Pain Processing Research Articles

Contribution of Small Extracellular Vesicles from Schwann Cells and Satellite Glial Cells to Pain Processing

Contribution of Small Extracellular Vesicles from Schwann Cells and Satellite Glial Cells to Pain Processing

Altered resting-state brain functional activities and networks in Crohn’s disease: a systematic review

BackgroundCrohn’s disease (CD) is a non-specific chronic inflammatory disease of the gastrointestinal tract and is a phenotype of inflammatory bowel disease (IBD). The current study sought to compile the resting-state functional differences in the brain between CD patients and healthy controls.MethodsThe online databases PubMed, Web of Science Core, and EMBASE were used to find the published neuroimage studies. The search period was from the beginning through December 15, 2023. The predetermined inclusion and exclusion criteria allowed for the identification of the studies. The studies were assembled by two impartial reviewers, who also assessed their quality and bias.ResultsThis review comprised 16 resting-state fMRI studies in total. The included studies generally had modest levels of bias. According to the research, emotional processing and pain processing were largely linked to increased or decreased brain activity in patients with CD. The DMN, CEN, and limbic systems may have abnormalities in patients with CD, according to research on brain networks. Several brain regions showed functional changes in the active CD group compared to the inactive CD group and the healthy control group, respectively. The abnormalities in brain areas were linked to changes in mood fluctuations (anxiety, melancholy) in patients with CD.ConclusionFunctional neuroimaging helps provide a better understanding of the underlying neuropathological processes in patients with CD. In this review, we summarize as follows: First, these findings indicate alterations in brain function in patients with CD, specifically affecting brain regions associated with pain, emotion, cognition, and visceral sensation; second, disease activity may have an impact on brain functions in patients with CD; and third, psychological factors may be associated with altered brain functions in patients with CD.

A mesocortical glutamatergic pathway modulates neuropathic pain independent of dopamine co-release

Dysfunction in the mesocortical pathway, connecting the ventral tegmental area (VTA) to the prefrontal cortex, has been implicated in chronic pain. While extensive research has focused on the role of dopamine, the contribution of glutamatergic signaling in pain modulation remains unknown. Using in vivo calcium imaging, we observe diminished VTA glutamatergic activity targeting the prelimbic cortex (PL) in a mouse model of neuropathic pain. Optogenetic activation of VTA glutamatergic terminals in the PL alleviates neuropathic pain, whereas inhibiting these terminals in naïve mice induces pain-like responses. Importantly, this pain-modulating effect is independent of dopamine co-release, as demonstrated by CRISPR/Cas9-mediated gene deletion. Furthermore, we show that VTA neurons primarily project to excitatory neurons in the PL, and their activation restores PL outputs to the anterior cingulate cortex, a key region involved in pain processing. These findings reveal a distinct mesocortical glutamatergic pathway that critically modulates neuropathic pain independent of dopamine signaling.

FACTORS INFLUENCING THE MOTIVATION OF POST-FRACTURE PATIENTS TO PERFORM EARLY MOBILIZATION IN THE DAPARTAMENT OF SURGERY HOSPITAL NACIONAL GUIDO VALADARES (HNGV) DILI IN 2023

In today's era of modern globalization, there are many traffic accidents involving trauma and injuries/fractures. According to the World Health Organization, by 2022 traffic accidents will be the eighth cause of death for people aged 15 to 29 in the world. And according to the WHO in 2020 states that the incidence of fractures is increasing, disability is about 13 million people with a prevalence of 2.7%, fractures in 2019 are about 15 million with a prevalence of 3.2%, a prevalence of 3.8% due to traffic accidents. Based on WHO (2020) mortality because of accident traffic in Timor Leste reach 154 or 2.18% of all deaths. In 2023 from January until June about 119 patients with fracture which is 90 male and 29 female that have been treated in department of surgery HNGV Dili. To know the factors that influence the motivation of post-fracture patients to perform early mobilization in the department of surgery Hospital Nacional Guido Valadares (HNGV) Dili in 2023. This study used a quantitative analytic method with a cross-sectional approach using non-probability sampling techniques and Total sampling techniques with a total of 40 respondents. researcher identifies 40 fracture patients which are treated in department of surgery 60% with good family support, 52.5% with moderate pain process and another variable shows 67.5% with sufficient knowledge that influence the motivation of post-fracture patients to perform early mobilization. When analyze test with statistic Spearman Rank Correlation to X1 and Y have p value = 0,000 < 0,05 and have correlation 0.606 it’s mean have a strong influence, X2 and Y have p value = 0,001 < 0,05 and have correlation 0.488 it’s mean have a sufficient influence, X3 and Y have p value = 0,000 < 0,05 and have correlation 0.623 it’s mean have a strong influence. This research shows that the results have a strong influence between family support factor, sufficient influence between pain factor and strong influence between knowledge factor that influence the motivation of post-fracture patients to perform early mobilization in the department of surgery Hospital Nacional Guido Valadares (HNGV) Dili in 2023.

Altered central pain processing in patients with degenerative lumbar diseases and its association with low physical activity levels after lumbar spinal surgeries: a retrospective cohort analysis.

To investigate the occurrence of altered central pain modulation in patients with degenerative lumbar diseases (DLDs) and to analyze its association with physical activity (PA) 3years after lumbar decompression and fusion. Preoperative assessments of pressure pain thresholds (PPTs), temporal summation (TS), conditioned pain modulation (CPM) and pain were, respectively, recorded in 304 patients. These patients further underwent International Physical Activity Questionnaire (IPAQ) and both pain-related and psychological assessments 3years post-operation. Preoperatively, the patients had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy subjects (P < 0.05). Postoperatively, 53.9% (164/304) patients showed PA below healthy-related thresholds (< 600 MET min/w). Low PA group showed a greater postoperative weight gain and bone loss and a higher postoperative prevalence of both moderate anxiety and marginal depression than high PA group (P < 0.05). All covariates with differences between the high and low PA groups were subjected to multivariate logistic regression, and long preoperative disease duration, low preoperative PPT in pain-free area, high preoperative TS, revision surgery, severe postoperative low back pain and significant postoperative pain catastrophizing thought were independently associated with low postoperative PA (P < 0.05). This study supports the existence of central sensitization (CS) caused by abnormal central pain modulation in DLDs. Pre-existing CS in these patients may be associated with low PA after lumbar surgeries, and this low-activity lifestyle may predispose patients to multiple adverse health outcomes. Preoperative dynamic quantitative sensory testing may provide information for the identification of at-risk patients.

Nociceptive Processing of Elite Athletes Varies between Sport-Specific Loads: An EEG-Based Study Approach.

For the downstream nociceptive processing of elite athletes, recent studies indicate that athletes probably tolerate more pain as compared with a normally active population. Phenotyping the nociceptive processing of athletes in different types of endurance sports can provide insight into training-specific effects, which may help in understanding the long-term effects of specific exercise. Twenty-six elite endurance athletes from the disciplines of rowing, triathlon, and running and 26 age- and sex-matched, recreationally active control subjects who participated in the subjective pain perception and processing of standardized noxious stimuli were investigated by EEG. This included standardized heat pain thresholds (HPT) and contact heat-evoked potentials from heat stimulation, measured with EEG as well as pinprick-evoked potentials from mechanical stimulation. After noxious stimulation, athletes showed a higher activation of the event-related spectral perturbation (ERSP) patterns in the N2P2 EEG response at the Cz Electrode compared with the controls. After noxious contact heat stimulation, triathletes had a higher ERSP activation compared with the controls, whereas the rowers had a higher ERSP activation after noxious mechanical stimulation. Also, HPT in triathletes were increased despite their increased central activation after thermal stimulation. We found a correlation between increased HPT and training hours and years, although athletes did not differ within these variables. Although we were able to identify differences between athletes of different endurance sports, the reasons and implications of these differences remain unclear. The study of sport-specific somatosensory profiles may help to understand the mechanisms of exercise-related long-term effects on pain processing and perception. Furthermore, sport-specific somatosensory effects may support the personalization of exercise interventions and identify risk factors for chronic pain in elite athletes.

Multilevel Pain Assessment with Functional Near-Infrared Spectroscopy: Evaluating ΔHBO2 and ΔHHB Measures for Comprehensive Analysis.

Assessing pain in non-verbal patients is challenging, often depending on clinical judgment which can be unreliable due to fluctuations in vital signs caused by underlying medical conditions. To date, there is a notable absence of objective diagnostic tests to aid healthcare practitioners in pain assessment, especially affecting critically-ill or advanced dementia patients. Neurophysiological information, i.e., functional near-infrared spectroscopy (fNIRS) or electroencephalogram (EEG), unveils the brain's active regions and patterns, revealing the neural mechanisms behind the experience and processing of pain. This study focuses on assessing pain via the analysis of fNIRS signals combined with machine learning, utilising multiple fNIRS measures including oxygenated haemoglobin (ΔHBO2) and deoxygenated haemoglobin (ΔHHB). Initially, a channel selection process filters out highly contaminated channels with high-frequency and high-amplitude artifacts from the 24-channel fNIRS data. The remaining channels are then preprocessed by applying a low-pass filter and common average referencing to remove cardio-respiratory artifacts and common gain noise, respectively. Subsequently, the preprocessed channels are averaged to create a single time series vector for both ΔHBO2 and ΔHHB measures. From each measure, ten statistical features are extracted and fusion occurs at the feature level, resulting in a fused feature vector. The most relevant features, selected using the Minimum Redundancy Maximum Relevance method, are passed to a Support Vector Machines classifier. Using leave-one-subject-out cross validation, the system achieved an accuracy of 68.51%±9.02% in a multi-class task (No Pain, Low Pain, and High Pain) using a fusion of ΔHBO2 and ΔHHB. These two measures collectively demonstrated superior performance compared to when they were used independently. This study contributes to the pursuit of an objective pain assessment and proposes a potential biomarker for human pain using fNIRS.

Beneficial Effects of Photoperiod Lengthening on Sleep Characteristics and Mechanical Hyperalgesia in Injured Rats.

Sleep and muscle injury-related pain are in negative relationship, and sleep extension may be a favorable countermeasure. In response to muscle injury, an adaptive sleep response has been described in rats, characterized by an increase in total sleep time (TST) and nonrapid eye movement (NREM) sleep. This study examined the effects of photoperiod lengthening (a model of sleep prolongation in rats) on the sleep characteristics of muscle-injured rats and whether this lengthening could benefit injury-induced mechanical hyperalgesia using the Von Frey test. Switching from the conventional 12:12 light/dark (LD) photoperiod (light on: 08:00-20:00) to LD 16:8 (light extended to 24:00) gives rats an extra window of sleep. Our results show higher TST and NREM sleep times in LD 16:8 versus LD 12:12 injured rats during 4 h of light lengthening for 7 d postinjury, showing the efficiency of photoperiod lengthening to increase sleep time in injured rats. In addition, a cumulative effect with the adaptive sleep response to muscle injury occurred with higher TST and NREM sleep times in LD 16:8 injured versus noninjured rats during the dark period, reflecting the high need for sleep after the injury. Greater stability and higher relative delta power of NREM sleep during the extended light period were also observed in injured rats. Finally, the extended photoperiod limits the muscle injury-induced mechanical hyperalgesia for 13 d and allows faster recovery of the baseline mechanical threshold. This is associated with reduced pro-inflammatory cytokines levels in the hippocampus, a brain structure involved in pain processing.

Clinical and preclinical evidence that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent diabetic peripheral neuropathy

Given possible involvement of the central and peripheral angiotensin system in pain processing, we conducted clinical and preclinical studies to test whether pharmacological inhibition of the angiotensin system would prevent diabetic peripheral neuropathy (DPN) accompanying type 2 diabetes mellitus (T2DM). In the preclinical study, the nociceptive sensitivity was determined in leptin-deficient ob/ob mice, a T2DM model. A clinical retrospective cohort study was conducted, using the medical records of T2DM patients receiving antihypertensives at three hospitals for nearly a decade. In the ob/ob mice, daily treatment with perindopril, an angiotensin-converting enzyme inhibitor (ACEI), or telmisartan, an angiotensin receptor blocker (ARB), but not amlodipine, an L-type calcium channel blocker (CaB), significantly inhibited DPN development without affecting the hyperglycemia. In the clinical study, the enrolled 7464 patients were divided into three groups receiving ACEIs, ARBs and the others (non-ACEI, non-ARB antihypertensives). Bonferroni’s test indicated significantly later DPN development in the ARB and ACEI groups than the others group. The multivariate Cox proportional analysis detected significant negative association of the prescription of ACEIs or ARBs and β-blockers, but not CaBs or diuretics, with DPN development. Thus, our study suggests that pharmacological inhibition of the angiotensin system is beneficial to prevent DPN accompanying T2DM.

Association between different composite dietary antioxidant indexes and low back pain in American women adults: a cross-sectional study from NHANES

BackgroundLow back pain is the leading cause of productivity loss, imposes a significant economic burden on the patients and society. Oxidative stress is considered a critical factor in the complex pathophysiological process and pathogenic mechanism of low back pain. Adjustment dietary pattern can effectively increase antioxidant biomarkers levels within the body to reduce oxidative stress. The composite dietary antioxidant index (CDAI) serves a reliable scoring system for quantifying the potential dietary antioxidant capacity of daily diets.ObjectiveWe aim to investigate the potential association between CDAI and low back pain, in order to enhance the management of low back pain through dietary guidance.MethodsThis study included 17,682 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2000, 2001–2002, 2003–2004 and 2009–2010. The weighted logistic regression model was used to investigate the association between CDAI and low back pain, while restricted cubic spline (RCS) was employed to examine non-linear trend and cutoffs.ResultsAfter adjusting for all confounders, the results showed that there was no significant association between CDAI and low back pain. However, individuals in the highest quartile of CDAI exhibited an 11.7% less likelihood of experiencing a low back pain than those in the lowest quartile (OR = 0.883; 95% CI [0.787,0.991], P = 0.034), and the trend test was also significant (P for trend < 0.001). RCS indicated a linear relationship between CDAI and low back pain (P for non-linear = 0.876). Gender subgroup analysis showed that this negative association was significant in the female population (OR = 0.983; 95% CI [0.968, 0.998], P = 0.027), and females in the highest quartile of CDAI were 19.7% less likely to suffer low back pain than those in the lowest quartile (OR = 0.803; 95% CI [0.682,0.945], P = 0.008). Additionally, the changes in zinc (OR = 1.009; 95% CI [1.002, 1.016], P = 0.015) and selenium (OR = 0.379; 95% CI [0.164, 0.875], P = 0.023) per milligram were independently associated with low back pain.ConclusionThe fully adjusted model showed no significant association between CDAI and low back pain, but it was significant in quartiles. Meanwhile, subgroup analysis by gender revealed a negative association between CDAI and low back pain in the female population. Additionally, the findings of this study also suggested that the antioxidant diets should be studied in a dietary pattern context.

Overview: Chronic Pain and Cannabis-Based Medicines.

Chronic pain is primarily conceptualized as a disease in its own right when it is associated with emotional distress and functional impairment. Pathophysiologically, dysfunction of the cortico-mesolimbic connectome is of major importance, with overlapping signals in the nociceptive and stress systems. The endocannabinoid system plays an important role in the central processing of nociceptive signals and regulates the central stress response. Clinically, there is moderate evidence that cannabis-based medicines (CBM) can contribute to a significant reduction in pain, especially the associated pain affect, and improvement in physical function and sleep quality in a proportion of patients with chronic pain. The analgesic effect appears to be largely independent of the cause of pain. In this context, CBM preferentially regulates stress-associated pain processing.

Perceived Health Benefits in Vestibular Schwannoma Patients with Long-Term Postoperative Headache: Insights from Personality Traits and Pain Coping-A Cross-Sectional Study.

Postoperative headaches (POHs) following retrosigmoid microsurgery for vestibular schwannoma (VS) can significantly impact patients' perceived health benefits (PHBs). In this cross-sectional observational study, 101 VS patients were investigated. For the assessment of pain, the Rostock Headache Compendium (RoKoKo) and the German pain processing questionnaire (FESV) were used. The perceived health benefits (PHBs) were assessed by the Glasgow Benefit Inventory (GBI) and Big Five personality traits were measured using the Ten-Item Personality Inventory (TIPI-G). We showed that 55% of the participants experienced POHs, leading to a marked reduction in overall PHBs compared to those without POHs. The correlation analysis revealed an association between decreased PHBs and elevated levels of pain-related helplessness, depression, anxiety, and anger. Positive correlations were identified between PHBs and action-planning competence, cognitive restructuring, and the experience of competence. Low emotional stability and openness yielded associations with pain-related psychological impairment. Hearing loss and facial paresis did not exert a significant impact on PHBs. The study highlights the influence of pain-related coping strategies on PHBs in long-term POH patients. Thus, coping mechanisms and personality traits should be assessed even before surgery for post-surgery pain prevention. The limitations of this study include a relatively small sample size, potential biases introduced by the overrepresentation of female patients, and the use of an online survey methodology. In conclusion, this research highlights that the interplay between headaches, PHBs, and psychological factors is also relevant in VS patients undergoing microsurgery. Short-term psychological interventions should therefore be taken into account to improve post-surgery adaptive coping strategies.

Headache Management in Individuals with Brain Tumor.

Headache occurs commonly in individuals diagnosed with cerebral neoplasm. Though the features of a brain tumor-associated headache may vary, a progressive nature of headache and a change in headache phenotype from a prior primary headache disorder often are identified. Pathophysiologic mechanisms proposed for headache associated with brain tumor include headache related to traction on pain-sensitive structures, activation of central and peripheral pain processes, and complications from surgical, chemotherapeutic and/or radiotherapy treatment(s). Optimization of headache management is important for an individual's quality of life. Treatments are based upon patient-specific goals of care and may include tumor-targeted medical and surgical interventions, as well as a multimodal headache treatment approach incorporating acute and preventive medications, nutraceuticals, neuromodulation devices, behavioral interventions, anesthetic nerve blocks, and lifestyles changes.

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.

Network analysis of monoamines involved in anxiety-like behavior in a rat model of osteoarthritis.

Chronic pain is a major health problem that affects a significant number of patients, resulting in personal suffering and substantial health care costs. One of the most commonly reported causal conditions is osteoarthritis (OA). In addition to sensory symptoms, chronic pain shares an inherent overlap with mood or anxiety disorders. The involvement of the frontal cortex, striatum and nucleus accumbens, in the affective processing of pain is still poorly understood. Male Wistar rats were divided into two groups: MIA (monoiodoacetate injected into the knee-model of OA) and sham (NaCl). Behavioral tests assessing pain, anxiety, and depressive behavior were performed at week 1, 3, 4, 6, 8, and 10. Neurochemical assays were conducted at weeks 3, 6, and 10 post-MIA injection, followed by the neurotransmitters and their metabolites correlation matrix and network analysis. OA animals developed rapid pain phenotype, whereas anxiety-like behavior accompanied the development of a pain phenotype from 6week post-MIA injection. We did not detect any depressive-like behavior. Instead, immobility time measured in the forced swimming test transiently decreased at 3weeks post-MIA in the OA group. We detected changes in noradrenaline and serotonin levels in analyzed structures at distinct time points. Network analysis revealed noradrenaline and serotonin neurotransmission changes in the nucleus accumbens, confirming it to be the key structure affected by chronic pain. Animals with chronic pain exhibit symptoms of anxiety-like behavior and we identified underlying neurochemical changes using network analysis.

Rowing and pain: does rowing lead to exercise-induced hypoalgesia?

Physical activity acutely alters pain processing known as exercise-induced hypoalgesia (EIH). This randomized controlled crossover study investigated the effects of two different rowing exercises on EIH and to explore whether possible EIH effects are related to individual rowing specific performance. Fifty male experienced rowers conducted two rowing sessions (submaximal: 30 min of moderate rowing (70% of maximum heart rate); maximal: 350 m in an all-out fashion) and a control session. Pre and post exercise pain sensitivity was measured bilaterally using pressure pain thresholds (PPT; Newton (N)) at the elbow, knee, ankle, sternum, and forehead. Individual performance was determined as maximum watt/kg and was tested for correlations with changes in PPT. Higher PPT values were observed after maximal exercise at all landmarks with a mean change ranging from 2.5±7.8N (right elbow; p=0.027; dz=0.323) to 10.0±12.2N (left knee; p≤0.001; dz=0.818). The submaximal (range from-1.6±8.8N (Sternum; p=0.205; dz=0.182) to 2.0±10.3N (right ankle; p=0.176; dz=0.194)) and control session (range from-0.5±7.6N (left elbow; p=0.627; dz=0.069) to 2.6±9.1N (right ankle; p=0.054; dz=0.279)) did not induce changes. Relative performance levels were not correlated to EIH (range from: r = -0.129 (p=0.373) at sternum to r=0.176 (p=0.221) at left knee). EIH occurred globally after a short maximal rowing exercise while no effects occurred after rowing for 30 min at submaximal intensity. EIH cannot be explained by rowing specific performance levels in experienced rowers. However, the sample may lack sufficient heterogeneity in performance levels to draw final conclusions.

Non-Invasive Hemoglobin Assessment with NIR Imaging of Blood Vessels in Transmittance Geometry: Monte Carlo and Experimental Evaluation

Non-invasive methods for determining blood hemoglobin (Hb) concentration are urgently needed to avoid the painful and time-consuming process of invasive venous blood sampling. Many such methods rely on assessing the average attenuation of light over a tissue area where hemoglobin is the dominant chromophore, without separating those areas corresponding to vessels and bloodless tissue. In this study, we investigate whether it is possible to determine hemoglobin levels in the blood by assessing the changes in light intensity when passing through large vessels in comparison to adjacent tissues, using this as a Hb level predictor. Using Monte Carlo light transport modeling, we evaluate the accuracy of determining hemoglobin levels via light intensity contrast and vessel widths estimated in the transmittance illumination geometry and estimate the influence of physiologically significant parameters such as vessel depth, dermis vascularization, and melanin content in the epidermis on the blood Hb prediction error. The results show that physiological variations in tissue parameters limit the mean absolute error of this method to ~15 g/L for blood Hb levels varying in the 60–160 g/L range, which finding is also supported by experimental data obtained for volunteers with different total blood Hb levels that have been determined invasively. We believe the application of new approaches to the non-invasive assessment of Hb levels will lead to the creation of reliable and accurate devices that are applicable in point-of-care and clinical practice.

Using Structural Equation Modeling to Investigate the Neural Basis of Altered Pain Processing in Fibromyalgia with Functional Magnetic Resonance Imaging

Participants with fibromyalgia (FM) and healthy controls (HC) experienced an identical ‘threat/safety’ experimental pain paradigm while undergoing functional magnetic resonance imaging (fMRI) to investigate the differences in pain processing between the two groups. In the ‘threat’ (Pain) imaging runs, participants were told that they would receive noxious heat stimuli to their right hands, calibrated to elicit subjectively moderate levels of pain. In the ‘safety’ (No-Pain) imaging runs, no stimulus was given. This design enabled the study of both continuous and reactive components of pain processing, as well as brain activity associated with anticipation and reward. The fMRI data were analyzed with a data-driven structural equation modeling approach, and significant group-level connectivity differences were identified in both study conditions, in both time periods of interest (Expectation, Stimulation). Group-level connectivity differences in the No-Pain condition occurred mainly during the expectation of pain, and involved regions associated with emotion and reward, suggesting FM may involve altered affective/reward processing. Group-level connectivity differences in the Pain condition occurred mainly during stimulation, with the FM group having decreased connectivity between the anterior cingulate cortex (ACC) and the amygdala, and increased connectivity between the posterior cingulate cortex (PCC) and the thalamus. The decreased ACC→Amygdala connectivity supports previous findings, suggesting FM likely involves altered responses in motivational-affective aspects of pain processing. The increased PCC→Thalamus connectivity may suggest the FM group experienced heightened saliency toward the noxious stimuli, which may contribute toward the mechanism which causes hyperalgesia in FM.

Contact-Heat Evoked Potentials: Insights into Pain Processing in CRPS Type I.

The pathophysiological mechanisms underlying the development of chronic pain in complex regional pain syndrome (CRPS) are diverse and involve both peripheral and central changes in pain processing, such as sensitization of the nociceptive system. The aim of this study was to objectively distinguish the specific changes occurring at both peripheral and central levels in nociceptive processing in individuals with chronic CRPS type I. Nineteen individuals with chronic CRPS type I and 16 age- and sex-matched healthy controls (HC) were recruited. All individuals underwent a clinical examination and pain assessment in the most painful limb, the contralateral limb, and a pain-free control area to distinguish between peripheral and central mechanisms. Contact-heat evoked potentials (CHEPs) were recorded after heat stimulation of the three different areas and amplitudes and latencies were analyzed. Additionally, quantitative sensory testing (QST) was performed in all three areas. Compared to HC, CHEP amplitudes in CRPS were only increased after stimulation of the painful area (p=0.025), while no increases were observed for the pain-free control area (p=0.14). None of the CHEP latencies were different between the two cohorts (all p>0.23). Furthermore, individuals with CRPS showed higher pain ratings after stimulation of the painful limb compared to their contralateral limb (p=0.013). Lastly, compared to HC, mechanical (p=0.012) and thermal (p=0.046) sensitivity was higher in the painful area of the CRPS cohort. This study provides neurophysiological evidence supporting an intact thermo-nociceptive pathway with signs of peripheral sensitization, such as hyperexcitable primary afferent nociceptors, in individuals with CRPS type I. This is further supported by the observation of mechanical and thermal gain of sensation only in the painful limb. Additionally, the increased CHEP amplitudes might be related to fear-induced alterations of nociceptive processing.

Analysing Factors that Enhance the Growth and Survival of Small and Medium Enterprises in Ghana

The economy of Ghana has been growing consistently during the recent years, and this growth has increased poverty and increased the number of middle-income countries in the region. Meanwhile, the current regional and global economic slowdown requires a new growth model for Ghana, with strengthened fluctuation for Small and Medium-sized enterprises (SMEs) to raise national productivity. Small and Medium Enterprises (SME’s) in Ghana play a dynamic role in the development of this nation, and this cannot be over- emphasized. It also serves as a means of employment in the country thus releasing the pressure on the civil and public sector in the case of employment. The study seeks to solve a problem of technology by Small and Medium Enterprises (SME’s) surveyed in Ghana by using PESTEL theory. It that painful process that Small and Medium Enterprise face to access the loan. Examine the various causes that hinder the growth and survival of small businesses in Ghana. To examine the variables that leads to the growth and survival of small businesses. To enumerate various sources of funds available to SMEs in Ghana and to ascertain the impact of hindrances by SME‟s to the growth of Ghana economy. Finally, the study also revealed that most of the entrepreneurs do not have much knowledge in using technology and it has affected the growth and the survival of SME. It is believed that if all the recommendations are taken into consideration, that entrepreneurs must regard the legal aspect of their day-to-day activities and process the necessary documents to avoid legal actions taken against them.