Changes In Pain Processing Research Articles

Neural dynamics of pain modulation by emotional valence.

Definitions of human pain acknowledge at least two dimensions of pain, affective and sensory, described as separable and thus potentially differentially modifiable. Using electroencephalography, we investigated perceptual and neural changes of emotional pain modulation in healthy individuals. Painful electrical stimuli were applied after presentation of priming emotional pictures (negative, neutral, positive) and followed by pain intensity and unpleasantness ratings. We found that perceptual and neural event-related potential responses to painful stimulation were significantly modulated by emotional valence. Specifically, pain unpleasantness but not pain intensity ratings were increased when pain was preceded by negative compared to neutral or positive pictures. Amplitudes of N2 were higher when pain was preceded by neutral compared to negative and positive pictures, and P2 amplitudes were higher for negative compared to neutral and positive pictures. In addition, a hierarchical regression analysis revealed that P2 alone and not N2, predicted pain perception. Finally, source analysis showed the anterior cingulate cortex and the thalamus as main spatial clusters accounting for the neural changes in pain processing. These findings provide evidence for a separation of the sensory and affective dimensions of pain and open new perspectives for mechanisms of pain modulation.

A FUNÇÃO DOS CANAIS DE SÓDIO NAV1.7 NA DOR NEUROPÁTICA: GENÉTICA, MECANISMOS MOLECULARES, BIOMARCADORES E PERSPECTIVAS TERAPÊUTICAS

The deepening understanding of the molecular mechanisms underlying neuropathic pain has highlighted the importance of the sodium channel Nav1.7, encoded by the SCN9A gene, as a critical element in regulating neuronal excitability and transmitting action potentials. Nav1.7 is found in nociceptive sensory neurons, playing a vital role in conducting pain signals in the peripheral nervous system. Its activity allows the depolarization of neuronal membranes in response to painful stimuli, facilitating the rapid influx of sodium ions into the cell and generating action potentials that are sent to the brain for pain perception. Mutations in the SCN9A gene are strongly linked to various neuropathic pain conditions. Mutations that increase Nav1.7 activity, such as the p.E1113K variant, intensify the excitability of sensory neurons, leading to conditions such as primary erythromelalgia. In contrast, mutations that reduce Nav1.7 functionality, such as p.I230T, result in lower neuronal excitability, culminating in congenital insensitivity to pain. Advances in neuroimaging and molecular genetics have been fundamental in identifying biomarkers of Nav1.7 dysfunctions. These methods allow the detection of changes in pain processing within the central nervous system, facilitating the identification of specific genetic mutations that contribute to neuropathic conditions. Advanced genetic techniques, such as exome and genome sequencing, enable detailed diagnoses and personalized therapeutic approaches. Promising therapies involve specific inhibitors for Nav1.7, aiming to reduce neuronal hyperexcitability. Additionally, gene therapies, including techniques such as CRISPR-Cas9, have been explored to correct mutations in the SCN9A gene. In conclusion, scientific progress allows for precise diagnoses and personalized treatments, promoting effective management of neuropathic pain.

Body composition and body mass index are independently associated with widespread pain and experimental pain sensitivity in older adults: a pilot investigation.

Chronic musculoskeletal (MSK) pain is prevalent in older adults and confers significant risk for loss of independence and low quality of life. While obesity is considered a risk factor for developing chronic MSK pain, both high and low body mass index (BMI) have been associated with greater pain reporting in older adults. Measures of body composition that distinguish between fat mass and lean mass may help to clarify the seemingly contradictory associations between BMI and MSK pain in this at-risk group. Twenty-four older adults (mean age: 78.08 ± 5.1 years) completed dual-energy x-ray absorptiometry (DEXA), and pain measures (Graded Chronic Pain Scale, number of anatomical pain sites, pressure pain threshold, mechanical temporal summation). Pearson correlations and multiple liner regression examined associations between body mass index (BMI), body composition indices, and pain. Significant positive associations were found between number of pain sites and BMI (b = 0.37) and total fat mass (b = 0.42), accounting for age and sex. Total body lean mass was associated with pressure pain sensitivity (b = 0.65), suggesting greater lean mass is associated with less mechanical pain sensitivity. The results from this exploratory pilot study indicate lean mass may provide additional resilience to maladaptive changes in pain processing in older adults, and highlights the importance of distinguishing body composition indices from overall body mass index to better understand the complex relationship between obesity and MSK pain in older adults.

Restoration of normal central pain processing following manual therapy in nonspecific chronic neck pain.

To determine if a 4-week manual therapy treatment restores normal functioning of central pain processing mechanisms in non-specific chronic neck pain (NSCNP), as well as the existence of a possible relationship between changes in pain processing mechanisms and clinical outcome. Cohort study. Sixty-three patients with NSCNP, comprising 79% female, with a mean age of 45.8 years (standard deviation: 14.3), received four treatment sessions (once a week) of manual therapy including articular passive mobilizations, soft tissue mobilization and trigger point treatment. Pressure pain thresholds (PPTs), conditioned pain modulation (CPM) and temporal summation of pain (TSP) were evaluated at baseline and after treatment completion. Therapy outcome was measured using the Global Rating of Change Scale (GROC), the Neck disability Index (NDI), intensity of pain during the last 24 hours, Tampa Scale of Kinesiophobia (TSK) and Pain Catastrophizing Scale (PCS). Two sets of generalized linear mixed models with Gaussian response and the identity link were employed to evaluate the effect of the intervention on clinical, psychological and psychophysical measures and the association between psychophysical and clinical outcomes. Following treatment, an increased CPM response (Coefficient: 0.89; 95% credibility interval = 0.14 to 1.65; P = .99) and attenuated TSP (Coefficient: -0.63; 95% credibility interval = -0.82 to -0.43; P = 1.00) were found, along with amelioration of pain and improved clinical status. PPTs at trapezius muscle on the side of neck pain were increased after therapy (Coefficient: 0.22; 95% credibility interval = 0.03 to 0.42; P = .98), but not those on the contralateral trapezius and tibialis anterior muscles. Only minor associations were found between normalization of TSP/CPM and measures of clinical outcome. Clinical improvement after manual therapy is accompanied by restoration of CPM and TSP responses to normal levels in NSCNP patients. The existence of only minor associations between changes in central pain processing and clinical outcome suggests multiple mechanisms of action of manual therapy in NSCNP.

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.

Quantitative Sensory Testing to Characterize Sensory Changes in Hidradenitis Suppurativa Skin Lesions

Pain is the most impactful symptom in patients with hidradenitis suppurativa (HS). Characterization of sensory profiles may improve understanding of pain mechanisms in HS and facilitate identification of effective pain management strategies. To characterize somatosensory profiles in patients with HS at clinically affected and nonaffected sites compared with pain-free reference data. This cross-sectional study was conducted at the Emory University Dermatology Clinic. It was hypothesized (1) that patients with HS would demonstrate hypersensitivity to pain in HS lesions and (2) that some patients would have sensory profiles consistent with complex pain mechanisms. Therefore, adults with dermatologist-diagnosed HS and at least 1 painful HS lesion at the time of testing were enrolled between September 10, 2020, and March 21, 2022. Patients with other diagnoses contributing to pain or neuropathy were excluded. Data analysis was conducted between March and April 2022. Quantitative sensory testing was performed on HS lesions and control skin according to a standardized protocol. Quantitative sensory testing outcomes included innocuous thermal and mechanical sensitivity (cold, warmth, and light touch detection thresholds), noxious thermal and mechanical sensitivity (cold, heat, pinprick, and deep pressure pain thresholds and suprathreshold pinprick sensitivity), temporal summation of pinprick, paradoxical thermal sensations, and dynamic mechanical allodynia (pain upon light stroking of the skin). Sensitivity in HS lesions was compared with sensitivity in a control location (the hand) and in pain-free controls using t tests. This study included 20 participants with a median age of 35.5 (IQR, 30.0-46.5) years, the majority of whom were women (15 [75%]). In terms of race and ethnicity, 2 participants (10%) self-identified as Asian, 11 (55%) as Black, 6 (30%) as White, and 1 (5%) as more than 1 race or ethnicity. Compared with site-specific reference values from healthy, pain-free control participants, HS lesions were insensitive to innocuous cold and warmth, noxious heat, and light touch (t = -5.69, -10.20, -3.84, and 4.46, respectively; all P < .001). In contrast, HS lesions also demonstrated significant hypersensitivity to deep pressure pain (t = 8.36; P < .001) and cutaneous pinprick (t = 2.07; P = .046). Hypersensitivity to deep pressure pain was also observed in the control site (t = 5.85; P < .001). A subset of patients with HS displayed changes in pain processing that are often seen in neuropathic and nociplastic pain conditions, including hypersensitivity to repetitive pinprick (5 [26%]), paradoxical thermal sensations (3 [15%]), and pain upon light stroking of the skin (10 [50%]). The findings of this cross-sectional study suggest that HS involves local changes in the skin or its free nerve endings, possibly leading to peripheral neuropathy and alterations in the transduction of innocuous and noxious thermal and mechanical stimuli. For some patients, central nervous system changes in somatosensory processing may also occur, but confirmatory evidence is needed. Better understanding of neuropathic and nociplastic mechanisms in HS pain could lead to individually tailored treatments.

Effects of remote ischemic conditioning on conditioned pain modulation and cardiac autonomic modulation in women with knee osteoarthritis: placebo-controlled randomized clinical trial protocol

BackgroundIt is estimated that over 240 million people worldwide have osteoarthritis, which is a major contributor to chronic pain and central changes in pain processing, including endogenous pain modulation. The autonomic nervous system plays a crucial role in the pain regulatory process. One of the main mechanisms of remote ischemic conditioning is neuronal signaling from the preconditioned extremity to the heart. This study aims to analyze the acute effect of remote ischemic conditioning on local pain, conditioned pain modulation, and cardiac autonomic control in women with knee osteoarthritis and to see if there is a correlation between them.MethodsWomen more than 50 years with knee osteoarthritis diagnosed according to the American College of Rheumatology criteria in the postmenopausal period will be considered eligible. The study will have blind randomization, be placebo-controlled, and be balanced in a 1:1 ratio. The total of 44 participants will be divided into two groups (22 participants per group): (i) remote ischemic conditioning and (ii) placebo remote ischemic conditioning. Protocol consisting of four cycles of total ischemia, followed immediately by four cycles of 5 min of vascular reperfusion, totaling 40 min. The primary outcomes in the protocol are conditioned pain modulation, which has the pressure pain threshold (kgf/cm2) as its primary outcome measure, and cardiac autonomic modulation, which has the indices found in heart rate variability as its primary outcome measure. Comparisons will be performed using generalized linear mixed models fitted to the data. For correlation, the Pearson or Spearman test will be used depending on the normality of the data. All analyses will assume a significance level of p < 0.05.DiscussionIt is believed that the results of this study will present a new perspective on the interaction between the pain processing system and the cardiovascular system; they will provide the professional and the patient with a greater guarantee of cardiovascular safety in the use of the intervention; it will provide knowledge about acute responses and this will allow future chronic intervention strategies that aim to be used in the clinical environment, inserted in the multimodal approach, for the treatment of osteoarthritis of the knee.Trial registrationClinicalTrials.gov NCT05059652. Registered on 30 August 2021. Last update on 28 March 2023.

Diagnosis of Chronic Musculoskeletal Pain by Using Functional Near-Infrared Spectroscopy and Machine Learning.

Chronic pain (CP) has been found to cause significant alternations of the brain's structure and function due to changes in pain processing and disrupted cognitive functions, including with respect to the prefrontal cortex (PFC). However, until now, no studies have used a wearable, low-cost neuroimaging tool capable of performing functional near-infrared spectroscopy (fNIRS) to explore the functional alternations of the PFC and thus automatically achieve a clinical diagnosis of CP. In this case-control study, the pain characteristics of 19 chronic pain patients and 32 healthy controls were measured using fNIRS. Functional connectivity (FC), FC in the PFC, and spontaneous brain activity of the PFC were examined in the CP patients and compared to those of healthy controls (HCs). Then, leave-one-out cross-validation and machine learning algorithms were used to automatically achieve a diagnosis corresponding to a CP patient or an HC. The current study found significantly weaker FC, notably higher small-worldness properties of FC, and increased spontaneous brain activity during resting state within the PFC. Additionally, the resting-state fNIRS measurements exhibited excellent performance in identifying the chronic pain patients via supervised machine learning, achieving F1 score of 0.8229 using only seven features. It is expected that potential FC features can be identified, which can thus serve as a neural marker for the detection of CP using machine learning algorithms. Therefore, the present study will open a new avenue for the diagnosis of chronic musculoskeletal pain by using fNIRS and machine learning techniques.

Lateral Elbow Pain and Muscle Function Impairments.

Although often described as a self-limiting condition and likely to resolve on its own, high recurrence rates and extended sick leave frame a need for effective non-surgical treatment for people with lateral elbow tendinopathy. The interrelationship of histological and structural changes to the tendon, the associated impairments in motor control, and potential changes in pain processing may all drive symptoms. This clinical practice guideline covers the epidemiology, functional anatomy and pathophysiology, risk factors, clinical course, prognosis, differential diagnosis, tests and measures, and interventions for managing lateral elbow tendinopathy in the physical therapy clinic. J Orthop Sports Phys Ther 2022;52(12):CPG1-CPG111. doi:10.2519/jospt.2022.0302.

Neuropathic pain as a trigger for histone modifications in limbic circuitry.

Chronic pain involves both central and peripheral neuronal plasticity that encompasses changes in the brain, spinal cord, and peripheral nociceptors. Within the forebrain, mesocorticolimbic regions associated with emotional regulation have recently been shown to exhibit lasting gene expression changes in models of chronic pain. To better understand how such enduring transcriptional changes might be regulated within brain structures associated with processing of pain or affect, we examined epigenetic modifications involved with active or permissive transcriptional states (histone H3 lysine 4 mono and trimethylation, and histone H3 lysine 27 acetylation) in periaqueductal gray (PAG), lateral hypothalamus (LH), nucleus accumbens (NAc), and ventral tegmental area (VTA) 5 weeks after sciatic nerve injury in mice to model chronic pain. For both male and female mice in chronic pain, we observed an overall trend for a reduction of these epigenetic markers in periaqueductal gray, LH, and NAc, but not VTA. Moreover, we discovered that some epigenetic modifications exhibited changes associated with pain history, while others were associated with individual differences in pain sensitivity. When taken together, these results suggest that nerve injury leads to chronic chromatin-mediated suppression of transcription in key limbic brain structures and circuits, which may underlie enduring changes in pain processing and sensitivity within these systems.

Abnormal Dynamics of Functional Connectivity Density Associated With Chronic Neck Pain

Background: Chronic neck pain (CNP) is highly prevalent and complicated, associated with limited movement, and accompanied by shoulder pain and other clinical manifestations such as dizziness, anxiety, and insomnia. Brain structural and functional abnormalities often occur in patients with CNP. However, knowledge of the brain’s functional organization and temporal dynamics in CNP patients is limited. Dynamic functional connectivity density (dFCD) can reflect the ability of brain areas or voxels to integrate information, and could become neuroimaging markers for objectively reflecting pain to a certain extent. Therefore, this study compared the dFCD between CNP patients and healthy controls (HCs) and investigated potential associations of the abnormal density variability in dynamic functional connectivity with pain characteristics in CNP patients.Methods: Resting functional magnetic resonance imaging was performed for 89 CNP patients and 57 HCs. After preprocessing resting-state fMRI images by the Data Processing and Analysis of Brain Imaging toolbox, the sliding window method was applied to investigate dFCD changes in CNP patients and HCs using the DynamicBC toolbox. Then we quantified dFCD variability using their standard deviation. Based on the pain-associated factors collected from the case report form of CNP patients, the mean dFCD variability values of each dFCD from region of interest were extracted to calculate Pearson’s correlation coefficient to study the potential correlation between dFCD abnormal variability and pain.Results: Compared with HCs, the dFCD values of the anterior cingulate cortex, occipital lobe, temporal lobe, and cerebellum were statistically different in patients with CNP. Subsequent correlation analysis showed that the variable dFCD in the related brain region was correlative with the course of the disease and clinical symptoms, such as pain and depression, in patients with CNP.Conclusion: Dynamic functional alterations were observed in the brain regions of CNP patients, and the dFCD of these brain regions could become neuroimaging markers for objectively reflecting pain to a certain extent. This suggests that chronic pain may cause changes in pain processing and emotional feedback and highlights the link between dynamic neural communication in brain regions and disease conditions, deepening our understanding of chronic pain diseases, and guiding clinical practice.

Altered Pain in the Brainstem and Spinal Cord of Fibromyalgia Patients During the Anticipation and Experience of Experimental Pain.

Chronic pain associated with fibromyalgia (FM) affects a large portion of the population but the underlying mechanisms leading to this altered pain are still poorly understood. Evidence suggests that FM involves altered neural processes in the central nervous system and neuroimaging methods such as functional magnetic resonance imaging (fMRI) are used to reveal these underlying alterations. While many fMRI studies of FM have been conducted in the brain, recent evidence shows that the changes in pain processing in FM may be linked to autonomic and homeostatic dysregulation, thus requiring further investigation in the brainstem and spinal cord. Functional magnetic resonance imaging data from 15 women with FM and 15 healthy controls were obtained in the cervical spinal cord and brainstem at 3 tesla using previously established methods. In order to investigate differences in pain processing in these groups, participants underwent trials in which they anticipated and received a predictable painful stimulus, randomly interleaved with trials with no stimulus. Differences in functional connectivity between the groups were investigated by means of structural equation modeling. The results demonstrate significant differences in brainstem/spinal cord network connectivity between the FM and control groups which also correlated with individual differences in pain responses. The regions involved in these differences in connectivity included the LC, hypothalamus, PAG, and PBN, which are known to be associated with autonomic homeostatic regulation, including fight or flight responses. This study extends our understanding of altered neural processes associated with FM and the important link between sensory and autonomic regulation systems in this disorder.

Transcranial Direct Current Stimulation (tDCS) Combined with Therapeutic Exercise and Cognitive Rehabilitation to Treat a Case of Burning Mouth Syndrome (BMS) Related Pain

Burning Mouth Syndrome (BMS) is a multifactorial, chronic pain condition with neuropathic and psychogenic mechanisms. Cortical activation as well as sustained attention and executive functions have proven to be affected by chronic pain. The main objectives of this work were to test the efficacy of a multidimensional personalized pain treatment protocol and to investigate if the effects are based on psychophysical pain processing changes or cognitive effects. A 74-year-old female with 2 years of BMS received 10 sessions of a combined protocol of anodal left dorsolateral prefrontal cortex tDCS, cognitive therapy, and therapeutic exercise. The subjective perception of pain decreased by 47% after treatment but returned to the baseline at 45 days. No changes were found in objective pain measurements apart from a transient worsening of conditioned pain modulation. A large effect size was found in all functional scales, processing speed and executive control as well as sustained attention that persisted during follow-up. No changes in anxiety and depression were found. A multimodal therapeutic approach combining TDCS, cognitive rehabilitation and therapeutic exercise produces improved quality of life, disability and pain perception correlated with improvements in processing speed, executive control and sustained attention but independent of changes in psychophysical pain processing.

Temporal changes in pain processing after whiplash injury, based on Quantitative Sensory Testing: A systematic review.

After whiplash injury, some patients develop chronic whiplash-associated disorders. The exact pathophysiology of this chronification is still unclear and more knowledge is needed regarding the different post-injury phases. Therefore, studies were searched that examined temporal changes in pain processing, measured by Quantitative Sensory Testing (QST). This systematic review searched three electronic databases (Medline, Web of Science and Embase) for articles meeting the eligibility requirements. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale. The 12 included studies presented moderate to good methodological quality. These studies showed altered pain processing within the first month after injury and normalization within 3months in 59%-78% of the patients. After 3months, recovery stagnates during the following years. Thermal and widespread mechanical hyperalgesia occur already in the acute phase, but only in eventually non-recovered patients. Differences in pain processing between recovering and non-recovering patients can be observed already in the acute phase. Early screening for signs of altered pain processing can identify patients with high risk for chronification. These insights in temporal changes show the importance of rehabilitation in the acute phase. Future research should target to develop a standardized (bed-site) QST protocol and collect normative data which could, in relation with self-reported pain parameters, allow clinicians to identify the risk for chronification. Altered pain processing is present soon after whiplash injury, but usually recovers within 3months. Non-recovering patients show little to no improvements in the following years. Differences between recovering and non-recovering patients can be observed by Quantitative Sensory Testing already in the acute phase. Therefore, it is considered a feasible and effective tool that can contribute to the identification of high-risk patients and the prevention of chronification.

Long-term consequences of aversive childhood experiences: effects on pain processing

Long-term consequences of aversive childhood experiences: effects on pain processing Abstract. Childhood experiences of stress due to neglect, physical, psychological or sexual abuse often lead to lasting changes in pain processing. Clinically, this is shown, among other things, in an increased sensitivity to pain, a stronger negative-affective connotation of pain and ultimately an increased risk of pain disorders in adulthood. George L. Engel already postulated in the 1960s a child's experience of stress can affect later pain behaviors. This narrative review sets out to summarize the current state of knowledge.

Effect of Expectation on Pain Processing: A Psychophysics and Functional MRI Analysis

Pain is a complex phenomenon that is highly modifiable by expectation. Whilst the intensity of incoming noxious information plays a key role in the intensity of perceived pain, this intensity can be profoundly shaped by an individual’s expectations. Modern brain imaging investigations have begun to detail the brain regions responsible for placebo and nocebo related changes in pain, but less is known about the neural basis of stimulus-expectancy changes in pain processing. In this functional magnetic resonance imaging study, we administered two separate protocols of the same noxious thermal stimuli to 24 healthy subjects. However, different expectations were elicited by different explanations to subjects prior to each protocol. During one protocol, pain intensities were matched to expectation and in the other protocol they were not. Pain intensity was measured continuously via a manually operated computerized visual analogue scale. When individuals expected the stimulus intensity to remain constant, but in reality it was surreptitiously increased or decreased, pain intensity ratings were significantly lower than when expectation and pain intensities were matched. When the stimulus intensities did not match expectations, various areas in the brain such as the amygdala, anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), and the midbrain periaqueductal gray matter (PAG) displayed significantly different patterns of activity compared to instances when stimulus intensity and pain expectations were matched. These results show that stimulus-expectancy manipulation of pain intensity alters activity in both higher brain and brainstem centers which are known to modulate pain under various conditions.

Pressure pain thresholds in adults with patellofemoral pain and patellofemoral joint osteoarthritis: a case-control study.

Patellofemoral pain (PFP) and patellofemoral joint osteoarthritis (PFJOA) are common non-self-limiting conditions causing significant pain and disability. The underlying pain pathologies lack consensus with evidence suggesting reduced pressure pain thresholds (PPTs) in adolescent females with PFP and individuals with knee osteoarthritis. A paucity of evidence exists for mixed-sex adults with PFP and PFJOA in isolation. Exploring if pain sensitisation is a dominant feature of PFP and PFJOA may have important implications for the delivery of a patient centred management approach. The primary aim was to measure local and remote PPTs in PFP and PFJOA patients compared to matched controls. Secondary aims were to evaluate the relationship between PPTs and (1) condition severity and (2) knee function. 13 PFP patients plus 20 matched controls and 15 PFJOA patients plus 34 matched controls were recruited from a UK mixed-sex adult population. Controls were matched on age, sex and activity level. Demographic details, Tegner activity level score, symptom duration, condition severity (Kujala and KOOS-PF scores for PFP and PFJOA, respectively) and knee function (Modified Whatman score rating of five single leg squats) were recorded. PPTs were measured at six sites: five local around the knee, one remote on the contralateral leg. Between-group differences were tested using a two-way mixed model analysis of variance with repeated measures. Strength of association between PPTs and condition severity and knee function were tested using Spearman's rank order correlation. No statistically significant difference in PPTs were observed between the PFP patients [F(1,31) = 0.687, p = 0.413, η2 = 0.022] or PFJOA patients [F(1,47) = 0.237, p = 0.629, η2 = 0.005] and controls. Furthermore, no correlation was found between PPTs and condition severity or knee function in PFP or PFJOA (p > 0.05). Results suggest mechanical pain sensitisation is not a dominant feature of UK mixed-sex adults with PFP or PFJOA. PFP and PFJOA remain persistent pain complaints which may not be well explained by objective measures of sensitivity such as PPTs. The findings suggest that peripheral pain processing changes leading to pain sensitisation is not a key feature in PFP or PFJOA. Instead the underlying pain pathway is likely to remain primary nociceptive, possibly with a subgroup of patients who experience pain sensitisation and might benefit from a more targeted management approach.

Short stem total hip arthroplasty: Potential explanations for persistent post-surgical thigh pain

Short stem uncemented femoral implants were developed with the aim of preserving proximal bone stock for future revisions, improving biomechanical reconstruction, aiding insertion through smaller incisions and potentially decreasing or limiting the incidence of thigh pain. Despite all the advantages of short stem designs, it remains unclear whether they are able to limit post-surgical thigh pain. In patients with short stem hip arthroplasty and persistent thigh pain, it is of the utmost importance to understand the potential etiologies of this chronic pain for selecting the appropriate treatment strategy. Therefore, this manuscript explores the hypothetical etiologies of persistent thigh pain in short stem total hip arthroplasty, including both peripheral factors (structural or biomechanical causes) and central factors (involvement of the central nervous system). First, intrinsic causes (e.g. aseptic femoral loosening and prosthetic joint infection) and extrinsic sources (e.g. muscle pathology or spinal pathology) of persistent thigh pain related to hip arthroplasty are explained. In addition, other specific peripheral causes for thigh pain related to the short stem prosthetic reconstruction (e.g. stem malalignment and micro-motion) are unraveled. Second, the etiology of persistent thigh pain after short stem hip arthroplasty is interpreted in a broader concept than the biomechanical approach where peripheral structural injury is believed to be the sole driver of persistent thigh pain. Over the past decades evidence has emerged of the involvement of sensitization of central nervous system nociceptive pathways (i.e. central sensitization) in several chronic pain disorders. In this manuscript it is explained that there might be a relevant role for altered central nociceptive processing in patients with persistent pain after joint arthroplasty or revision surgery. Recognition of a potential role for centrally-mediated changes in pain processing in total hip replacement surgery has important implications for treatment. Comprehensive treatment addressing peripheral factors as well as neurophysiological changes occurring in the nervous system may help to improve outcomes in patients with short stem hip arthroplasty and chronic thigh pain. Working within a biopsychosocial approach in orthopaedic surgery, specifically in relation to total hip arthroplasty, could be very important and may lead to more satisfaction. Further research is warranted.

Differences in Pain Processing Between Patients with Chronic Low Back Pain, Recurrent Low Back Pain, and Fibromyalgia

Background: The impairment in musculoskeletal structures in patients with low back pain (LBP) is often disproportionate to their complaint. Therefore, the need arises for exploration of alternative mechanisms contributing to the origin and maintenance of non-specific LBP. The recent focus has been on central nervous system phenomena in LBP and the pathophysiological mechanisms underlying the various symptoms and characteristics of chronic pain. Knowledge concerning changes in pain processing in LBP remains ambiguous, partly due to the diversity in the LBP population. Objective: The purpose of this study is to compare quantitative sensory assessment in different groups of LBP patients with regard to chronicity. Recurrent low back pain (RLBP), mild chronic low back pain (CLBP), and severe CLBP are compared on the one hand with healthy controls (HC), and on the other hand with fibromyalgia (FM) patients, in which abnormal pain processing has previously been reported. Study Design: Cross-sectional study. Setting: Department of Rehabilitation Sciences, Ghent University, Belgium. Methods: Twenty-three RLBP, 15 mild CLBP, 16 severe CLBP, 26 FM, and 21 HC participated in this study. Quantitative sensory testing was conducted by manual pressure algometry and computercontrolled cuff algometry. A manual algometer was used to evaluate hyperalgesia as well as temporal summation of pain and a cuff algometer was used to evaluate deep tissue hyperalgesia, the efficacy of the conditioned pain modulation and spatial summation of pain. Results: Pressure pain thresholds by manual algometry were significantly lower in FM compared to HC, RLBP, and severe CLBP. Temporal summation of pain was significantly higher in FM compared to HC and RLBP. Pain tolerance thresholds assessed by cuff algometry were significantly lower in FM compared to HC and RLBP and also in severe CLBP compared to RLBP. No significant differences between groups were found for spatial summation or conditioned pain modulation. Limitations: No psychosocial issues were taken into account for this study. Conclusion: The present results suggest normal pain sensitivity in RLBP, but future research is needed. In mild and severe CLBP some findings of altered pain processing are evident, although to a lesser extent compared to FM patients. In conclusion, mild and severe CLBP presents within a spectrum, somewhere between completely healthy persons and FM patients, characterized by pain augmentation. Key words: Low back pain, fibromyalgia, pain assessment, quantitative sensory testing, central sensitization, hypersensitivity, temporal summation, spatial summation, conditioned pain modulation

Functional interictal changes of pain processing in migraine with ictal cutaneous allodynia.

Objective A prospective clinical imaging study has been conducted to investigate pain processing functional pathways during trigeminal heat stimulation (THS) in patients with migraine without aura experiencing ictal cutaneous allodynia (CA) (MwoA CA+). Methods Using whole-brain BOLD-fMRI, functional response to THS at three different intensities (41°, 51° and 53℃) was investigated interictally in 20 adult MwoA CA+ patients compared with 20 MwoA patients without ictal CA (MwoA CA-) and 20 healthy controls (HCs). Secondary analyses evaluated associations between BOLD signal change and clinical features of migraine. Results During moderate-noxious THS (51℃), we observed a significantly greater activation in (a) the anterior cingulate cortex in MwoA CA+ patients compared to HCs and (b) the middle frontal gyrus in MwoA CA+ patients compared to both MwoA CA- patients and HCs. Furthermore, during high-noxious THS (53℃) a significantly decreased activation in the secondary somatosensory cortices was observed in (a) MwoA CA- patients compared to both MwoA CA+ patients and HCs and (b) MwoA CA+ patients compared to HCs. CA severity was positively correlated with the secondary somatosensory cortices activation. Conclusions Our findings suggest that CA may be subtended by both a dysfunctional analgesic compensatory mechanism and an abnormal internal representation of pain in migraine patients.