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This study investigated the prevalence of long-term musculoskeletal post-COVID pain and their risk factors in a large cohort of COVID-19 survivors. A multicenter cohort study including patients hospitalised because of COVID-19 in 5 hospitals of Madrid (Spain) during the first wave of the pandemic was conducted. Hospitalisation and clinical data were collected from medical records. Patients were scheduled for a telephone interview after hospital discharge for collecting data about the musculoskeletal post-COVID pain. Anxiety/depressive levels and sleep quality were likewise assessed. From 2000 patients recruited, a total of 1969 individuals (46.4% women, age: 61 years, SD: 16 years) were assessed on average at 8.4 (SD: 1.5) months after discharge. At the time of the study, 887 (45% women) reported musculoskeletal post-COVID pain. According to the presence of previous pain symptoms, the prevalence of “de novo” (new-onset) musculoskeletal post-COVID pain was 74.9%, whereas 25.1% experienced an increase in previous symptoms (exacerbated COVID-related pain). Female sex (odds ratio [OR]: 1.349, 95% confidence interval [CI]: 1.059-1.720), history of musculoskeletal pain (OR 1.553, 95% CI 1.271-1.898), presence of myalgia (OR 1.546, 95% CI 1.155-2.070) and headache (1.866, 95% CI 1.349-2.580) as COVID-19–associated onset symptoms, and days at hospital (OR 1.013, 95% CI 1.004-1.022) were risk factors associated with musculoskeletal post-COVID pain. In conclusion, musculoskeletal post-COVID pain is present in 45.1% of COVID-19 survivors at 8 months after hospital discharge with most patients developing de novo post-COVID pain. Female sex, history of musculoskeletal pain, presence of myalgia and headache as COVID-19 symptoms at the acute phase, and days at hospital were risk factors associated with musculoskeletal post-COVID pain.

Our aim was to assess the association between four inflammatory polymorphisms with the development of post-COVID pain and to associate these polymorphisms with the clinical pain phenotype in individuals who had been hospitalized by COVID-19. Three potential genotypes of IL-6 (rs1800796), IL-10 (rs1800896), TNF-α (rs1800629), and IFITM3 (rs12252) single nucleotide polymorphisms (SNPs) were obtained from no-stimulated saliva samples from 293 (49.5% female, mean age: 55.6 ± 12.9 years) previously hospitalized COVID-19 survivors by polymerase chain reactions. Pain phenotyping consisted of the evaluation of pain features, sensitization-associated symptoms, anxiety levels, depressive levels, sleep quality, catastrophizing, and kinesiophobia levels in patients with post-COVID pain. Analyses were conducted to associate clinical features with genotypes. One hundred and seventeen (39.9%) patients experienced post-COVID pain 17.8 ± 5.2 months after hospital discharge. No significant differences in the distribution of the genotype variants of any SNPs were identified between COVID-19 survivors with and without post-COVID pain (all, p > 0.47). Similarly, the clinical pain phenotype was not significantly different between patients with and without post-COVID pain since no differences in any variable were observed for any SNPs. In conclusion, four SNPs associated with inflammatory and immune responses did not appear to be associated with post-COVID pain in previously hospitalized COVID-19 survivors. Further, neither of the SNPs were involved in the phenotyping features of post-COVID pain.

Objective: To investigate the association of different, selected pain polymorphisms with the presence of de novo long-COVID pain symptoms and to analyze the association between these polymorphisms with clinical, sensory-related, cognitive and psychological variables in COVID-19 survivors. Methods: Two hundred and ninety-three (n = 293, 49.5% female, mean age: 55.6 ± 12.9 years) previously hospitalized COVID-19 survivors participated. Three genotypes of the following single nucleotide polymorphisms (SNPs) were obtained from non-stimulated saliva: OPRM1 (rs1799971), COMT (rs4680), BDNF (rs6265), and HTR1B (rs6296) by polymerase chain reactions in all participants. Further, clinical (intensity/duration of pain), sensory-related (sensitization-associated symptoms, neuropathic pain features), psychological (anxiety or depressive levels, sleep quality), and cognitive (catastrophizing, kinesiophobia) variables were collected in those COVID-19 survivors suffering from post-COVID pain. Analyses were carried out to associate clinical features with genotype. Results: Participants were assessed 17.8 ± 5.2 months after hospitalization. One hundred and seventeen (39.9%) experienced post-COVID pain (particularly of musculoskeletal origin). The distributions of the genotype variants of any SNP were not significantly different between COVID-19 survivors with and without long-term post-COVID pain (all, p > 0.178). No differences in sensitization-associated symptoms, neuropathic pain features, catastrophizing, kinesiophobia levels, anxiety and depressive levels or sleep quality according to the genotype variant in any SNPs were found. No effect of gender was identified. Conclusion: The four SNPs generally associated with pain did not appear to predispose to the development of de novo long-COVID pain symptoms in previously hospitalized COVID-19 survivors. The SNPs were not involved in the phenotypic features of post-COVID pain either.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is associated with psychological/emotional disturbances. This study aimed to assess internal consistency, reliability, and construct validity of the Hospital Anxiety and Depressive Scale (HADS), as a patient-reported outcome measure (PROM) for evaluating emotional consequences of SARS-CoV-2 in hospitalized COVID-19 survivors with long COVID. The LONG-COVID-EXP-CM is a multicenter cohort study including patients hospitalized by COVID-19 during the first wave of the pandemic in five hospitals in Madrid. A total of 1969 (age: 61 ± 16 years, 46.5% women) COVID-19 survivors experiencing post-COVID symptoms a mean of 8.4 ± 1.5 months after hospital discharge completed HADS. Internal consistency (Cronbach α), reliability (item-internal consistency, item-discriminant validity), construct validity (confirmatory factor analysis), and floor effect and ceiling effect were calculated. The mean time for fulfilling HADS was 65 ± 12 s. A ceiling effect ranging from 1.99% to 13.74% and a floor effect ranging from 43.05% to 77.77% was observed. Based on the item-scale correlation coefficients, the Cronbach’s alpha values reflecting the internal consistency reliability were 0.890 for the anxiety scale (HADS-A) and 0.856 for the depressive scale (HADS-D) The correlation coefficient between HADS-A and HADS-D scores was excellent (r: 0.878). The confirmatory factor analysis revealed that five out of the seven fitness indexes were excellent: CFI = 0.969, NNFI = 0.963; TLI = 0.963; AGFI = 0.951; GFI = 0.972), supporting good construct validity. In conclusion, this study indicates that both anxiety and depressive symptoms scales of HADS had overall good psychometric properties to be used for assessing psychological and emotional stress in COVID-19 survivors with long COVID.

Background: Multicentre studies focussing on specific long-term post-COVID-19 symptoms are scarce. Objective: The aim of this study was to determine the levels of fatigue and dyspnoea, repercussions on daily life activities, and risk factors associated with fatigue or dyspnoea in COVID-19 survivors at long term after hospital discharge. Methods: Age, gender, height, weight, symptoms at hospitalization, pre-existing medical comorbidity, intensive care unit admission, and the presence of cardio-respiratory symptoms developed after severe acute respiratory syndrome coronavirus 2 infection were collected from patients who recovered from COVID-19 at 4 hospitals in Madrid (Spain) from March 1 to May 31, 2020 (first COVID-19 wave). The Functional Impairment Checklist was used for evaluating fatigue/dyspnoea levels and functional limitations. Results: A total of 1,142 patients (48% women, age: 61, standard deviation [SD]: 17 years) were assessed 7.0 months (SD 0.6) after hospitalization. Fatigue was present in 61% patients, dyspnoea with activity in 55%, and dyspnoea at rest in 23.5%. Only 355 (31.1%) patients did not exhibit fatigue and/or dyspnoea 7 months after hospitalization. Forty-five per cent reported functional limitations with daily living activities. Risk factors associated with fatigue and dyspnoea included female gender, number of pre-existing comorbidities, and number of symptoms at hospitalization. The number of days at hospital was a risk factor just for dyspnoea. Conclusions: Fatigue and/or dyspnoea were present in 70% of hospitalized COVID-19 survivors 7 months after discharge. In addition, 45% patients exhibited limitations on daily living activities. Being female, higher number of pre-existing medical comorbidities and number of symptoms at hospitalization were risk factors associated to fatigue/dyspnoea in COVID-19 survivors 7 months after hospitalization.

IntroductionKnee and hip osteoarthritis are two highly prevalent musculoskeletal pain conditions. Unsuccessful rates after hip/knee replacement range from 10% to 20%. Subjects with sensitisation manifestations are vulnerable to worse clinical outcomes. Most studies have analysed outcomes up to 1 year after surgery. The aim of this 2-year longitudinal study will be to evaluate sensory-related, psychological and psychophysical pain sensitisation manifestations and a potential epigenetic biomarker as prognostic clinical outcomes for the development of chronic postoperative pain after knee or hip replacement.Methods and analysisA prospective longitudinal study with a 2-year follow-up period will be conducted. The prognostic variables will include pain, function, related-disability, anxiety, depression, quality of life, sensitisation-associated symptoms, kinesiophobia, neuropathic pain and catastrophising, and expectative of the intervention will be assessed before surgery. We will also evaluate the presence of the Val158Met polymorphism as a possible epigenetic marker. Clinical outcomes including pain, related-disability and self-perceived satisfaction, sensitisation-associated symptoms and neuropathic pain will be assessed 3, 6, 12, 18 and 24 months after surgery. These variables will be used to construct three prediction models: (1) pain and function, (2) sensitisation-associated symptomatology and (3) neuropathic pain features classifying those patients in responders and non-responders. Data from knee or hip osteoarthritis will be analysed separately. Statistical analyses will be conducted with logistic regressions.Ethics and disseminationThe study has been approved by the Ethics Committee of both institutions involved (Hospital Universitario Fundación Alcorcón (HUFA) 19–141 and Universidad Rey Juan Carlos (URJC) 0312201917319). Participants will sign the written informed consent before their inclusion. Study results will be disseminated through peer-reviewed publications and presentations at scientific meetings.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is associated with a plethora of long-lasting symptoms (long-COVID). The presence of long-COVID symptoms causes decreased functionality. This study described the psychometric properties of the Functional Impairment Checklist (FIC), a disease-specific patient-reported outcome measure (PROM) used for evaluating the functional consequences of SARS in previously hospitalized COVID-19 survivors with long-COVID symptoms. The LONG-COVID-EXP-CM is a multicenter cohort study including patients hospitalized with COVID-19 during the first wave of the pandemic in five hospitals in Madrid. A total of 1969 (age: 61 ± 16 years, 46.4% women) COVID-19 survivors with long-COVID completed the FIC at a long-term follow-up after hospitalization (mean: 8.4 ± 1.5 months). Internal consistency (Cronbach alpha value), reliability (item-internal consistency, item-discriminant validity), construct validity (exploratory factor analysis), floor effect and ceiling effect were calculated. The mean time for fulfilling the FIC was 62 ± 11 s. The Cronbach’s alpha values reflecting the internal consistency reliability were 0.864 for FIC-symptoms and 0.845 for FIC-disability. The correlation coefficient between the FIC-symptoms and FIC-disability scale was good (r: 0.676). The ceiling effect ranged from 2.29% to 9.02%, whereas the floor effect ranged from 38.56% to 80.19%. The exploratory factor analysis showed factor loadings from 0.514 to 0.866, supporting good construct validity. Women exhibited greater limitations in all physical symptoms and disability-related domains of the FIC compared with men (all, p < 0.001). Further, younger patients (those aged

Background : : To investigate the analgesic effects of vibro-acupuncture (VA), a novel acuvibrator was developed. Objectives: To compare the analgesic effects of VA with those of manual acupuncture (MA) and placebo acupuncture (PA) on subjects with normal sensory perception (Study I), experimentally induced acute pain (Study II), and clinical chronic pain (Study III). Methods : : Thirty healthy volunteers (21 males, age: 20-30 years) participated in Study I. Fourteen healthy volunteers (8 males, age: 20-32 years) participated in Study II in which experimental pain was induced by injection of hypertonic saline. Fourteen patients suffering from unilateral epicondylalgia (9 males, age: 30-61 years) participated in Study III. All participants received VA, MA, and PA at LI4 and LI10 points in a randomized, crossover, and double-blinded manner. Quantitative sensory testing (QST) was performed on the ipsilateral forearm before and after each treatment. Data were analyzed using repeated-measures (RM) ANOVA. Results : : A significantly higher vibration detection threshold (VDT) was observed after treatment of VA than after MA and PA (p < 0.001). No significant treatment effect on experimental pain intensity was detected (p > 0.086). Significantly lower pain intensity (p = 0.005) and a smaller drawing area (p = 0.011) of unilateral epicondylalgia were found after VA treatment than after PA. Conclusion : : A specific effect on the VDT beyond that of MA and PA was evoked by VA. Patients with epicondylitis showed significantly lower pain intensity during VA than during PA. This study indicated that VA may be beneficial in individuals with clinical chronic musculoskeletal pain; however, further studies are needed.

Objectives To analyze the association between the rs4680 catechol-O-methyltransferase Val158Met polymorphism and to determine the association of this polymorphism with clinical, psychological, and pain sensitivity variables in women with episodic or chronic migraine. Methods Fifty women with episodic migraine, 50 with chronic migraine, and 50 matched healthy women participated. After amplifying the Val158Met polymorphism by polymerase chain reaction, we assessed genotype frequencies and allele distributions. Participants were classified according to the Val158Met polymorphism genotype into Val/Val, Val/Met, or Met/Met. A headache diary was used for collecting migraine pain features. Disability was assessed with the Migraine Disability Assessment Scale, trait/state anxiety levels with the State-Trait Anxiety Inventory, and depression/anxiety with the Hospital Anxiety and Depression Scale. Pressure pain thresholds (PPTs) were bilaterally assessed over the temporalis, the upper trapezius, the second metacarpal, and the tibialis anterior. Results The distribution of the rs4680 Val158Met genotype was not significantly different between women with and without migraine (P = 0.157). No differences in migraine features were found to be dependent on the Val158Met genotype. Women with the Met/Met genotype showed higher migraine-related disability than those with the Val/Val or Val/Met genotype in both migraine groups (P Conclusions The Val158Met rs4680 polymorphism does not appear to be involved in predisposition to suffer from migraine; however, this genetic factor may be involved in the phenotypic expression of chronic migraine, as anxiety, depression, and widespread pressure pain sensitivity were greater in those women with chronic, but not episodic, migraine with the Met/Met genotype.

Objectives: The aims of this study were: (1) to investigate the association between the rs4680 Val158Met polymorphism in frequent episodic tension-type headache (FETTH) and chronic tension-type headache (CTTH); and (2) to analyze the association between the rs4680 Val158Met polymorphism with clinical, psychological, or psychophysical variables. Methods: In total, 50 women with FETTH, 50 with CTTH, and 50 matched headache-free women participated. After amplifying Val158Met polymorphism by polymerase chain reaction, the genotype frequencies and allele distributions based on restriction fragment length polymorphism were assessed. Participants were classified according to the Val158Met polymorphism rs4680 genotype (Val/Val, Val/Met, or Met/Met). A headache diary collected clinical features. Disability (Headache Disability Inventory), sleep quality (Pittsburgh Sleep Quality Index), and depression/anxiety levels (Hospital Anxiety and Depression Scale) were also assessed. Pressure pain thresholds were assessed bilaterally over the temporalis, upper trapezius, second metacarpal, and tibialis anterior by a blinded assessor. Results: The distribution of rs4680 Val158Met genotype was not significantly different between women with/without headache (P=0.796). No differences in headache features, disability, anxiety, or sleep quality were observed depending on the rs4680 Val158Met genotype. Women with CTTH, but not FETTH, carrying the Met/Met genotype had lower widespread pressure pain thresholds and higher depressive symptoms than those with Val/Val or Val/Met genotype (P

Background There is evidence suggesting a clinical effect of Kinesiotaping® on the upper trapezius of individuals with neck pain; however, the underlying effect is not still understood. One potential mechanism is a mechanical effect of the Kinesiotaping® on the targeted tissue, the muscle. The assessment of changes in the upper trapezius muscle with ultrasound imaging can help to elucidate this mechanical effect. Objective The aim of this randomized clinical trial was to investigate changes in upper trapezius and subcutaneous thickness with rehabilitative ultrasound imaging associated to changes in cervical range of motion and the related-disability in patients with neck pain. Methods A randomized clinical trial was conducted. Thirty patients (73% female, mean age: 22±4 years) with mechanical neck pain were randomly assigned to an experimental (Kinesiotaping®) or control (sham Kinesiotaping®) group. The experimental group received Kinesiotaping® to the cervical spine according to international guideline and the placebo group received a sham Kinesiotaping® (no tension) application. Outcomes including subcutaneous thickness and muscle thickness of the upper trapezius muscle assessed with ultrasound imaging and cervical range of motion were collected at baseline and 2-days after the application of the tape by an assessor blinded to the treatment allocation of the patients. In addition, neck pain related-disability, assessed with the Neck Disability Index (NDI), was also assessed before and 1-week after the application of Kinesiotaping®. Results No significant Group*Time interactions were observed for NDI (F=0.068, P=0.796) and cervical range of motion (F=0.053, P=0.820): both groups showed similar changes in neck pain related-disability and cervical range of motion after the application of either tape. Similarly, no significant Group*Time interactions were observed for changes in subcutaneous thickness (F=0.096, P=0.759) and muscle thickness (F=1.558, P=0.222) of the upper trapezius muscle: no significant changes were found after the application of Kinesiotaping®. Conclusions The application of real Kinesiotaping® was not more effective than placebo (no-tensioned) Kinesiotaping® for improving neck pain related-disability and cervical range of motion in people with neck pain. Inclusion of proper tension in the Kinesiotaping® did not exert changes in ultrasound outcomes on the upper trapezius muscle.

Objective: The objective of this study was to investigate somatosensory nerve fiber function by applying different quantitative sensory testing including thermal, mechanical, and vibration thresholds over latent trigger points (TrP) and in its associated referred pain area. Methods: A total of 20 patients with unilateral latent TrPs in the extensor carpi radialis brevis were included. Warmth detection threshold (WDT), cold detection threshold (CDT) and heat/cold pain thresholds (HPT, CPT), mechanical detection (MDT) and pain (MPT) thresholds, vibration threshold (VT), and pressure pain thresholds (PPT) were blinded assessed over the TrP, in the referred pain area, and in the respective contralateral mirror areas. A multilevel mixed-model ANOVA with site (TrP, referred pain area) and side (real or contralateral) as within-patient factors and sex as between-patients factor was conducted. Results: No significant differences for thermal detection (WDT, CDT) or thermal pain thresholds (HPT, CPT) were found (all, Ps>0.141). The assessments over the TrP area showed lower PPT and MDT compared with the mirror contralateral TrP area (P

DESIGN: Randomized clinical trial. OBJECTIVE: To investigate the association of the Val158Met polymorphism with pain and function outcomes in women with carpal tunnel syndrome (CTS) who received surgery or manual therapy including desensitization manoeuvres of the central nervous system. METHODS: A pre-planned secondary analysis of a randomized controlled trial investigating the efficacy of manual therapy including desensitization manoeuvres of the central nervous system vs. surgery in 120 women with CTS was conducted. Women were randomized to receive 3 sessions of manual therapy (n = 60) or decompression of the carpal tunnel (n = 60). The primary outcome was intensity of pain (mean pain and the worst pain), and secondary outcomes included function and symptoms severity subscales of the Boston Carpal Tunnel Questionnaire. Outcomes were assessed at baseline, and 1, 3, 6, and 12 months after the intervention. Rs4680 genotypes were determined after amplifying the Val158Met polymorphism by polymerase chain reactions. We classified subjects according to their Val158Met polymorphism: Val/Val, Val/Met, or Met/Met. The primary aim (treatment group*Val158Met*time) was examined with repeated measures ANCOVA with intention-to-treat analysis. RESULTS: At 12 months, 111 (92%) women completed the follow-up. No interaction was observed between the Val158Met genotype and any outcome: mean pain intensity (F = 0.60; P = 0.69), worst pain intensity (F = 0.49; P = 0.61), function (F = 0.12; P = 0.88) or symptom severity (F = 0.01; P = 0.98). CONCLUSION: The current clinical trial did not show an association between the Val158Met polymorphism and changes in pain and function outcomes after either surgery or physical therapy in women with CTS. Funding: The study was funded by a research project grant (FIS PI11/01223) from the Health Institute Carlos III and PN I+D+I 2012-2014, Spanish Government.

Resumen El sindrome de compresion del plexo braquial en el desfiladero entre el musculo escaleno anterior y medio es un tema de debate. Mujer, 70 anos, con dolor cervical y en la mano desde hace 3 anos, y progresivo. La paciente ha recibido tratamientos previos (masoterapia, microonda y TENS) sin resultados. El test de Adson fue positivo. Se pautan 8 sesiones mediante tecnicas de liberacion del escaleno, movilizaciones articulares (C5-T1), tecnica de deslizamiento del nervio mediano y ejercicios de control motor cervical. El dolor espontaneo antes del tratamiento era de 6 puntos (0-10) y una funcionalidad del 40% segun el Cuestionario de Michigan de la Mano. Un mes despues del tratamiento, manifestaba un 1/10 en el dolor en reposo y una funcionalidad del 75%. El abordaje fisioterapeutico de terapia manual en el sindrome compresivo toracico podria ser efectivo en la reduccion del dolor y el incremento de la funcionalidad y la fuerza.

Identification of subjects with different sensitization mechanisms can help to identify better therapeutic strategies for carpal tunnel syndrome (CTS). The aim of the current study was to identify subgroups of women with CTS with different levels of sensitization.A total of 223 women with CTS were recruited. Self-reported variables included pain intensity, function, disability, and depression. Pressure pain thresholds (PPT) were assessed bilaterally over median, ulnar, and radial nerves, C5-C6 joint, carpal tunnel, and tibialis anterior to assess widespread pressure pain hyperalgesia. Heat (HPT) and cold (CPT) pain thresholds were also bilaterally assessed over the carpal tunnel and the thenar eminence to determine thermal pain hyperalgesia. Pinch grip force between the thumb and the remaining fingers was calculated to determine motor assessment. Subgroups were determined according to the status on a previous clinical prediction rule: PPT over the affected C5-C6 joint 137 kPa, HPT on affected carpal tunnel 39.6ºC, and general health 66 points.The ANOVA showed that women within group 1 (positive rule, n = 60) exhibited bilateral widespread pressure hyperalgesia (P 0.001) and bilateral thermal thresholds (P 0.001) than those within group 2 (negative rule, n = 162). Women in group 1 also exhibited higher depression than those in group 2 (P = 0.023). No differences in self-reported variables were observed.This study showed that a clinical prediction rule originally developed for identifying women with CTS who are likely to respond favorably to manual physical therapy was able to identify women exhibiting higher widespread pressure hyper-sensitivity and thermal hyperalgesia. This subgroup of women with CTS exhibiting higher sensitization may need specific therapeutic programs.

Our aim was to assess the relationship of the Val158Met polymorphism to pain, anxiety, depression, functional ability, and pressure pain sensitivity in women with fibromyalgia (FMS). One hundred (n = 100) women with FMS diagnosed according to the American College of Rheumatology criteria participated. A numerical pain rate scale (0-10) was used to assess the intensity of pain; the Hospital Anxiety and Depression Scale was calculated to determine anxiety and depression; and functional ability was determined with the Fibromyalgia Impact Questionnaire. Further, pressure pain thresholds (PPTs) were bilaterally assessed over C5-C6 zygapophyseal joints, second metacarpal, and tibialis anterior muscles. Finally, after amplifying Val158Met polymorphisms by polymerase chain reaction, catechol-O-methyltransferase (COMT) genotype was divided into Val/Val, Val/Met, or Met/Met genotypes. Women with FMS with the Met/Met genotype exhibited higher disability (F = 11.836; P.001), anxiety (F = 13.385; P.001), and depression (F = 6.931; P = .002) than those with Val/Val and Val/Met genotypes. No differences for the intensity of widespread pain (F = .154; P = .857) and PPT levels over C5-C6 joints (F = 1.014; P = .336), second metacarpal (F = .216; P = .806), and tibialis anterior muscle (F = 1.179; P = .311) were found. Our results suggest that the Val158Met COMT polymorphism modulated some psychological variables but not pressure pain sensitivity in FMS, because women carrying the Met/Met genotype show higher disability, depression, and anxiety but similar PPTs than those with Val/Met or Val/Val genotypes. This study is important because it strives to understand potential genetic factors that predispose some women with FMS to exhibit a more severe phenotypic expression of the disease. Future studies are needed to elucidate potential relevance of the differences.This study suggests that the Val158Met COMT polymorphism modulated some psychological variables but not pressure pain sensitivity in FMS because women with FMS carrying the Met/Met genotype exhibit higher disability, depression, and anxiety than but similar PPTs to those with Val/Met and Val/Val genotypes. This study provides further evidence of potential genetic factors that predispose women with FMS to exhibit the disease more severely.

Resumen El sindrome del tunel del carpo (STC) es responsable de elevados costes a la sociedad y ultimamente se ha demostrado la existencia de sensibilizacion central en el STC. Mujer, 35 anos, diagnostico clinico y electromiografico de STC moderado en la mano derecha, con un cuadro de sensibilizacion central. Se pauta un tratamiento de 3 sesiones fisioterapeuticas, con objeto de modular la sensibilizacion mediante tecnicas de liberacion de tejidos blandos y movilizacion neural del nervio mediano. El dolor espontaneo al comienzo era de 4 puntos en una escala numerica de dolor, una discapacidad de 2 y severidad de 2,8 puntos segun el cuestionario de Boston para el STC. El dolor en reposo alcanzo valor 0 al finalizar el tratamiento, y durante los 6 meses de seguimiento al igual que en la discapacidad y la severidad de los sintomas. El abordaje fisioterapeutico basado en la neuromodulacion de la sensibilizacion podria constituir una intervencion eficaz en el STC.

Cancer-related fatigue and pain after surgery are the most frequent and most incapacitating cancer-related symptoms after breast cancer treatment. Genetic influence of cancer-related fatigue and pain has not been previously investigated. Our aim was to examine the influence of catechol-O-methyltransferase (COMT) Val158Met genotypes on cancer-related fatigue, post-mastectomy pain, and pressure pain hypersensitivity in breast cancer survivors. One-hundred and twenty-eight (n = 128) breast cancer survivors who were treated with radiotherapy and chemotherapy participated in this study. After amplifying Val158Met polymorphisms by polymerase chain reaction, COMT genotype was divided into Val/Val, valine/methionine (Val/Met), or Met/Met. The Piper fatigue scale (PFS) was used to assess cancer-related fatigue. Neck and shoulder/axillary pain intensity was assessed with a numerical pain rate scale (0–10). Finally, pressure pain thresholds (PPT) were assessed bilaterally over the C5–C6 zygapophyseal joints, deltoid muscles, second metacarpal, and tibialis anterior muscles. Breast cancer survivors carrying the Met/Met genotype reported higher levels of fatigue (all subscales, P < 0.001), higher neck pain intensity, and lower PPT over C5–C6 joints and deltoid muscles (all, P < 0.001) relative to those with Val/Met or Val/Val genotypes. The results suggest that breast cancer survivors carrying the Met/Met genotype exhibit higher fatigue, neck pain, and pressure pain hypersensitivity over the neck and shoulder area. This study is important because it strives to understand the factors that predispose some breast cancer survivors to more cancer-related fatigue and increased pain sensitivity.

Aim: To investigate the differences in cortisol and melatonin concentrations between children with frequent episodic tension-type headache (FETTH) and healthy children. Methods: Forty-four children, 12 boys/32 girls (age: 9 ± 2 years) with FETTH associated to peri-cranial tenderness and 44 age- and sex- matched healthy children participated. Both salivary cortisol and melatonin concentrations were collected from non-stimulated saliva following standardized guidelines. A headache diary for 4 weeks was used for collecting intensity, frequency and duration of headache. Results: No significant differences for cortisol (t = −0.431; p = 0.668), and melatonin (z = −1.564; p = 0.118) concentrations and salivary flow rate (z = −1.190; p = 0.234) were found between both groups. No significant effect of age or gender was found. In addition, no significant association between cortisol-melatonin concentrations and between cortisol-melatonin concentrations and headache clinical parameters were found. Conclusion: These results suggest that children with FETTH, at first instance, do not present deficits in the secretion of these cortisol and melatonin. Prospective longitudinal studies are needed to further elucidate the direction of current findings, particularly the synchronism of cortisol and melatonin and the course of the headache.

Our aim was to describe the referred pain pattern and areas from trigger points (TrPs) in head, neck, and shoulder muscles in children with chronic tension type headache (CTTH). Fifty children (14 boys, 36 girls, mean age: 8 ± 2) with CTTH and 50 age- and sex- matched children participated. Bilateral temporalis, masseter, superior oblique, upper trapezius, sternocleidomastoid, suboccipital, and levator scapula muscles were examined for TrPs by an assessor blinded to the children’s condition. TrPs were identified with palpation and considered active when local and referred pains reproduce headache pain attacks. The referred pain areas were drawn on anatomical maps, digitalized, and also measured. The total number of TrPs was significantly greater in children with CTTH as compared to healthy children (P

OBJECTIVES: The objective of this study was to analyze the presence of generalized pressure pain hypersensitivity over nerve tissues in trigeminal and nontrigeminal regions in children with frequent episodic tension-type headache (FETTH). METHODS: Thirty children, 7 boys and 23 girls (mean age: 8.8 ± 1.7 years) with FETTH and 50 age- and gender-matched healthy children (14 boys, 36 girls; mean age: 8.5 ± 2.1 years; P = .743) were recruited. Pressure pain thresholds (PPTs) were bilaterally assessed over supra-orbital (V1), infra-orbital (V2), mental (V3), median (C5), radial (C6), and ulnar (C7) nerves by an assessor who was blinded to the patient's condition. RESULTS: The analysis of variance showed that PPT levels were significantly bilaterally decreased over both trigeminal (supra-orbital, infra-orbital, and mental) and nontrigeminal (median, ulnar, and radial) nerves in children with FETTH as compared with control subjects (all sites, P < .001). There was a greater magnitude of PPT decrease within trigeminal nerves as compared with nontrigeminal nerves (P < .03). PPTs over infra-orbital (rs = −0.4, P < .05) and radial (rs = −0.5, P < .01) nerves were negatively correlated with the duration of headache attacks (P < .05). CONCLUSIONS: Our study revealed bilateral and generalized pressure hypersensitivity over both trigeminal and nontrigeminal nerves in children with FETTH. Diffuse hypersensitivity of peripheral nerves evidences the presence of hyperexcitability of the central nervous system in children with FETTH.

The genetic influence of Val158Met polymorphisms, one of the potential genetic determinants for nociceptive processing, has not been previously investigated in women with carpal tunnel syndrome (CTS).To investigate the association between the Val158Met polymorphism with CTS and to assess the relationship between the Val158Met polymorphism and the clinical outcomes and widespread pressure pain hypersensitivity in women with CTS.Case control study.Neurology department at an urban hospital.One hundred nine (n = 109) women (mean age: 47 ± 9 years) with a clinical and electrodiagnostic diagnosis of CTS and 109 matched healthy women participated. After amplifying the Val158Met polymorphism by polymerase chain reactions, rs4680 genotype frequencies and allele distributions were calculated. We classified individuals according to their Val158Met polymorphism: Val/Val, Val/Met, Met/Met. The intensity of the pain was assessed with a numeric rating scale (0-10) and disability was determined with the Boston Carpal Tunnel Questionnaire. Pressure pain thresholds were bilaterally assessed over median, radial, and ulnar nerve trunks; C5-C6 facet joints; and carpal tunnel and tibialis anterior muscles.Institutional Review Board: The study project was approved by the local human research committee (HUFA-12/14). All participants signed an informed consent prior to their inclusion in the study.The distribution of the 3 Val158Met genotypes (Val/Val, Val/Met, Met/Met) and alleles was not significantly different between women with CTS and healthy women (Chi-Square = 0.498; P = 0.780). Women with CTS carrying the Met/Met genotype showed higher levels of pain and disability than those with the Val/Met genotype (P0.01) and with the Val/Val genotype (P0.001). No differences in the years with pain (P = 0.954), age (P = 0.740), depression (P = 0.530), severity of CTS (P = 0.744) or presence of unilateral-bilateral symptoms (P = 0.279) existed depending on the rs4680 Val158Met genotype. No significant differences in widespread pressure pain sensitivity were observed in any of the points depending on the rs4680 Val158Met genotype (P0.315).We only recruited women from a specialized department.Current results indicated that the Val158Met polymorphism seems not to be a risk factor for the development of CTS; however, it was associated with increased perception of pain and higher disability scores.

Alterations in the rs4680 Val158Met polymorphism are associated with the presence of pain. No study has investigated the role of Val158Met polymorphism in the susceptibility to exhibit pain in multiple sclerosis (MS). Our aim was to investigate the relationship between Val158Met polymorphism (rs4680) and the presence of pain in MS. One hundred eight (n = 108) patients (mean age: 44 ± 8 years) with a definitive diagnosis of MS and 108 matched controls participated. Fifty-eight patients (54%) had pain and 50 (46%) did not report pain. After amplifying Val158Met polymorphisms by polymerase chain reactions, rs4680 genotype frequencies and allele distributions were calculated. We classified individuals according to their Val158Met polymorphism: Val/Val, Val/Met, and Met/Met. The results showed that distribution of rs4680 Val158Met genotypes was not significantly different between individuals with MS in general and healthy people (χ 2 = 2.212, P = .331). When we differentiate MS patients with pain and those without pain, the prevalence of Val158Met genotypes was significantly different (χ 2 = 9,610, P = .046): Patients experiencing pain exhibited higher prevalence of Met/Met genotype than those without pain and healthy controls. Current results suggest that the Met allele of Val158Met polymorphism could be a potential risk factor for the development of pain in MS but not for the predisposition of MS itself. Perspective This study suggests that the Val158Met polymorphism is associated with the presence of pain in MS, but it is not a risk factor for MS itself because the presence of the Met/Met genotype was more prevalent in those patients with pain. This study provides further evidence of potential genetic factors that predispose patients with MS to develop pain.

Objective: The purpose of this prospective case series was to examine the combined effects of soft tissue mobilization and nerve slider neurodynamic technique on pain and pressure sensitivity in women with chronic carpal tunnel syndrome (CTS). Methods: Eighteen women with a clinical and electromyographic diagnosis of CTS participated. Patients completed the numerical pain rating scale (NPRS) for current, worst, and lowest pain intensity and underwent pain pressure threshold (PPT) testing over the median, radial, and ulnar nerves; the C5-C6 zygapophyseal joint; the carpal tunnel; and the tibialis anterior muscle. Pain was assessed at baseline and 1-week follow-up, whereas PPT were assessed at baseline and immediately after and 1-week after intervention. Each received soft tissue mobilization and nerve slider neurodynamic technique directed at different anatomical sites of potential entrapment of the median nerve. Results: A decrease in the mean current intensity and worst level of hand pain (P b .01) was found 1 week after the treatment session (mean changes, 2.2 ± 1.1 points). A treatment effect for PPT levels over the C5-C6 zygapophyseal joint (P b .001) was found: PPT increased bilaterally 1 week after the intervention. No other significant changes in PPT levels were found (P N .195). Conclusions: The application of soft tissue mobilization and neurodynamic technique decreased the intensity of pain but did not change pressure pain sensitivity in this group of women with chronic CTS. (J Manipulative Physiol Ther 2012;35:420-427)

The purpose of this study is to describe differences in the presence of masseter and temporalis muscle trigger points (TrPs) and jaw opening between individuals with mechanical neck pain and healthy controls.Twenty patients with mechanical neck pain (60% women) without symptoms in the orofacial region, aged 20 to 37 years old, and 20 matched controls participated. Temporalis and masseter muscles were examined for the presence of TrPs in a blinded design. Trigger points were considered active if the subject recognized the pain as a familiar symptom, whereas the TrPs was considered latent if the pain was not recognized as a symptom. Jaw opening was assessed with a ruler.A greater number (P.001) of TrPs in the masticatory muscles were found in patients than in controls. None of the patients or healthy controls recognized the referred pain as familiar; thus, latent rather than active TrPs were found. The distribution of TrPs between groups was different for the masseter (left odds ratio [OR], 3.4; right OR, 8.1; P.001) and temporalis (left OR, 2.8; right OR, 5.7; P.001) muscles. Patients with neck pain had smaller jaw opening than controls (P.001). A negative correlation between active jaw opening and the number of TrPs within the masticatory muscles (r(s) = -0.6; P.001) was found: the greater the number of TrPs, the smaller the jaw opening.For the subjects in this study, those with mechanical chronic neck pain had more latent TrPs in the masticatory muscles and reduced jaw opening compared to healthy controls. These findings may suggest the spread of sensitization from the cervical segment to the trigeminal brain stem sensory nuclear complex.

Our aim was to investigate the relationship between Val158Met polymorphisms, headache, and pressure hypersensitivity in children with chronic tension-type headache (CTTH). A case-control study with blinded assessor was conducted. Seventy children with CTTH associated with pericranial tenderness and 70 healthy children participated. After amplifying Val158Met polymorphism by polymerase chain reactions, we assessed genotype frequencies and allele distributions. We classified children according to their Val158Met polymorphism: Val/Val, Val/Met, Met/Met. Pressure pain thresholds (PPT) were bilaterally assessed over the temporalis, upper trapezius, second metacarpal, and tibialis anterior muscles. The distribution of Val158Met genotypes was not significantly different (p = 0.335), between children with CTTH and healthy children, and between boys and girls (p = 0.872). Children with CTTH with the Met/Met genotype showed a longer headache history compared with those with Met/Val (p = 0.001) or Val/Val (p = 0.002) genotype. Children with CTTH with Met/Met genotype showed lower PPT over upper trapezius and temporalis muscles than children with CTTH with Met/Val or Val/Val genotype (p0.01). The Val158Met catechol-O-methyltransferase (COMT) polymorphism does not appear to be involved in predisposition to suffer from CTTH in children; nevertheless, this genetic factor may be involved in the phenotypic expression, as pressure hypersensitivity was greater in those CTTH children with the Met/Met genotype.

Stress can play an important role in development of cancer-related fatigue (CRF) by activating the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS), and altering the immune system. This study examined the influence of catechol-O-methyltransferase (COMT) Val158Met genotypes on salivary markers of HPA axis (cortisol), SNS (α-amylase) and immune (IgA) systems, as well as on CRF in breast cancer survivors (BCS). One-hundred BCS participated. After amplifying Val158Met COMT polymorphisms by polymerase chain reaction, three COMT genotypes were considered: Val/Val, Val/Met, Met/Met. Salivary cortisol, α-amylase activity, salivary flow rate, and IgA concentration were collected from non-stimulated saliva. CRF was assessed with the fatigue subscale of the Profile of Mood State (POMS) questionnaire. We found that BCS carrying Met/Met genotype reported higher cortisol concentration, α-amylase activity and greater CRF than those with Val/Met (P0.05) and Val/Val (P0.001) genotypes. No differences in salivary flow rate or IgA concentration (P0.20) were found. The results suggest that BCS carrying Met/Met genotype exhibit greater dysfunction of the HPA axis and SNS system associated with severe CRF. This study is important because it strives to understand biological factors that predispose some BCS to higher levels of CRF.

To investigate the differences in cortisol and melatonin concentrations between children with frequent episodic tension-type headache (FETTH) and healthy children.Forty-four children, 12 boys/32 girls (age: 9 ± 2 years) with FETTH associated to peri-cranial tenderness and 44 age- and sex- matched healthy children participated. Both salivary cortisol and melatonin concentrations were collected from non-stimulated saliva following standardized guidelines. A headache diary for 4 weeks was used for collecting intensity, frequency and duration of headache.No significant differences for cortisol (t = -0.431; p = 0.668), and melatonin (z = -1.564; p = 0.118) concentrations and salivary flow rate (z = -1.190; p = 0.234) were found between both groups. No significant effect of age or gender was found. In addition, no significant association between cortisol-melatonin concentrations and between cortisol-melatonin concentrations and headache clinical parameters were found.These results suggest that children with FETTH, at first instance, do not present deficits in the secretion of these cortisol and melatonin. Prospective longitudinal studies are needed to further elucidate the direction of current findings, particularly the synchronism of cortisol and melatonin and the course of the headache.

Objective The tudy was designed to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical[HPA] axis), immunoglobulin A (IgA) (immune system) concentrations and α-amylase (sympathetic nervous system [SNS]) activity between children with chronic tension-type headache (CTTH) and healthy children. Methods Thirty-six children, 10 boys and 26 girls (age: 9±2 years) with CTTH and 36 age - and sex-matched healthy children were recruited. Salivary cortisol, αm-amylase activity, salivary flow rate, IgA concentration and IgA rate were collected from non-stimulated saliva. A headache diary was used for collecting data on intensity, frequency and duration of headache for four weeks. Results Children with CTTH showed lower IgA concentration (p = .008) and IgA rate (p = .039), but not lower cortisol concentration (p = .447), salivary flow rate (p = .289) or α-amylase activity (p = .559), as compared to healthy children. Neither age (p < .582) nor gender (p < .227) influenced salivary markers. A significant association between the number of years with headache and IgA concentration (rs = - 0.385; p = .023) was found: the greater the number of years with headache, the lower the IgA concentration. Conclusions These results suggest that children with CTTH present with deficits in the immune system, but not dysfunction in the HPA axis or SNS. Future studies are needed to elucidate the direction of these relationships.

Case-control study with blinded examiner.To investigate if pressure pain sensitivity is related to specific nerve trunks in the upper extremity of patients with either unilateral lateral epicondylalgia (LE) or carpal tunnel syndrome (CTS).In the clinical setting, patients with LE tend to exhibit radial nerve trunk tenderness, whereas patients with CTS exhibit median nerve tenderness. No studies have investigated if specific nerve pressure pain hypersensitivity exists in patients with either LE or CTS.Sixteen women with unilateral LE (mean±SD age, 43±7 years), 17 women with unilateral CTS (43±6 years), and 17 healthy women (43±6 years) were included in this study. Pressure pain thresholds (PPT) were bilaterally assessed over the median, ulnar, and radial nerve trunks, as well as over the C5-6 zygapophyseal joints, by an examiner blinded to the subjectsí condition. A mixed-model analysis of variance was used to evaluate differences in PPT among groups (LE, CTS, or controls) and between sides (affected/nonaffected or dominant/nondominant).The individuals in both the LE and CTS groups demonstrated lower PPT bilaterally over the median (group, P.001; side, P=.437), radial (group, P.001; side, P=.556), and ulnar (group, P.001; side, P=.938) nerve trunks as compared to controls. Additionally, radial (P.001) and ulnar (P=.005) nerves were more sensitive bilaterally in patients with LE than in patients with CTS. The median nerve was more sensitive bilaterally in patients with CTS than patients with LE (P=.002). Lower PPT over the cervical spine (group, P.001; side, P=.233) were found bilaterally in both the LE and CTS groups. Further, patients with CTS exhibited lower cervical PPT than patients with LE (P.001). PPT was negatively correlated with both pain intensity and duration of symptoms in both the LE and CTS groups (P.001).Bilateral mechanical nerve pain hypersensitivity is related to specific and particular nerve trunks in women with either unilateral LE or CTS. Our results suggest the presence of central and peripheral sensitization mechanisms in individuals with either LE or CTS.

Introduction: The aim was to investigate bilateral, wide-spread pressure pain hyperalgesia in symptomatic (trigeminocervical) and non-symptomatic (pain-free distant) regions in children with frequent episodic tension-type headache (FETTH). Methods: Twenty-five children, 6 boys and 19 girls (mean age, 8.9 ± 1.8 years) with FETTH and 50 age- and sex-matched healthy children (12 boys, 38 girls; mean age: 8.8 ± 1.7 years) were recruited. Pressure pain thresholds (PPTs) were bilaterally assessed over temporalis muscle, upper trapezius muscle, second metacarpal and tibialis anterior muscles in a blinded design. Results: The results showed that PPT levels were significantly decreased bilaterally over the temporalis, upper trapezius and tibialis muscles, and the second metacarpal in children with FETTH as compared to controls (all sites, P s = −0.415; P = 0.045). Conclusions: The findings revealed bilateral, wide-spread pressure pain hypersensitivity in children with FETTH suggesting that wide-spread central sensitisation is involved in children with this headache pain condition.

BACKGROUND:The genetic influence of Val158Met polymorphisms, one of the potential genetic determinants for nociceptive processing, has not been previously investigated in women with carpal tunnel syndrome (CTS). OBJECTIVES:To investigate the association between the Val158Met polymorphism with CTS and to assess the relationship between the Val158Met polymorphism and the clinical outcomes and widespread pressure pain hypersensitivity in women with CTS. STUDY DESIGN:Case control study. SETTING:Neurology department at an urban hospital. METHOD:One hundred nine (n = 109) women (mean age: 47 ± 9 years) with a clinical and electrodiagnostic diagnosis of CTS and 109 matched healthy women participated. After amplifying the Val158Met polymorphism by polymerase chain reactions, rs4680 genotype frequencies and allele distributions were calculated. We classified individuals according to their Val158Met polymorphism: Val/Val, Val/Met, Met/Met. The intensity of the pain was assessed with a numeric rating scale (0-10) and disability was determined with the Boston Carpal Tunnel Questionnaire. Pressure pain thresholds were bilaterally assessed over median, radial, and ulnar nerve trunks; C5-C6 facet joints; and carpal tunnel and tibialis anterior muscles.Institutional Review Board: The study project was approved by the local human research committee (HUFA-12/14). All participants signed an informed consent prior to their inclusion in the study. RESULTS:The distribution of the 3 Val158Met genotypes (Val/Val, Val/Met, Met/Met) and alleles was not significantly different between women with CTS and healthy women (Chi-Square = 0.498; P = 0.780). Women with CTS carrying the Met/Met genotype showed higher levels of pain and disability than those with the Val/Met genotype (P < 0.01) and with the Val/Val genotype (P < 0.001). No differences in the years with pain (P = 0.954), age (P = 0.740), depression (P = 0.530), severity of CTS (P = 0.744) or presence of unilateral-bilateral symptoms (P = 0.279) existed depending on the rs4680 Val158Met genotype. No significant differences in widespread pressure pain sensitivity were observed in any of the points depending on the rs4680 Val158Met genotype (P > 0.315). LIMITATIONS:We only recruited women from a specialized department. CONCLUSION: Current results indicated that the Val158Met polymorphism seems not to be a risk factor for the development of CTS; however, it was associated with increased perception of pain and higher disability scores. Fisioterapia, Terapia Ocupacional, Rehabilitación y Medicina Física