Pain Biomarkers Research Articles

Traumatic Brain Injury and Posttraumatic Stress Disorder Are Associated with Physical Health Burden among Post-9/11 Women Veterans.

Background: Little research focuses on physical health outcomes of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) among post-9/11 women veterans (WVs). This study examined lifetime TBI, current PTSD, and their associations with biomarkers of cardiometabolic health, sleep, pain, and functional disability among post-9/11 WVs. Methods: WVs (n = 90) from the Translational Research Center for TBI and Stress Disorders longitudinal cohort study were included in this study. Gold standard clinician administered interviews assessed lifetime TBI (Boston Assessment of TBI-Lifetime) and current PTSD symptoms (Clinician-Administered PTSD Scale-IV). Objective measures of health included waist-hip ratio (WHR) and fasted blood biomarker (high density lipoprotein [HDL], low density lipoprotein [LDL], blood glucose, triglycerides) levels. Self-reported surveys assessed sleep, pain, and functional disability. Results: Just under two-thirds (58.9%) of WVs experienced a lifetime TBI, and just over half (53.3%) of this sample had a current PTSD diagnosis at the time of testing. Lifetime TBI was significantly associated with higher WHR, triglycerides levels, and worse pain and sleep (ps = <0.01 to 0.02; ds = 0.01 to 1.12). Current PTSD was significantly associated with higher WHR, lower HDL, and worse pain and sleep (ps = <0.01 to 0.02; ds = 0.009 to 1.19). PTSD was significantly associated with lower total functioning and each of its subdomains (βs = -0.58 to 0.63; ps = <0.001 to 0.02). Lifetime TBI was significantly associated with total functioning, mobility, and life/work (βs = -0.20 to 0.30; ps = <0.01 to 0.02). Conclusions: These findings highlight the importance of screening for lifetime TBI and cardiovascular disease for WVs and support transdiagnostic treatment approaches targeting physical health outcomes.

The independence and predictivity of resting pain-free slow alpha frequency as a biomarker of pain: A reply to Mazaheri et al.

In response to Mazaheri et al.'s critique, we revisited our study (Valentini et al., 2022) on the relationship between peak alpha frequency (PAF) and pain. Their commentary prompted us to reassess our data to address the independence between slow and slowing alpha brain oscillations, as well as the predictivity of slow alpha oscillations in pain perception. Bayesian correlation analyses revealed mixed support for independence. Investigating predictivity, we found inconsistent associations between pre-PAF and unpleasantness ratings. We critically reflected on methodological and theoretical issues on the path to PAF validation as a pain biomarker. We emphasized the need for diversified methodology and analytical approaches as well as robust findings across research groups.

Interhemispheric and Corticothalamic White-Matter Dysfunction Underlies Affective Morbidity and Impaired Pain Modulation in Chronic Pain.

Although patients with chronic pain show behavioral signs of impaired endogenous pain modulation, responsible cerebral networks have yet to be anatomically delineated. We used diffusion tensor imaging (DTI) to examine the white-matter alterations in patients with chronic pain compared with healthy subjects. We further measured thermal pain modulatory responses using the offset analgesia (OA) paradigm. We tested whether the white-matter indices be associated with psychophysical parameters reflecting morbidity and modulatory responses of pain in patients, and whether they could serve as diagnostic biomarkers of chronic pain. Twenty-six patients with chronic pain and 18 age- and gender-matched healthy controls were enrolled. After completing psychophysical questionnaires, they underwent OA measurement and whole-brain DTI in a 3 Tesla magnetic resonance imaging scanner. Fractional anisotropy (FA) and radial diffusivity (RD) of the white-matter were computed and compared between the groups with tract-based spatial statistics using the FMRIB Software Library (FSL) software. Correlations were sought among white-matter indices, thermal pain responses, and psychophysical parameters. The white-matter indices and OA-related parameters were tested whether they distinguish patients from controls by receiver operating characteristic analysis. During OA, patients showed a shorter latency to the maximum (maximum visual analog scale [VAS] latency, 16.0 ± 3.7 vs 18.9 ± 3.1 second [mean ± standard deviation, SD]; P = .032) but a longer latency to the minimum pain (OA latency, 15.6 ± 3.5 vs 11.1 ± 4.2 seconds; P = .004) than controls. They showed a smaller mean FA (0.44 ± 0.12 vs 0.45 ± 0.11; P = .012) and a larger mean RD of the global white-matter (0.00057 ± 0.00002 vs 0.00056 ± 0.00002; P = .038) than controls, at specific areas including the corpus callosum, anterior thalamic radiation, and forceps major. FA of the splenium of the corpus callosum was associated with maximum VAS latency (r = 0.493) and OA latency (r = -0.552). The Pain Catastrophizing Scale scores showed strong negative correlations with FA across those specific areas (r = -0.405). Those latencies during OA and white-matter metrics distinguished patients from controls (P < .05). Patients with chronic pain showed dysfunction of the white matter concerned with interhemispheric communication of sensorimotor information as well as descending corticothalamic modulation of pain in association with affective morbidity and altered temporal dynamics of pain perception. We suggest that an impaired interhemispheric modulation of pain, through the corpus callosum, might be a novel cerebral mechanism in chronification of pain.

Efficacy assessment of novel methanimine derivatives in chronic constriction injury-induced neuropathic model: An in-vivo, ex-vivo and In-Silico approach

The multicomponent etiology, complex clinical implications, dose-based side effect and degree of pain mitigation associated with the current pharmacological therapy is incapable in complete resolution of chronic neuropathic pain patients which necessitates the perpetual requirement of novel medication therapy. Therefore, this study explored the ameliorative aptitude of two novel methanimine imitative like (E)-N-(4-nitrobenzylidene)-4‑chloro-2-iodobenzamine (KB 09) and (E)-N-(4-methylbenzylidene)-4‑chloro-2-iodobenzamine (KB 10) in chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rat model. Standard behavioral tests like dynamic and static allodynia, cold, thermal and mechanical hyperalgesia along with rotarod activity were performed at various experimental days like 0, 3, 7, 14 and 21. Enzyme linked immunosorbent assay (ELISA) on spinal tissue and antioxidant assays on sciatic nerve were executed accompanied by molecular docking and simulation studies. Prolonged ligation of sciatic nerve expressively induced hyperalgesia as well as allodynia in rats. KB 09 and KB 10 substantially attenuated the CCI elicited hyperalgesia and allodynia. They significantly reduced the biomarkers of pain and inflammation like Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in ELISA and while enhanced the GSH, SOD and CAT and diminished the MDA levels during antioxidant assays. KB 09 displayed -9.62 kcal/mol with TNF-α and -7.68 kcal/mol binding energy with IL-6 whereas KB 10 exhibited binding energy of -8.20 kcal/mol with IL-6 while -11.68 kcal/mol with TNF-α and hence both trial compounds ensured stable interaction with IL-6 and TNF-α during computational analysis. The results advocated that both methanimine derivatives might be novel candidates for attenuation of CCI-induced neuropathic pain prospects via anti-nociceptive, anti-inflammatory and antioxidant mechanisms.

Ambulatory Brain Biomarkers of Chronic Pain: Towards Closed Loop Brain Stimulation

Ambulatory Brain Biomarkers of Chronic Pain: Towards Closed Loop Brain Stimulation

Meningococcal Disease Presenting with Acute Myopericarditis and Concurrent Acute Meningitis

Emergency department physicians uncommonly associate myopericarditis with bacterial infection and, even more rarely, encounter myopericarditis caused by meningococcal infection. This case report describes a 38-year-old man who presented with chest pain, electrocardiographic changes, and cardiac biomarkers consistent with acute myopericarditis and rapidly developed central nervous system symptoms that were concerning for acute bacterial meningitis. The diagnosis of Neisseria meningitidis infection was confirmed by blood cultures. Once identified, the patient made a full recovery following a course of intravenous antibiotic therapy. This case underscores the difficulty of diagnosing this rare, but potentially life-threatening, condition in the emergency department.

Wearable Movement Data as a Potential Digital Biomarker for Chronic Pain: An Investigation Using Deep Learning

Wearable Movement Data as a Potential Digital Biomarker for Chronic Pain: An Investigation Using Deep Learning

The biology of mental pain: a systematic review to map the different expressions, definitions, hypotheses, experimental paradigms, investigation methods and candidate biomarkers of mental pain in human subjects

IntroductionMental pain is a transdiagnostic symptom, predictive of suicide and reported as a critical outcome by patients. A previous systematic review of epidemiological and clinical research has shown a lack of consensual definition of mental pain in clinical research and high heterogeneity across the different measurement instruments of mental pain. Up today there is no systematic review synthetizing all published biological investigations on mental pain.ObjectivesThis study aims to map the field of biological investigations of mental pain in human to identify what and how biomarkers are investigated with a meta-research approach, by providing a critical appraisal of the terms and definitions of mental pain, the studies’ hypotheses, the experimental paradigms used to induce or mimic mental pain and the measurement instruments used to measure mental pain.MethodsWe conducted a systematic review (compliant with PRISMA guidelines) of all primary research reporting to investigate candidate biomarkers of mental pain in human subjects as stated by the authors. We searched from inception to June 23rd, 2022, the 3 databases MEDLINE, Web of Science and EMBASE. We extracted the study characteristics (e.g., year of publication, population, etc.), the terms used for meaning mental pain, the definition of mental pain, the method to induce mental pain and its rational, the hypotheses and aims, the measurement instruments of mental pain, the candidate biomarkers, and their method of investigation. We performed descriptive statistics of the sample’s characteristics and the extracted data, a qualitative analysis of the definitions, hypothesis, aims and experimental paradigms, and a data visualization linking candidate biomarkers, experimental paradigms, and their investigation methods.Results The search retrieved 5685 papers of which we included 72 primary research publications constituting 78 distinct research studies. Only 37.5% of studies reported a definition of mental pain. 11.5% of studies did not show a measurement instrument of mental pain. The Cyberball (a social exclusion paradigm) was the most frequently used paradigm in experimental studies (62.7%). The cingulate cortex was the most frequently investigated biomarker category (15.3% of all candidate biomarkers), with fMRI as the most frequent investigation method (53.7% of all investigation methods).ConclusionsThe field of biological investigations on mental pain shows a marked heterogeneity of definitions, terms, hypotheses, experimental paradigms, and measurement instruments, with an over-representation of the construct of social pain and the Cyberball. These could compromise the comparison and combination of studies results in evidence synthesis and their translation into clinical practice.Disclosure of InterestNone Declared

A Pilot Study of Urine Oxytocin as an Objective Biomarker for Chronic Pain

Background: Measuring pain objectively or quantitatively is difficult. Since urine oxytocin (OXT) concentration has been reported to be potentially associated with chronic pain. Purpose: We conducted a pilot study to evaluate the relationship between changes in numerical rating scale (NRS) score following nerve block and urine OXT concentration in patients with chronic pain. Methods: We investigated 19 chronic pain patients who were admitted to our hospital for nerve intervention. NRS score and urine OXT concentration were assessed before and after the nerve block. Results: NRS scores were 7 [6, 9] and 2 [1, 4] (median [interquartile range]) before and after the treatment intervention, respectively. Urinary OXT levels were 523 [293, 743] and 531 [308, 887] pg/mL (median [interquartile range]) before and after the treatment, respectively. We compared the group with greater improvement in NRS after the treatment intervention and those with less improvement. The group with greater improvement in NRS after the treatment intervention showed a greater increase in OXT level. However, baseline urine OXT concentrations were highly variable in patients with chronic pain and the changes in urinary OXT concentrations were also variable. Conclusion: Based on this pilot study, the utility of urine OXT concentration as an objective biomarker of chronic pain needs further investigation.

Can the neural representation of physical pain predict empathy for pain in others?

The question of whether physical pain and vicarious pain have some shared neural substrates is unresolved. Recent research has argued that physical and vicarious pain are represented by dissociable multivariate brain patterns by creating biomarkers for physical pain (Neurologic Pain Signature, NPS) and vicarious pain (Vicarious Pain Signature, VPS), respectively. In the current research, the NPS and two versions of the VPS were applied to three fMRI datasets (one new, two published) relating to vicarious pain which focused on between-subject differences in vicarious pain (Datasets 1 and 3) and within-subject manipulations of perspective taking (Dataset 2). Results show that (i) NPS can distinguish brain responses to images of pain vs no-pain and to a greater extent in vicarious pain responders who report experiencing pain when observing pain and (ii) neither version of the VPS mapped on to individual differences in vicarious pain and the two versions differed in their success in predicting vicarious pain overall. This study suggests that the NPS (created to detect physical pain) is, under some circumstances, sensitive to vicarious pain and there is significant variability in VPS measures (created to detect vicarious pain) to act as generalizable biomarkers of vicarious pain.

Pain and salivary biomarkers of stress in temperomandibular disorders were affected by maxillary splints.

Longitudinal intervention studies on treatment options in temporomandibular dysfunction (TMD) including self reports and salivary biomarkers of stress are rare and the exact therapeutic function of occlusal splints widely unknown. We examined the therapeutic effects of a Michigan splint with occlusal relevance in patients with TMD using a placebo-controlled, delayed-start design. Two intervention groups received a Michigan splint, while one of them had a placebo palatine splint for the first 3 weeks. We collected pain intensities (at rest and after five occlusal movements), salivary measures associated with stress (cortisol and alpha-amylase) and self-reported psychological distress (stress, anxiety, catastrophizing) at baseline and 3 and 7 weeks after onset of intervention. At baseline, we observed increased pain intensity and psychological distress in TMD patients compared to 11 matched healthy controls. Baseline anxiety was linked to movement pain intensity through stress. Over therapy reductions in pain intensity and morning cortisol were more pronounced in those patients starting immediately with the Michigan splint, while psychological distress decreased similarly in both groups. Our results suggest that perceived stress plays a role for the association between anxiety and TMD pain and underlines the need for an interdisciplinary perspective on the pathogenesis and therapy of TMD in a setting where psychotherapeutic knowledge is still scarce or rarely applied.

ISSLS PRIZE in Basic Science 2024: superiority of nucleus pulposus cell- versus mesenchymal stromal cell-derived extracellular vesicles in attenuating disc degeneration and alleviating pain

PurposeTo investigate the therapeutic potential of extracellular vesicles (EVs) derived from human nucleus pulposus cells (NPCs), with a specific emphasis on Tie2-enhanced NPCs, compared to EVs derived from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a coccygeal intervertebral disc degeneration (IDD) rat model.MethodsEVs were isolated from healthy human NPCs cultured under standard (NPCSTD-EVs) and Tie2-enhancing (NPCTie2+-EVs) conditions. EVs were characterized, and their potential was assessed in vitro on degenerative NPCs in terms of cell proliferation and senescence, with or without 10 ng/mL interleukin (IL)-1β. Thereafter, 16 Sprague–Dawley rats underwent annular puncture of three contiguous coccygeal discs to develop IDD. Phosphate-buffered saline, NPCSTD-EVs, NPCTie2+-EVs, or BM-MSC-derived EVs were injected into injured discs, and animals were followed for 12 weeks until sacrifice. Behavioral tests, radiographic disc height index (DHI) measurements, evaluation of pain biomarkers, and histological analyses were performed to assess the outcomes of injected EVs.ResultsNPC-derived EVs exhibited the typical exosomal morphology and were efficiently internalized by degenerative NPCs, enhancing cell proliferation, and reducing senescence. In vivo, a single injection of NPC-derived EVs preserved DHI, attenuated degenerative changes, and notably reduced mechanical hypersensitivity. MSC-derived EVs showed marginal improvements over sham controls across all measured outcomes.ConclusionOur results underscore the regenerative potential of young NPC-derived EVs, particularly NPCTie2+-EVs, surpassing MSC-derived counterparts. These findings raise questions about the validity of MSCs as both EV sources and cellular therapeutics against IDD. The study emphasizes the critical influence of cell type, source, and culture conditions in EV-based therapeutics.

Association between oxidative stress and chronic orofacial pain and potential druggable targets: Evidence from a Mendelian randomization study.

Oxidative stress indicators affect chronic orofacial pain (COFP), but how to reduce these effects is uncertain. 11 oxidative stress biomarkers were collected as exposures, while four forms of COFP were chosen as outcomes for Mendelian randomization (MR) study. The effect estimates between oxidative stress and COFP were calculated using inverse variance-weighted MR (IVW-MR). Then, functional mapping and annotation (FUMA) was utilized in order to carry out SNP-based functional enrichment analyses. In addition, the IVW-MR method was applied to combine effect estimates when using genetic variants associated with oxidative stress biomarkers as an instrument for exploring potential druggable targets. The results indicated that oxidative stress biomarkers (causal OR of uric acid (UA), 0.998 for myofascial pain, 95% CI 0.996-1.000, p < .05; and OR of glutathione transferase (GST), 1.002 for dentoalveolar pain, 95% CI 1.000-1.003, p < .05) were significantly linked with the probability of COFP. Functional analysis also demonstrated that UA and myofascial pain genes were prominent in nitrogen and uracil metabolism, while GST and dentoalveolar pain genes were enriched in glutathione metabolism. Also, the study provided evidence that solute carrier family 2 member 9 (SLC2A9) and glutathione S-transferase alpha 2 (GSTA2) cause discomfort in the myofascial pain (OR = 1.003, 95% CI 1.000-1.006; p < .05) and dentoalveolar region (OR = 1.001, 95% CI 1.000-1.002; p < .05), respectively. In conclusion, this MR study indicates that genetically predicted myofascial pain was significantly associated with decreased UA and dentoalveolar pain was significantly associated with increased GST level. SLC2A9 inhibitor and GSTA2 inhibitor were novel chronic orofacial pain therapies and biomarkers, but clinical trials are called to examine if these oxidative biomarkers have the protective effect against orofacial pain, and further research are needed to explore the underlying mechanisms.

Randomized placebo-controlled, double-blind clinical trial of nanoemulsion curcumin in women with aromatase inhibitor-induced arthropathy: an Alliance/NCORP pilot trial

PurposeAromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain.MethodsWe conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22_Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months. The primary objective was to determine the feasibility of using Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) to detect changes from 0 (T0) to 3 months (T3) of NEC treatment in AI-induced symptoms and well-being; secondary objectives included evaluation of changes in Disabilities of the Shoulder, Arm, and Hand (DASH), Brief Pain Inventory-short form (BPI-SF), grip strength, and biomarkers at T0 and T3.ResultsForty-two patients were randomized to NEC or placebo; 34 women completed the 3-month study. Patient-reported outcome measures (PROMs: FACT-ES, DASH, BPI-SF) and biospecimens were collected at T0-T3 in > 80% of participants. Adherence was ≥ 90% for both arms. PROMs and grip strength did not differ significantly by treatment arm. Plasma curcumin was detected only in NEC arm participants. Serum estradiol and estrone levels were below detection or low on study agent. Gastrointestinal adverse effects were commonly reported in both arms.ConclusionNEC versus placebo in a multisite randomized trial is feasible and well-tolerated. Additional studies with larger sample size are needed to further evaluate the efficacy and safety of NEC in treatment of AIIA.ClinicalTrials.gov Identifier: NCT03865992, first posted March 7, 2019.

Influence of controlled environmental conditions in potential salivary ocular pain biomarkers for enhancing the assessment of ocular pain.

We endeavored to identify objective salivary biomarkers for pain, a subjective sensation with a biological basis, using molecules already described related to pain. The study aimed to analyze inter-individual differences and intersession variability in salivary potential ocular pain biomarkers on healthy subjects, in samples obtained under the influence of controlled environmental conditions. Thirty-four healthy subjects, 20 male, 14 female, median age 35.44 years (range 30-40) were exposed for 30 minutes under standard environmental conditions (T: 22°C, 50% relative humidity) in the Controlled Environmental Research Laboratory (CE-Lab, Vision R&D, Valladolid Spain) in two separate visits (V1, V2) at least 24 hours apart. Saliva was collected after the exposure in each of the visits, and cortisol, α-amylase (sAA), secretory IgA (sIgA), testosterone, and soluble fraction of TNFα receptor II (sTNFαRII) were analyzed by ELISA. Repeatability of inter-subject inter-session measurements was assayed by intraclass correlation coefficient (ICC). There were no significant inter-session differences in testosterone (p = 0.2497), sTNFαRII (p = 0.6451) and sIgA (p = 0.9689) salivary levels. The reproducibility for salivary cortisol, sAA, testosterone, sTNFαRII and sIgA were 0.98 ng/ml, 20.58 U/ml, 21.07 μg/ml, 24.68 pg/ml and 0.19 pg/ml, respectively. Salivary cortisol, sAA, testosterone, sTNFαRII and sIgA yielded the following ICCs: 0.506, 0.569, 0.824, 0.870 and 0.4295, respectively; all these ICCs (except that for cortisol and sIgA) were found to be improved compared to those found previously by our group in a previous study in salivary samples obtained from healthy subjects under non-controlled environmental conditions; Cortisol´s ICC didn´t improve and was in both cases at the limit of acceptability. Environmental factors such as temperature and relative humidity affect the reproducibility of measurement of some salivary molecules which have been proposed as potential pain biomarkers. The exposure of subjects to standard controlled environmental conditions before salivary sample obtention would improve the reproducibility of these molecule measures' as potential biomarkers of chronic ocular pain.

Metabolite Biomarkers of Prolonged and Intensified Pain and Distress in Head and Neck Cancer Patients Undergoing Radio- or Chemoradiotherapy by Means of NMR-Based Metabolomics-A Preliminary Study.

Treatment of head and neck squamous cell carcinoma (HNSCC) has a detrimental impact on patient quality of life. The rate of recognized distress/depression among HNSCC patients ranges from 9.8% to 83.8%, and the estimated prevalence of depression among patients receiving radiotherapy is 63%. Shorter overall survival also occurs in preexisting depression or depressive conditions. The present study analyzes the nuclear magnetic resonance (NMR) blood serum metabolic profiles during radio-/chemoradiotherapy and correlates the detected alterations with pain and/or distress accumulated with the disease and its treatment. NMR spectra were acquired on a Bruker 400 MHz spectrometer and analyzed using multivariate methods. The results indicate that distress and/or pain primarily affect the serum lipids and metabolites of energy (glutamine, glucose, lactate, acetate) and one-carbon (glycine, choline, betaine, methanol, threonine, serine, histidine, formate) metabolism. Sparse disturbances in the branched-chain amino acids (BCAA) and in the metabolites involved in protein metabolism (lysine, tyrosine, phenylalanine) are also observed. Depending on the treatment modality-radiotherapy or concurrent chemoradiotherapy-there are some differences in the altered metabolites.

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.

The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation.

Chronic pain is sustained, in part, through the intricate process of central sensitization (CS), marked by maladaptive neuroplasticity and neuronal hyperexcitability within central pain pathways. Accumulating evidence suggests that CS is also driven by neuroinflammation in the peripheral and central nervous system. In any chronic disease, the search for perpetuating factors is crucial in identifying therapeutic targets and developing primary preventive strategies. The brain-derived neurotrophic factor (BDNF) emerges as a critical regulator of synaptic plasticity, serving as both a neurotransmitter and neuromodulator. Mounting evidence supports BDNF's pro-nociceptive role, spanning from its pain-sensitizing capacity across multiple levels of nociceptive pathways to its intricate involvement in CS and neuroinflammation. Moreover, consistently elevated BDNF levels are observed in various chronic pain disorders. To comprehensively understand the profound impact of BDNF in chronic pain, we delve into its key characteristics, focusing on its role in underlying molecular mechanisms contributing to chronic pain. Additionally, we also explore the potential utility of BDNF as an objective biomarker for chronic pain. This discussion encompasses emerging therapeutic approaches aimed at modulating BDNF expression, offering insights into addressing the intricate complexities of chronic pain.

Cerebrospinal Fluid Lysophosphatidylcholine Species for Distinguishing Narrowing of the Lumbar Spine

ContextReoperation, sometimes multiple, is common with progressively worse outcomes in patients with degenerative lumbar spine diseases. Lysophosphatidylcholine (LPC), a precursor of lysophosphatidic acid, in the cerebrospinal fluid (CSF) is a possible biomarker for neuropathic pain and discriminating neuropathic pain caused by lumbar spinal canal stenosis (LSCS) from other etiologies. This study aimed to explore this possible use of LPC species in the CSF. DesignUsing liquid chromatography-tandem mass spectrometry, we measured six LPC species, (16:0), (18:0), (18:1), (18:2), (20:4), and (22:6), in the CSF. Setting[Multi-site observational study] ParticipantsPatients with LSCS (n=137) and persistent spinal pain syndrome (PSPS, n=22). InterventionsCSF collection using lumbar puncture. Outcome MeasuresWe compared the LPC values between the groups and determined the cutoff levels that could efficiently discriminate the groups with high accuracy. ResultsThe levels of all measured LPC species were significantly higher in the LSCS group than the PSPS group. Four LPC species demonstrated more than 0.80 area under the curve obtained from the receiver operating characteristic curve analysis. Although the specificity of cutoff levels for the six LPC species was low to moderate, their sensitivity was consistently high. ConclusionThe existing diagnostic protocols combining physical examinations and morphological imaging studies for lumbar spinal pain have limited sensitivity. Measuring LPC species in the CSF is a promising objective laboratory test and could be suitable for detecting the presence of lumbar spinal stenosis and can help indications for surgery.

Substance P Level in Patients with Degenerative Lumbar Spine Disorder undergoing Decompressive Surgery: An Observational Study

Introduction: Patients with degenerative lumbar spine disorders experience Chronic Low Back Pain (CLBP) for which they undergo decompressive surgery. Substance P (SP), a neurotransmitter which acts as a modulator of pain perception and transmits nociceptive signals via primary afferent fibers to the spinal cord and brainstem. In chronic painful conditions, SP level can be associated with the severity of pain and gets altered; however, this correlation is not present in acute pain. Aim: To evaluate serum SP level in CLBP patients undergoing decompressive spine surgery. Materials and Methods: The present study was a prospective observational study, in which 30 patients with CLBP undergoing decompressive spine surgery were enrolled. Along with them, one first-degree relative of each patient and an equal number of healthy volunteers were included in the study group. Patients were followed-up on the 5th postoperative day and at two months after surgery for the evaluation of SP levels and Visual Analogue Scale (VAS) scores. Statistical data analysis was carried out using IBM PASW Statistics (SPSS) 25.0 version software. SP levels followed a non normal distribution and were compared by Mann-Whitney U or Kruskal Wallis test (for 2 or more groups, respectively) and correlated using Spearman rank correlation. Results: Patients undergoing decompressive spine surgery had a significantly higher SP level (97.5 picogram/mL (pg/mL)) than healthy volunteers (23.22 pg/mL), p-value &lt;0.001. The serum SP levels in patients were found to be significantly reduced on the 5th postoperative day (31.7 pg/mL) and at two months after surgery (48.5 pg/mL), p-value=0.043. In contrast, there was no discernible change in the VAS score, which did not correlate with the fall in SP levels on the 5th postoperative day. Conclusion: SP level was elevated in subjects with degenerative lumbar spine disorders undergoing decompressive surgery. Higher levels of SP can be attributed to CLBP in those patients. SP can be contemplated as a biomarker of pain due to degenerative lumbar spine pathology. However, further studies are warranted to substantiate this.