Modulation Of Pain Perception Research Articles

Words hurt: common and distinct neural substrates underlying nociceptive and semantic pain.

Recent studies have shown that processing semantic pain, such as words associated with physical pain, modulates pain perception and enhances activity in regions of the pain matrix. A direct comparison between activations due to noxious stimulation and processing of words conveying physical pain may clarify whether and to what extent the neural substrates of nociceptive pain are shared by semantic pain. Pain is triggered also by experiences of social exclusion, rejection or loss of significant others (the so-called social pain), therefore words expressing social pain may modulate pain perception similarly to what happens with words associated with physical pain. This event-related fMRI study aims to compare the brain activity related to perceiving nociceptive pain and that emerging from processing semantic pain, i.e., words related to either physical or social pain, in order to identify common and distinct neural substrates. Thirty-four healthy women underwent two fMRI sessions each. In the Semantic session, participants were presented with positive words, negative pain-unrelated words, physical pain-related words, and social pain-related words. In the Nociceptive session, participants received cutaneous mechanical stimulations that could be either painful or not. During both sessions, participants were asked to rate the unpleasantness of each stimulus. Linguistic stimuli were also rated in terms of valence, arousal, pain relatedness, and pain intensity, immediately after the Semantic session. In the Nociceptive session, the 'nociceptive stimuli' vs. 'non-nociceptive stimuli' contrast revealed extensive activations in SI, SII, insula, cingulate cortex, thalamus, and dorsolateral prefrontal cortex. In the Semantic session, words associated with social pain, compared to negative pain-unrelated words, showed increased activity in most of the same areas, whereas words associated with physical pain, compared to negative pain-unrelated words, only activated the left supramarginal gyrus and partly the postcentral gyrus. Our results confirm that semantic pain partly shares the neural substrates of nociceptive pain. Specifically, social pain-related words activate a wide network of regions, mostly overlapping with those pertaining to the affective-motivational aspects of nociception, whereas physical pain-related words overlap with a small cluster including regions related to the sensory-discriminative aspects of nociception. However, most regions of overlap are differentially activated in different conditions.

Non-pharmaceutical management of chronic pain

Chronic pain is a complex and pervasive condition that challenges both individuals and healthcare systems. In light of concerns about overreliance on pharmacological interventions, non-pharmacological approaches have gained prominence in chronic pain management. This article explores the scientific basis and benefits of diverse non-pharmacological interventions, including physical exercise, manual therapies, cognitive-behavioral therapy (CBT), meditation, acupuncture, and herbal medicine, in alleviating chronic pain. Each intervention's mechanisms of action are elucidated, shedding light on their physiological and psychological effects. Physical exercise has emerged as a cornerstone of non-pharmacological pain management, offering benefits such as pain reduction, enhanced mobility, and improved quality of life. Mechanisms encompass endorphin release, anti-inflammatory effects, and central nervous system modulation. Manual therapies, represented by chiropractic manipulation, osteopathic manipulative treatment , and massage therapy, demonstrate significant pain relief through mechanisms involving joint mobilization, muscle relaxation, and neurophysiological responses. Cognitive-behavioral therapy (CBT) operates through cognitive restructuring, behavioral modification, and pain perception modulation. Meditation practices, such as mindfulness and meditation-based pain relief, cultivate mindfulness and promote emotional regulation, leading to reduced pain perception and improved overall well-being. Acupuncture, a traditional Chinese therapy, involves needling specific points to achieve pain relief through mechanisms like endorphin release, neural pathway modulation, and anti-inflammatory effects. Herbal medicine, with its rich pharmacopeia, contributes to pain management through anti-inflammatory, analgesic, and muscle relaxant properties. Mechanisms encompass modulation of neurotransmitters, prostaglandins, and ion channels. Collectively, these non-pharmacological interventions empower individuals to actively engage in their pain management and improve their quality of life.

Same but different: how agency modulates pain perception.

Why is analgesic treatment more effective when it is self-administered? Strube et al. compare two possible accounts and show that the effect of agency on perception is linked to a shift in expectation (prior) rather than to reduced likelihood precision, highlighting that agency has a profound impact on the entire perceptual process.

Serotonergic 5-HT7 Receptors as Modulators of the Nociceptive System.

The biogenic amine serotonin modulates pain perception by activating several types of serotonergic receptors, including the 5-HT7 type. These receptors are widely expressed along the pain axis, both peripherally, on primary nociceptors, and centrally, in the spinal cord and the brain. The role of 5-HT7 receptors in modulating pain has been explored in vivo in different models of inflammatory and neuropathic pain. While most studies have reported an antinociceptive effect of 5-HT7 receptor activation, some authors have suggested a pronociceptive action. Differences in pain models, animal species and gender, receptor types, agonists, and route of administration could explain these discrepancies. In this mini-review, some of the main findings concerning the function of 5-HT7 receptors in the pain system have been presented. The expression patterns of the receptors at the different levels of the pain axis, along with the cellular mechanisms involved in their activity, have been described. Alterations in receptor expression and/or function in different pain models and the role of 5-HT7 receptors in controlling pain transmission have also been discussed. Finally, some of the future perspectives in this field have been outlined.

Candidate gene association study suggests potential role of dopamine beta-hydroxylase in pain heterogeneity in sickle cell disease.

Introduction: Pain is a lifelong companion of individuals with sickle cell disease (SCD) and has a severe impact on their quality of life. Both acute crisis pain and chronic non-crisis pain exhibit high variability between individuals, making it difficult to effectively manage sickle cell-related pain. We investigated the role of dopamine beta-hydroxylase (DBH) gene polymorphisms on pain variability in SCD. DBH is a key enzyme in the catecholamine biosynthesis pathway that catalyzes the conversion of dopamine to norepinephrine, both of which are known mediators of pain and pain-related behaviors. Methods: Acute crisis pain-related utilization and non-crisis chronic pain scores of 131 African Americans with SCD were obtained. Results and discussion: Association analyses revealed that the T allele of upstream variant rs1611115 and downstream variant rs129882 correlated with higher severity of chronic pain in an additive model. On the other hand, the A allele of missense variant rs5324 associated with lower risk of both acute crisis pain and chronic pain. Similarly, the C allele of intronic variant rs2797849 was associated with lower incidence of acute crisis pain in the additive model. In addition, tissue-specific eQTL revealed that the T allele of rs1611115 correlated with decreased expression of DBH in the frontal cortex and anterior cingulate cortex (GTEx), and decreased expression of DBH-AS1 in blood (eQTLGen). Bioinformatic approaches predicted that rs1611115 may be altering a transcription factor binding site, thereby, contributing to its potential effect. Taken together, findings from this study suggest that potential functional polymorphisms of DBH may modulate pain perception in SCD.

Low concentrations of tricyclic antidepressants stimulate TRPC4 channel activity by acting as an opioid receptor ligand.

Traditionally prescribed for mood disorders, tricyclic antidepressants (TCAs) have shown promising therapeutic effects on chronic neuralgia and irritable bowel syndrome. However, the mechanism by which these atypical effects manifest is unclear. Among the proposed mechanisms is the well-known pain-related inhibitory G-protein coupled receptor, namely the opioid receptor (OR). Here, we confirmed that TCA indeed stimulates OR and regulates the gating of TRPC4, a downstream signaling of the Gi-pathway. In an ELISA to quantify the amount of intracellular cAMP, a downstream product of OR/Gi-pathway, treatment with amitriptyline (AMI) showed a decrease in [cAMP]i similar to that of the μOR agonist. Next, we explored the binding site of TCA by modeling the previously revealed ligand-bound structure of μOR. A conserved aspartate residue of ORs was predicted to participate in salt bridge interaction with the amine group of TCAs, and in aspartate-to-arginine mutation, AMI did not decrease the FRET-based binding efficiency between the ORs and Gαi2. As an alternative way to monitor the downstream signaling of Gi-pathway, we evaluated the functional activity of TRPC4 channel, as it is well known to be activated by Gαi. TCAs increased the TRPC4 current through ORs, and TCA-evoked TRPC4 activation was abolished by an inhibitor of Gαi2 or its dominant-negative mutant. As expected, TCA-evoked activation of TRPC4 was not observed in the aspartate mutants of OR. Taken together, OR could be proclaimed as a promising target among numerous binding partners of TCA, and TCA-evoked TRPC4 activation may help to explain the nonopioid analgesic effect of TCA.NEW & NOTEWORTHY Endogenous opioid systems modulate pain perception, but concerns about opioid-related substance misuse limit their use. This study has raised TRPC4 channel as a candidate target for alternative analgesics, tricyclic antidepressants (TCAs). TCAs have been shown to bind to and activate opioid receptors (ORs), leading to downstream signaling pathways involving TRPC4. The functional selectivity and biased agonism of TCA towards TRPC4 in dependence on OR may provide a better understanding of its efficacy or side effects.

Effect of transcutaneous auricular vagal nerve stimulation on the fatigue syndrome in patients with gastrointestinal cancers — FATIVA: a randomized, placebo-controlled pilot study protocol

BackgroundCancer-related fatigue (CRF) is defined as a “distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.” CRF is frequently observed in cancer patients even before the initiation of tumor therapy. Its cause is not clear, but in addition to primary effects of therapy, a tumor-induced elevated level of inflammatory cytokines may play a role. Transcutaneous auricular vagal nerve stimulation (taVNS) is a noninvasive way to activate central nervous pathways and modulate pain perception and the immune system. It has positive effects on autoimmune conditions and can also improve fatigue associated with Sjogren’s syndrome. It is the main purpose of this feasibility study to investigate the feasibility of daily taVNS against CRF. Therefore, the stimulation protocol of the newly introduced smartphone app of the manufacturer is evaluated. Additionally, the effect taVNS on CRF and quality of life (QoL) shall be evaluated.MethodsThirty adult patients with gastrointestinal tumors during or after treatment, relevant CRF (Hornheide questionnaire) and life expectancy > 1 year, are enrolled. Patients are randomized to treatment or sham arm and be informed that they will either feel the stimulation or not. Treatment group will receive left-sided tragus above-threshold stimulation with 25 Hz, 250 µs pulse width, and 28-s/32-s on/off paradigm for 4 h throughout the day for 4 weeks. Sham group will receive no stimulation via a nonfunctional electrode. A daily stimulation protocol with time and average intensity is automatically created by a smartphone app connected to the stimulator via Bluetooth®. Multidimensional Fatigue Inventory-20, Short-Form 36 and Beck Depression Inventory questionnaires will be filled out before and after 4 weeks of stimulation.DiscussionPrimarily, the patients’ daily stimulation time and intensity will be evaluated through the electronic protocol after 4 weeks. Secondarily, the effect of taVNS on cancer-related fatigue and QoL will be measured through the questionnaires. As taVNS seems to modulate inflammatory cytokines, this noninvasive method may — if accepted by the patients — be a promising adjunct in the treatment of cancer-related fatigue.Trial registrationThe study was approved by local ethics committee (21–7395) and registered at the DRKS database (DRKS00027481).

An illusion of disownership over one’s own limb is associated with pain perception

Viewing one’s body and even a fake/virtual body experienced as one’s own has been suggested to modulate pain perception. However, what happens to pain perception when one’s own body part is felt as not belonging to one? We designed a paradigm to induce an illusory feeling of disownership regarding one’s limb, investigating whether the feeling affects pain threshold. Participants observed right-side images of their bodies from a third-person perspective via a head-mounted display in real-time. Following instructions, they moved their left hand while keeping their left elbow behind the upper body, so that the connection of their arm to the torso was not visible (test condition), or in front of it, so they could see the arm being part of them (control condition). Then, pain threshold was tested with a thermal stimulator. We found a significantly higher strength of disownership in the test condition than in the control condition. While there was no pain modulation within and between conditions, disownership ratings negatively correlated with pain-threshold changes, where the participants reporting explicit disownership showed lower pain-threshold changes than the others. The finding suggests that while multisensory disintegration had no modulatory effect, the individual sense of disownership was associated with pain perception.

Effect of stress on contextual pain sensitivity in the preoperative period- A proof of concept study.

The importance of non-noxious contextual inputs in the interplay of pain with neurophysiologic and behavioral factors is gaining recognition. Stress of impending surgery can act as a negative context, leading to a decrease in pain threshold in patients. This study was conducted to assess the influence of stress conferred by the imminent and other contextual inputs such as anxiety, socioeconomic status, prior painful experience, and the effect of gender on modulation of pain perception in patients undergoing elective surgery. In total, 120 patients aged between 18 and 60 years of either gender posted for elective gastrointestinal surgery under general anesthesia were recruited. Data were collected on preoperative anxiety level, socioeconomic status, education, and any prior painful experience. A pressure algometer was used to measure the pressure pain thresholds and pain tolerance on the day before surgery and on the morning of surgery in the preoperative suite. There was a statistically significant decrease in both pain threshold (P < 0.0001) and pain tolerance in the immediate preoperative period in comparison to the baseline readings taken the day before surgery (P = 0.048). The magnitude of change in pain scalars was greater in females (P < 0.001), those with a high anxiety score, and a history of severe painful experience in the past. Preoperative surgical stress lowers the pain threshold and pain tolerance. Contextual modulation of pain by factors such as anxiety and memory of prior painful experience, especially in the female gender, could influence postoperative patient outcomes and warrants further research.

Molecular determinants of tetrahydrocannabinol binding to the glycine receptor.

The recognition of Cannabis as a source of new compounds suitable for medical use has attracted strong interest from the scientific community in its research, and substantial progress has accumulated regarding cannabinoids' activity; however, a thorough description of their molecular mechanisms of action remains a task to complete. Highlighting their complex pharmacology, the list of cannabinoids' interactors has vastly expanded beyond the canonical cannabinoid receptors. Among those, we have focused our study on the glycine receptor (GlyR), an ion channel involved in the modulation of nervous system responses, including, to our interest, sensitivity to peripheral pain. Here, we report the use of computational methods to investigate possible binding modes between the GlyR and Δ9 -tetrahydrocannabinol (THC). After obtaining a first pose for the THC binding from a biased molecular docking simulation and subsequently evaluating it by molecular dynamic simulations, we found a dynamic system with an identifiable representative binding mode characterized by the specific interaction with two transmembrane residues (Phe293 and Ser296). Complementarily, we assessed the role of membrane cholesterol in this interaction and positively established its relevance for THC binding to GlyR. Lastly, the use of restrained molecular dynamics simulations allowed us to refine the description of the binding mode and of the cholesterol effect. Altogether, our findings contribute to the current knowledge about the GlyR-THC mode of binding and propose a new starting point for future research on how cannabinoids in general, and THC in particular, modulate pain perception in view of its possible clinical applications.

Neurofeedback Training without Explicit Phantom Hand Movements and Hand-Like Visual Feedback to Modulate Pain: A Randomized Crossover Feasibility Trial

Phantom limb pain is attributed to abnormal sensorimotor cortical representations, although the causal relationship between phantom limb pain and sensorimotor cortical representations suffers from the potentially confounding effects of phantom hand movements. We developed neurofeedback training to change sensorimotor cortical representations without explicit phantom hand movements or hand-like visual feedback. We tested the feasibility of neurofeedback training in fourteen patients with phantom limb pain. Neurofeedback training was performed in a single-blind, randomized, crossover trial using two decoders constructed using motor cortical currents measured during phantom hand movements; the motor cortical currents contralateral or ipsilateral to the phantom hand (contralateral and ipsilateral training) were estimated from magnetoencephalograms. Patients were instructed to control the size of a disk, which was proportional to the decoding results, but to not move their phantom hands or other body parts. The pain assessed by the visual analogue scale was significantly greater after contralateral training than after ipsilateral training. Classification accuracy of phantom hand movements significantly increased only after contralateral training. These results suggested that the proposed neurofeedback training changed phantom hand representation and modulated pain without explicit phantom hand movements or hand-like visual feedback, thus showing the relation between the phantom hand representations and pain. PERSPECTIVE: Our work demonstrates the feasibility of using neurofeedback training to change phantom hand representation and modulate pain perception without explicit phantom hand movements and hand-like visual feedback. The results enhance the mechanistic understanding of certain treatments, such as mirror therapy, that change the sensorimotor cortical representation.

The Relationship between Environmental Racism and Mechanisms of the Native American Pain Disparity: Preliminary Results from the Oklahoma Study of Native American Pain Risk (OK-SNAP)

Native Americans (NAs) experience higher rates of chronic pain than the general U.S. population and we have recently shown that pain-free NAs are ∼3x more likely than non-Hispanic Whites (NHWs) to prospectively develop chronic pain. Moreover, this pain disparity is partially mediated by stress-related factors (discrimination, psychological stress, cardiometabolic allostatic load) and a unique NA pain risk phenotype we call "silent" spinal sensitization (sensitization of the nociceptive flexion reflex [NFR] during a conditioned pain modulation [CPM] task without sensitization of pain experience). NAs have endured and continue to endure structural racism and discrimination (SRD) due to colonization (eg, genocide, cultural oppression), including forced removal from Native lands and policies that lead to desecration of the natural environment. Most NA traditional beliefs include a sacred connection to nature; thus, environmental SRD may be particularly relevant for this population. The present study examined the impact of environmental SRD (racialized distribution of environmental pollutions/hazards) on mechanisms of the NA pain disparity in 282 healthy NAs and NHWs. CPM was used to assess individual differences in modulation of pain perception and the NFR. The Environmental Protection Agency's 11 publicly-available environmental (in)justice variables at the Oklahoma census block level were used to form a latent variable that was linked to participants via geocoding. This latent variable: a) explained 87% of the variance in the original 11 injustice variables, b) correlated with the proportion of NAs within a census region suggesting it assesses racialized NA exposure to pollution, and c) formed an indirect (mediated) pathway with NFR sensitization, but not pain sensitization, via stress-related mechanisms. This indirect path was significant in NAs, but not NHWs. These preliminary findings suggest that SRD may contribute to pain inequities in NAs. This research was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number R01MD007807, and by the University of Tulsa Office of Research and Sponsored Programs. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the University of Tulsa.

Facial expressions modulate pain perception in patients with chronic migraine.

First, we investigated whether the exposure to different visual feedback conditions may modulate pain perception by means of visual induced analgesia in patients with chronic migraine. Second, to comprehend the way emotional face expressions could induce visual analgesia, we evaluated the degree of identification with the four experimental conditions. In a 1 × 4 within-subject study design, 38 female chronic migraine patients were exposed to different visual stimuli - positive face, neutral face, negative face, and control (white screen) - during a migraine attack. Visual stimuli were presented 3 times in a randomized order (each condition lasted 40 seconds). Migraine pain ratings and identification scores were assessed immediately after the observation of each visual condition. We observed a significant difference in pain ratings between the positive (median: 30, 95% CI 26.69 to 38.20) and the negative (median: 30, 95% CI 33.09 to 44.13) (z = -4.46, p < 0.0001) facial expressions or the neutral facial expression (median: 30, 95% CI 31.89 to 42.41) (z = 3.41, p < 0.001). Participants identified more with the neutral face condition than with the other conditions. Observation of a positive emotional face resulted sufficient to modulate pain perception possibly via the mediation of emotion regulation for positive emotions. This study paves the way for the integration of new cognitive behavioural interventions based on the adoption of visual induced analgesia to further control pain perception in chronic migraine patients.

Tonic pain reduces autonomic responses and EEG functional connectivity elicited by affective stimuli.

Most pain studies have focused on only two aspects of pain: the influence of pain on attentional processing and the modulation of pain perception by affective stimuli. However, the influence of tonic pain on the attentional processing of affective stimuli has not been studied. In this study, we investigated the effects of tonic pain on the attentional processing of affective stimuli, focusing on autonomic responses and their relationship with both EEG power and functional connectivity. Forty participants (20 men and 20 women) received tonically painful and nonpainful thermal stimulation while viewing blocks of pleasant, unpleasant, or neutral images. The galvanic skin conductance response (SCR), electrocardiographic activity, and electroencephalographic (EEG) activity in the delta and theta bands were recorded. Participants rated the unpleasantness of the pain at the end of each block. Typical affective SCR and heart rate (HR) patterns were found in the no‐pain condition, but when the pain was delivered, these patterns disappeared. EEG power and functional connectivity results showed that tonic pain affected the delta band in the central region during pleasant and unpleasant image blocks. Our findings suggest that tonic pain captured attentional focus and reduced the cognitive resources available for processing affective stimuli, altering the emotional experience associated with pain.

The consequence of endothelial remodelling on the blood spinal cord barrier and nociception.

Nociception is a fundamental acute protective mechanism that prevents harm to an organism. Understanding the integral processes that control nociceptive processing are fundamental to our appreciation of which cellular and molecular features underlie this process. There is an extensive understanding of how sensory neurons interpret differing sensory modalities and intensities. However, it is widely appreciated that the sensory neurons do not act alone. These work in harmony with inflammatory and vascular systems to modulate pain perception. The spinal cord has an extensive interaction with the capillary network in the form of a blood spinal cord barrier to ensure homeostatic control of the spinal cord neuron milieu. However, there is an extensive appreciation that disturbances in the blood spinal cord barrier contribute to the onset of chronic pain. Enhanced vascular permeability and impaired blood perfusion have both been highlighted as contributors to chronic pain manifestation. Here, we discuss the evidence that demonstrates alterations in the blood spinal cord barrier influences nociceptive processing and perception of pain.

Fullerene-Filtered Light Spectrum and Fullerenes Modulate Emotional and Pain Processing in Mice

The most symmetric molecule, Buckminster fullerene C60, due to its unique properties, has been intensively studied for various medical and technological advances. Minimally invasive and minimally toxic treatments hold great promise for future applications. With this in mind, this research exploited the physical properties of fullerene molecules for potential therapeutic effects. Pristine fullerenes have peak absorbance in the 380–500 nm range, making them an attractive violet-blue light filter. Since spectral quality of light can affect behavior, this research used resting state functional magnetic resonance imaging (rs fMRI) and behavioral testing to directly evaluate the effects of fullerene-filtered light on brain processing and behavior in mice. The same method was used to study if hydroxyl fullerene water complexes (3HFWC), with or without fullerene-filtered light, modulated brain processing. A month-long, daily exposure to fullerene-filtered light led to decreased activation of the brain area involved in emotional processing (amygdala). Water supplemented with 3HFWC resulted in an activation of brain areas involved in pain modulation and processing (periaqueductal gray), and decreased latency to first reaction when tested with a hot plate. The combination of fullerene-filtered light with 3HFWC in drinking water led to restored sensitivity to a hot plate and activation of brain areas involved in cognitive functions (prelimbic, anterior cingulate and retrosplenial cortex). These results uncovered the potential of fullerene-filtered light to impact emotional processing and modulate pain perception, indicating its further use in stress and pain management.

Regulatory Effects of Acupuncture on Emotional Disorders in Patients With Menstrual Migraine Without Aura: A Resting-State fMRI Study.

Background: Menstrual migraine without aura (MMoA) refers to a specific type of migraine that is associated with the female ovarian cycle. It is particularly serious and has brought huge life pressure and mental burden to female patients. Acupuncture has been commonly used to prevent migraines and relieve concomitant emotional disorders; however, the physiological mechanism underlying this intervention remains unclear. This study aimed to use resting-state functional magnetic resonance imaging (rsfMRI) to investigate whether acupuncture can modulate brain function and if the potential influence on brain activity correlates with improving emotional symptoms in MMoA patients.Methods: Overall, 44 patients were randomly divided into a true acupuncture (TA) group and the sham acupuncture (SA) group. Patients underwent rsfMRI before and after 3-month treatment, the amplitude of low-frequency fuctuations (ALFF) and regional homogeneity (ReHo) in rsfMRI were calculated. Zung self-rating anxiety scale (SAS), Zung self-rating depression scale (SDS), frequency of migraine attacks, visual analog scale, and intensity of the migraine were used for evaluate the clinical effect. The clinical changes of variables were also used to further assess the correlation with brain activity in MMoA patients.Results: After acupuncture treatment, the emotional symptoms of both groups of patients improved, and the clinical symptoms of migraine were alleviated. The major finding of our study was that patients with MMoA showed lower ALFF value in the left anterior cingulate and the value was positively correlated with the decreases in the SAS and SDS scores. In the SA group, common brain regions responded both in ALFF and regional homogeneity values mainly in the insula, and no significant correlations were observed between brain regions and clinical variables.Conclusions: These results indicated that both two acupuncture treatments were helpful in treating migraine and could improve emotion symptoms. TA had a relatively better effect in reducing the frequency of migraine attack than SA. The two therapies have different modulation effects as TA regulates emotional disorders by modulating the frontal-limbic regions, and SA may modulate pain perception through the placebo effect on insula and by indirectly regulating emotional disorders. These findings provided evidence that acupuncture is a complementary and alternative therapy to relieve clinical symptoms in female patients with migraines and could help enhance clinical diagnosis and treatment.Clinical Trial Registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR-IOR-15006648. Registered 23 June 2015].

Neuron-Glia-Immune Triad and Cortico-Limbic System in Pathology of Pain

Pain is an unpleasant sensation that alerts one to the presence of obnoxious stimuli or sensations. These stimuli are transferred by sensory neurons to the dorsal root ganglia-spinal cord and finally to the brain. Glial cells in the peripheral nervous system, astrocytes in the brain, dorsal root ganglia, and immune cells all contribute to the development, maintenance, and resolution of pain. Both innate and adaptive immune responses modulate pain perception and behavior. Neutrophils, microglial, and T cell activation, essential components of the innate and adaptive immune responses, can play both excitatory and inhibitory roles and are involved in the transition from acute to chronic pain. Immune responses may also exacerbate pain perception by modulating the function of the cortical-limbic brain regions involved in behavioral and emotional responses. The link between an emotional state and pain perception is larger than what is widely acknowledged. In positive psychological states, perception of pain along with other somatic symptoms decreases, whereas in negative psychological states, these symptoms may worsen. Sex differences in mechanisms of pain perception are not well studied. In this review, we highlight what is known, controversies, and the gaps in this field.

Impacto del ejercicio físico en variables relacionadas con el bienestar emocional y funcional en adultos mayores

Background and aimThe benefits of the physical exercise in aging, and specially in frailty, have been associated with reduced risk of mortality, chronic disease, and cognitive and functional impairments. Multi-component training, which combines strength, endurance, balance, and gait training, represents the most beneficial kind of physical exercise in older adults. MethodsGiven the effectiveness of the multi-component training, a physical exercise program «Actívate» (based on the methodology Vivifrail), with the focus on «active aging», was conducted in the present study. Forty-nine older adults over 60 years participated in this program. ResultsThe physical exercise intervention led to a reduction in diastolic blood pressure, pain threshold and sleep disturbances (e. g. hypersomnia) (t ≥ 2.72, p < 0.01), as well as an increase of walking speed (t = 7.84, p ≤ 0.001). Further, quality of life factors (GENCAT scale), like emotional well-being, personal development, physical well-being, self-determination, and social inclusion, were greater after intervention (t ≥ −2.06, p < 0.05). ConclusionsThese findings underline the benefits of multi-component training in functionality of older adults, and further, provide relevant aspects about the modulation of pain perception, sleep disturbances, social factors and physical and emotional well-being. Physical exercise programs such as «Actívate» should be promoted, in order to encourage healthy lifestyle habits, in the older adults’ population.

How expectations of pain elicited by consciously and unconsciously perceived cues unfold over time

Expectation can shape the perception of pain within a fraction of time, but little is known about how perceived expectation unfolds over time and modulates pain perception. Here, we combine magnetoencephalography (MEG) and machine learning approaches to track the neural dynamics of expectations of pain in healthy participants with both sexes. We found that the expectation of pain, as conditioned by facial cues, can be decoded from MEG as early as 150 ms and up to 1100 ms after cue onset, but decoding expectation elicited by unconsciously perceived cues requires more time and decays faster compared to consciously perceived ones. Also, results from temporal generalization suggest that neural dynamics of decoding cue-based expectation were predominately sustained during cue presentation but transient after cue presentation. Finally, although decoding expectation elicited by consciously perceived cues were based on a series of time-restricted brain regions during cue presentation, decoding relied on the medial prefrontal cortex and anterior cingulate cortex after cue presentation for both consciously and unconsciously perceived cues. These findings reveal the conscious and unconscious processing of expectation during pain anticipation and may shed light on enhancing clinical care by demonstrating the impact of expectation cues.