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Background and aims Persistent tendinopathies were previously considered solely as peripheral conditions affecting the local tendinous tissue until quantitative sensory testing identified involvement of altered pain processing. In similar fashion, pain in patients with persistent plantar fasciopathy may also involve more than local tissue. The aim of this pilot study was to investigate potential differences in conditioned pain modulation and pressure and thermal pain thresholds, between individuals with PF and healthy pain-free controls, as a precursor to a larger-scale study. Methods We assessed 16 individuals with plantar fasciopathy and 11 pain-free controls. Plantar fasciopathy diagnosis was: palpation pain of the medial calcaneal tubercle or the proximal plantar fascia, duration ≥3 months, pain intensity ≥2/10, and ultrasound-measured plantar fascia thickness ≥4 mm. Quantitative sensory tests were performed locally at the plantar heel and remotely on the ipsilateral elbow. Assessments included pain thresholds for pressure, heat and cold, and conditioned pain modulation measured as change in local resting pressure pain threshold with cold water hand immersion. Participants rated pain intensity at pain threshold. Additionally, the area and distribution of plantar fasciopathy pain was drawn on a digital body chart of the lower limbs. Descriptive analyses were performed and between-group differences/effects expressed as standardised mean differences (d). Results There was no conditioned pain modulation difference between participants with plantar fasciopathy and controls (d = 0.1). Largest effects were on local pressure pain threshold and reported pain intensity on pressure pain threshold (d > 1.8) followed by pain intensity for heat and cold pain thresholds (d = 0.3-1.5). According to the digital body chart, pain area extended beyond the plantar heel. Conclusions The unlikelihood of a difference in conditioned pain modulation yet a pain area extending beyond the plantar heel provide a basis for exploring altered pain processing in a larger-scale study. Implications This was the first study to investigate the presence of altered pain processing in individuals with plantar fasciopathy using a conditioned pain modulation paradigm and thermal pain thresholds. We found no indication of an altered pain processing based on these measures, however, patients rated pain higher on thresholds compared to controls which may be important to clinical practice and warrants further exploration in the future.

Asunto(s)

Dolor Crónico/fisiopatología , Fascitis Plantar/fisiopatología , Hiperalgesia/fisiopatología , Umbral del Dolor/fisiología , Adulto , Estudios de Casos y Controles , Frío , Fascitis Plantar/complicaciones , Femenino , Humanos , Hiperalgesia/complicaciones , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Proyectos Piloto , Encuestas y Cuestionarios

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OBJECTIVE: To evaluate, in vivo, the impact of ongoing chronic migraine (CM) attacks on the endogenous µ-opioid neurotransmission. BACKGROUND: CM is associated with cognitive-emotional dysfunction. CM is commonly associated with frequent acute medication use, including opioids. METHODS: We scanned 15 migraine patients during the spontaneous headache attack (ictal phase): 7 individuals with CM and 8 with episodic migraine (EM), as well as 7 healthy controls (HC), using positron emission tomography (PET) with the selective µ-opioid receptor (µOR) radiotracer [11C]carfentanil. Migraineurs were scanned in two paradigms, one with thermal pain threshold challenge applied to the site of the headache, and one without thermal challenge. Multivariable analysis was performed between the µ-opioid receptor availability and the clinical data. RESULTS: µOR availability, measured with [11C]carfentanil nondisplaceable binding potential (BPND), in the left thalamus (P-value = 0.005) and left caudate (P-value = 0.003) were decreased in CM patients with thermal pain threshold during the ictal phase relative to HC. Lower µOR BPND in the right parahippocampal region (P-value = 0.001) and right amygdala (P-value = 0.002) were seen in CM relative to EM patients. Lower µOR BPND values indicate either a decrease in µOR concentration or an increase in endogenous µ-opioid release in CM patients. In the right amygdala, 71% of the overall variance in µOR BPND levels was explained by the type of migraine (CM vs. EM: partial-R2 = 0.47, P-value<0.001, Cohen's effect size d = 2.6SD), the severity of the attack (pain area and intensity number summation [P.A.I.N.S.]: partial-R2 = 0.16, P-value = 0.031), and the thermal pain threshold (allodynia: partial-R2 = 0.08). CONCLUSIONS: Increased endogenous µ-opioid receptor-mediated neurotransmission is seen in the limbic system of CM patients, especially in right amygdala, which is highly modulated by the attack frequency, pain severity, and sensitivity. This study demonstrates for the first time the negative impact of chronification and exacerbation of headache attacks on the endogenous µ-opioid mechanisms of migraine patients. ClinicalTrials.gov identifier: NCT03004313.

Asunto(s)

Amígdala del Cerebelo/metabolismo , Trastornos Migrañosos/metabolismo , Trastornos Migrañosos/fisiopatología , Nocicepción/fisiología , Umbral del Dolor/fisiología , Giro Parahipocampal/metabolismo , Receptores Opioides mu/metabolismo , Adulto , Amígdala del Cerebelo/diagnóstico por imagen , Analgésicos Opioides/farmacocinética , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/metabolismo , Enfermedad Crónica , Femenino , Fentanilo/análogos & derivados , Fentanilo/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/diagnóstico por imagen , Giro Parahipocampal/diagnóstico por imagen , Estimulación Física , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Índice de Severidad de la Enfermedad , Tálamo/diagnóstico por imagen , Tálamo/metabolismo , Adulto Joven

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Although the majority of mobile phone (MP) users do not attribute adverse effects on health or well-being to MP-emitted radiofrequency (RF) electromagnetic fields (EMFs), the exponential increase in the number of RF devices necessitates continuing research aimed at the objective investigation of such concerns. Here we investigated the effects of acute exposure from Long Term Evolution (LTE) MP EMFs on thermal pain threshold in healthy young adults. We use a protocol that was validated in a previous study in a capsaicin-induced hyperalgesia model and was also successfully used to show that exposure from an RF source mimicking a Universal Mobile Telecommunications System (UMTS) MP led to mildly stronger desensitization to repeated noxious thermal stimulation relative to the sham condition. Using the same experimental design, we did not find any effects of LTE exposure on thermal pain threshold. The present results, contrary to previous evidence obtained with the UMTS modulation, are likely to originate from placebo/nocebo effects and are unrelated to the brief acute LTE EMF exposure itself. The fact that this is dissimilar to our previous results on UMTS exposure implies that RF modulations might differentially affect pain perception and points to the necessity of further research on the topic.

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Teléfono Celular , Campos Electromagnéticos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Nocicepción , Umbral del Dolor , Ondas de Radio/efectos adversos , Adulto , Método Doble Ciego , Femenino , Voluntarios Sanos , Humanos , Masculino , Adulto Joven

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We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord. Minocycline treatment, however, accelerated the decreased conduction velocity of sciatic nerve and suppressed Notch-1expression and activity in diabetic rats. Similar to DAPT treatment, minocycline administration also prolonged thermal withdrawal latency (TWL) and increase mechanical withdrawal threshold (MWT) in diabetic rats in response to heat or mechanical stimulation via inhibition the expression and the activity of Notch-1 in spinal cord. Combination of DAPT and minocycline further inhibited Notch-1 receptor signaling and reduce neuropathic pain exhibited as improved TWL and MWT. Our study revealed a novel mechanism of Notch-1 receptor inhibition in spinal cord induced by minocycline administration, and suggested that the combination of minocycline and DAPT has the potential to treat DNP.

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Neuropatías Diabéticas/tratamiento farmacológico , Minociclina/uso terapéutico , Receptores Notch/metabolismo , Transducción de Señal , Médula Espinal/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/patología , Neuropatías Diabéticas/fisiopatología , Dipéptidos/farmacología , Glucosa/metabolismo , Minociclina/administración & dosificación , Minociclina/farmacología , Conducción Nerviosa/efectos de los fármacos , Ratas Sprague-Dawley , Nervio Sural/efectos de los fármacos , Nervio Sural/fisiopatología

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Exercise acutely reduces pain sensitivity, termed exercise-induced hypoalgesia (EIH). The mechanisms underlying EIH remain unclear. Caffeine, a non-specific adenosine receptor antagonist has been shown to attenuate EIH in animals-suggesting the involvement of the adenosinergic system. This pilot study investigated the effects of caffeine on pain sensitivity following cycling exercise in college-aged men. Pressure pain threshold (PPT) and thermal pain threshold (TPT) were assessed in thirteen low caffeine consuming men prior to ingestion of a counter-balanced 5mg·kg(-1) dose of caffeine or a placebo (Pre), 60min following ingestion (Post-In), and then following a 15min bout of cycling exercise (Post-Ex) at an intensity eliciting a quadriceps muscle pain rating of 3 out of 10. Nine of the men completed follow-up testing which was identical except that the exercise consisted of 10min of cycling eliciting a pain rating of 5 out of 10. Caffeine had no effect compared to placebo on PPT (p≥0.15) or TPT (p≥0.41) 60min following ingestion and following exercise. PPT increased from 599±176kPa to 648±202kPa (p=0.009) and from 578±217kPa to 666±278kPa (p=0.01) following 15 and 10min of cycling, respectively. TPT increased from 46.2±2.9°C to 46.8±2.6°C (p=0.008) following the 15min exercise bout, but did not change (46.4±3.6°C vs. 46.8±3.3°C; p=0.24) following the shorter, higher intensity exercise bout. The results from this study indicate cycling exercise reduces pain sensitivity, especially to pressure stimuli. Caffeine ingestion did not alter the EIH response-suggesting adenosine may not play a prominent role in the EIH response in humans.

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Cafeína/metabolismo , Estimulantes del Sistema Nervioso Central/metabolismo , Ejercicio Físico , Hipoestesia/tratamiento farmacológico , Hipoestesia/etiología , Adolescente , Adulto , Análisis de Varianza , Cafeína/uso terapéutico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Calor/efectos adversos , Humanos , Masculino , Umbral del Dolor/fisiología , Estimulación Física/efectos adversos , Proyectos Piloto , Factores de Tiempo , Adulto Joven

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Objective To investigate the role of astrocytes activation in post herpetic neuralgia (PHN). Methods The kunming mice (20-25 g) were used in this study. Resiniferatoxin was injected into the peritoneal cavity.Immunofuorescence was used to detect the activation of astrocytes , mechanical paw withdrawal threshold (MWT)and thermal withdrawal latency (TWL) were used to assay the mechanical allodynia and thermal hyperalgesia, respectively. Fluorocitrate, an inhibitor of astrocytes was intrathecally (i.t.) or intraperitonealy (i. p.) injected into the mice. Results Compared with the vehicle group, MWT was decreased, and TWL was increased significantly in the RTX group. Pre-treatments of fluorocitrate (Fc, i.t.,or i.p.) inhibited the decrease of MWT. Conclusion The activation of astrocytes mediates the post herpetic neuralgia.

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BACKGROUND: Repetitive magnetic stimulation (rMS) modulates thermal somatosensory function at both low (0.2-1.0Hz) and high (5.0-20.0Hz) frequencies within the conditioned dermatome. However the effects of 1Hz and 20Hz cervical (C6-C7) rMS on thermosensory thresholds and contact heat evoked potentials (CHEPs) tested within local and remote spinal dermatomes are not known. METHODS: Thirty healthy subjects participated in the study. Warm and cold detection threshold, heat and cold pain thresholds, and Cz/Fz CHEPs were evaluated within the C6, T10 and extrasegmental V3 control dermatome, before and after random assignment of subjects to sham, 1 or 20Hz C6-C7 rMS. RESULTS: Following both 1 and 20Hz cervical rMS, warm detection threshold increased within the local C6 dermatome. Furthermore 1Hz cervical rMS increased warm detection threshold within the remote T10 dermatome, but not within the V3-trigeminal control area. Cervical rMS failed to modulate cold detection threshold, heat and cold pain threshold or Cz/Fz CHEP amplitude from the dermatomal test sites. CONCLUSION: Both 1 and 20Hz cervical rMS modulated warm detection threshold within the locally conditioned C6 dermatome. The concomitant increase in warm detection threshold within the T10 dermatome following 1Hz rMS provides evidence for remote neuromodulation of thermosensory function via intraspinal control mechanisms.

Asunto(s)

Calor , Imanes , Umbral Sensorial , Piel/inervación , Médula Espinal/fisiología , Adulto , Frío , Potenciales Evocados Somatosensoriales , Femenino , Humanos , Masculino , Dolor/fisiopatología , Umbral del Dolor , Estimulación Física , Núcleo Espinal del Trigémino/fisiología