results suggest that activation of μ-opioid receptors in the amygdala may contribute to the anti-nociceptive effects of HNCS. The lack of RIII-reflex modulation further suggests that μ-opioid receptor activation in the amygdala contributes to decrease pain-related brain activity through a cerebral mechanism independent of descending modulation., (Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

The analgesic effect of heterotopic noxious counter-stimulation (HNCS; "pain inhibits pain") has been shown to decrease in older persons, while some neuropsychological studies have suggested a reduction in cognitive inhibition with normal aging. Taken together, these findings may reflect a generalized reduction in inhibitory processes. The present study assessed whether the decline in the efficacy of pain inhibition processes is associated with decreased cognitive inhibition in older persons. Healthy young (18-46 years old; n=21) and older (56-75 years old; n=23) adult volunteers participated in one experimental session to assess the effect of HNCS (cold pain applied on the left forearm) on shock pain and RIII reflex induced by transcutaneous electrical stimulation of the right sural nerve. In the same session, participants also performed a modified Stroop task, including a target condition requiring the frequent switching between inhibition and no inhibition of the meaning of color words. The analgesic effect induced by HCNS was significantly smaller in older participants for both shock-pain ratings (P<0.001) and RIII-reflex amplitude (P<0.05). The Stroop effect was significantly larger in elderly participants in the inhibition trials of the switching condition. Increased cognitive interference (ie, larger Stroop effect) correlated with smaller inhibition of the RIII reflex by HNCS across groups (r=-.34, P=0.025). This association was independent from the age-related slowing observed in control reading and naming tasks. These results suggest a generalized age-related reduction in inhibitory processes affecting both executive functions and cerebrospinal processes involved in the regulation of pain-related responses induced by competing nociceptive threats., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

By incorporating two linearly chirped ultrabroadband fiber Bragg gratings of opposite dispersion in an all-fiber ring laser, we demonstrate a mode-locking regime in which a femtosecond pulse evolving in the normal dispersion gain segment is locally transformed into a highly chirped picosecond pulse that propagates in the remaining section of the cavity. By minimizing nonlinear effects and avoiding soliton pulse shaping in this anomalous-dispersion section, low repetition rate fiber lasers can be made to produce high-energy ultrashort pulses. Using this approach, 98 fs pulses with 0.96 nJ of energy are obtained from an erbium-doped fiber laser operated in the highly anomalous dispersion regime at a repetition rate of 9.4 MHz.

Background: We conducted a retrospective case review of patients with mastoid cavity and active or inactive chronic otitis media (COM) who underwent cochlear implantation and ear obliteration in a single-stage procedure. The objectives of this review are to assess the rates of complications and postoperative infections and to evaluate post-implantation audiologic performance., Materials and Methods: All patients with COM and mastoid cavity, associated or not with active disease, who undergo cochlear implantation and obliteration of the ear as a single-stage procedure from November 2004 to April 2013, were included in the review. All the complications were recorded. Open-set sentence scores were used to evaluate the audiologic gain after implantation., Results: Twenty-seven patients were included in our review: Ten with active COM and seventeen with inactive COM. Overall, nine patients (9/27) presented post-operative complications (7/9 were minor): three were amongst active COM patients (30%) as compared to six amongst inactive COM patients (35%), which included the two major complications. A mean gain of 55.9% on open-set sentence scores was obtained after cochlear implantation., Discussion: We found that complications rate of the one-stage cochlear implantation was higher in patients with COM than in global implant population, but most complications were minors and there was no statistical difference between active and inactive COM. In addition, these patients had audiologic scores similar to those found in patients with normal temporal bone anatomy., Conclusion: Cochlear implantation performed as a one-stage procedure could be considered as an option of treatment to avoid staging in patients with active and inactive COM. Although these patients need a regular follow-up, they present good post-implantation audiometric scores.

The aim of this study was to examine gastric motility and blood flow during nociceptive hypertonic saline injections (HS) in paraspinal muscles of urethane-anaesthetised rats. Gastric pressure was not affected by HS in intact or vagotomised conditions. After cervical spinalisation, it was decreased by injections at T13 or L6 but not T2. Moreover, HS injections at T13 produced greater gastric pressure decreases compared with L6 and T2 and increased gastric sympathetic nerve activity. Blood pressure and gastric blood flow were decreased by T13 injections in spinal cord intact but not spinalised rats. Besides, isotonic saline injections (non-nociceptive) produced non-significant or marginal effects. These results indicate that gastric motility is decreased by nociceptive input from paraspinal muscles in spinalised rats through activation of the gastric sympathetic nerve. Although gastric blood flow was also decreased by nociceptive stimulation at T13 in spinal cord intact rats, these changes seem to depend on blood pressure.

We propose a simple laser-driven electron acceleration scheme based on tightly focused radially polarized laser pulses for the production of femtosecond electron bunches with energies in the few-hundreds-of-keV range. In this method, the electrons are accelerated forward in the focal volume by the longitudinal electric field component of the laser pulse. Three-dimensional test-particle and particle-in-cell simulations reveal the feasibility of generating well-collimated electron bunches with an energy spread of 5% and a temporal duration of the order of 1 fs. These results offer a route towards unprecedented time resolution in ultrafast electron diffraction experiments.

The voluntary control of respiration is used as a common means to regulate pain and emotions and is fundamental to various relaxation and meditation techniques. The aim of the present study was to examine how breathing frequency and phase affect pain perception, spinal nociceptive activity (RIII-reflex) and brain activity (scalp somatosensory-evoked potentials - SEP's). In 20 healthy volunteers, painful electric shocks individually adjusted to 120% of the RIII-reflex threshold were delivered to the sural nerve near the end of inspiration or expiration phases, during three cued-breathing conditions: (1) slow breathing (0.1 Hz) with slow (4s) inspiration (0.1Hz-SlowIns), (2) slow breathing (0.1 Hz) with fast (2s) inspiration (0.1 Hz-FastIns), and (3) normal breathing (0.2 Hz) with fast (2s) inspiration (0.2 Hz). Pain ratings were not affected by breathing patterns (p=0.3), but were significantly lower during inspiration compared with expiration (p=0.02). This phase effect was also observed on the N100 component of SEP's, but only in the 0.1-Hz-FastIns condition (p=0.03). In contrast, RIII-reflex amplitude was greater during inspiration compared with expiration (p=0.02). It was also decreased in the 0.1-Hz-SlowIns compared with the 0.2-Hz condition (p=0.01). Slow breathing also increased the amplitude of respiratory sinus arrhythmia (RSA), although these changes were not significantly associated with changes in pain responses. In conclusion, this study shows that pain and pain-related brain activity may be reduced during inspiration but these changes are dissociated from spinal nociceptive transmission. The small amplitude of these effects suggests that factors other than respiration contribute to the analgesic effects of relaxation and meditation techniques., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

We implement switching laser mode coherent anti-Stokes Raman-scattering (SLAM-CARS) microscopy to enhance the spatial resolution and contrast in label-free vibrational microscopy. The method, based on the intensity difference between two images obtained with Gaussian and doughnut-shaped modes, does not depend on the specimen and relies on minimal modifications of the typical CARS setup. We demonstrate subdiffraction resolution imaging of myelin sheaths in a mouse brainstem. A lateral resolution of 0.36λ(p) is achieved.

Background Context: Alterations of the neuromuscular control of the lumbar spine have been reported in patients with chronic low back pain (LBP). During trunk flexion and extension tasks, the reduced myoelectric activity of the low back extensor musculature observed during full trunk flexion is typically absent in patients with chronic LBP., Purpose: To determine whether pain expectations could modulate neuromuscular responses to experimental LBP to a higher extent in patients with chronic LBP compared with controls., Study Design: A cross-sectional, case-control study., Patient Sample: Twenty-two patients with nonspecific chronic LBP and 22 age- and sex-matched control participants., Methods: Trunk flexion-extension tasks were performed under three experimental conditions: innocuous heat, noxious stimulation with low pain expectation, and noxious stimulation with high pain expectation. Noxious stimulations were delivered using a contact heat thermode applied on the skin of the lumbar region (L4-L5), whereas low or high pain expectations were induced by verbal and visual instructions., Outcome Measures: Surface electromyography of erector spinae at L2-L3 and L4-L5, as well as lumbopelvic kinematic variables were collected during the tasks. Pain was evaluated using a numerical rating scale. Pain catastrophizing, disability, anxiety, and fear-avoidance beliefs were measured using validated questionnaires., Results: Two-way mixed analysis of variance revealed that pain was significantly different among the three experimental conditions (F2,84=317.5; p<.001). Increased myoelectric activity of the low back extensor musculature during full trunk flexion was observed in the high compared with low pain expectations condition at the L2-L3 level (F2,84=9.5; p<.001) and at the L4-L5 level (F2,84=3.7; p=.030). At the L4-L5 level, this effect was significantly more pronounced for the control participants compared with patients with chronic LBP (F2,84=3.4; p=.045). Pearson correlation analysis revealed that increased lumbar muscle activity in full flexion induced by expectations was associated with higher pain catastrophizing in patients with chronic LBP (r=0.54; p=.012)., Conclusions: Repeated exposure to pain appears to generate rigid and less variable patterns of muscle activation in patients with chronic LBP, which attenuate their response to pain expectations. Patients with high levels of pain catastrophizing show higher myoelectric activity of lumbar muscles in full flexion and exhibit greater neuromechanical changes when expecting strong pain., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Unlabelled: Patients with irritable bowel syndrome (IBS) are affected by chronic abdominal pain and show decreased pain inhibition. Moreover, they exhibit differences in brain morphology compared with healthy volunteers. The aim of this study was to examine whether decreased pain inhibition is associated with altered brain morphology in IBS patients. Structural magnetic resonance imaging scans were acquired in 14 female patients with diarrhea-predominant IBS and 14 controls. Pain and anxiety modulation were characterized using electrical stimulation of the sural nerve and heterotopic noxious counterstimulation. IBS patients reported decreased pain inhibition (P = .02) as well as increased shock anxiety, pain catastrophizing, depressive symptoms, and trait anxiety (P's ≤ .05). IBS patients also showed a thicker right posterior insula (pINS), associated with longer IBS duration (r = .67, P = .02). In addition, thicker right lateral orbitofrontal cortex was strongly associated with less pain inhibition in both IBS patients (r = .70, P = .02) and controls (r = .68, P = .01). Results are consistent with the role of the insula in interoception and pain and suggest that IBS may induce thickening of the pINS. Reduced pain inhibition may further involve a modification of the regulatory influence of the orbitofrontal cortex on pain-related processes., Perspective: This study investigated the brain morphology of IBS patients. IBS patients showed thicker right pINS, associated with longer disease duration but not with psychological symptoms. This suggests that IBS induces thickening of pINS, which may contribute to its pathophysiology, consistent with the role of the pINS in interoception and pain., (Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.)

The cortical area located in the lateral portion of the posteromedial suprasylvian sulcus (PMLS) is considered a key area for motion processing. It receives major projections from areas 17 and 18 but also from the lateral posterior-pulvinar complex where neurons exhibit, for the most part, complex receptive fields (RF). Based on these inputs, complex-like RFs would be expected for PMLS neurons and results from hand-plot mapping support this idea. However, PMLS neurons' first-order spatiotemporal RF profiles and their role in shaping neuronal response characteristics is currently unknown. In this study, the first-order spatiotemporal characteristics of PMLS cells were revealed using reverse correlation analysis, based on responses elicited by coarse white noise stimuli. Experiments were carried out in adult anesthetized cats. Detailed RF profiles were obtained by analyzing bright and dark subfields separately. Results indicate that the average maximal spike probability is higher for dark subfields than for their paired bright subfields. Spatial RF analysis shows that neurons exhibit oval RF subfields and that their size is larger for dark subfields. The majority of cells have complex-like profiles, with spatially overlapping RF subfields. Temporal analysis showed that for the majority of cells, subfields are coincidentally activated; however, a subset of neurons exhibit time-dissociated subfield peak activity windows. Correlation analysis between spatial and temporal parameters of RF subfields and their neuron's response characteristics to gratings was also performed. The data show that the direction index is positively correlated with subfield size difference and negatively correlated with spatial subfield overlap. Modulation index is negatively correlated with the degree of temporal subfield activity overlap. We conclude that first-order RF structures are important functional factors that shape PMLS neurons response characteristics., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Neuroimaging methods such as functional magnetic resonance imaging (fMRI) have been used extensively to investigate pain-related cerebral mechanisms. However, these methods rely on a tight coupling of neuronal activity to hemodynamic changes. Because pain may be associated with hemodynamic changes unrelated to local neuronal activity (eg, increased mean arterial pressure [MAP]), it is essential to determine whether the neurovascular coupling is maintained during nociceptive processing. In this study, local field potentials (LFP) and cortical blood flow (CBF) changes evoked by electrical stimulation of the left hind paw were recorded concomitantly in the right primary somatosensory cortex (SI) in 15 rats. LFP, CBF, and MAP changes were examined in response to stimulus intensities ranging from 3 to 30 mA. In addition, LFP, CBF, and MAP changes evoked by a 10-mA stimulation were examined during immersion of the tail in non-nociceptive or nociceptive hot water (counter-stimulation). SI neurovascular coupling was altered for stimuli of nociceptive intensities (P<0.001). This alteration was intensity-dependent and was strongly associated with MAP changes (r=0.98, P<0.001). However, when the stimulus intensity was kept constant, SI neurovascular coupling was not significantly affected by nociceptive counter-stimulation (P=0.4), which similarly affected the amplitude of shock-evoked LFP and CBF changes. It remains to be determined whether such neurovascular uncoupling occurs in humans, and whether it also affects other regions usually activated by painful stimuli. These results should be taken into account for accurate interpretation of fMRI studies that involve nociceptive stimuli associated with MAP changes., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Laser scanning microscopy allows for three-dimensional imaging of cells with molecular specific labeling. However the spatial resolution of optical microscopy is fundamentally limited by the diffraction of light. In the last two decades many techniques have been introduced to enhance the resolution of laser scanning microscopes. However most of these techniques impose strong constraints on the specimen or rely on complex optical systems. These constraints limit the applicability of resolution improvement to various imaging modalities and sample types. To overcome these limitations, we introduce here a novel approach, which we called Switching LAser Mode (SLAM) microscopy, to enhance resolution and contrast in laser scanning microscopy. SLAM microscopy relies on subtracting images obtained with dark and bright modes, and exploits the smaller dimensions of the dark spot of the azimuthally polarized TE 01 mode. With this approach, resolution is improved by a factor of two in confocal microscopy. The technique is not based on complex nonlinear processes and thus requires laser power similar to that used in conventional imaging, minimizing photo-damage. The flexibility of the approach enables retrofitting in commercial confocal and two-photon microscopes and opens avenues for resolution enhancement in fluorescence-independent microscopy.

In the study of laser-driven electron acceleration, it has become customary to work within the framework of paraxial wave optics. Using an exact solution to the Helmholtz equation as well as its paraxial counterpart, we perform numerical simulations of electron acceleration with a high-power TM(01) beam. For beam waist sizes at which the paraxial approximation was previously recognized valid, we highlight significant differences in the angular divergence and energy distribution of the electron bunches produced by the exact and the paraxial solutions. Our results demonstrate that extra care has to be taken when working under the paraxial approximation in the context of electron acceleration with radially polarized laser beams.

Biofeedback training is an efficient means to gain control over a physiological function typically considered involuntary. Accordingly, learning to self-regulate nociceptive physiological activity may improve pain control by activating endogenous modulatory processes. The aim of the present study was to assess whether trial-by-trial visual feedback of nociceptive flexion reflex (RIII-reflex) responses (an index of spinal nociception) evoked by brief painful shocks applied to the sural nerve could be beneficial to guide participants in adopting strategies aiming at modulating pain perception. In order to determine specific changes induced by biofeedback, the modulation of RIII-reflex amplitude and pain ratings was compared following instructions to increase or decrease RIII-reflex amplitude in three groups, including a biofeedback group receiving a visual signal corresponding to the RIII-reflex amplitude (valid feedback), a sham biofeedback group (similar but invalid feedback), and a control group receiving no feedback. Results indicate that participants in all three groups could gain control over RIII-reflex (p<0.001), resulting in the modulation of pain intensity (p<0.001) and pain unpleasantness (p<0.001). The biofeedback group was not significantly superior to the sham and the control groups in the modulation of RIII-reflex amplitude, pain intensity or unpleasantness. These results are consistent with the notion that RIII-reflex amplitude and pain perception can be modulated voluntarily by various cognitive strategies. However, immediate retrospective visual feedback of acute nociceptive responses presented iteratively in successive trials may not improve the efficacy of these self-regulation processes., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: The present study examined the contribution of expectations to analgesia induced by heterotopic noxious counter-stimulation (HNCS) in healthy volunteers assigned to a control group or 1 of 3 experimental groups in which expectations were either assessed (a priori expectations) or manipulated using suggestions (hyperalgesia and analgesia). Acute shock-pain, the nociceptive flexion reflex (RIII-reflex), and shock-related anxiety were measured in response to electrical stimulations of the right sural nerve in the baseline, HNCS, and recovery periods. Counter-stimulation was applied on the contralateral forearm using a flexible cold pack. A priori expectations were strongly associated with the actual magnitude of the analgesia induced by HNCS. In comparison to the control condition, suggestions of hyperalgesia led to an increase in RIII-reflex amplitude and shock-pain, while suggestions of analgesia resulted in a greater decrease in RIII-reflex amplitude, which confirms that the analgesic process normally activated by HNCS can be blocked or enhanced by the verbal induction of expectations through suggestions. Changes in shock-anxiety induced by these suggestions were correlated to changes in shock-pain and RIII-reflex, but these changes did not emerge as a mediator of the association between manipulated expectations and HNCS analgesia. Overall, the results demonstrate that HNCS analgesia is modulated by expectations, either from a priori beliefs or suggestions, and this appears to be independent of anxiety processes., Perspective: This study demonstrates that a priori and manipulated expectations can enhance or block HNSC analgesia. Results also suggest that expectations might influence responses to analgesic treatments by altering descending modulation and contribute to observed deficit in pain inhibition processes of chronic pain patients., (Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.)

The evaluation of spinal cord neuronal activity in humans with functional magnetic resonance imaging (fMRI) is technically challenging. Major difficulties arise from cardiac and respiratory movement artifacts that constitute significant sources of noise. In this paper we assessed the Correction of Structured noise using spatial Independent Component Analysis (CORSICA). FMRI data of the cervical spinal cord were acquired in 14 healthy subjects using gradient-echo EPI. Nociceptive electrical stimuli were applied to the thumb. Additional data with short TR (250 ms, to prevent aliasing) were acquired to generate a spatial map of physiological noise derived from Independent Component Analysis (ICA). Physiological noise was subsequently removed from the long-TR data after selecting independent components based on the generated noise map. Stimulus-evoked responses were analyzed using the general linear model, with and without CORSICA and with a regressor generated from the cerebrospinal fluid region. Results showed higher sensitivity to detect stimulus-related activation in the targeted dorsal segment of the cord after CORSICA. Furthermore, fewer voxels showed stimulus-related signal changes in the CSF and outside the spinal region, suggesting an increase in specificity. ICA can be used to effectively reduce physiological noise in spinal cord fMRI time series., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate the alteration of pain-induced neuromuscular trunk responses by expectations in healthy volunteers., Methods: Twenty-three asymptomatic participants performed series of flexion-extension movements in 3 different experimental conditions: innocuous heat stimulation (control) and noxious heat stimulation associated with expectations of low or high pain intensity. These stimuli were administered by a contact thermode placed over the lumbar region (L4 and L5) to assess the modulation of neuromuscular responses and kinematics during the flexion-extension task. Surface electromyography (EMG) of lumbar erector spinae at L2 and L3 and L4 and L5 as well as lumbopelvic kinematic variables were compared across conditions., Results: Noxious stimulation significantly altered EMG responses but only in full trunk flexion. Interestingly, this alteration was significant only for muscles where noxious stimulation was applied (L4 and L5) and not for the other segment (L2 and L3). Conversely, expectations significantly altered EMG activity at L2 and L3 but not at the segment where noxious stimulation was applied., Conclusion: These results confirm previous findings and indicate that experimental pain can alter neuromuscular responses during a trunk flexion-extension task. Furthermore, this study suggests that expectations can alter some of these alterations. Future studies should determine whether neuromuscular changes induced by expectations may contribute to the transition from acute to chronic low-back pain., (Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.)

Heterotopic noxious counterstimulation (HNCS) by the application of a sustained noxious stimulus has been shown to inhibit nociceptive processes and decrease pain induced by a competing noxious stimulus. However, it is still not clear how attentional processes contribute to these effects. The main objective of this study was to compare the analgesic effects of HNCS in 2 sessions during which top-down attention was manipulated. Acute shock pain and the nociceptive flexion reflex were evoked by transcutaneous electrical stimulations of the right sural nerve in 4 blocks (15 stimuli/block): baseline, heterotopic innocuous counterstimulation (HICS), HNCS, and recovery. Counterstimulation was applied on the left upper limb with a thermode (HICS) or a cold pack (HNCS). Attention was manipulated between sessions by instructing participants to focus their attention on shock pain or counterstimulation. Shock pain ratings decreased significantly during counterstimulation (P<.001) with stronger effects of HNCS vs HICS in both sessions (P<.01). Furthermore, shock pain inhibition during HNCS relative to baseline was stronger with attention focusing on counterstimulation compared to attention focusing on shocks (P = .015). However, the relative decrease in pain ratings during HNCS vs HICS was not significantly affected by the direction of attention (P = .7). As for spinal nociceptive processes, nociceptive flexion reflex amplitude was significantly decreased during counterstimulation (P<.001) with larger reductions during HNCS compared to HICS (P = .03). However, these effects were not altered by attention (P = .35). Together, these results demonstrate that top-down attention and HNCS produce additive analgesic effects. However, attentional modulation of HNCS analgesia seems to depend on supraspinal processes., (Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Optical beams exhibiting a long depth of focus and a minimum spot size can be obtained with the tight focusing of a narrow annulus of radially polarized light, leading to a needle of longitudinally polarized light. Such beams are of increasing interest for their applications, for example in optical data storage, particle acceleration, and biomedical imaging. Hence one needs to characterize the needles of longitudinally polarized light obtained with different focusing optics and incident beams. In this paper, we present analytical expressions for the electric field of such a nearly nondiffracting, subwavelength beam obtained with a parabolic mirror or an aplanatic lens. Based on these results, we give expressions of the transverse and longitudinal full widths at half maximum of the focal lines as a function of the width of the incident annular beam and we compare the performances of the two focusing systems. Then, we propose a practical solution to produce a needle of longitudinally polarized light with a tunable axial extent and a transverse width reaching the theoretical limit of 0.36λ.

Exact closed-form solutions to Maxwell's equations are used to investigate the acceleration of electrons in vacuum driven by ultrashort and nonparaxial radially polarized laser pulses. We show that the threshold power above which significant acceleration takes place is greatly reduced by using a tighter focus. Moreover, electrons accelerated by tightly focused single-cycle laser pulses may reach around 80% of the theoretical energy gain limit, about twice the value previously reported with few-cycle paraxial pulses. Our results demonstrate that the direct acceleration of electrons in vacuum is well within reach of current laser technology.

Remote terahertz (THz) generation from two-color filamentation is investigated as a function of the onset position of filaments. THz signals emitted by filaments produced at distances up to 55 m from the laser source were measured. However, from 9 m to 55 m, the THz signal decayed monotonically for increasing onset positions. With a simple calculation, the dominant factors associated to this decay were identified as group velocity mismatch of the two-color pulses and linear diffraction induced by focusing and propagating the second harmonic pulse.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving abdominal pain and bowel dysfunction. IBS pain symptoms have been hypothesized to depend on peripheral and central mechanisms, but the pathophysiology is still unclear. The aim of the present study was to assess the contribution of cerebral and cerebrospinal processes to pain inhibition deficits in IBS. Fourteen female patients with diarrhea-predominant IBS (IBS-D) and 14 healthy female volunteers were recruited. Acute pain and the nociceptive withdrawal reflex (RIII reflex) were evoked by transcutaneous electrical stimulation of the right sural nerve with modulation by hetero-segmental counter-irritation produced by sustained cold pain applied on the left forearm. Psychological symptoms were assessed by questionnaires. Shock pain decreased significantly during counter-irritation in the controls (P<0.001) but not in IBS patients (P=0.52). Similarly, RIII-reflex amplitude declined during counter-irritation in the controls (P=0.009) but not in IBS patients (P=0.11). Furthermore, pain-related anxiety increased during counter-irritation in IBS patients (P=0.003) but not in the controls (P=0.74). Interestingly, across all subjects, counter-irritation analgesia was positively correlated with RIII-reflex inhibition (r=0.39, P=0.04) and negatively with pain-related anxiety (r=-0.61, P<0.001). In addition, individual differences in counter-irritation analgesia were predicted independently by the modulation of RIII responses (P=0.03) and by pain catastrophizing (P=0.01), with the latter mediating the effect of pain-related anxiety. In conclusion, these results demonstrate that pain inhibition deficits in female IBS-D patients depend on two potentially separable mechanisms reflecting: (1) altered descending modulation and (2) higher-order brain processes underlying regulation of pain and affect., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Studies of electromyographic (EMG) activity and lumbopelvic rhythm have led to a better understanding of neuromuscular alterations in chronic low back pain (cLBP) patients. Whether these changes reflect adaptations to chronic pain or are induced by acute pain is still unclear. This work aimed to assess the effects of experimental LBP on lumbar erector spinae (LES) EMG activity and lumbopelvic kinematics during a trunk flexion-extension task in healthy volunteers and LBP patients. The contribution of disability to these effects was also examined. Twelve healthy participants and 14 cLBP patients performed flexion-extension tasks in three conditions; control, innocuous heat and noxious heat, applied on the skin over L5 or T7. The results indicated that noxious heat at L5 evoked specific increases in LES activity during static full trunk flexion and extension, irrespective of participants' group. Kinematic data suggested that LBP patients adopted a different movement strategy than controls when noxious heat was applied at the L5 level. Besides, high disability was associated with less kinematic changes when approaching and leaving full flexion. These results indicate that experimental pain can induce neuromechanical alterations in cLBP patients and healthy volunteers, and that higher disability in patients is associated with decreased movement pattern changes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A deformable mirror made of a magnetic liquid has been used to produce conical surfaces with subwavelength (λ/4) accuracy. The surface profile of the liquid mirror is controlled by 91 small magnetic coils. The mirror exhibits a linear response with respect to the currents driving the coils, and it allows for real-time changes of its surface profile. The magnetic liquid deformable mirror has been used to produce reflected beams having a conical wavefront; the propagation of the reflected beams was verified to be consistent with that of Bessel beams in the near and far field. The large dynamic range of such a deformable mirror has made it possible to generate Bessel beams with a broad range of beam parameters., (© 2011 Optical Society of America)

A parabolic mirror illuminated with an incident collimated beam whose axis of propagation does not exactly coincide with the axis of revolution of the mirror shows distortion and strong coma. To understand the behavior of such a focused beam, a detailed description of the electric field in the focal region of a parabolic mirror illuminated with a beam having a nonzero angle of incidence is required. We use the Richards-Wolf vector field equation to investigate the electric energy density distribution of a beam focused with a parabolic mirror. The explicit aberration function of this focused field is provided along with numerically calculated electric energy densities in the focal region for different angles of incidence. The location of the peak intensity, the Strehl ratio and the full-width at half-maximum as a function of the angle of incidence are given and discussed. The results confirm that the focal spot of a strongly focused beam is affected by severe coma, even for very small tilting of the mirror. This analysis provides a clearer understanding of the effect of the angle of incidence on the focusing properties of a parabolic mirror as such a focusing device is of growing interest in microscopy., (© 2011 Optical Society of America)

Background and Aims: To investigate associations between plasma adiponectin concentration and very-low density lipoprotein-triglyceride (VLDL-TG) secretion and catabolism in postmenopausal women., Methods and Results: This cross-sectional study included 30 postmenopausal women. Plasma adiponectin concentration was measured by ELISA. Insulin sensitivity was assessed by a 2-h euglycemic-hyperinsulinemic clamp. Fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) were measured during an oral glucose tolerance test. The calculation of VLDL-TG fractional catabolic rate (FCR) and VLDL-TG total secretion rate (TSR) were based on the monoexponential decrease of TG-[²H₅] glycerol values obtained following the administration of a ²H₅-glycerol bolus. Plasma adiponectin concentration was negatively associated with VLDL-TG TSR (r=-0.50; p=0.005) and positively associated with VLDL-TG FCR (r=0.54; p<0.002). This latter association remained significant after further adjustments for insulin sensitivity, visceral adipose tissue, HDL-C, FPG and 2hPG concentrations. In a multivariate model including adiponectin, insulin sensitivity and 2hPG, plasma adiponectin level was the strongest correlate of VLDL-TG FCR., Conclusions: Elevated plasma adiponectin concentration is associated with a favourable VLDL-TG metabolism., (Copyright © 2009 Elsevier B.V. All rights reserved.)

In animals, somatic stimulation of the limbs can evoke sympathetic reflexes of supraspinal origin. In addition, spinal reflexes can be elicited by stimulation of somatic tissues of the trunk. However, limited evidence is available concerning the specific modulation of sympathetic reflexes by afferents from the thoracic spine. This has also been largely overlooked in healthy humans. The aim of the present study was to determine whether tonic noxious heat (NH) applied to the skin over T3-T5 could segmentally increase supraspinal sympathetic reflexes (skin conductance responses - SCRs) induced by phasic electrical stimulation of the sural nerve. In addition, the effect of spinal manipulation (SM) on SCR amplitude and SCR amplification by NH was investigated. During the control session, palmar and plantar SCR amplitude was stable, showing no significant modulation. During NH and SM, however, palmar SCR amplitude was respectively increased and decreased in comparison to baseline, leading to a robust difference in SCR amplitude between the 2 conditions (p<0.001). Moreover, these changes were also significantly and marginally different compared to the control session (p=0.041 and p=0.053, respectively). Interestingly, when applied immediately before NH, SM had a preventive effect on palmar SCR amplification induced by NH. In sharp contrast, changes in plantar SCRs were not significantly different between sessions (p=0.42). Altogether, these results indicate that somatic stimulation of the thoracic spine may modulate somato-sympathetic reflexes segmentally in conscious, healthy volunteers., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The Richards-Wolf theory and the complex point-source method are both used to express the phasor of the electric field of tightly focused beams, but the connection between these two approaches is not straightforward. In this paper, the Richards-Wolf vector field equations are used to find the electromagnetic field of a TM(01) beam in the neighborhood of the focus of a 4π focusing system, such as a parabolic mirror with infinite transverse dimensions. Closed-form solutions are found for the distribution of the fields at any point in the vicinity of the focus; these solutions are identical to the electromagnetic field obtained with the complex source-point method in which sources are accompanied by sinks. This work thus establishes a connection between the Richards-Wolf theory and the complex sink/source model. The vector magnetic potential is introduced to simplify the computation of the six electromagnetic field components. The method is then used to find analytical expressions for the electromagnetic field of strongly focused TM(01) beams affected by primary aberrations such as curvature of field, coma, astigmatism and spherical aberration.

Background: In postmenopausal women, a population at risk for the metabolic syndrome, the relative contribution of central fat versus peripheral muscle fat to the metabolic risk profile is unknown. This study explored the relationship between muscle fat infiltration derived from computed tomography (CT) scans and metabolic syndrome., Methods: Mid-thigh CT scans measured the surface of muscle with low attenuation (LAMS) [0-34 Hounsfield units (HU)], which represented the specific component of fat-rich muscle. Insulin sensitivity was evaluated by an euglycemic-hyperinsulinemic clamp. National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria were used to determine the presence of the metabolic syndrome., Results: A total of 103 postmenopausal women were studied. Metabolic syndrome was found in 43 women with significantly higher levels of abdominal adiposity, higher LAMS (27 +/- 8 vs. 23 +/- 7 cm(2)), and lower insulin sensitivity compared to those without the metabolic syndrome. Women with higher levels of LAMS presented higher metabolic risk features such as higher blood pressure, abdominal adiposity, inflammatory markers, and blood lipid levels. LAMS and visceral adipose tissue correlated significantly with the presence of metabolic syndrome, but these relationships were lost when LAMS was adjusted for visceral adipose tissue but not when visceral adipose tissue was adjusted for LAMS., Conclusions: These results suggest that postmenopausal women who present with metabolic syndrome had increased fat-rich mid-thigh muscle. Moreover, women with more fat-rich muscle had many features of the metabolic syndrome. These relations were weakened when visceral adipose tissue was taken into account suggesting that LAMS may play a relatively smaller role, compared to VAT, in the contribution to the metabolic syndrome.

Vascular changes associated with brain functions are thought to be tightly coupled with neuronal activity through neuronal glucose consumption or the local release of vasoactive agents. In contrast, another view suggests that cortical blood flow is strongly regulated by the nucleus basalis of Meynert (NBM), independently of regional metabolism. Thus, although cortical regional cerebral blood flow (rCBF) variations induced by somatosensory stimulation are strongly linked to neuronal activity, they may also be partly controlled by the NBM. In the present study, cortical rCBF alterations in response to innocuous brushing of the hindlimb (HL) were investigated by laser speckle contrast imaging. The contribution of NBM to these changes was examined after injection of the GABAergic agonist muscimol into the right NBM, allowing comparison of somatosensory-evoked cortical rCBF modifications before and after NBM inactivation. As expected, HL brushing elicited a robust rCBF increase in the contralateral parietal cortex (PC), over the representation of the HL. However, these alterations were decreased, by approximately 40%, in the hemisphere ipsilateral to muscimol inactivation of NBM, whereas vehicle injection did not produce any significant variation. The results demonstrate that cortical rCBF changes induced by somatosensory stimulation are partly regulated by NBM.

In the past two decades, functional brain imaging has considerably advanced our knowledge of cerebral pain processing. However, many important links are still missing in our understanding of brain activity in relation to the regulation of pain-related physiological responses. This fMRI study investigates the cerebral correlates of pain (rating), motor responses (RIII-reflex) and autonomic activity (skin conductance response; SCR) evoked by noxious electrical stimulation. Stimulus intensity was adjusted individually based on the RIII threshold to control for differences in peripheral processes and baseline spinal activation. Covariance analyses were used to reveal individual differences in brain activity uniquely associated with individual differences in pain, RIII and SCR. Shock-evoked activity in cingulate, medial orbitofrontal and parahippocampal regions predicted pain sensitivity. Moreover, lateral orbitofrontal and cingulate areas showed strong positive associations with individual differences in motor reactivity but negative associations with autonomic reactivity. Notably, individual differences in OFC activation was almost fully accounted by the combination of individual measures of autonomic and motor reactivity (R(2)=0.93). Additionally, trial-to-trial fluctuations of RIII-reflex and SCR (within-subjects) were proportional to shock-evoked responses in subgenual cingulate cortex (RIII), anterior insula (SCR) and midcingulate cortex (SCR and RIII). Together, these results confirm that individual differences in perceptual, motor, and autonomic components of pain reflect robust individual differences in brain activity. Furthermore, the brain correlates of trial-to-trial fluctuations in pain responses provide additional evidence for a partial segregation of sub-systems involved more specifically in the ongoing monitoring, and possibly the regulation, of pain-related motor and autonomic responses.

There is ample evidence that motor sequence learning is mediated by changes in brain activity. Yet the question of whether this form of learning elicits changes detectable at the spinal cord level has not been addressed. To date, studies in humans have revealed that spinal reflex activity may be altered during the acquisition of various motor skills, but a link between motor sequence learning and changes in spinal excitability has not been demonstrated. To address this issue, we studied the modulation of H-reflex amplitude evoked in the flexor carpi radialis muscle of 14 healthy individuals between blocks of movements that involved the implicit acquisition of a sequence versus other movements that did not require learning. Each participant performed the task in three conditions: "sequence"-externally triggered, repeating and sequential movements, "random"-similar movements, but performed in an arbitrary order, and "simple"- involving alternating movements in a left-right or up-down direction only. When controlling for background muscular activity, H-reflex amplitude was significantly more reduced in the sequence (43.8 +/- 1.47%. mean +/- SE) compared with the random (38.2 +/- 1.60%) and simple (31.5 +/- 1.82%) conditions, while the M-response was not different across conditions. Furthermore, H-reflex changes were observed from the beginning of the learning process up to when subjects reached asymptotic performance on the motor task. Changes also persisted for >60 s after motor activity ceased. Such findings suggest that the excitability in some spinal reflex circuits is altered during the implicit learning process of a new motor sequence.

Neurodegenerative disorders are a class of diseases that have been linked to apoptosis induced by elevated levels of reactive oxygen species (ROS). ROS activates the apoptotic cascade through mitochondrial dysfunction and damage to lipids, proteins and DNA. Recently, fruit and tea-derived polyphenols have been found to be beneficial in decreasing oxidative stress and increasing overall health. Further, polyphenols including epigallocatechin gallate (EGCG) have been reported to inhibit apoptotic signaling and increase neural cell survival. In an effort to better understand the beneficial properties associated with polyphenol consumption, the aim of this study was to explore the neuroprotective effects of EGCG, methyl gallate (MG), gallic acid (GA) and N-acetylcysteine (NAC) on H(2)O(2)-induced apoptosis in PC12 cells and elucidate potential protective mechanisms. Cell viability data demonstrates that MG and NAC pre-treatments significantly increase viability of H(2)O(2)-stressed cells, while pre-treatments with EGCG and GA exacerbates stress. Quantitation of apoptosis and mitochondrial membrane potential shows that MG pre-treatment prevents mitochondria depolarization, however does not inhibit apoptosis and is thus evidence that MG can inhibit mitochondria-mediated apoptosis. Subsequent analysis of DNA degradation and caspase activation reveals that MG inhibits activation of caspase 9 and has a partial inhibitory effect on DNA degradation. These findings confirm the involvement of both intrinsic and extrinsic apoptotic pathways in H(2)O(2)-induced apoptosis and suggest that MG may have potential therapeutic properties against mitochondria-mediated apoptosis., (Copyright 2010 Elsevier Inc. All rights reserved.)

The mechanisms of chronic pain in irritable bowel syndrome (IBS) have been widely investigated but remain unclear. The present study investigated the relation between visceral hypersensitivity, cutaneous thermal sensitivity, and central pain mechanisms. Rectal sensitivity was assessed with a barostat, and forearm and calf sensitivity with a contact thermode. Central mechanisms were assessed by counterirritation using sustained cold-pain to the hand and painful electric shocks to the ankle. Psychological symptoms were also assessed, using questionnaires. Female volunteers with diarrhea-predominant IBS (n=27) and healthy controls (n=25) participated in the study. IBS patients had lower rectal and calf pain thresholds compared to controls (p's<0.05). IBS patients also reported more pain than controls for rectal distensions, and heat pain on the calf and forearm (all p's<0.001). Cold-pain inhibited shock-pain in controls but not IBS patients (controls: -13.5+/-5.3 vs IBS: +1.9+/-10.5; p<0.01). In addition, visceral hypersensitivity was significantly correlated to cutaneous thermal hypersensitivity and pain inhibition deficits, although effects were only weak and moderate, respectively. Furthermore, covariance analyses indicated that psychological factors accounted for group differences in visceral hypersensitivity and pain inhibition deficits. In conclusion, this study confirms the relation between altered pain inhibition processes and widespread hypersensitivity in IBS. The present results also suggests that psychological symptoms and altered pain processing in IBS patients may reflect at least in part, common underlying mechanisms., (Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Emotions have powerful effects on pain perception. However, the brain mechanisms underlying these effects remain largely unknown. In this study, we combined functional cerebral imaging with psychophysiological methods to explore the neural mechanisms involved in the emotional modulation of spinal nociceptive responses (RIII-reflex) and pain perception in healthy participants. Emotions induced by pleasant or unpleasant pictures modulated the responses to painful electrical stimulations in the right insula, paracentral lobule, parahippocampal gyrus, thalamus, and amygdala. Right insula activation covaried with the modulation of pain perception, consistent with a key role of this structure in the integration of pain signals with the ongoing emotion. In contrast, activity in the thalamus, amygdala, and several prefrontal areas was associated with the modulation of spinal reflex responses. Last, connectivity analyses suggested an involvement of prefrontal, parahippocampal, and brainstem structures in the cerebral and cerebrospinal modulation of pain by emotions. This multiplicity of mechanisms underlying the emotional modulation of pain is reflective of the strong interrelations between pain and emotions, and emphasizes the powerful effects that emotions can have on pain.