Acute Pain Stimuli Research Articles

Cardiac autonomic response to acute painful stimulus in individuals with chronic neck pain: A case-control study

PurposeCharacterize heart rate and cardiac autonomic response to painful stimulus on neck pain. MethodsTwenty-five individuals with neck pain and 25 healthy subjects were included. Heart rate variability and heart rate were assessed in the conditioned pain modulation test at pretest rest, during testing and in recovery. Heart rate variability indices were obtained using linear and nonlinear methods. ResultsNo significant differences were observed between groups regarding heart rate and the linear methods (p > 0.05). However, significant difference was observed between groups regarding nonlinear methods (standard deviation of the instantaneous variability of beat-to-beat interval variability, p = 0.005) ConclusionsIndividuals with chronic neck pain showed autonomic responses similar to those of their healthy counterparts during the conditioning stimulus.

Low-Intensity Focused Ultrasound to the Human Dorsal Anterior Cingulate Attenuates Acute Pain Perception and Autonomic Responses.

The dorsal anterior cingulate cortex (dACC) is a critical brain area for pain and autonomic processing, making it a promising noninvasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to noninvasively modulate the dACC for effects on behavioral and cardiac autonomic responses using transient heat pain stimuli. A N = 16 healthy human volunteers (6 M/10 F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included pain ratings, heart rate variability, EDR response, blood pressure, and the amplitude of the contact heat-evoked potential (CHEP).LIFU reduced pain ratings by 1.09 ± 0.20 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low-frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on the blood pressure or EDR. LIFU resulted in a 38.1% reduction in the P2 CHEP amplitude. Results demonstrate LIFU to the dACC reduces pain and alters autonomic responses to acute heat pain stimuli. This has implications for the causal understanding of human pain and autonomic processing in the dACC and potential future therapeutic options for pain relief and modulation of homeostatic signals.

Adolescent Alcohol Exposure Produces Sex-Specific Long-term Hyperalgesia via Changes in Central Amygdala Circuit Function

BackgroundExposure to alcohol during adolescence produces many effects that last well into adulthood. Acute alcohol use is analgesic, and people living with pain report drinking alcohol to reduce pain, but chronic alcohol use produces increases in pain sensitivity. MethodsWe tested the acute and lasting effects of chronic adolescent intermittent ethanol (AIE) exposure on pain-related behavioral and brain changes in male and female rats. We also tested the long-term effects of AIE on synaptic transmission in midbrain (ventrolateral periaqueductal gray [vlPAG])-projecting central amygdala (CeA) neurons using whole-cell electrophysiology. Finally, we used circuit-based approaches (DREADDs [designer receptors exclusively activated by designer drugs]) to test the role of vlPAG-projecting CeA neurons in mediating AIE effects on pain-related outcomes. ResultsAIE produced long-lasting hyperalgesia in male, but not female, rats. Similarly, AIE led to a reduction in synaptic strength of medial CeA cells that project to the vlPAG in male, but not female, rats. Challenge with an acute painful stimulus (i.e., formalin) in adulthood produced expected increases in pain reactivity, and this effect was exaggerated in male rats with a history of AIE. Finally, CeA-vlPAG circuit activation rescued AIE-induced hypersensitivity in male rats. ConclusionsOur findings are the first, to our knowledge, to show long-lasting sex-dependent effects of adolescent alcohol exposure on pain-related behaviors and brain circuits in adult animals. This work has implications for understanding the long-term effects of underage alcohol drinking on pain-related behaviors in humans.

The impact of the social context on the development of secondary hyperalgesia: an experimental study.

Social support has been shown to reduce pain ratings and physiological responses to acute pain stimuli. Furthermore, this relationship is moderated by adult attachment styles. However, these effects have not been characterized in experimentally induced symptoms of chronic pain, such as secondary hyperalgesia (SH) which is characterized by an increased sensitivity of the skin surrounding an injury. We aimed to examine whether social support by handholding from a romantic partner can attenuate the development of experimentally induced SH. Thirty-seven women, along with their partners, participated in 2 experimental sessions 1 week apart. In both sessions, SH was induced using an electrical stimulation protocol. In the support condition, the partner was seated across from the participant holding the participant's hand during the electrical stimulation, whereas in the alone condition, the participant went through the stimulation alone. Heart rate variability was measured for both the participant as well as the partner before, during, and after the stimulation. We found that the width of the area of hyperalgesia was significantly smaller in the support condition. Attachment styles did not moderate this effect of social support on the area width. Increasing attachment avoidance was associated with both a smaller width of hyperalgesia and a smaller increase in the sensitivity on the stimulated arm. For the first time, we show that social support can attenuate the development of secondary hyperalgesia and that attachment avoidance may be associated with an attenuated development of secondary hyperalgesia.

The effect of sex on sympathetic transduction during an acute pain stimulus

Previously, we have noted sex differences in beat-by-beat fluctuations in blood pressure following sequences of muscle sympathetic nerve activity (MSNA; i.e. sympathetic transduction) during acute sympatho-inhibition but not at rest. However, sex differences in sympathetic transduction during sympatho-excitation have yet to be examined. Therefore, we tested the hypothesis that sympathetic transduction during acute sympatho-excitation and recovery from sympatho-excitation are greater in men than women. We tested healthy women (n=5) and men (n=5) of similar age (26±4 vs 23±2y, respectively; P=0.3). Integrated MSNA (microneurography; NeuroAmp, ADInstruments) and beat-by-beat blood pressure (finger photoplethysmography; Finometer MIDI) were assessed during 10 minutes of supine rest, an acute pain stimulus (6-minute cold pressor test; CPT), and recovery (6-minutes). Custom software was used to calculate sympathetic transduction: beat-by-beat changes in mean arterial pressure (MAP) were tracked for 15 subsequent cardiac cycles (expressed relative to the cardiac cycle associated with the final burst or non-burst in the sequence). Like sequences were overlaid and averaged. Prevailing MSNA and MAP were not different between women and men at rest (9±8 vs 8±5 bursts/min, P=0.8; 88±6 vs 97±6 mmHg, P=0.06) or during the CPT (21±10 vs 16±6 bursts/min, P=0.3; 98±5 vs 104±6 mmHg, P=0.1). However, during recovery, MSNA was greater in women than men (21±8 vs 10±4 bursts/min, P=0.03), despite similar MAP (95±5 vs 99±6 mmHg, P=0.3). Peak and nadir changes in sympathetic transduction following burst and non-burst sequences were not different between women and men at rest (burst: 1.55±0.46 vs 1.67±0.27mmHg, P=0.6; non-burst: -2.21±1.88 vs -2.26±0.36mmHg, P=0.9) or during the CPT (burst: 1.06±0.32 vs 0.45±0.47mmHg, P=0.08; non-burst: -3.24±1.44 vs 1.90±0.46mmHg, P=0.1). Sympathetic transduction following a burst of MSNA did not differ between the sexes during recovery (1.73±0.34 vs 1.65±0.23mmHg, P=0.7), while nadir decreases in MAP following non-burst sequences during recovery were more pronounced in women than men (-2.81±0.75 vs -1.56±0.91mmHg, P=0.04). Taken together, although sympathetic transduction did not differ between the sexes during the CPT, these data suggest that women may require heightened MSNA during recovery from acute stress to maintain equivalent blood pressure. This project was funded by McGill University, FRQS, and NSERC. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Climbing behavior by mice as an endpoint for preclinical assessment of drug effects in the absence and presence of pain.

This study evaluated climbing in mice as a tool to assess the expression and treatment of pain-related behavioral depression in male and female ICR mice. Mice were videotaped during 10-min sessions in a vertical plexiglass cylinder with wire mesh walls, and "Time Climbing" was scored by observers blind to treatments. Initial validation studies demonstrated that baseline climbing was stable across repeated days of testing and depressed by intraperitoneal injection of dilute lactic acid (IP acid) as an acute pain stimulus. Additionally, IP acid-induced depression of climbing was blocked by the positive-control non-steroidal anti-inflammatory drug (NSAID) ketoprofen but not by the negative control kappa opioid receptor agonist U69593. Subsequent studies examined effects of single-molecule opioids (fentanyl, buprenorphine, naltrexone) and of fixed-proportion fentanyl/naltrexone mixtures (10:1, 3.2:1, and 1:1) that vary in their efficacy at the mu opioid receptor (MOR). Opioids administered alone produced a dose- and efficacy-dependent decrease in climbing, and fentanyl/naltrexone-mixture data indicated that climbing in mice is especially sensitive to disruption by even low-efficacy MOR activation. Opioids administered as a pretreatment to IP acid failed to block IP acid-induced depression of climbing. Taken together, these findings support the utility of climbing in mice as an endpoint to evaluate candidate-analgesic effectiveness both to (a) produce undesirable behavioral disruption when the test drug is administered alone, and (b) produce a therapeutic blockade of pain-related behavioral depression. The failure of MOR agonists to block IP acid-induced depression of climbing likely reflects the high sensitivity of climbing to disruption by MOR agonists.

The effect of background liked music on acute pain perception and its neural correlates.

Music shows tremendous promise in pain relief, especially when considering its non-pharmacological nature. However, our understanding of the precise mechanisms behind music-induced analgesia (MIA) remains poor. The positive emotional state induced by music is one of the key components explaining MIA. To test this possibility and reveal its neural correlates, the present study applied nociceptive laser stimuli to 28 healthy participants when their liked or disliked songs were played as background music, or when they were resting in silence. Differences among conditions were quantified by self-reports of pain intensity and unpleasantness, as well as brain activations in response to acute laser stimuli. As expected, liked music significantly lowered pain ratings to acute painful stimuli compared to disliked music and no music. Consistent with this observation, brain activations in response to acute painful stimuli were deceased within brain areas encoding sensory components of pain, such as the right precentral and postcentral gyri (PreCG/PoCG), brain areas related to affective components of pain, such as the anterior cingulate cortex and bilateral putamen, and brain areas associated with motor control and avoidance reactions to pain, such as the left cerebellum, when liked music was played in the background in comparison to disliked music. Importantly, the relationship between music listening and differences in pain ratings of two music conditions was mediated by the magnitude of right PreCG/PoCG and left cerebellum activations. These findings deepened our understanding of the analgesic benefits of background liked music, a property relevant to clinical applications.

A novel computational approach to pain perception modelling within a Bayesian framework using quantitative sensory testing

Pain perception can be studied as an inferential process in which prior information influences the perception of nociceptive input. To date, there are no suitable psychophysical paradigms to measure this at an individual level. We developed a quantitative sensory testing paradigm allowing for quantification of the influence of prior expectations versus current nociceptive input during perception. Using a Pavlovian-learning task, we investigated the influence of prior expectations on the belief about the varying strength of association between a painful electrical cutaneous stimulus and a visual cue in healthy subjects (N = 70). The belief in cue-pain associations was examined with computational modelling using a Hierarchical Gaussian Filter (HGF). Prior weighting estimates in the HGF model were compared with the established measures of conditioned pain modulation (CPM) and temporal summation of pain (TSP) assessed by cuff algometry. Subsequent HGF-modelling and estimation of the influence of prior beliefs on perception showed that 70% of subjects had a higher reliance on nociceptive input during perception of acute pain stimuli, whereas 30% showed a stronger weighting of prior expectations over sensory evidence. There was no association between prior weighting estimates and CPM or TSP. The data demonstrates relevant individual differences in prior weighting and suggests an importance of top-down cognitive processes on pain perception. Our new psychophysical testing paradigm provides a method to identify individuals with traits suggesting greater reliance on prior expectations in pain perception, which may be a risk factor for developing chronic pain and may be differentially responsive to learning-based interventions.

Functional connectivity response to acute pain assessed by fNIRS is associated with BDNF genotype in fibromyalgia: an exploratory study

Fibromyalgia is a heterogenous primary pain syndrome whose severity has been associated with descending pain modulatory system (DPMS) function and functional connectivity (FC) between pain processing areas. The brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism has been linked to vulnerability to chronic pain. In this cross-sectional imaging genetics study, we investigated fibromyalgia, the relationship between BDNF Val66Met heterozygous genotypes (Val/Met), and the functional connectivity (FC) response pattern to acute pain stimulus in the motor (MC) and prefrontal (PFC) cortex assessed by near-infrared spectroscopy (fNIRS) before and after a cold pressor test utilizing water (0–1 °C). Also, we assessed the relationship between this genotype with the DPMS function and quality of life. We included 42 women (Val/Val = 30; Val/Met = 12) with fibromyalgia, ages 18–65. The MANCOVA comparing Val/Met to Val/Val genotypes showed higher ΔFC between left(l)-PFC—l-MC (β = 0.357, p = 0.048), l-PFC—right(r)-PFC (β = 0.249, p = 0.012), l-PFC—r-MC (β = 0.226, p = 0.022), and l-MC—r-PFC (β = 0.260, p = 0.016). Val/Met genotypes showed higher efficiency of the DPMS and lower disability due to pain. Here we show that fibromyalgia patients carrying the Val/Met BDNF genotype presented an increased ΔFC across MC and PFC in response to acute pain associated with differences in acute pain perception and fibromyalgia symptoms.

Cellular and circuit diversity determines the impact of endogenous opioids in the descending pain modulatory pathway.

The descending pain modulatory pathway exerts important bidirectional control of nociceptive inputs to dampen and/or facilitate the perception of pain. The ventrolateral periaqueductal gray (vlPAG) integrates inputs from many regions associated with the processing of nociceptive, cognitive, and affective components of pain perception, and is a key brain area for opioid action. Opioid receptors are expressed on a subset of vlPAG neurons, as well as on both GABAergic and glutamatergic presynaptic terminals that impinge on vlPAG neurons. Microinjection of opioids into the vlPAG produces analgesia and microinjection of the opioid receptor antagonist naloxone blocks stimulation-mediated analgesia, highlighting the role of endogenous opioid release within this region in the modulation of nociception. Endogenous opioid effects within the vlPAG are complex and likely dependent on specific neuronal circuits activated by acute and chronic pain stimuli. This review is focused on the cellular heterogeneity within vlPAG circuits and highlights gaps in our understanding of endogenous opioid regulation of the descending pain modulatory circuits.

Contextual control of conditioned pain tolerance and endogenous analgesic systems.

The mechanisms underlying the transition from acute to chronic pain are unclear but may involve the persistence or strengthening of pain memories acquired in part through associative learning. Contextual cues, which comprise the environment in which events occur, were recently described as a critical regulator of pain memory; both male rodents and humans exhibit increased pain sensitivity in environments recently associated with a single painful experience. It is unknown, however, how repeated exposure to an acute painful unconditioned stimulus in a distinct context modifies pain sensitivity or the expectation of pain in that environment. To answer this question, we conditioned mice to associate distinct contexts with either repeated administration of a mild visceral pain stimulus (intraperitoneal injection of acetic acid) or vehicle injection over the course of 3 days. On the final day of experiments, animals received either an acid injection or vehicle injection prior to being placed into both contexts. In this way, contextual control of pain sensitivity and pain expectation could be tested respectively. When re-exposed to the noxious stimulus in a familiar environment, both male and female mice exhibited context-dependent conditioned analgesia, a phenomenon mediated by endogenous opioid signaling. However, when expecting the presentation of a painful stimulus in a given context, males exhibited conditioned hypersensitivity whereas females exhibited endogenous opioid-mediated conditioned analgesia. These results are evidence that pain perception and engagement of endogenous opioid systems can be modified through their psychological association with environmental cues. Successful determination of the brain circuits involved in this sexually dimorphic anticipatory response may allow for the manipulation of pain memories, which may contribute to the development of chronic pain states.

Altered Pain Processing Associated with Administration of Dopamine Agonist and Antagonist in Healthy Volunteers.

Striatal dopamine dysfunction is associated with the altered top-down modulation of pain processing. The dopamine D2-like receptor family is a potential substrate for such effects due to its primary expression in the striatum, but evidence for this is currently lacking. Here, we investigated the effect of pharmacologically manipulating striatal dopamine D2 receptor activity on the anticipation and perception of acute pain stimuli in humans. Participants received visual cues that induced either certain or uncertain anticipation of two pain intensity levels delivered via a CO2 laser. Rating of the pain intensity and unpleasantness was recorded. Brain activity was recorded with EEG and analysed via source localisation to investigate neural activity during the anticipation and receipt of pain. Participants completed the experiment under three conditions, control (Sodium Chloride), D2 receptor agonist (Cabergoline), and D2 receptor antagonist (Amisulpride), in a repeated-measures, triple-crossover, double-blind study. The antagonist reduced an individuals’ ability to distinguish between low and high pain following uncertain anticipation. The EEG source localisation showed that the agonist and antagonist reduced neural activations in specific brain regions associated with the sensory integration of salient stimuli during the anticipation and receipt of pain. During anticipation, the agonist reduced activity in the right mid-temporal region and the right angular gyrus, whilst the antagonist reduced activity within the right postcentral, right mid-temporal, and right inferior parietal regions. In comparison to control, the antagonist reduced activity within the insula during the receipt of pain, a key structure involved in the integration of the sensory and affective aspects of pain. Pain sensitivity and unpleasantness were not changed by D2R modulation. Our results support the notion that D2 receptor neurotransmission has a role in the top-down modulation of pain.

What Are the Interactions Between the Midbrain Dopamine System in Pain?

There is both experimental and indirect clinical evidence that dopaminergic neurons in the ventral tegmental area (VTA) respond to acute painful stimuli and are involved in the perception, modulation, and behavioral response of chronic pain (reviewed in references 1 and 2). However, the precise role of this system remains poorly understood given the functional heterogeneity of these neurons, including their different targets and their differential response to acute painful stimuli, plastic changes in response to nerve injury associated with neuropathic pain, and effects on different forebrain areas involved in emotion, reward processing, and motivation.1-4 Most of the recent insights into the role of dopaminergic VTA neurons in mechanisms of pain result from elegant studies in rodents combining optogenetics, chemogenetics, calcium imaging, viral tracing, single-cell recording, and behavioral measures, both in response to acute noxious stimulation and in experimental models of chronic pain, typically that induced by peripheral nerve injury.5-11 Whereas these results may not be easily extrapolated to clinical situations in humans, they provide evidence that chronic pain is associated with dysfunction of the midbrain dopaminergic system and its targets. This has been demonstrated indirectly using neuroimaging modalities in humans12-14 and is clinically relevant given the function of this system at the interface between pain and reward, motivation, and drug-seeking behavior.4,15,16 This subject has been the topic of comprehensive reviews1,2,15,16 and other concepts are briefly discussed here.

Changes in prefrontal cerebral hemodynamics during intermittent pain stimulation to gingiva: Preliminary study using functional near infrared spectroscopy

Background/purposeElucidating the transmission mechanism of pain signals from the orofacial area and the corresponding modification mechanism will not only aid in the understanding of pain mechanisms but also provide useful information regarding the development of pain mitigation methods. In this study, the involvement of the pain suppression system in the trigeminal area was investigated through an analysis of the activation status over time in the prefrontal cortex using functional near-infrared spectroscopy (fNIRS). Materials and methodsIn 28 healthy, right-handed male volunteers (average age, 30.1 ± 4.2 years) as subjects, a mild, intermittent, acute pain stimulus was administered through the implementation of pocket probing of the gingiva surrounding the right maxillary central incisor. In the prefrontal cortex, the levels of hemoglobin (Hb) were measured using the fNIRS measurement system. Average values of both oxy-Hb and deoxy-Hb were calculated at four stages: rest stage, 20 s prior to the pain stimulus application, and three stages at 20-s intervals within 1 min of stimulation. One-way analysis of variance and multiple comparisons were used to compare representative values to investigate the changes due to pain. ResultsOxy-Hb levels decreased the most during the 20 s stage directly after stimulus application. This change was seen mainly on the contralateral side, after which it returned to the resting baseline level before the stimulus application. ConclusionOur data demonstrate that in healthy males, a mechanism exists to mitigate pain involving the pain suppression system in the 20 s after feeling mild pain to the gingiva.

The effect of music on pain sensitivity in healthy adults

ABSTRACT Background Previous work suggests mediating effects of music on acute pain processing. This quasi-experimental pilot study examined the effects of music on experimental pain sensitivity. Methods Healthy adults (N = 40) completed quantitative sensory tests during three music conditions (silence, listening, and singing). Repeated Measures ANOVA , Friedman’s Test, and post hoc comparisons determined differences in pain intensity and time to cold pain threshold and tolerance between conditions.. Pearson partial correlations evaluated the association of musical factorswith pain sensitivity. Results Participants demonstrated longer time intervals until perceiving pain and tolerated pain for longer durations when singing compared to listening. Greater self-reported singing proficiency was associated with higher tolerance. Several musical factors were significantly correlated with time from pain threshold to reaching tolerance. Conclusion Singing during an acute painful stimulus may increase tolerance. Various musical characteristics impact volunteers’ central pain responses and singing may be an important adjunct pain management strategy.

Trunk stiffness decreases and trunk damping increases with experimental low back pain

Movement adaptations to low back pain (LBP) are believed to protect the painful area. Increased trunk stiffness and decreased trunk damping have been shown in people with recurrent LBP. However, no study has examined these properties using external force perturbations to the trunk during acute LBP when protective adaptations might be expected to have most relevance.Adaptations to an acute painful stimulus via unilateral injection of hypertonic saline into the right longissimus muscle were assessed using a trunk force perturbation paradigm and a mass-spring-damper model to describe effective trunk dynamical properties. Equal weights (15% body weight) were connected to the front and back of the trunk via a cable. Either one was dropped at random to perturb the trunk. Effective trunk dynamical properties were estimated in fourteen males (mean (standard deviation) age 25 (6) years) assuming that trunk movement can be modelled as a second order linear system. Effective trunk dynamical properties were compared before, during and after the experimentally induced painful period.Estimates of effective trunk stiffness (K) decreased and damping (B) increased during pain compared to both before ([mean contrast, 95% CI] K: −403 [−651 to −155] Nm−1, B: 28 [9–50] Nms−1) and after (K: −324 [−58 to −591] Nm−1, B: 20 [4–33] Nms−1) the experimentally induced painful period. We interpret our results to show that, when challenged by a step force perturbation, a healthy system adapts to noxious input by controlling trunk velocity rather than trunk displacement, in contrast to observations during remission from recurrent clinical LBP.

Mice lacking spinal α2GABAA receptors: Altered GABAergic neurotransmission, diminished GABAergic antihyperalgesia, and potential compensatory mechanisms preventing a hyperalgesic phenotype

Diminished synaptic inhibition in the superficial spinal dorsal horn contributes to exaggerated pain responses that accompany peripheral inflammation and neuropathy. α2GABAA receptors (α2GABAAR) constitute the most abundant GABAAR subtype at this site and are the targets of recently identified antihyperalgesic compounds. Surprisingly, hoxb8-α2−/− mice that lack α2GABAAR from the spinal cord and peripheral sensory neurons exhibit unaltered sensitivity to acute painful stimuli and develop normal inflammatory and neuropathic hyperalgesia. Here, we provide a comprehensive analysis of GABAergic neurotransmission, of behavioral phenotypes and of possible compensatory mechanisms in hoxb8-α2−/− mice. Our results confirm that hoxb8-α2−/− mice show significantly diminished GABAergic inhibitory postsynaptic currents (IPSCs) in the superficial dorsal horn but no hyperalgesic phenotype. We also confirm that the potentiation of dorsal horn GABAergic IPSCs by the α2-preferring GABAAR modulator HZ-166 is reduced in hoxb8-α2−/− mice and that hoxb8-α2−/− mice are resistant to the analgesic effects of HZ-166. Tonic GABAergic currents, glycinergic IPSCs, and sensory afferent-evoked EPSCs did not show significant changes in hoxb8-α2−/− mice rendering a compensatory up-regulation of other GABAAR subtypes or of glycine receptors unlikely. Although expression of serotonin and of the serotonin producing enzyme tryptophan hydroxylase (TPH2) was significantly increased in the dorsal horn of hoxb8-α2−/− mice, ablation of serotonergic terminals from the lumbar spinal cord failed to unmask a nociceptive phenotype. Our results are consistent with an important contribution of α2GABAAR to spinal nociceptive control but their ablation early in development appears to activate yet-to-be identified compensatory mechanisms that protect hoxb8-α2−/− mice from hyperalgesia.

Pain-modulating effects of oxytocin in patients with chronic low back pain

The neuropeptide oxytocin (OT) has been shown to play a modulatory role in nociception. However, analgesic effects of OT in chronic pain conditions remain elusive and the neural underpinnings have not yet been investigated in humans. Here, we conducted an exploratory, randomized, placebo-controlled, cross-over study to examine effects of intranasal OT in male patients suffering from chronic low back pain (CBP) versus healthy controls (HC). N = 22 participants with CBP and 22 HCs were scanned using functional magnetic resonance imaging (fMRI) while they continuously rated either spontaneously occurring back pain or acute thermal pain stimuli applied to the lower back. During heat pain processing we found that OT versus PL attenuated pain intensity ratings and increased BOLD responses in the caudate nucleus of the striatum in CBP versus HCs. Spontaneously experienced pain in contrast to heat pain was associated with activation changes in the medial frontal cortex (MFC) and the anterior cingulate cortex (ACC) as reported in previous studies. However, we did not observe OT effects on spontaneously experienced pain in CBP patients. Overall, our preliminary data may suggest that the striatum is a key structure underlying the pain-modulating effects of OT in patients with chronic pain and adds to the growing evidence linking the neuropeptide to pain modulation in humans. Further studies on neuronal OT effects in larger samples of chronic back pain patients are needed to understand probable mechanisms of OT effects in chronic pain.This article is part of the special issue on Neuropeptides.

Evaluation of pain in vaginal and caesarean section birth newborns before and after intramuscular injection

ABSTRACT BACKGROUND AND OBJECTIVES: It is already known that the painful experiences to which the newborn is subjected may be related to future reactions and differences in the behavioral response to pain in newborns from different birth routes. This study aimed to evaluate the response to pain in infants born by cesarean section and vaginal delivery routes. METHODS: This is a prospective cohort study. Newborns born at full term were allocated into two groups: cesarean section and vaginal delivery. The intramuscular vitamin K injection was performed as an acute pain stimulus because it is a routine injection at birth. The newborns were evaluated for pain on two scales, a one-dimensional, the Neonatal Facial Coding System, and a multidimensional, the COMFORT Behavior Scale (Comfort b), in addition to heart rate counting, moments before, immediately after and 10 minutes after the stimuli. Students t-test was used for statistical analyzes, and the level of significance was 5%. RESULTS: Eighty-three children were evaluated. The pain intensity assessed by both scales before the pain stimulus was higher in the cesarean section group, but not statistically significant. Heart rate values after the stimulus showed a statistically significant difference (p<0.05), higher in the cesarean section group than in the vaginal delivery. CONCLUSION: The results did not suggest that there are differences in the perception of pain among newborns born vaginally and cesarean section.

Neonatal pain detection in videos using the iCOPEvid dataset and an ensemble of descriptors extracted from Gaussian of Local Descriptors

Diagnosing pain in neonates is difficult but critical. Although approximately thirty manual pain instruments have been developed for neonatal pain diagnosis, most are complex, multifactorial, and geared toward research. The goals of this work are twofold: 1) to develop a new video dataset for automatic neonatal pain detection called iCOPEvid (infant Classification Of Pain Expressions videos), and 2) to present a classification system that sets a challenging comparison performance on this dataset. The iCOPEvid dataset contains 234 videos of 49 neonates experiencing a set of noxious stimuli, a period of rest, and an acute pain stimulus. From these videos 20 s segments are extracted and grouped into two classes: pain (49) and nopain (185), with the nopain video segments handpicked to produce a highly challenging dataset. An ensemble of twelve global and local descriptors with a Bag-of-Features approach is utilized to improve the performance of some new descriptors based on Gaussian of Local Descriptors (GOLD). The basic classifier used in the ensembles is the Support Vector Machine, and decisions are combined by sum rule. These results are compared with standard methods, some deep learning approaches, and 185 human assessments. Our best machine learning methods are shown to outperform the human judges.