Simultaneous EEG/MEG yields complementary information of nociceptive evoked responses.

OBJECTIVE: Nociceptive stimuli have been studied either by dipolar modelling using electroencephalography (EEG) or magnetoencephalography (MEG), but rarely using both techniques simultaneously. This study aims to investigate the spatiotemporal representation of cortical activity in response to non-nociceptive (tactile) and nociceptive (laser) stimuli using parallel EEG-MEG recordings. METHODS: We performed simultaneous EEG and MEG recordings in 12 healthy subjects by applying pneumatic tactile and nociceptive laser stimuli on the right- and left-hand dorsum. We analyzed brain responses for both modalities and methods by means of global field power (GFP), and dipole source locations, strengths and orientations calculated in the depth to identify similarities and differences. RESULTS: Prominent GFP peaks were similar in EEG and MEG for tactile responses but different for nociceptive responses. CONCLUSIONS: Methodically, MEG was superior to EEG in detecting the earliest nociceptive laser-evoked components with earlier latency in primary- and secondary somatosensory cortices, whereas EEG was superior to MEG in detecting late nociceptive components due to radially oriented deeper cortical activity. SIGNIFICANCE: EEG and MEG revealed in part differential nociceptive waveform patterns, peak latencies, and source orientations, making combined recordings favorable to examine pain-related activity as a whole in high temporal-spatial resolution.

Review of techniques useful for the assessment of sensory small fiber neuropathies: Report from an IFCN expert group.

Nerve conduction studies (NCS) are an essential aspect of the assessment of patients with peripheral neuropathies. However, conventional NCS do not reflect activation of small afferent fibers, including Aδ and C fibers. A definitive gold standard for laboratory evaluation of these fibers is still needed and therefore, clinical evaluation remains fundamental in patients with small fiber neuropathies (SFN). Several clinical and research techniques have been developed for the assessment of small fiber function, such as (i) microneurography, (ii) laser evoked potentials, (iii) contact heat evoked potentials, (iv) pain-related electrically evoked potentials, (v) quantitative thermal sensory testing, (vi) skin biopsy-intraepidermal nerve fiber density and (vii) corneal confocal microscopy. The first five are physiological techniques, while the last two are morphological. They all have advantages and limitations, but the combined use of an appropriate selection of each of them would lead to gathering invaluable information for the diagnosis of SFN. In this review, we present an update on techniques available for the study of small afferent fibers and their clinical applicability. A summary of the anatomy and important physiological aspects of these pathways, and the clinical manifestations of their dysfunction is also included, in order to have a minimal common background.

Cerebral processing of sharp mechanical pain measured with arterial spin labeling.

INTRODUCTION: Arterial spin labeling (ASL) is a functional neuroimaging technique that has been frequently used to investigate acute pain states. A major advantage of ASL as opposed to blood-oxygen-level-dependent functional neuroimaging is its applicability for low-frequency designs. As such, ASL represents an interesting option for studies in which repeating an experimental event would reduce its ecological validity. Whereas most ASL pain studies so far have used thermal stimuli, to our knowledge, no ASL study so far has investigated pain responses to sharp mechanical pain. METHODS: As a proof of concept, we investigated whether ASL has the sensitivity to detect brain activation within core areas of the nociceptive network in healthy controls following a single stimulation block based on 96 s of mechanical painful stimulation using a blunt blade. RESULTS: We found significant increases in perfusion across many regions of the nociceptive network such as primary and secondary somatosensory cortices, premotor cortex, posterior insula, inferior parietal cortex, parietal operculum, temporal gyrus, temporo-occipital lobe, putamen, and the cerebellum. Contrary to our hypothesis, we did not find any significant increase within ACC, thalamus, or PFC. Moreover, we were able to detect a significant positive correlation between pain intensity ratings and pain-induced perfusion increase in the posterior insula. CONCLUSION: We demonstrate that ASL is suited to investigate acute pain in a single event paradigm, although to detect activation within some regions of the nociceptive network, the sensitivity of our paradigm seemed to be limited. Regarding the posterior insula, our paradigm was sensitive enough to detect a correlation between pain intensity ratings and pain-induced perfusion increase. Previous experimental pain studies have proposed that intensity coding in this region may be restricted to thermal stimulation. Our result demonstrates that the posterior insula encodes intensity information for mechanical stimuli as well.

Posterior insular activity contributes to the late laser-evoked potential component in EEG recordings.

OBJECTIVE: Nociceptive activity in some brain areas has concordantly been reported in EEG source models, such as the anterior/mid-cingulate cortex and the parasylvian area. Whereas the posterior insula has been constantly reported to be active in intracortical and fMRI studies, non-invasive EEG and MEG recordings mostly failed to detect activity in this region. This study aimed to determine an appropriate inverse modeling approach in EEG recordings to model posterior insular activity, assuming the late LEP (laser evoked potential) time window to yield a better separation from other ongoing cortical activity. METHODS: In 12 healthy volunteers, nociceptive stimuli of three intensities were applied. LEP were recorded using 32-channel EEG recordings. Source analysis was performed in specific time windows defined in the grand-average dataset. Two distinct dipole-pairs located close to the operculo-insular area were compared. RESULTS: Our results show that posterior insular activity yields a substantial contribution to the latest part (positive component) of the LEP. CONCLUSIONS: Even though the initial insular activity onset is in the early LEP time window,modelingthe insular activity in the late LEP time window might result in better separation from other ongoing cortical activity. SIGNIFICANCE: Modeling the late LEP activity might enable to distinguish posterior insular activity.

Modality-specific facilitation of noninjurious sharp mechanical pain by topical capsaicin.

We had previously shown that a "blunt blade" stimulator can mimic the noninjurious strain phase of incisional pain, but not its sustained duration. Here, we tested whether acute sensitization of the skin with topical capsaicin can add the sustained phase to this noninvasive surrogate model of intraoperative pain. Altogether, 110 healthy volunteers (55 male and 55 female; 26 ± 5 years) participated in several experiments using the "blunt blade" (0.25 × 4 mm) on normal skin (n = 36) and on skin pretreated by a high-concentration capsaicin patch (8%, Qutenza; n = 36). These data were compared with an experimental incision (n = 40) using quantitative and qualitative pain ratings by numerical rating scale and SES Pain Perception Scale descriptors. Capsaicin sensitization increased blade-induced pain magnitude and duration significantly (both P < 0.05), but it failed to fully match the sustained duration of incisional pain. In normal skin, the SES pattern of pain qualities elicited by the blade matched incision in pain magnitude and pattern of pain descriptors. In capsaicin-treated skin, the blade acquired a significant facilitation only of the perceived heat pain component (P < 0.001), but not of mechanical pain components. Thus, capsaicin morphed the descriptor pattern of the blade to become more capsaicin-like, which is probably explained best by peripheral sensitization of the TRPV1 receptor. Quantitative sensory testing in capsaicin-sensitized skin revealed hyperalgesia to heat and pressure stimuli, and loss of cold and cold pain sensitivity. These findings support our hypothesis that the blade models the early tissue-strain-related mechanical pain phase of surgical incisions.

The glutamate to γ-aminobutyric acid ratio in the posterior insula is associated with pain perception in healthy women but not in women with borderline personality disorder.

This study aimed to investigate whether the differences in pain perception between patients with borderline personality disorder (BPD) and healthy subjects (HCs) can be explained by differences in the glutamate/GABA ratio in the posterior insula. In total, 29 BPD patients and 31 HCs were included in the statistical analysis. Mechanical pain sensitivity was experimentally assessed with pinprick stimuli between 32 and 512 mN on a numeric rating scale. The metabolites were measured in the right posterior insula using the MEshcher-GArwood Point-RESolved Spectroscopy sequence for single-voxel magnetic resonance spectroscopy (1H-MRS). The 256- and the 512-mN pinprick stimuli were perceived as significantly less painful by the BPD patient group compared with HCs. No differences were found between groups for the glutamate/GABA ratios. A positive correlation between the glutamate/GABA ratio and the pain intensity ratings to 256- and 512-mN pinpricks could be found in the combined and in the HC group. In the BPD patient group, the correlations between the glutamate/GABA ratio and the pain intensity ratings to 256- and 512-mN pinpricks did not reach significance. In conclusion, the study showed that individual differences in pain perception may in part be explained by the individual glutamate/GABA ratio in the posterior insula. However, this possible mechanism does not explain the differences in pain perception between BPD patients and HCs.

Differential perception of sharp pain in patients with borderline personality disorder.

BACKGROUND: Cutting is the most common method of non-suicidal self-injury (NSSI) to reduce inner tension in patients with Borderline Personality Disorder (BPD). Aim of this study was to compare pain perception induced by an incision and by application of a surrogate model for sharp mechanical pain (a non-invasive "blade") in BPD. METHODS: 22 female patients and 20 healthy controls (HC) received a small incision into the volar forearm, a 7s-blade application on the same side, and non-invasive phasic stimuli (pinprick, blade, laser, tactile). Pain intensity as well as affective versus sensory components were assessed. RESULTS: Incision was rated similarly by both groups (BPD: 28.6 ± 5.5 vs. HC: 33.9 ± 6.6; mean maximum pain ± SEM; p > 0.8), without significant difference for "7-s-blade" (BPD: 18.1 ± 3.8 vs. HC: 25.3 ± 3.6; mean maximum pain ± SEM; p > 0.17) or between "7-s-blade" and incision (BPD: p > 0.12; HC: p > 0.84). However, patients' intensity ratings returned significantly faster to baseline after incision (BPD: 38.9 ± 12.6 s vs. HC: 74.52 ± 11.5 s; p < 0.05), and patients evaluated "blade" and incision without any affective and with different sensory descriptors, indicating an altered evaluation of NSSI-like stimulation with qualitative in addition to quantitative differences-especially for the sharp pain component. CONCLUSIONS: The reduced perception of suprathreshold nociceptive stimuli is based on a missing affective component and specific loss of the perception of "sharpness" as part of the sensory component of pain. The results further demonstrate the usefulness of the "blade" for the perception of sharpness in patients. SIGNIFICANCE: Patients with Borderline Personality Disorder (BPD) who engage in non-suicidal self-injury (NSSI) report less pain in response to phasic nociceptive stimuli. In comparing an invasive pain stimulus to phasic nociceptive stimuli in BPD patients, the "blade" as non-invasive surrogate model for sharp mechanical pain in psychiatric patients is used. In contrast to healthy volunteers, BPD patients do not report significant affective ratings and specifically display a reduced sensory component for sharpness.

Effects of a Painful Stimulus on Stress Regulation in Male Patients With Borderline Personality Disorder: A Pilot Study.

Pain processing in relation to stress has so far not been investigated in male patients with borderline personality disorder (BPD). This experimental pilot study examined 17 male BPD patients and 20 male healthy controls (HCs) to assess the effects of a pain stimulus on arousal, aggression, pain (ratings), and heart rate. At baseline, BPD patients showed significantly higher arousal and aggression; however, there was no significant difference in heart rate compared to the HC group. Following stress induction, a noninvasive mechanical pain stimulus was applied. No significant differences in pain ratings or heart rates were found between the groups. For arousal, a significantly stronger decrease was revealed in the BPD group compared to the HC group (t = 2.16, p = .038). Concerning aggression, the BPD group showed a significantly greater decrease after the pain stimulus than the HC group (t = 3.25, p = .002). This data showed that nonsuicidal self-injury can reduce arousal and aggression in male BPD.

Stress reactivity and pain-mediated stress regulation in remitted patients with borderline personality disorder.

Objective: Patients with borderline personality disorder (BPD) use nonsuicidal self-injury (NSSI) to cope with states of elevated inner tension. It is unclear to what extent remitted BPD patients experience these states and whether the experience of pain still regulates emotion. The purpose of this study was the investigation of baseline stress levels, stress reactivity, and pain-mediated stress regulation in remitted BPD patients. Method: Subjective and objective stress parameters were assessed in 30 remitted BPD patients, 30 current BPD patients, and 30 healthy controls. After stress induction, a non-nociceptive tactile stimulus, a tissue-injuring, or a noninvasive pain stimulus was applied to the right volar forearm. Results: Baseline stress levels of remitted BPD patients lie in between the stress levels of current BPD patients and healthy controls. Urge for NSSI increased significantly more in current than remitted BPD patients. The experience of pain led to a greater decrease of arousal in current compared to remitted BPD patients and healthy controls. Conclusions: States of increased tension still seem to appear in remitted BPD patients. The role of pain-mediated stress regulation appears to be reduced in remitted patients.

Evaluation of psychosocial and biological parameters in women seeking for a caesarean section and women who are aiming for vaginal delivery: a cross-sectional study.

PURPOSE: To investigate psychosocial and biological parameters that may influence decision-making concerning the mode of delivery in women with caesarean section on maternal request (CSMR). METHODS: Two hundred and two women were enrolled prospectively. The study sample (n = 93) consisted of women who aimed for CSMR, the control sample were women who seeked for vaginal delivery (n = 109). Parturients of both samples were enrolled during the pre-birth counselling at the delivery room at the University Medical Centre Mannheim, University Heidelberg, Germany. Women completed standardised questionnaires regarding psychosocial burden (SCL-R 90), fear of childbirth (W-DEQ) and anxiety (STAI), personality structure (HEXACO-Pi-R), and ambiguity tolerance (PFI, PNS, and NFC), social support (F-SozU) as well as one questionnaire assessing demographic parameters and further factors potentially influencing their choice of the mode of delivery. Hair cortisol concentration as a marker for chronic psychological stress and pressure pain threshold with a pressure algometer was assessed. RESULTS: Women in the CSMR sample had less social support (F-SozU: 2.99 ± 0.52 vs. 3.12 ± 0.32; p = 0.043) and were less educated (high school or university degree: 37 vs. 71%, p = 0.001) compared to parturients of the control sample. Women who underwent CSMR were less open-minded (HEXACO-Pi-R: 3.08 ± 0.57 vs. 3.26 ± 0.50; p = 0.016) and less extroverted (HEXACO-Pi-R: 3.34 ± 0.36 vs. 3.46 ± 0.41; p = 0.041). The control collective showed higher scores in negative appraisal of the birth ('W-DEQ-negative appraisal': 2.5 ± 0.8 vs. 2.2 ± 0.9; p = 0.006), whereas "lack of positive anticipation" was higher in the study collective ('W-DEQ-lack of positive anticipation': 3.2 ± 1.2 vs. 2.8 ± 0.8; p = 0.015). The study collective had higher pressure pain threshold values (5.07 ± 2.06 vs. 4.35 ± 1.38; p = 0.007), while no significant differences were observed in hair cortisol concentration comparing both groups (5.0 ± 11.4 vs. 4.9 ± 8.3; p = 0.426). The majority of the control collective (80%) had chosen the vaginal route as their mode of delivery before pregnancy, whereas only 21% of the women in the study collective decided to undergo CSMR before conception. The advice of social sources including both medical and non-medical aspects was rated less important in the study sample, with significant differences indicating a lower relevance of counsel from friends (p = 0.002) and midwives (p < 0.001). CONCLUSION: Women who inquired a CSMR had lower social support, were less educated, more anxious, and had a lower sensitivity for physical pain compared to women seeking for spontaneous delivery. This should be considered when counselling women requiring CSMR and could be leverage points to intervene to reduce the continuously increasing CSMR rate.

Changes in birth-related pain perception impact of neurobiological and psycho-social factors.

PURPOSE: To analyse post-partum short- and long-term pain sensitivity and the influence of endogenous pain inhibition as well as distinct psycho-social factors on birth-related pain. METHODS: Pain sensitivity was assessed in 91 primiparous women at three times: 2-6 weeks before, one to 3 days as well as ten to 14 weeks after childbirth. Application of a pressure algometer in combination with a cold pressor test was utilised for measurement of pain sensitivity and assessment of conditioned pain modulation (CPM). Selected psycho-social factors (anxiety, social support, history of abuse, chronic pain and fear of childbirth) were evaluated with standardised questionnaires and their effect on pain processing then analysed. RESULTS: Pressure pain threshold, cold pain threshold and cold pain tolerance increased significantly directly after birth (all p < 0.001). While cold pain parameters partly recovered on follow-up, pressure pain threshold remained increased above baseline (p < 0.001). These pain-modulating effects were not found for women with history of abuse. While CPM was not affected by birth, its extent correlated significantly (r = 0.367) with the drop in pain sensitivity following birth. Moreover, high trait anxiety predicted an attenuated reduction in pain sensitivity (r = 0.357), while there was no correlation with fear of childbirth, chronic pain and social support. CONCLUSION: Pain sensitivity showed a decrease when comparing post-partum with prepartum values. The extent and direction of CPM appear to be a trait variable that predicted post-partum hypalgesia without being changed itself. Post-partum hypalgesia was reduced in women with a history of abuse and high trait anxiety, which suggests that individual differences in CPM affect childbirth experience.

Posterior Insular GABA Levels Inversely Correlate with the Intensity of Experimental Mechanical Pain in Healthy Subjects.

This study aimed to investigate the relation of GABA and glutamate levels in the posterior insula and mechanical pain sensitivity in healthy subjects. Nineteen healthy female individuals underwent single voxel magnetic resonance spectroscopy (MRS) at 3 T. Metabolites were measured in the right posterior insula using MEGA-PRESS spectral editing. Mechanical pain sensitivity was experimentally assessed with pinprick stimuli on a numeric rating scale. Ratings of perceived intensity of 256 mN and 512 mN pinprick stimuli were negatively correlated with GABA levels and positively with glutamate levels in the posterior insula. Pinprick pain ratings were also positively correlated with the glutamate/GABA ratio. No significant correlation for pinprick stimuli of lower forces than 256 mN was observed. The results of our study support the hypothesis that excitatory and inhibitory neurotransmitter levels and/or the ratio of glutamate/GABA levels in the posterior insula are related to individual differences in pain sensitivity. These results are in line with chronic pain studies, where elevated glutamate/GABA ratios in the insular cortex of patients with chronic pain syndromes were observed.

The role of nociceptive input and tissue injury on stress regulation in borderline personality disorder.

Approximately 60% to 90% of patients with borderline personality disorder (BPD) show nonsuicidal self-injurious behavior (NSSI) with cutting being the most frequently applied method. One of NSSI's functions is to reduce aversive tension. Previous studies have found a tension-reducing effect of painful tissue injury by an incision. It is still unclear whether this effect is based on the effect of tissue injury or the effect of pain experience, or both. The aim of this study was to determine whether tissue injury leads to a stronger stress reduction than a sole pain stimulus in patients with BPD. After stress induction, 57 BPD patients and 60 healthy controls (HCs) received either an incision or a non-tissue-injuring mechanical nociceptive stimulus ("blade") typically perceived as painful or a non-nociceptive tactile sham stimulus (blunt end of scalpel). Participants were unaware of which procedure was applied. For stress assessment, subjective and objective parameters were measured. As immediate response to the stimulus application, we found greater stress reduction after both painful stimuli (incision and blade) in BPD patients but no difference in stress decrease between the tissue-injuring incision and the non-tissue-injuring pain stimulus (blade). Compared with HCs, incision and blade were followed by greater immediate decrease of arousal in BPD patients. Our findings confirm that among BPD patients, the nociceptive input leads to stress reduction. In contrast, the impact of tissue damage on stress reduction was relatively small. In addition, the results suggest that painful stimuli lead to a greater stress reduction in BPD patients compared with HCs.

The role of seeing blood in non-suicidal self-injury in female patients with borderline personality disorder.

Patients with Borderline Personality Disorder (BPD) often engage in non-suicidal self-injury (NSSI), to reduce arousal levels under stress. However, the importance of seeing blood for the effect of NSSI is yet unknown. The present pilot study examined 20 female BPD patients and 20 healthy controls (HC) to assess the role of seeing blood on arousal, pain, urge for NSSI (ratings) and heart rate (continuously measured). Participants completed two sessions consisting of stress induction (forced mental arithmetics with white noise), followed by a seven second non-invasive pain stimulus with a blade to the volar forearm. At one session, only the painful blade stimulus was applied, at the other, artificial blood was added. For arousal, a significantly stronger decrease was revealed in the BPD than in the HC group, however with no significant effects between blood and non-blood conditions. Concerning urge for NSSI, the BPD showed a significantly greater decrease in blood condition over time than the HC group. Interestingly, heart rate decreased stronger over time in the HC group during the blood condition than in BPD. For tension relief by non-damaging mechanical painful stimulus the addition of visible blood showed neither subjective (arousal, urge for NSSI), nor objective (heart rate) advantages.

Detection of central circuits implicated in the formation of novel pain memories.

Being able to remember physically and emotionally painful events in one's own past may shape behavior, and can create an aversion to a variety of situations. Pain imagination is a related process that may include recall of past experiences, in addition to production of sensory and emotional percepts without external stimuli. This study aimed to understand 1) the central nervous system processes that underlie pain imagination, 2) the retrieval of pain memories, and 3) to compare the latter with visual object memory. These goals were achieved by longitudinally investigating brain function with functional magnetic resonance imaging in a unique group of healthy volunteers who had never experienced tooth pain. In these subjects, we compared brain responses elicited during three experimental conditions in the following order: imagination of tooth pain (pain imagination), remembering one's own house (object memory), and remembrance of tooth pain following an episode of induced acute tooth pain (pain memory). Key observations stemming from group-level conjunction analyses revealed common activation in the posterior parietal cortex for both pain imagination and pain memory, while object and pain memory each had strong activation predominantly within the middle frontal gyrus. When contrasting pain imagination and memory, significant activation differences were observed in subcortical structures (ie, parahippocampus - pain imagination > pain memory; midbrain - pain memory > pain imagination). Importantly, these findings were observed in the presence of consistent and reproducible psychophysical and behavioral measures that informed on the subjects' ability to imagine novel and familiar thoughts, as well as the subjects' pain perception.

Emotion Elicitation: A Comparison of Pictures and Films.

Pictures and film clips are widely used and accepted stimuli to elicit emotions. Based on theoretical arguments it is often assumed that the emotional effects of films exceed those of pictures, but to date this assumption has not been investigated directly. The aim of the present study was to compare pictures and films in terms of their capacity to induce emotions verified by means of explicit measures. Stimuli were (a) single pictures presented for 6 s, (b) a set of three consecutive pictures with emotionally congruent contents presented for 2 s each, (c) short film clips with a duration of 6 s. A total of 144 participants rated their emotion and arousal states following stimulus presentation. Repeated-measures ANOVAs revealed that the film clips and 3-picture version were as effective as the classical 1-picture method to elicit positive emotions, however, modulation toward positive valence was little. Modulation toward negative valence was more effective in general. Film clips were less effective than pictorial stimuli in producing the corresponding emotion states (all p < 0.001) and were less arousing (all p ≤ 0.02). Possible reasons for these unexpected results are discussed.

A novel human surrogate model of noninjurious sharp mechanical pain.

We propose a blade as a noninjurious nociceptive stimulus modeling sharp mechanical pain and yielding acute pain and hyperalgesia responses with closer proximity to incision-induced pain/hyperalgesia than punctate or blunt pressure mechanical pain models. Twenty-six healthy men and women were investigated to compare a small incision in the left forearm with noninvasive stimuli of different shapes and modalities to the right forearm. The magnitude and time course of incisional and blade-induced pain were assessed by numerical rating scales. Affective vs sensory components of pain experience were differentiated using a pain sensation questionnaire. The magnitude and time course of the axon reflex vasodilator response and of secondary hyperalgesia following a 7-second blade application were assessed. The maximum blade or incisional pain was similar (visual analogue scale [mean ± SD]: 32.9 ± 22.5 [blade] vs. 33.6 ± 29.8 [incision]), and both time courses matched closely in the first 10 seconds (paired t test; P = 0.5-1.0), whereas incision but not blade was followed by a second phase of pain, probably related to the tissue injury (decrease to half maximum pain 8 ± 2 vs. 33 ± 35 seconds; P < 0.01). Affective pain scores were significantly lower than sensory scores for all stimuli (P < 0.001). Comparing blade and incision, patterns of affective and sensory pain descriptors exhibited a remarkably similar pattern. Hence, we suggest the blade as novel model of sharp mechanical pain, which will be useful in investigating postoperative/mechanical pain and the role of self-injurious behavior in, eg, patients with borderline personality disorder.

Pain in Borderline Personality Disorder.

Pain processing in patients with borderline personality disorder (BPD) is abnormal primarily with respect to pain thresholds which are typically elevated or perception of phasic nociceptive stimuli which is reduced. In spite of this common finding, nonsuicidal self-injury (NSSI), often expressed as cutting, is a hallmark sign of the disease and serves to release aversive inner tension. The question thus arises, how does a painful stimulus release inner tension when these patients feel less pain than healthy people? However, intensity discrimination is normal in these patients. Imaging data have provided evidence that inhibitory top-down modulation is increased in BPD patients, and that processing of the affective-emotional pain component is altered. Recent studies have focused on the role of pain, tissue injury and seeing blood in the context of NSSI. Preliminary findings suggest a significant role of pain irrespective of concomitant tissue injury, and of seeing blood expressed as a stronger immediate stress release. Taken together, BPD patients exhibit altered pain processing that can be assigned to altered processing of nociceptive stimuli in prefrontal and limbic brain areas, which may help to mechanistically explain the clinical behavior.

Incision and stress regulation in borderline personality disorder: neurobiological mechanisms of self-injurious behaviour.

BACKGROUND: Patients with borderline personality disorder frequently show non-suicidal self-injury (NSSI). In these patients, NSSI often serves to reduce high levels of stress. AIMS: Investigation of neurobiological mechanisms of NSSI in borderline personality disorder. METHOD: In total, 21 women with borderline personality disorder and 17 healthy controls underwent a stress induction, followed by either an incision into the forearm or a sham treatment. Afterwards participants underwent resting-state functional magnetic resonance imaging while aversive tension, heart rate and heart rate variability were assessed. RESULTS: We found a significant influence of incision on subjective and objective stress levels with a stronger decrease of aversive tension in the borderline personality disorder group following incision than sham. Amygdala activity decreased more and functional connectivity with superior frontal gyrus normalised after incision in the borderline personality disorder group. CONCLUSIONS: Decreased stress levels and amygdala activity after incision support the assumption of an influence of NSSI on emotion regulation in individuals with borderline personality disorder and aids in understanding why these patients use self-inflicted pain to reduce inner tension.

Assessment of small fibers using evoked potentials.

Background and purpose Conventional neurophysiological techniques do not assess the function of nociceptive pathways and are inadequate to detect abnormalities in patients with small-fiber damage. This overview aims to give an update on the methods and techniques used to assess small fiber (Aδ- and C-fibers) function using evoked potentials in research and clinical settings. Methods Noxious radiant or contact heat allows the recording of heat-evoked brain potentials commonly referred to as laser evoked potentials (LEPs) and contact heat-evoked potentials (CHEPs). Both methods reliably assess the loss of Aδ-fiber function by means of reduced amplitude and increased latency of late responses, whereas other methods have been developed to record ultra-late C-fiber-related potentials. Methodological considerations with the use of LEPs and CHEPs include fixed versus variable stimulation site, application pressure, and attentional factors. While the amplitude of LEPs and CHEPs often correlates with the reported intensity of the stimulation, these factors may also be dissociated. It is suggested that the magnitude of the response may be related to the saliency of the noxious stimulus (the ability of the stimulus to stand out from the background) rather than the pain perception. Results LEPs and CHEPs are increasingly used as objective laboratory tests to assess the pathways mediating thermal pain, but new methods have recently been developed to evaluate other small-fiber pathways. Pain-related electrically evoked potentials with a low-intensity electrical simulation have been proposed as an alternative method to selectively activate Aδ-nociceptors. A new technique using a flat tip mechanical stimulator has been shown to elicit brain potentials following activation of Type I A mechano-heat (AMH) fibers. These pinprick-evoked potentials (PEP) have a morphology resembling those of heat-evoked potentials following activation of Type II AMH fibers, but with a shorter latency. Cool-evoked potentials can be used for recording the non-nociceptive pathways for cooling. At present, the use of cool-evoked potentials is still in the experimental state. Contact thermodes designed to generate steep heat ramps may be programmed differently to generate cool ramps from a baseline of 35◦C down to 32◦C or 30◦C. Small-fiber evoked potentials are valuable tools for assessment of small-fiber function in sensory neuropathy, central nervous system lesion, and for the diagnosis of neuropathic pain. Recent studies suggest that both CHEPs and pinprick-evoked potentials may also be convenient tools to assess sensitization of the nociceptive system. Conclusions In future studies, small-fiber evoked potentials may also be used in studies that aim to understand pain mechanisms including different neuropathic pain phenotypes, such as cold- or touch-evoked allodynia, and to identify predictors of response to pharmacological pain treatment. Implications Future studies are needed for some of the newly developed methods.