Neuropathic Pain Symptom Inventory Research Articles

Is there a relationship between somatosensory impairment and the perception of pain in stroke survivors? An exploratory study.

Pain and somatosensory impairments are commonly reported following stroke. This study investigated the relationship between somatosensory impairments (touch detection, touch discrimination and proprioceptive discrimination) and the reported presence and perception of any bodily pain in stroke survivors. Stroke survivors with somatosensory impairment (N = 45) completed the Weinstein Enhanced Sensory Test (WEST), Tactile Discrimination Test, and Wrist Position Sense Test for quantification of somatosensation in both hands and the McGill Pain Questionnaire, visual analog scale and the Neuropathic Pain Symptom Inventory (NPSI) for reporting presence and perception of pain. No relationship was observed between somatosensory impairment (affected contralesional hand) of touch detection, discriminative touch or proprioceptive discrimination with the presence or perception of pain. However, a weak to moderate negative relationship between touch detection in the affected hand (WEST) and perception of pain intensity (NPSI) was found, suggesting that stroke survivors with milder somatosensory impairment of touch detection, rather than severe loss, are likely to experience higher pain intensity [rho = -0.35; 95% confidence interval (CI), -0.60 to -0.03; P = 0.03]. Further, a moderate, negative relationship was found specifically with evoked pain (NPSI) and touch detection in the affected hand (rho = -0.43; 95% CI, -0.72 to -0.02; P = 0.03). In summary, our findings indicate a weak to moderate, albeit still uncertain, association, which prevents making a definitive conclusion. Nevertheless, our findings contribute to our understanding of the complexities surrounding the experience of pain in survivors of stroke and provide direction for future studies.

Associations between Corneal Nerve Structure and Function in a Veteran Population.

Background: We evaluate the relationship between corneal nerve structure and function in a veteran population. Methods: 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans Affairs (VA) eye clinic were included in this study. Each individual filled out questionnaires to evaluate ocular symptoms (5-Item Dry Eye Questionnaire, DEQ5; Ocular Surface Disease Index, OSDI) and ocular pain (Numerical Rating Scale, NRS; Neuropathic Pain Symptom Inventory modified for the Eye, NPSI-Eye). The individuals also underwent an ocular surface examination that captured functional nerve tests including corneal sensation, corneal staining, and the Schirmer test for tear production. Corneal sub-basal nerve analysis was conducted using in vivo confocal microscopy (IVCM) images with corneal nerve density, length, area, width, and fractal dimension captured. IVCM and functional corneal metrics from the right eye were examined using correlational and linear regression analysis. Results: Most corneal structural metrics were not related to functional metrics, except for weak correlations between various IVCM metrics and tear production. In addition, corneal nerve fiber area was positively related to corneal sensation (r = 0.3, p = 0.01). On linear regression analyses, only the corneal fractal dimension remained significantly related to tear production (β = -0.26, p = 0.02) and only the corneal nerve fiber area remained significantly related to corneal sensation (β = 0.3, p = 0.01). Conclusions: Most corneal nerve structural metrics did not relate to functional metrics in our veteran population, apart from a few weak correlations between structural metrics and tear production. This suggests that using corneal nerve anatomy alone may be insufficient for predicting corneal function.

Modulation of microRNA-133B in Post Mastectomy Pain Syndrome Following Yoga Intervention

Objectives: This study aimed to compare the efficacy of yoga combined with an integrated multimodal approach on the incidence and severity of post-mastectomy pain syndrome (PMPS) and the role of miR-133B expressions in patients undergoing breast cancer surgery. Methods: With approval from the institutional ethics committee and informed consent obtained from each participant, forty patients of ASA grade I - II, aged 20 - 65 years, undergoing breast cancer surgery were included. Patients received a thoracic paravertebral block for up to 72 hours and pregabalin until the end of the fourth postoperative week. Patients were randomly allocated into two groups: “Control” and “yoga.” Patients in the Yoga group practiced the yogic exercise “Anulom-vilom" from the third day until the 90th day postoperatively. The delta-CT of miRNA-133B expression of genes on the 90th postoperative day was compared to the baseline, along with various pain intensity and quality of life parameters. Results: In the Yoga group, a significant up-regulation in miR-133B expression was observed on days 30 and 90 postoperatively. Patients with PMPS in the Yoga group showed a decreased ΔCT of miR-133B, indicating an up-regulation of gene expression, compared to the control group. A lower incidence of PMPS (10% vs. 30%) was observed in the experimental group, along with a significant enhancement of quality of life in post-mastectomy patients and decreased mean Visual Analogue Scale )VAS( pain scores, Pain Detect Questionnaire )PDQ( ، and Neuropathic Pain Symptom Inventory )NPSI( scores in the Yoga group; however, these were not statistically significant. Conclusions: The study demonstrated the feasibility of integrating yoga with a multimodal pain management approach and highlighted the role of miR-133B in the pathogenesis of PMPS.

Neuropathic pain development and maintenance and its association with motor recovery after cervical spinal cord injury

Background In our published randomized controlled trial, we revealed that patients with acute ASIA Grade C incomplete cervical spinal cord injury (SCI) who underwent early surgery (within 24 h post-injury) had accelerated motor recovery at six months than those with delayed surgery (>2 weeks post-injury); however, neuropathic pain (NeP) worsened regardless of surgery timing. Here, we conducted post-hoc analyses to intensively assess NeP development and maintenance. Methods Of 44 patients (median 64.5 years; three female; early intervention, n = 26), NeP was categorized into at-level and below-level pain and evaluated at  two weeks and one year after injury using the Neuropathic Pain Symptom Inventory (NPSI). We compared the two groups based on background characteristics. A mixed-design analysis of variance with sex as a covariate was conducted to analyze motor recovery and Health-related quality of life (HRQOL) in groups with severe (NPSI ≥ 10) or mild (NPSI < 10) pain. Results Upper and lower limb motor impairments were comparable between both groups regardless of pain severity. Severe at-level pain remained stable and worsened at one year than mild at-level pain; however, the upper- and lower-limb motor scores and HRQOL had comparable recovery. Background characteristics did not affect severity or time course of NeP. Patients with severe below-level pain demonstrated slower lower-limb motor recovery than those with mild below-level pain, whereas HRQOL improved regardless of pain severity. Conclusions Both at-level and below-level NeP developed and persisted relatively early in the course of traumatic SCI with incomplete motor paralysis; their severities worsened over time or remained severe since onset.

Efficacy of topical 0.05% cyclosporine A and 0.1% sodium hyaluronate in post-refractive surgery chronic dry eye patients with ocular pain

BackgroundThe management of post-refractive surgery dry eye disease (DED) can be challenging in clinical practice, and patients usually show an incomplete response to traditional artificial tears, especially when it is complicated with ocular pain. Therefore, we aim to investigate the efficacy of combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment in post-refractive surgery DED patients with ocular pain unresponsive to traditional artificial tears.MethodsWe enrolled 30 patients with post-refractive surgery DED with ocular pain who were unresponsive to traditional artificial tears. Topical 0.05% cyclosporine A and 0.1% sodium hyaluronate were used for 3 months. They were evaluated at baseline and 1 and 3 months for dry eye and ocular pain symptoms and objective parameters, including Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), corneal sensitivity, and corneal nerve morphology. In addition, tear levels of inflammatory cytokines and neuropeptides were measured using the Luminex assay.ResultsAfter 3 months of treatment, patients showed a statistically significant improvement in the ocular surface disease index (OSDI), TBUT, SIt, CFS, and corneal sensitivity (all P < 0.01) using linear mixed models. As for ocular pain parameters, the NRS and NPSI-Eye scores were significantly reduced (both P < 0.05) and positively correlated with the OSDI and CFS scores. Additionally, tear IL-1β, IL-6, and TNF-α levels were improved better than pre-treatment (P = 0.01, 0.03, 0.02, respectively).ConclusionIn patients with post-refractive surgery DED with ocular pain, combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment improved tear film stability, dry eye discomfort, and ocular pain, effectively controlling ocular inflammation.Trial registrationRegistration number: NCT06043908.

Clinical evaluation of post-surgical scar hyperaesthesia: a longitudinal observational pilot study.

The mechanisms underlying persistent scar pain are not fully elucidated and evidence for the clinical evaluation of scar pain is limited. This pilot observational study investigated participation data and sought to identify objective clinical scar evaluation measures for future trials. With ethical approval and consent, adults undergoing planned hand surgery were enrolled from one NHS hospital. At 1- and 4-months post-surgery scar thermal and mechanical pain thresholds were evaluated with quantitative sensory testing; peri-scar inflammation with infrared thermometry and pliability with durometry. Participation data were analysed with descriptive statistics; the association of clinical measures with patient reported scar pain was analysed. Twenty-one participants (22% eligible patients) enrolled before study closure due to the COVID-19 pandemic; 13 completed follow up. No adverse events or dropouts resulted from clinical scar evaluation. Seventy percent of participants reported undertaking topical, nonprescription scar treatment independently. Neuropathic Pain Symptom Inventory (NPSI) scores were dispersed across the score range, capturing variability in participant-reported scar symptoms. Scar morphology, pliability and inflammation were not associated with scar pain. Differences between scar and contralateral skin in thermal and mechanical pain sensitivity were identified. People with acute hand scars participate in clinical research and independently initiate scar treatment. Clinical testing of acute post-surgical hand scars is well tolerated. The NPSI demonstrates utility for exploring scar pain symptoms and may support the elucidation of mechanisms of persistent scar pain. Clinical tests of thermal and mechanical and sensitivity are promising candidate clinical measures of scar pain for future trials. Background: it is unknown why some scars remain painful long-term. We do not know if scar flexibility, inflammation or sensitivity to temperature or pressure relate to scar pain. We investigated if patients would enrol in scar research, if scar testing was tolerated and if clinical tests are useful for future scar studies. Study conduct: with ethical approval and consent, adult hand surgery patients were enrolled from one NHS hospital. Scar pain, inflammation and response to thermal, sharp and pressure tests were assessed at 1- and 4-months after surgery. Statistically, we analysed study participation, tolerance for clinical scar tests and if the scar tests related to scar pain. Findings: 21 participants (22% eligible patients) enrolled before study closure due to the COVID-19 pandemic; 13 completed follow up. No participants were injured due to scar testing. 70% of participants reported treating their scar independently. Neuropathic Pain Symptom Inventory (NPSI) allows participants to give a broad range of answers about their scar symptoms. Scores for clinical tests of scar flexibility and inflammation did not relate to participant-reported scar pain. Scars were more sensitive to tests of pin prick and cold than unaffected skin. What we learned: people with new hand scars participate in research and independently initiate scar treatment. Clinical testing of post-surgical hand scars is well tolerated. The NPSI is useful for exploring scar pain symptoms and may help us to learn about persistent scar pain. Pinprick and cold clinical tests may be useful objective pain tests for future scar research.

Associations between dry eye disease and sleep quality: a cross-sectional analysis

Background/aimsTo investigate relationships between dry eye (DE) disease and sleep quality, with a focus on which aspects of sleep most closely relate to DE.Methods141 veterans (mean age: 56±5) seen at...

Comparison of intermittent theta burst stimulation and high-frequency repetitive transcranial magnetic stimulation on spinal cord injury-related neuropathic pain: A sham-controlled study

Objective To compare the effects of intermittent theta burst stimulation (iTBS) and high-frequency repetitive transcranial magnetic stimulation (rTMS) on spinal cord injury-related neuropathic pain with sham controls, using neuropathic pain-specific evaluation tools. Design A randomized, double-blind, sham-controlled trial. Setting Rehabilitation medicine department of a university hospital. Participants Thirty-three patients with spinal cord injury-related neuropathic pain. Interventions Patients were randomly allocated to one of three groups (real iTBS, real rTMS, and sham rTMS). Each patient underwent five sessions of assigned stimulation. Outcome Measures Before and after completion of the five sessions, patients were evaluated using the self-completed Leeds Assessment of Neuropathic Symptoms and Signs, Numeric Rating Scale, Neuropathic Pain Symptom Inventory, and Neuropathic Pain Scale. Results Real iTBS and real rTMS reduced pain levels after stimulation according to all the evaluation tools, and the changes were significant when compared to the values of the sham rTMS group. No significant differences were found between the real iTBS and real rTMS groups. Conclusion Both iTBS and rTMS were effective in reducing spinal cord injury-related neuropathic pain. When safety, convenience, and compliance are considered, iTBS would have an advantage over rTMS in clinical situations with spinal cord injury-related neuropathic pain. Trial Registration: This trial was registered with the Clinical Research Information Service (registration no. KCT0004976).

Autologous Fat Grafting for Post-mastectomy Pain Syndrome: A Systematic Review and Meta-Analysis.

Fat grafting has been described as a potential treatment for post-mastectomy pain syndrome (PMPS)following oncological breast surgery. The study's aim was to compare and contrast the current literature using a systematic review and meta-analysis to quantify the evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Databases, including MEDLINE, Google Scholar, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Central Register of Controlled Trials (CENTRAL), were searched. Data synthesis was conducted using Review Manager 5.4 (Cochrane Collaboration, London, UK), with 95% confidence intervals. All randomised controlled trials (RCT) and observational studies comparing lipofilling for PMPS were included. A total of six studies met the inclusion criteria with five articles being used in data analysis for the mean percentage reduction in visual analogue scale (VAS) score. The primary outcome measure was the mean percentage reduction in the VASpain score. Secondary outcomes included the Neuropathic Pain Symptom Inventory (NPSI) and the quality of life assessments post treatment. Overall, a total of 266 patients received fat transfer for PMPS, and 164 were in the control group. The mean percentage reduction in VAS score was 19.8 (10.82, 28.82;p < 0.0001). Secondary outcomes, including health-related quality of life, showed good outcomes post fat transfer. This involved breast softness, cosmesis, and psychosocial well-being. The results from this meta-analysis suggest that autologous fat grafting is an efficacious treatment for reducing pain caused by PMPS. The authors suggest more high-quality trials are needed to enhance the current evidence base.

Periaqueductal/periventricular gray deep brain stimulation for the treatment of neuropathic facial pain.

The Periaqueductal gray (PAG) and the periventricular gray (PVG) are the anatomical targets for deep brain stimulation (DBS) to treat severe, refractory neuropathic pain. Seven (four female and three male) patients were qualified for PAG/PVG DBS because of neuropathic facial pain. Frame-based unilateral implantations of DBS were conducted according to indirect planning of the PAG/PVG, contralateral to reported pain (3389, Activa SC 37603, Medtronic). The efficacy of PAG/PVG DBS on pain was measured with Numeric Pain Rating Scale (NRS) and Neuropathic Pain Symptom Inventory (NPSI) before surgery and 3, 12, and 24 months after surgery. The mean age of the group at the implantation was 43.7 years (range: 28-62; SD: 12.13). The mean duration of pain varied from 2 to 12 years (mean: 7.3; SD: 4.11). Five patients suffered from left-sided facial pain and two suffered right-sided facial pain. The etiology of pain among four patients was connected to ischemic brain stroke and in one patient to cerebral hemorrhagic stroke. Patients did not suffer from any other chronic medical condition The beginnings of ailments among two patients were related to craniofacial injury. NRS decreased by 54% at the 3 months follow-up. The efficacy of the treatment measured with mean NRS decreased at one-year follow-up to 48% and to 45% at 24 months follow-up. The efficacy of the treatment measured with NPSI decreased from 0.27 to 0.17 at 2 years follow-up (mean reduction by 38%). The most significant improvement was recorded in the first section of NPSI (Q1: burning- reduced by 53%). The records of the last section (number five) of the NPSI (paresthesia/dysesthesia- Q11/Q12) have shown aggravation of those symptoms by 10% at the two-years follow-up. No surgery- or hardware-related complications were reported in the group. Transient adverse effects related to the stimulation were eliminated during the programming sessions. PAG/PVG DBS is an effective and safe method of treatment of medically refractory neuropathic facial pain. The effectiveness of the treatment tends to decrease at 2 years follow-up. The clinical symptoms which tend to respond the best is burning pain. Symptoms like paresthesia and dysesthesia might increase after DBS treatment, even without active stimulation.

Clinical and pathology characterization of small nerve fibers neuro(no)pathy in Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome.

biallelic mutation/expansion of the gene RFC1 has been described in association with a spectrum of manifestation ranging from isolate sensory neuro(no)pathy to a complex presentation as Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS). Our aim was to define the frequency and characteristics of small fiber neuropathy (SFN) in RFC1-disease at different stages. RFC1-cases were screened for SFN using the Neuropathic Pain Symptom Inventory (NPSI) and Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaires. Clinical data were retrospectively collected. If available, lower limb skin biopsy samples were evaluated for somatic epidermal and autonomic subepidermal structures innervation and compared to healthy controls (HC). we enrolled 40 patients, median age at onset 54 years (IQR 49-61) and disease duration 10 years (IQR 6-16). Mild-to-moderate positive symptoms (median NPSI score 12.1/50, IQR 5.5-22.3) and relevant autonomic disturbances (median COMPASS-31 score 37.0/100, IQR 17.7-44.3) were frequently reported and showed scarce correlation with disease duration. A non-length-dependent impairment in nociception was evident on both clinical and paraclinical investigations. An extreme somatic denervation was observed in all patients at both proximal (fibers/mm RFC1-cases 0.0 vs HC 20.5, p < .0001) and distal sites (fibers/mm RFC1-cases 0.0 vs HC 13.1, p < .0001), instead only a slight decrease was observed in cholinergic and adrenergic innervation of autonomic structures. RFC1-disease is characterized by a severe and widespread somatic SFN. Skin denervation may potentially represent the earliest feature and drive towards the suspicion of this disorder.

Genome Wide Association Study of Neuropathic Ocular Pain

To conduct a genome-wide association study (GWAS) of individuals with neuropathic ocular pain (NOP) symptoms to identify genomic variants that may predispose to NOP development. Prospective study of individuals with NOP. Three hundred twenty-nine patients recruited from the Miami Veterans Affairs eye clinic. The Neuropathic Pain Symptom Inventory modified for the eye (NPSI-Eye) was completed to calculate a NPSI-Eye-Sub-Score (summed ratings of burning and wind sensitivity) as an indicator of NOP severity. A GWAS was performed for the NPSI-Eye-Sub-Score with a significance threshold of P<5× 10-8. A gene-based analysis was performed using the multimarker analysis of genomic annotation software (in the functional mapping and annotation of GWAS online platform). The 13 865 778 single nucleotide polymorphisms (SNPs) from our GWAS analysis were mapped to 10 834 protein coding genes, and significant genes were run through gene set enrichment analysis. Identification of SNPs and protein products that may be associated with the development of NOP. One hundred seventy-one SNPs reached a threshold of P<10-5, of which 10 SNPs reached the suggestive level of significance of P<5× 10-7 and 1 SNP met our genome-wide significance threshold of P<5×10-8. This lead SNP, rs140293404 (P=1.23×10-8), is an intronic variant found within gene ENSG00000287251 coding for transcript ENST00000662732.1. Rs140293404 is in linkage disequilibrium with exon variant rs7926353 (r2 > 0.8) within ENSG00000279046 coding for transcript ENST00000624288.1. The most significant genes from gene-based tests were matrix metalloproteinase-19 (MMP19) (P=1.12× 10-5), zinc finger RNA-binding motif and serine/arginine rich-1 (ZRSR1) (P=1.48× 10-4), CTC-487M23.8 (P=1.79× 10-4), receptor expression-enhancing protein-5 (REEP5) (P=2.36× 10-4), and signal recognition particle-19 (SRP19) (P=2.56× 10-4). From gene set enrichment analysis, the sensory perception (false discovery rate=6.57× 10-3) and olfactory signaling (false discovery rate=1.63× 10-2) pathways were enriched with the most significant genes. Our GWAS revealed genes with protein products that may impact sensory perception, lending biological plausibility to a role for SNPs identified by our GWAS in the development of NOP. A better understanding of the biological relevance of these genes and pathways in the pathophysiology associated with NOP may facilitate future novel mechanism-based treatments. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Paradoxical heat sensation as a manifestation of thermal hypesthesia: a study of 1090 patients with lesions of the somatosensory system.

Paradoxical heat sensation (PHS) is the perception of warmth when the skin is cooled. Paradoxical heat sensation rarely occurs in healthy individuals but more frequently in patients suffering from lesions or disease of the peripheral or central nervous system. To further understand mechanisms and epidemiology of PHS, we evaluated the occurrence of PHS in relation to disease aetiology, pain levels, quantitative sensory testing parameters, and Neuropathic Pain Symptom Inventory (NPSI) items in patients with nervous system lesions. Data of 1090 patients, including NPSI scores from 404 patients, were included in the analysis. We tested 11 quantitative sensory testing parameters for thermal and mechanical detection and pain thresholds, and 10 NPSI items in a multivariate generalised linear model with PHS, aetiology, and pain (yes or no) as fixed effects. In total, 30% of the neuropathic patients reported PHS in contrast to 2% of healthy individuals. The frequency of PHS was not linked to the presence or intensity of pain. Paradoxical heat sensation was more frequent in patients living with polyneuropathy compared with central or unilateral peripheral nerve lesions. Patients who reported PHS demonstrated significantly lower sensitivity to thermal perception, with lower sensitivity to normally painful heat and cold stimuli. Neuropathic Pain Symptom Inventory scores were lower for burning and electric shock-like pain quality for patients with PHS. Our findings suggest that PHS is associated with loss of small thermosensory fibre function normally involved in cold and warm perception. Clinically, presence of PHS could help screening for loss of small fibre function as it is straightforward to measure or self-reported by patients.

Court-Type Thai Traditional Massage for Patients with Intractable Peripheral Neuropathic Pain: a Randomized Controlled Trial

Objective: Neuropathic pain management involves both pharmacological and non-pharmacological interventions. Despite this, no prior research has demonstrated the efficacy of court-type Thai traditional massage (CTTM) for neuropathic pain relief. This study aimed to investigate the potential benefits of CTTM in alleviating neuropathic pain. Materials and Methods: A preliminary single-blind randomized controlled trial was conducted on 28 participants with peripheral neuropathic pain, who were equally assigned to 2 groups. Both groups received standard drug treatment; however, the intervention group additionally received CTTM and hot herbal compression, while the active control group only received HHC. The adjuvant treatments were administered twice weekly for 4 weeks (V1-V8). A follow-up was conducted 4 weeks posttreatment (V9). Outcome measures were assessed at V1, V4, V8, and V9 using a numerical rating scale and the Thai versions of the Neuropathic Pain Symptom Inventory, the Brief Pain Inventory, and the EQ‑5D‑5L health questionnaire. Results: The data revealed that the intervention and active control groups had statistically significant differences in their pain intensity scores (P &lt; 0.001), total neuropathic pain intensity scores (P = 0.001), and utility of health scores (P = 0.007) during the follow-up period. When comparing outcomes between V1 and V8, the groups exhibited significant differences in pain reduction (P = 0.003) and quality of life (P = 0.027). Conclusion: This study provides initial evidence supporting the potential benefits of CTTM in alleviating peripheral neuropathic pain and improving quality of life. Future research should further investigate the application of CTTM in managing peripheral neuropathic pain conditions.

Clinical Characteristics and Tear Film Biomarkers in Patients With Chronic Dry Eye Disease After Femtosecond Laser-Assisted Laser in Situ Keratomileusis.

To investigate clinical characteristics and tear film biomarkers of patients with chronic dry eye disease (DED) following femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). Patients were divided into the chronic DED after FS-LASIK (n = 36), DED without FS-LASIK (n = 39), and normal control (without FS-LASIK; n = 34) groups. Dry eye, pain, and psychological-related symptoms were evaluated using the Ocular Surface Disease Index (OSDI), Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory Modified for the Eye (NPSI-Eye), and Hamilton Anxiety Rating Scale (HAMA) questionnaires. Ocular surface parameters, tear cytokines, and neuropeptide concentrations were evaluated with specific tests. The DED after FS-LASIK group showed higher corneal fluorescein staining scores, but lower OSDI and NPSI-Eye scores than the DED without FS-LASIK group (all P < .05). Corneal sensitivity and nerve density decreased in the DED after FS-LASIK group (all P < .01). Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-17A, IL-23, alpha-melanocyte stimulating hormone (α-MSH), oxytocin, and substance P levels were highest in the DED after FS-LASIK group, followed by the DED without FS-LASIK and normal control groups (all P < .05). Interferon-γ and neurotensin levels were only significantly higher in the DED after FS-LASIK group (all P < .05). Patients with chronic DED after FS-LASIK showed milder ocular symptoms, greater epithelial damage, and higher levels of tear inflammatory cytokines and neuropeptides than patients with DED without FS-LASIK, indicating that the nervous and immune systems may play significant roles in FS-LASIK-related chronic DED development. [J Refract Surg. 2023;39(8):556-563.].

Cutaneous nerve fiber and peripheral Nav1.7 assessment in a large cohort of patients with postherpetic neuralgia.

The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.7) blocker. Intraepidermal nerve fibers and subepidermal Nav1.7 immunolabeled fibers were quantified in skin punch biopsies from the area of maximal PHN pain, as well as from the contralateral, homologous (mirror image) region. Across the entire study population, a 20% reduction in nerve fibers on the PHN-affected side compared with that in the contralateral side was noted; however, the reduction was much higher in older individuals, approaching 40% in those aged 70 years or older. There was a decrease in contralateral fiber counts as well, also noted in prior biopsy studies, the mechanism of which is not fully clear. Nav1.7-positive immunolabeling was present in approximately one-third of subepidermal nerve fibers and did not differ on the PHN-affected vs contralateral sides. Using cluster analysis, 2 groups could be identified, with the first cluster showing higher baseline pain, higher NPSI scores for squeezing and cold-induced pain, higher nerve fiber density, and higher Nav1.7 expression. While Nav1.7 varies from patient to patient, it does not seem to be a key pathophysiological driver of PHN pain. Individual differences in Nav1.7 expression, however, may determine the intensity and sensory aspects of pain.

103-OR: LX9211, an Orally-Administered, Non-opioid, AAK1 Inhibitor for Painful Diabetic Peripheral Neuropathy—Results from a Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study

Diabetic peripheral neuropathy (DPN) is a common complication in individuals with diabetes with high morbidity and mortality. Painful DPN impacts quality of life and is very challenging to treat. The efficacy and safety of LX9211, a potent, non-opioid inhibitor of a novel target, AP2-associated protein kinase 1 (AAK1) was evaluated in a Phase 2 randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical study (RELIEF-DPN 1). The baseline characteristics [mean (SD)] of 319 adults were age 62.2 (9.94) years, A1C 7.7 (1.28) %, BMI 32.07 (4.45) kg/m2, and average daily pain score (ADPS) after placebo run-in period 6.55 (1.089). Patients were randomized to either placebo, LX9211 100 mg/10 mg (100 mg Day 1, 10 mg thereafter-Low Dose arm), or LX9211 200 mg/20 mg (200 mg Day 1, 20 mg thereafter-High Dose arm) for 6 weeks followed by 5-week safety follow-up period. At Week 6, LX9211 was associated with significant improvement in Neuropathic Pain Symptom Inventory (NPSI) total score (Low Dose: -5.18, p=0.064; High Dose: -7.22, p=0.008), burning pain (Low Dose: -1.40; p&amp;lt;0.001; High Dose: -0.89, p=0.017), pain interference on sleep (Low Dose: -0.96, p=0.005; High Dose: -1.04, p=0.002) and Patient Global Impression of Change score (Low Dose: -0.35, p=0.031; High Dose: -0.15, p=0.351) compared to placebo while achieving the primary endpoint (change from placebo in ADPS) in the low dose arm. LX9211 was safe (no treatment-related SAEs or deaths) and did not affect key cardiometabolic parameters (body weight, blood pressure, glucose control, cholesterol levels). RELIEF-DPN 1 demonstrated significant improvements in validated neuropathic pain instruments and in other patient reported outcomes suggesting that LX9211 is a promising, opioid independent new avenue to treat people with painful DPN. Confirmation of these positive results are planned in future Phase 3 trials. Disclosure R.Busui: Board Member; American Diabetes Association, Consultant; Averitas Pharma, Inc., Lexicon Pharmaceuticals, Inc., Nevro Corp., Novo Nordisk, Roche Diagnostics, Procter &amp; Gamble, Research Support; Novo Nordisk, Medtronic, National Institutes of Health. A.Patel: Other Relationship; Lexicon Pharmaceuticals, Inc. C.N.Sang: Consultant; Arena Pharmaceuticals, Inc., Covance, SOLVD, Other Relationship; Kolon, Research Support; AbbVie Inc., Merck &amp; Co., Inc., Tonix, Lexicon Pharmaceuticals, Inc., Vivozon, Helixmith. C.B.Granowitz: None. P.L.Banks: Employee; Lexicon Pharmaceuticals, Inc. P.Pierce: Employee; Lexicon Pharmaceuticals, Inc. F.W.Sun: Employee; Lexicon Pharmaceuticals, Inc. S.Gopinathan: Employee; Lexicon Pharmaceuticals, Inc. Funding Lexicon Pharmaceuticals, Inc.

Chronic post-thoracotomy pain after lung cancer surgery: a prospective study of preoperative risk factors.

The objective of this longitudinal cohort study was to investigate if preoperative pain mechanisms, anxiety, and depression increase risk of developing chronic post-thoracotomy pain (CPTP) after lung cancer surgery. Patients with suspected or confirmed lung cancer undergoing surgery by either video-assisted thoracoscopic surgery or anterior thoracotomy were recruited consecutively. Preoperative assessments were conducted by: quantitative sensory testing (QST) (brush, pinprick, cuff pressure pain detection threshold, cuff pressure tolerance pain threshold, temporal summation and conditioned pain modulation), neuropathic pain symptom inventory (NPSI), and the Hospital Anxiety and Depression Scale (HADS). Clinical parameters in relation to surgery were also collected. Presence of CPTP was determined after six months and defined as pain of any intensity in relation to the operation area on a numeric rating scale form 0 (no pain) to 10 (worst pain imaginable). A total of 121 patients (60.2 %) completed follow-up and 56 patients (46.3 %) reported CPTP. Development of CPTP was associated with higher preoperative HADS score (p=0.025), higher preoperative NPSI score (p=0.009) and acute postoperative pain (p=0.042). No differences were observed in relation to preoperative QST assessment by cuff algometry and HADS anxiety and depression sub-scores. High preoperative HADS score preoperative pain, acute postoperative pain intensity, and preoperative neuropathic symptoms were was associated with CPTP after lung cancer surgery. No differences in values of preoperative QST assessments were found. Preoperative assessment and identification of patients at higher risk of postoperative pain will offer opportunity for further exploration and development of preventive measures and individualised pain management depending on patient risk profile.

Treatment of Painful Diabetic Neuropathy Using Frequency Rhythmic Electro Magnetic Neural Stimulation (FREMS); Effectiveness in Daily Practice.

Painful diabetic peripheral neuropathy (PDPN) is common and difficult to treat with limited treatment options. We assessed the efficacy of frequency rhythmic electromagnetic neural stimulation (FREMS) in patients with PDPN. An uncontrolled prospective survey of patients with PDPN and pain despite at least two lines of pharmacotherapy. The primary outcome, 50% reduction in pain scores at 1 and/or 3 months post FREMS. FREMS was applied to both legs below the knees using 4 sets of electrodes per leg; the treatment consisted of 10 sessions of 35 min applications given over 14 days. FREMS was repeated every 4 months and patients were followed up for 12 months. Pain was assessed using the neuropathic pain symptom inventory (NPSI) and quality of life (QOL) by the EQ-5D. Out of 336 subjects, 248 patients met the inclusion criteria (56% men), average age and diabetes duration were 65 and 12.6 years respectively. FREMS was associated with a median decrease NPSI of 31% at M1 (range -100;+93%), and a median decrease of -37.5% at M3 (range -100;+250%). The 50% reduction in pain was reached in 80/248 (32.3%) and 87/248 (35.1%) after M1 and M3 respectively. The change in NPSI was accompanied by a decrease in self reported use of opiates of >50%. FREMS treatment was associated with a significant reduction in pain severity over a three months period in patients who did not have adequate response to pharmacotherapy. Randomised (sham)-controlled trials examining the role of FREMS as a treatment for PDPN in non-responders to pharmacotherapy are needed.

Pyridostigmine Bromide Pills and Pesticides Exposure as Risk Factors for Eye Disease in Gulf War Veterans.

To examine associations between the pyridostigmine bromide (PB) pill and/or pesticide exposure during the 1990-1991 Gulf War (GW) and eye findings years after deployment. A cross-sectional study of South Florida veterans who were deployed on active duty during the GW Era (GWE). Information on GW exposures and ocular surface symptoms were collected via standardized questionnaires and an ocular surface examination was performed. Participants underwent spectral domain-ocular coherence tomography (SD-OCT) imaging that included retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and macular maps. We examined for differences in eye findings between individuals exposed versus not exposed to PB pills or pesticides during service. A total of 40.7% (n = 44) of individuals reported exposure to PB pills and 41.7% (n = 45) to pesticides; additionally, 24 reported exposure to both in the GW arena. Demographics were comparable across groups. Individuals exposed to PB pills reported higher dry eye (DE) symptoms scores (the 5-Item Dry Eye Questionnaire, DEQ-5: 9.3 ± 5.3 vs. 7.3 ± 4.7, p = 0.04) and more intense ocular pain (average over the last week: 2.4 ± 2.6 vs. 1.5 ± 1.8, p = 0.03; Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-E): 18.2 ± 20.0 vs. 10.8 ± 13.8, p = 0.03) compared to their non-exposed counterparts. DE signs were comparable between the groups. Individuals exposed to PB pills also had thicker OCT measurements, with the largest difference in the outer temporal segment of the macula (268.5 ± 22.2 μm vs. 260.6 ± 14.5 μm, p = 0.03) compared to non-exposed individuals. These differences remained significant when examined in multivariable models that included demographics and deployment history. Individuals exposed to pesticides had higher neuropathic ocular pain scores (NPSI-E: 17.1 ± 21.1 vs. 11.6 ± 12.9, p = 0.049), but this difference did not remain significant in a multivariable model. Individuals exposed to PB pills during the GWE reported more severe ocular surface symptoms and had thicker OCT measures years after deployment compared to their non-exposed counterparts.