Long-Term Environmental Methylmercury Exposure Is Associated with Peripheral Neuropathy and Cognitive Impairment among an Amazon Indigenous Population.

Widespread contamination of the Amazon basin with mercury has been reported to occur since at least the mid-80s due to heavy gold mining activity. Although initial studies have indicated that this may lead to deleterious neurological consequences to the indigenous populations living in the region, further research is needed to better characterize the neurological burden of such long-term exposure. With this aim, a cross-sectional exploratory study has been conducted with the Yanomami indigenous population residing in a northern Amazon region. All participants underwent a structured interview; detailed neurological examination, including assessment for cognitive, motor, coordination, and sensory functions; and laboratorial testing for serum hemoglobin, blood glucose, and methylmercury levels in hair samples. This study enrolled 154 individuals of 30.9 ± 16.8 years of age, of which 56.1% were female. Mean methylmercury levels in hair were 3.9 ± 1.7 µg/g. Methylmercury levels in hair > 6.0 µg/g were found in 10.3%. Among participants with hair methylmercury levels ≥ 6.0 µg/g, the prevalences of peripheral neuropathy and reduced cognitive performance were, respectively, 78.8% (95%CI 15-177%, p = 0.010) and 95.9% (95%CI 16-230.8%, p = 0.012) higher than those of individuals with lower levels. These results suggest that chronic mercury exposure may lead to significant and potentially irreversible neurotoxicity to Yanomami population living in the northern Amazon basin.

Assessment of Human Fetuses Undergoing Acute Pain: Validation of the Fetal-7 Scale.

Improvements in fetal ultrasound have allowed for the diagnosis and treatment of fetal diseases in the uterus, often through surgery. However, little attention has been drawn to the assessment of fetal pain. To address this gap, a fetal pain scoring system, known as the Fetal-7 scale, was developed. The present study is a full validation of the Fetal-7 scale. The validation involved 2 steps: 1) 4 fetuses with the indication of surgery were evaluated in 3 conditions perioperatively: acute pain, rest, and under loud sound stimulation. Facial expressions were assessed by 30 raters using screenshots from 4D high-definition ultrasound films; 2) assessment of sensitivity and specificity of the Fetal-7 scale in 54 healthy fetuses and 2 fetuses undergoing acute pain after preoperative anesthetic intramuscular injection. There was high internal consistency with Cronbach's alpha (α) of .99. Intrarater reliability of the Fetal-7 scale (test-retest) calculated by intraclass correlation coefficient was .95, and inter-rater reliability was .99. The scale accurately differentiated between healthy fetuses at rest and those experiencing acute pain (sensitivity of 100% and specificity of 94.4%). The Fetal-7 scale is a valid tool for assessing acute pain-related behavior in third-trimester fetuses and may be of value in guiding analgesic procedures efficacy in these patients. Further research is warranted to explore the presence of postoperative pain in fetuses and its effects after birth. PERSPECTIVE: Recordings with 3-dimensional ultrasound of human fetuses undergoing preoperative anesthetic injections revealed complex facial expressions during acute pain, similar to those collected in newborns. This study presented the validation process and cut-off value of the Fetal-7 scale, paving the way for the study of pain before birth in humans.

Motor corticospinal excitability abnormalities differ between distinct chronic low back pain syndromes.

OBJECTIVES: It is not known whether cortical plastic changes reported in low-back pain (LBP) are present in all etiologies of LBP. Here we report on the assessment of patients with three LBP conditions: non-specific-LBP (ns-LBP), failed back surgery syndrome (FBSS), and sciatica (Sc). METHODS: Patients underwent a standardized assessment of clinical pain, conditioned pain modulation (CPM), and measures of motor evoked potential (MEPs)-based motor corticospinal excitability (CE) by transcranial magnetic stimulation, including short interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Comparisons were also made with normative data from sex- and age-matched healthy volunteers. RESULTS: 60 patients (42 women, 55.1±9.1 years old) with LBP were included (20 in each group). Pain intensity was higher in patients with neuropathic pain [FBSS (6.8±1.3), and Sc (6.4±1.4)] than in those with ns-LBP (4.7±1.0, P<0.001). The same was shown for pain interference (5.9±2.0, 5.9±1.8, 3.2±1.9, P<0.001), disability (16.4±3.3, 16.3±4.3, 10.4±4.3, P<0.001), and catastrophism (31.1±12.3, 33.0±10.4, 17.4±10.7, P<0.001) scores for FBSS, Sc, and ns-LBP groups, respectively. Patients with neuropathic pain (FBSS, Sc) had lower CPM (-14.8±1.9, -14.1±16.7, respectively) compared to ns-LBP (-25.4±16.6; P<0.02). 80.0% of the FBSS group had defective ICF compared to the other two groups (52.5% for ns-LBP, P=0.025 and 52.5% for Sc, P=0.046). MEPs (140%-rest motor threshold) were low in 50.0% of patients in the FBSS group compared to 20.0% of ns-LBP (P=0.018) and 15.0% of Sc (P=0.001) groups. Higher MEPs were correlated with mood scores (r=0.489), and with lower neuropathic pain symptom scores(r=-0.415) in FBSS. CONCLUSIONS: Different types of LBP were associated with different clinical, CPM and CE profiles, which were not uniquely related to the presence of neuropathic pain. These results highlight the need to further characterize patients with LBP in psychophysics and cortical neurophysiology studies.

Pain paths among post-COVID-19 condition subjects: A prospective cross-sectional study with in-person evaluation.

BACKGROUND: New-onset chronic pain has been acknowledged as part of the post-COVID-19 condition. However, available fine-grained data about its clinical phenotype, trajectories and main associated characteristics remain scarce. We described the distinct temporal evolutions of post-COVID-19 pain and their epidemiological and phenotypical features. METHODS: A prospective cross-sectional study enrolled post-COVID-19 condition patients (i.e. who had persisting COVID-19-related symptoms over 30 days since their first positive laboratory test), whose COVID-19 diagnosis had been supported by RT-PCR of oral/nasopharyngeal swab or serology. They underwent in-person evaluations with a structured interview, pain and quality-of-life-related questionnaires and thorough physical examination. Chronic pain (CP) and probable neuropathic pain (NP) were defined according to IASP criteria. RESULTS: The present study included 226 individuals, 177 (78.3%) of whom presented over 3 months since their first COVID-19 symptom. New-onset pain occurred in 170 (75.2%) participants and was chronic in 116 (68.2%). A chronic course was associated with COVID-19-related hospitalization, new-onset fatigue, lower cognitive performance, motor and thermal sensory deficits, mood and sleep impairments and overall lower quality-of-life levels. Probable NP occurred in only 7.6% new-onset pain patients, and was associated with pain chronification, new-onset fatigue, motor and thermal sensory deficits, mechanical allodynia and lower rates of SARS-CoV-2 vaccination. Previous CP was reported by 86 (38.1%) individuals and had aggravated after the infection in 66 (76.7%) of them, which was associated with orthostatic hypotension. CONCLUSIONS: Post-COVID pain phenomena follow different paths, which are associated with specific clinical and epidemiological features, and possibly distinct underlying mechanisms, prognostic and therapeutic implications. SIGNIFICANCE: COVID-19-related pain usually follows a chronic course and is non-neuropathic. Its possible courses and phenotypes are associated with distinct clinical and epidemiological features. This suggests differing underlying mechanisms, which may have significant prognostic and therapeutic implications.

Trayectorias del dolor en sujetos con afección post-COVID-19: estudio prospectivo y transversal con evaluación presencial / Pain paths among post-COVID-19 condition subjects: a prospective cross-sectional study with in-person evaluation

Antecedentes: El dolor crónico de nueva aparición se considera que forma parte de la condición o afección post-COVID-19. Sin embargo, los datos detallados existentes sobre el fenotipo clínico, las trayectorias y las principales características asociadas siguen siendo escasos. Describimos las distintas evoluciones temporales del dolor post-COVID-19 y sus rasgos epidemiológicos y fenotípicos. Métodos: Estudio prospectivo y transversal de pacientes con afección post-COVID-19 (es decir, con síntomas persistentes relacionados con la COVID-19 durante 30 días desde la primera prueba positiva de laboratorio) cuyo diagnóstico de COVID-19 estuviera basado en la RT-PCR de un frotis oral/nasofaríngeo o una serología. Se sometieron a evaluaciones presenciales mediante una entrevista estructurada, cuestionarios de dolor y calidad de vida y una exploración física exhaustiva. El dolor crónico (DC) y el dolor neuropático (DN) probablemente se definieron conforme a los criterios IASP.Resultados: El presente estudio incluyó 226 individuos, 177 (78,3 %) de los cuales se presentaron pasados más de 3 meses desde el primer síntoma de COVID-19. Tenían dolor de nueva aparición 170 (75,2 %) de los participantes y dolor crónico 116 (68,2 %). El curso crónico se asociaba a hospitalización por COVID-19, fatiga de nueva aparición, menor rendimiento cognitivo, déficits motores y sensitivos térmicos, alteraciones del ánimo y el sueño, y niveles generalmente inferiores de calidad de vida. El DN probable afectaba a solo el 7,6 % de los pacientes con dolor de nueva aparición y se asociaba a cronificación del dolor, fatiga de nueva aparición, déficits motores y de sensación térmica, alodinia mecánica y tasas menores de vacunación frente al SARS-CoV-2. Referían DC previo 86 (38,1 %) individuos, y este había empeorado tras la infección en 66 (76,7 %) de ellos, lo que se asociaba a hipotensión ortostática...(AU)

Background: New-onset chronic pain has been acknowledged as part of the post-COVID-19 condition. However, available fine-grained data about its clinical phenotype, trajectories and main associated characteristics remain scarce. We described the distinct temporal evolutions of post-COVID-19 pain and their epidemiological and phenotypical features.Methods: A prospective cross-sectional study enrolled post-COVID-19 condition patients (i.e. who had persisting COVID-19-related symptoms over 30 days since their first positive laboratory test), whose COVID-19 diagnosis had been supported by RT-PCR of oral/nasopharyngeal swab or serology. They underwent in-person evaluations with a structured interview, pain and quality-of-life-related questionnaires and thorough physical examination. Chronic pain (CP) and probable neuropathic pain (NP) were defined according to IASP criteria.Results: The present study included 226 individuals, 177 (78.3 %) of whom presented over 3 months since their first COVID-19 symptom. Newonset pain occurred in 170 (75.2 %) participants and was chronic in 116 (68.2 %). A chronic course was associated with COVID-19-related hospitalization, new-onset fatigue, lower cognitive performance, motor and thermal sensory deficits, mood and sleep impairments and overall lower quality-of-life levels. Probable NP occurred in only 7.6 % new-onset pain patients, and was associated with pain chronification, new-onset fatigue, motor and thermal sensory deficits, mechanical allodynia and lower rates of SARSCoV-2 vaccination. Previous CP was reported by 86 (38.1 %) individuals and had aggravated after the infection in 66 (76.7 %) of them, which was associated with orthostatic hypotension.Conclusions: Post-COVID pain phenomena follow different paths, which are associated with specific clinical and epidemiological features, and possibly distinct underlying mechanisms, prognostic and therapeutic implications...(AU)