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BACKGROUND: Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients' quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. PURPOSE: Investigate the effects of tDCS on pain and physical function in patients with KOA. METHODS: Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. RESULTS: Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. CONCLUSIONS: The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.
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Osteoartritis de la Rodilla , Dimensión del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Osteoartritis de la Rodilla/terapia , Osteoartritis de la Rodilla/fisiopatología , Resultado del Tratamiento , Dimensión del Dolor/métodos , Artralgia/terapia , Artralgia/diagnóstico , Artralgia/fisiopatología , Artralgia/etiología , Umbral del Dolor , Manejo del Dolor/métodos , Calidad de Vida , Articulación de la Rodilla/fisiopatologíaRESUMEN
The aim of this study was to compare the acute effects of compression contrast therapy (CT) and dry needling therapy (DN) on muscle tension (MT), muscle strength (Fmax), pressure pain threshold (PPT), and perfusion (PU) following fatigue of forearm muscles (e.g., flexor carpi radialis) in combat sports athletes. A single-blind randomized controlled trial was employed. Participants first underwent muscle fatigue induction, which involved sustaining an isometric handgrip at 60% of their maximum voluntary contraction in 5-second cycles. This was followed by exposure to one of the regenerative therapies. Forty-five participants were randomly assigned to one of three groups: CT/DN (n = 15), CT/ShDN (n = 15), and ShCT/DN (n = 15). The sham condition (Sh) involved a simulated version of the technique. Measurements were taken at four time points: (i) at rest; (ii) immediately after exercise that led to a state of fatigue; (iii) 5 minutes after therapy (PostTh5min); and (iv) 24 hours after therapy (PostTh24h). Each participant was exposed to one experimental condition and one control condition, thereby undergoing evaluation in two sessions. Significant differences between groups were found in MT during the PostTh5min (p = 0.005), as well as in PU during the PostTh5min (p < 0.001) and PU during the PostTh24h (p < 0.001). All groups showed significant improvements at 5 minutes post-therapy compared to immediately post-muscle fatigue. As conclusions, CT/DN seems to be significantly better for enhancing MT and PU after 5 minutes of muscle fatigue induction. Using either CT, DN, or both combined is recommended to enhance the recovery of muscle functionality and properties, favoring recovery and potentially speeding up performance enhancement.
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Punción Seca , Antebrazo , Contracción Isométrica , Fatiga Muscular , Músculo Esquelético , Umbral del Dolor , Humanos , Método Simple Ciego , Fatiga Muscular/fisiología , Adulto Joven , Masculino , Músculo Esquelético/fisiología , Umbral del Dolor/fisiología , Punción Seca/métodos , Adulto , Fuerza de la Mano/fisiología , Fuerza Muscular/fisiología , Artes Marciales/fisiología , FemeninoRESUMEN
Recent studies have shown that the extramuscular connective tissue (ECT) is thickened and stiffened in delayed onset muscle soreness (DOMS). However, contrarily to the normal population, severe DOMS is rare in athletes or highly trained individuals. The present randomized, controlled trial therefore aimed to investigate pain as well as microcirculation and stiffness of the ECT and the erector spinae muscle following submaximal eccentric trunk extension exercise not causing DOMS. The effect of manual treatment by a therapist (myofascial release; MFR) on these parameters was to be studied. Trained healthy participants (n = 21; 31.3 ± 9.6 years; > 4 h exercise per week) performed submaximal eccentric exercise of the trunk extensors. One group was manually treated (n = 11), while the other group (n = 10) received placebo treatment with sham laser therapy. Stiffness of the ECT and the erector spinae muscle (shear wave elastography), microcirculation (white light and laser Doppler spectroscopy), palpation pain (100 mm visual analogue scale, VAS) and pressure pain threshold (indentometry, PPT) were assessed before (t0), 24 h (t24) and 48 h (t48) after conditions. Erector spinae muscle stiffness increased after eccentric exercise from t0 to t24 (0.875 m/s) and from t0 to t48 (0.869 m/s). After MFR, erector spinae muscle stiffness decreased in contrast to placebo treatment at t24 (-0.66 m/s), while ECT stiffness remained unchanged. Oxygen saturation increased (17-20.93%) and relative haemoglobin decreased (-9.1 - -12.76 AU) after eccentric exercise and MFR differed from placebo treatment at t48 (-3.71 AU). PPT differed after MFR from placebo treatment at t48 (20.69 N/mm), while VAS remained unchanged. Multiple linear regression showed that ECT stiffness and group membership predicted erector spinae muscle stiffness. MFR could have a positive effect on pain, microcirculation and muscle stiffness after submaximal eccentric exercise, suggesting better recovery, which needs to be confirmed by future work.
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Ejercicio Físico , Microcirculación , Mialgia , Humanos , Microcirculación/fisiología , Adulto , Masculino , Femenino , Mialgia/terapia , Mialgia/fisiopatología , Ejercicio Físico/fisiología , Manipulaciones Musculoesqueléticas/métodos , Región Lumbosacra/irrigación sanguínea , Región Lumbosacra/fisiología , Adulto Joven , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/fisiología , Umbral del Dolor/fisiología , Torso/fisiología , Dimensión del Dolor , Músculos Paraespinales/fisiología , Músculos Paraespinales/diagnóstico por imagen , Músculos Paraespinales/irrigación sanguíneaRESUMEN
C-C Motif Chemokine Ligand 17 (CCL17) is a chemokine that binds and signals through the G-protein coupled CC-chemokine receptor 4 and has been implicated in the development of inflammatory and arthritic pain. GSK3858279 is a high-affinity, first-in-class, monoclonal antibody, binding specifically to CCL17 and inhibiting downstream signaling. In this phase I, randomized, single-center, double-blind, placebo-controlled, three-period, incomplete-block crossover study (NCT04114656), the analgesic effects and safety of intravenous GSK3858279 were assessed in a battery of evoked acute pain assessments on healthy, adult (aged ≥18 years), male participants. Participants were randomized 1:1 to receive either one placebo (0.9% w/v NaCl) dose followed by two GSK3858279 doses (PAA treatment sequence), or one GSK3858279 dose followed by two placebo doses (APP treatment sequence). The co-primary end points were ultraviolet B heat pain detection threshold (°C), cold pressor time to pain tolerance threshold (PTT, sec), and electrical PTT (mA, single stimulus). Twenty-one participants were enrolled (PAA = 11; APP = 10). Mean age (standard deviation) was 29.3 (7.9) years for PAA, 31.1 (7.7) years for APP. No significant differences were observed in the analgesic effect between GSK3858279 and placebo for any end point. Exposure to GSK3858279 was similar between Period 1 (APP sequence), and Periods 2 and 3 (PAA sequence), with some GSK3858279 carry-over. Changes in serum CCL17 levels were consistent with the expected GSK3858279 activity. All drug-related adverse events were mild in intensity and caused no discontinuations. The absence of an efficacy signal in this acute pain model does not preclude efficacy in chronic pain states.
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Quimiocina CCL17 , Estudios Cruzados , Voluntarios Sanos , Dimensión del Dolor , Humanos , Masculino , Adulto , Método Doble Ciego , Quimiocina CCL17/sangre , Adulto Joven , Umbral del Dolor/efectos de los fármacos , Persona de Mediana Edad , Analgésicos/administración & dosificación , Analgésicos/efectos adversos , Administración Intravenosa , Dolor/tratamiento farmacológico , Dolor/diagnóstico , Dolor/etiologíaRESUMEN
When designing footwear products, designers and kinesiologists usually factor in plantar surface pressure, motion capture data, and subjective comfort evaluations. However, these factors alone are not sufficient to guide the design of truly comfortable shoes. Pressure pain threshold (PPT) is a parameter that establishes a connection between psychological quantities and physical quantities. The purpose of this study was to construct a high-precision PPT map of the whole foot. Overall, 20 participants were included in this study, and an electronic, mechanical algometer was used to apply constant pressure to the participants' feet. A MATLAB graphical user interface was developed to simplify the data-collecting process and generate visual representations of the data. Finally, several high-precision unisex, different sex, and dominant side PPT maps were generated. The findings revealed that the foot dorsum area and the medial foot region exhibited the lowest PPTs (indicative of high sensitivity). Notably, the foot dorsum area near the toes displayed the highest pain sensitivity (indicative of the lowest PPT), while the plantar area demonstrated comparatively lower pain sensitivity. The heel area exhibited the lowest pain sensitivity. Simultaneously, the study observed that women's feet exhibited lower pain thresholds than men's. In the future, it is imperative to delve deeper into the correlation between short-term pain sensitivity and the daily, long-term exercise state, as well as other physiological data. This exploration will contribute to a more nuanced guide for footwear comfort design.
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Pie , Umbral del Dolor , Presión , Zapatos , Humanos , Masculino , Femenino , Pie/fisiología , Adulto Joven , Adulto , Factores Sexuales , Diseño de Equipo , Dimensión del Dolor/métodosRESUMEN
Homeostasis models posit that nonsuicidal self-injury (NSSI) serves, in part, to upregulate the endogenous opioid system in order to compensate for an opioid deficiency. A few studies have demonstrated lower basal levels of beta-endorphin (BE), an endogenous opioid, in individuals with NSSI. However, longitudinal studies are missing. Hence, the present study aimed to investigate the longitudinal associations between NSSI, comorbid psychopathology (i.e., borderline personality disorder and depressive symptoms), pain sensitivity and basal BE levels in adolescents with NSSI. N = 53 adolescents with NSSI disorder undergoing specialized treatment participated in baseline and one-year follow-up assessments. BE was measured in plasma; pain sensitivity was assessed with a heat pain stimulation paradigm. Associations between BE and change in NSSI, borderline personality disorder and depressive symptoms as well as pain sensitivity were examined using negative binomial and linear regression analyses. We found that an increase in basal BE was significantly associated with a decrease in depressive symptoms. No associations between BE and NSSI, borderline personality disorder symptoms or pain sensitivity were observed. Our findings may confirm a role of plasma BE in the etiology of depressive symptoms but challenge current models of endogenous opioid homeostasis in NSSI.
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Trastorno de Personalidad Limítrofe , Comorbilidad , Depresión , Conducta Autodestructiva , betaendorfina , Humanos , betaendorfina/sangre , Femenino , Masculino , Adolescente , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/sangre , Trastorno de Personalidad Limítrofe/epidemiología , Trastorno de Personalidad Limítrofe/sangre , Estudios Longitudinales , Depresión/epidemiología , Depresión/sangre , Umbral del Dolor/fisiologíaRESUMEN
Schizophrenia is a complex neuropsychiatric disorder with positive, negative, and cognitive symptoms. In rats, sub-chronic administration of ketamine is used for the induction of schizophrenia model. Increased locomotor activity is one of the most important features of psychotic-like symptoms in rodents. On the other hand, risperidone is a potent antipsychotic medication that is approved for the treatment of schizophrenia and bipolar disorder. In the present research, we aimed to investigate the effect of sub-chronic treatment of ketamine on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) expression level in the prefrontal cortex. Also, we assessed the efficacy of risperidone on cognitive and behavioral impairments induced by ketamine. Possible sex differences were also measured. Ketamine was intraperitoneally injected at the dose of 30 mg/kg for five consecutive days. Risperidone was also intraperitoneally injected at the dose of 2 mg/kg. Novel object recognition memory, pain threshold, locomotor activity, rearing behavior, and BDNF level were evaluated. The results showed that ketamine injection for five consecutive days impaired the acquisition of long-term recognition memory and decreased BDNF level in the prefrontal cortex in both sexes. Also, it decreased pain threshold in females, increased rearing behavior in males, and induced hyperlocomotion with greater effect in females. On the other hand, risperidone restored or attenuated the effect of ketamine on all the behavioral effects and BDNF level. In conclusion, we suggested that there were sex differences in the effects of ketamine on pain perception, locomotion, and rearing behavior in a rat model of schizophrenia.
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Factor Neurotrófico Derivado del Encéfalo , Modelos Animales de Enfermedad , Ketamina , Corteza Prefrontal , Risperidona , Esquizofrenia , Caracteres Sexuales , Animales , Ketamina/farmacología , Ketamina/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/inducido químicamente , Esquizofrenia/fisiopatología , Masculino , Femenino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Risperidona/farmacología , Risperidona/administración & dosificación , Ratas , Antipsicóticos/farmacología , Antipsicóticos/administración & dosificación , Reconocimiento en Psicología/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Ratas Wistar , Conducta Animal/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Actividad Motora/efectos de los fármacosRESUMEN
Minipigs are widely used in biomedical research for translational studies. However, information about pain elicited by experimental procedures is lacking. Non-invasive methods as quantitative sensory testing and conditioned pain modulation are particularly attractive. Our overarching aim was to explore and refine these methods for assessing post-operative pain in minipigs after myocardial infarction. As first step, we aimed at defining mechanical and thermal thresholds in healthy adults Göttingen Minipigs, evaluating their reliability, and testing their modifications after the application of a conditioning stimulus. Thresholds were assessed at different body sites before and after a painful conditioning stimulus (CS) (cuffed tourniquet) and sham CS (uncuffed tourniquet) in eleven animals. Thresholds' reliability was assessed using interclass correlation coefficient (ICC). The effect of the CS was assessed calculating absolute change, percentage change of the thresholds and standard error of measurement. Baseline mechanical thresholds (Newton) were: left hindlimb 81 [73; 81]; left forearm 81 [72.1; 81]; right forearm 81 [76; 81]; left chest 80.5 [68; 81]; right chest 81 [76.5; 81]; left neck 81 [70.3; 81]; right neck 74.8 [62.3; 80.5]. Reliability of mechanical thresholds was good at right chest (ICC = 0.835) and moderate at left chest (ICC = 0.591), left hindlimb (ICC = 0.606) and left neck (ICC = 0.518). Thermal thresholds showed poor reliability in all the tested sites. A modulatory effect was present at right chest, but it was seen when both a painful CS and a sham CS was applied. Minipigs tendentially showed a pro-nociceptive profile (i.e. conditioning pain facilitation). The measured thresholds are a reference for future trials in this species. Mechanical thresholds showed to be more reliable and, therefore, more useful, than thermal ones. The pain facilitation might be explained by the phenomenon of stress induced hyperalgesia, but this finding needs to be further investigated with a stricter paradigm.
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Umbral del Dolor , Porcinos Enanos , Animales , Porcinos , Umbral del Dolor/fisiología , Masculino , Femenino , Reproducibilidad de los Resultados , Dimensión del Dolor/métodos , Dolor Postoperatorio/fisiopatología , Infarto del Miocardio/fisiopatologíaRESUMEN
ABSTRACT: Rodents and human studies indicate that the hippocampus, a brain region necessary for memory processing, responds to noxious stimuli. However, the hippocampus has yet to be considered a key brain region directly involved in the human pain experience. One approach to answer this question is to perform quantitative sensory testing on patients with hippocampal damage-ie, medial temporal lobe epilepsy. Some case studies and case series have performed such tests in a handful of patients with various types of epilepsy and have reported mixed results. Here, we aimed to determine whether mechanical pain sensitivity was altered in patients diagnosed with temporal lobe epilepsy. We first investigated whether mechanical pain sensitivity in patients with temporal lobe epilepsy differs from that of healthy individuals. Next, in patients with temporal lobe epilepsy, we evaluated whether the degree of pain sensitivity is associated with the degree of hippocampal integrity. Structural integrity was based on hippocampal volume, and functional integrity was based on verbal and visuospatial memory scores. Our findings show that patients with temporal lobe epilepsy have lower mechanical pain sensitivity than healthy individuals. Only left hippocampal volume was positively associated with mechanical pain sensitivity-the greater the hippocampal damage, the lower the sensitivity to mechanical pain. Hippocampal measures of functional integrity were not significantly associated with mechanical pain sensitivity, suggesting that the mechanisms of hippocampal pain processing may be different than its memory functions. Future studies are necessary to determine the mechanisms of pain processing in the hippocampus.
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Epilepsia del Lóbulo Temporal , Hipocampo , Imagen por Resonancia Magnética , Umbral del Dolor , Humanos , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Hipocampo/fisiopatología , Masculino , Femenino , Adulto , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/complicaciones , Umbral del Dolor/fisiología , Persona de Mediana Edad , Dimensión del Dolor/métodos , Adulto Joven , Hiperalgesia/fisiopatología , Hiperalgesia/patología , Dolor/fisiopatología , Dolor/patología , Dolor/diagnóstico por imagen , Estimulación FísicaRESUMEN
Experimental pain studies have revealed inter-individual variations in pain perception that are influenced by age, sex, and country of origin. This study aimed to explore the age and sex differences in pressure pain thresholds within the Iranian general population. To assess the pressure pain thresholds, a handheld pressure algometer was applied bilaterally to the middle fingers of both hands. The participants also completed the short form of the McGill Pain Questionnaire to provide a clinical pain rating. This cross-sectional study included 1610 adult subjects (54.96% female, mean age 40.13â ±â 10.18 years). The findings indicated that females generally exhibited lower pain thresholds than males when assessing pain detection and tolerance parameters (Pâ <â .001). Females also demonstrated a significant lower pressure thresholds and clinical pain ratings compared with men (Pâ <â .001). Additionally, significant differences were observed between age groups in terms of pain detection and tolerance thresholds (Pâ =â .02 and Pâ =â .03, respectively). However, the interaction between sex and age was not significant. No significant differences in pain detection thresholds were observed between the right and left hand (Pâ =â .11). This study underscores the potential utility of algometry as a valuable tool for objectifying pain in the Iranian population.
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Dimensión del Dolor , Umbral del Dolor , Humanos , Adulto , Femenino , Masculino , Umbral del Dolor/fisiología , Estudios Transversales , Persona de Mediana Edad , Factores de Edad , Dimensión del Dolor/métodos , Factores Sexuales , Irán , Presión , Adulto Joven , AncianoRESUMEN
BACKGROUND: Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. METHODS: Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. RESULTS: We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. CONCLUSION: These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.
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Núcleos Talámicos Ventrales , Animales , Ratones , Masculino , Neuralgia del Trigémino/fisiopatología , Neuralgia/fisiopatología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Optogenética , Umbral del Dolor/fisiologíaRESUMEN
While rodents are used extensively for studying pain, there is a lack of reported direct comparisons of thermal and mechanical pain testing methods in rats of different genetic backgrounds. Understanding the range of interindividual variability of withdrawal thresholds and thermal latencies based on these testing methods and/or genetic background is important for appropriate experimental design. Testing was performed in two common rat genetic backgrounds: outbred Sprague-Dawley (SD) and inbred Fischer 344 (F344). Male and female, 10- to 14-wk-old F344 and SD rats were used to assess withdrawal thresholds in 3 different modalities: the Randall-Selitto test (RST), Hargreaves test (HT), and tail flick test (TFT). The RST was performed by using an operator-controlled handheld instrument to generate a noxious pressure stimulus to the left hind paw. The HT and the TFT used an electronically controlled light source to deliver a noxious thermal stimulus to the left hind paw or tail tip, respectively. Rats of each sex and genetic background underwent one type of test on day 0 and day 7. Withdrawal thresholds and thermal latencies were compared among tests. No significant differences were observed. Our findings can serve as a guide for researchers considering these nociceptive tests for their experiments.
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Calor , Dimensión del Dolor , Umbral del Dolor , Ratas Endogámicas F344 , Ratas Sprague-Dawley , Animales , Femenino , Masculino , Ratas , Dimensión del Dolor/métodos , Dimensión del Dolor/veterinaria , Dolor/fisiopatologíaRESUMEN
The multidimensional etiology of pain may explain the beneficial effects of regular physical activity, as evidenced by increased pain tolerance. Physically active people find it easier to exert themselves, which enables them to increase their physical activity, which in turn leads to a reduction in pain. However, no study investigated the physical activity and exercise tests as modulators of pain sensitivity in pregnant women. Therefore, this study aimed to investigate the changes in pain perception in pregnant women during pregnancy, with a particular interest in the effects of maximal progressive exercise test (CPET) and self-performed physical activity (PA). Thirty-one women with an uncomplicated singleton pregnancy (aged 23-41 years; M = 31.29, SD = 4.18) were invited to participate in pain sensitivity measurements before and after CPET twice during pregnancy (with an 8-week break). We found that pregnant women had a significantly lower pain threshold after a maximal exercise test than before, regardless of whether the test was performed in the second or third trimester of pregnancy. This effect was most pronounced in women with low levels of physical activity. Second, women with high physical activity had higher pain tolerance than women with moderate and low physical activity. In addition, physical activity levels predicted changes in pain tolerance over the course of pregnancy, with negative changes in women with low physical activity and positive changes in women with moderate physical activity. Finally, these associations were not reflected in differences in the subjective pain experience.
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Prueba de Esfuerzo , Ejercicio Físico , Umbral del Dolor , Humanos , Femenino , Embarazo , Adulto , Umbral del Dolor/fisiología , Prueba de Esfuerzo/métodos , Adulto Joven , Ejercicio Físico/fisiología , Dimensión del Dolor/métodos , Dolor/fisiopatologíaRESUMEN
Sexual dimorphism among mammals includes variations in the pain threshold. These differences are influenced by hormonal fluctuations in females during the estrous and menstrual cycles of rodents and humans, respectively. These physiological conditions display various phases, including proestrus and diestrus in rodents and follicular and luteal phases in humans, distinctly characterized by varying estrogen levels. In this study, we evaluated the capsaicin responses in male and female mice at different estrous cycle phases, using two murine acute pain models. Our findings indicate that the capsaicin-induced pain threshold was lower in the proestrus phase than in the other three phases in both pain assays. We also found that male mice exhibited a higher pain threshold than females in the proestrus phase, although it was similar to females in the other cycle phases. We also assessed the mRNA and protein levels of TRPV1 in the dorsal root and trigeminal ganglia of mice. Our results showed higher TRPV1 protein levels during proestrus compared to diestrus and male mice. Unexpectedly, we observed that the diestrus phase was associated with higher TRPV1 mRNA levels than those in both proestrus and male mice. These results underscore the hormonal influence on TRPV1 expression regulation and highlight the role of sex steroids in capsaicin-induced pain.
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Capsaicina , Dolor , Canales Catiónicos TRPV , Animales , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Capsaicina/farmacología , Masculino , Femenino , Ratones , Dolor/metabolismo , Dolor/genética , Hormonas Esteroides Gonadales/metabolismo , Ciclo Estral/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Ganglio del Trigémino/metabolismo , Ganglio del Trigémino/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Caracteres Sexuales , ARN Mensajero/metabolismo , ARN Mensajero/genéticaRESUMEN
BACKGROUND: Chronic alcohol drinking increases the risk of alcohol use disorders, causing various neurological disorders. However, the impact of different ethanol levels on a spectrum of behaviors during chronic drinking remains unclear. In this study, we established an intermittent access to ethanol in a two-bottle choice (IA2BC) procedure to explore the dose-dependent effects of ethanol on the behavioral performance of C57BL/6â¯J mice. METHODS: Adult male C57BL/6â¯J mice were provided voluntary access to different ethanol concentrations (0â¯%, 5â¯%, 10â¯%, and 20â¯% ethanol) under a 12-week IA2BC paradigm. A battery of behavioral tests was administered to assess alterations in pain threshold, anxiety-like behaviors, locomotor activity, motor coordination, and cognition. Ethanol consumption and preference were monitored during each session. Moreover, the liver, heart, and lung tissues were examined using pathological microscopy. RESULTS: The average (standard deviation) ethanol consumption of mice under the IA2BC paradigm increased dose-dependently to 5.1 (0.2), 8.7 (0.7), and 15.9 (0.8) g/kg/24â¯h with 5â¯%, 10â¯%, and 20â¯% ethanol, respectively. However, there is no significant difference in ethanol preference among all the ethanol groups. Chronic ethanol drinking caused hyperalgesia, cognitive impairment, and motor incoordination, but caused no changes in body temperature, locomotor activity, or anxiety-like behaviors. Minor histopathological alterations in the liver were detected; however, no major abnormal pathology was observed in the heart or lungs. CONCLUSION: These findings clarify the link between ethanol dosage and behavioral changes in mice over a 12-week IA2BC paradigm, thereby bridging the knowledge gap regarding the effects of chronic ethanol drinking on neurological disorders.
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Consumo de Bebidas Alcohólicas , Ansiedad , Conducta Animal , Etanol , Ratones Endogámicos C57BL , Animales , Masculino , Etanol/farmacología , Etanol/administración & dosificación , Ratones , Ansiedad/inducido químicamente , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Umbral del Dolor/efectos de los fármacos , Conducta de Elección/efectos de los fármacos , Conducta de Elección/fisiología , Depresores del Sistema Nervioso Central/farmacología , Depresores del Sistema Nervioso Central/administración & dosificación , Locomoción/efectos de los fármacosRESUMEN
BACKGROUND: Pressure pain threshold (PPT) measurements require standardised verbal instructional cues to ensure that the increasing pressure is stopped at the correct time consistently. This study aimed to compare how PPT values and their test-retest reliability were affected by different instructional cues. METHODS: At two separate sessions, two PPT measurements were taken at the anterior knee for each of four different instructional cues: the cue of the German Neuropathic Research Network instructions ('DFNS'), the point where pressure first feels uncomfortable ('Uncomfortable'), 3/10 on the numerical pain rating scale ('3NPRS'), and where pain relates to an image from the pictorial-enhanced NPRS scale ('Pictorial'). Linear mixed modeling was used to quantify differences between pairs of instructional cues. Test-retest reliability was estimated using intraclass correlation coefficients (ICC[2,1] and ICC[2,k]). RESULTS: Twenty participants were recruited. The cue resulting in greatest PPT value was DFNS (394.32 kPa, 95%CI [286.32 to 543.06]), followed by Pictorial (342.49 kPa, 95%CI [248.68 to 471.68]), then Uncomfortable (311.85 kPa, 95%CI [226.43 to 429.48]), and lastly 3NPRS (289.78 kPa, 95%CI [210.41 to 399.09]). Five of six pairwise contrasts were statistically significant. Regardless of the cues, the point estimates of ICC (2,1) ranged from 0.80 to 0.86, and the ICC (2,k) values ranged from 0.89 to 0.93. No statistically significant differences were found between any pairwise contrasts of reliability indices. CONCLUSION: Words matter when instructing people when to stop testing in pressure algometry. Clinicians should use the same instructional cue when assessing pain thresholds to ensure reliability.
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Señales (Psicología) , Dimensión del Dolor , Umbral del Dolor , Humanos , Masculino , Femenino , Umbral del Dolor/fisiología , Adulto , Reproducibilidad de los Resultados , Voluntarios Sanos , Presión , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: The present study aimed to investigate whether subjective and objective measures of pain habituation can be used as potential markers for central sensitization across various chronic pain patients. METHODS: Two blocks of contact-heat stimuli were applied to a non-painful area in 93 chronic pain patients (low back pain, neuropathic pain, and complex regional pain syndrome) and 60 healthy controls (HC). Habituation of pain ratings, contact-heat evoked potentials (CHEP), and sympathetic skin responses (SSR) was measured. RESULTS: There was no significant difference in any measure of pain habituation between patients and HC. Even patients with apparent clinical signs of central sensitization showed no reduced pain habituation. However, prolonged baseline CHEP and SSR latencies (stimulation block 1) were found in patients compared to HC (CHEP: Δ-latency = 23 ms, p = 0.012; SSR: Δ-latency = 100 ms, p = 0.022). CONCLUSION: Given the performed multimodal neurophysiological testing protocol, we provide evidence indicating that pain habituation may be preserved in patients with chronic pain and thereby be of limited use as a sensitive marker for central sensitization. These results are discussed within the framework of the complex interactions between pro- and antinociceptive mechanism as well as methodological issues. The prolonged latencies of CHEP and SSR after stimulation in non-painful areas may indicate subclinical changes in the integrity of thermo-nociceptive afferents, or a shift towards antinociceptive activity. This shift could potentially affect the relay of ascending signals. SIGNIFICANCE: Our findings challenge the prevailing views in the literature and may encourage further investigations into the peripheral and central components of pain habituation, using advanced multimodal neurophysiological techniques.
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Dolor Crónico , Habituación Psicofisiológica , Humanos , Masculino , Dolor Crónico/fisiopatología , Femenino , Habituación Psicofisiológica/fisiología , Persona de Mediana Edad , Adulto , Anciano , Dimensión del Dolor/métodos , Neuralgia/fisiopatología , Calor , Umbral del Dolor/fisiología , Sensibilización del Sistema Nervioso Central/fisiologíaRESUMEN
Pain is a crucial protective mechanism for the body. It alerts us to potential tissue damage or injury and promotes the avoidance of harmful stimuli. Injury-induced inflammation and tissue damage lead to pain sensitization, which amplifies responses to subsequent noxious stimuli even after an initial primary injury has recovered. This phenomenon, commonly referred to as hyperalgesic priming, was investigated in male and female mice to determine whether it is specific to the site of previous injury. We used 10µl of 50 % Freund's complete adjuvant (CFA) administered to the left hind paw as a model of peripheral injury. Both male and female mice exhibited robust site-specific mechanical hypersensitivity after CFA, which resolved within one-week post-injection. After injury resolution, only male CFA-primed mice showed enhanced and prolonged mechanical sensitivity in response to a chemical challenge or a single 0.5 mA electric footshock. Among CFA-primed male mice, shock-induced mechanical hypersensitivity was expressed in both the left (previously injured) and the right (uninjured) hind paws, suggesting a pivotal role for altered centralized processes in the expression of pain sensitization. These findings indicate that pain history regulates sensory responses to subsequent mechanical and chemical pain stimuli in a sex-specific manner-foot-shock-induced hyperalgesic priming expression among male mice generalized beyond the initial injury site.
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Adyuvante de Freund , Hiperalgesia , Inflamación , Animales , Masculino , Femenino , Hiperalgesia/fisiopatología , Hiperalgesia/etiología , Inflamación/inducido químicamente , Ratones , Modelos Animales de Enfermedad , Dolor/etiología , Dolor/fisiopatología , Ratones Endogámicos C57BL , Umbral del Dolor/fisiología , Caracteres Sexuales , Factores Sexuales , Dimensión del DolorRESUMEN
CONTEXT: We designed this study to investigate the effects of 2 myofascial release techniques, Instrument-Assisted Soft Tissue Mobilization (IASTM) and Foam Roller (FR), on pain, joint range of motion, and muscle strength in athletes suffering from iliotibial band (ITB) tightness. DESIGN: A total of 39 male soccer players were enrolled in this randomized controlled trial, aged between 18 and 23 years who were divided into 3 groups: Only Exercise, IASTM, and FR. METHODS: All participants performed daily strengthening and stretching exercises, while 1 group added IASTM, and the other added FR to the exercise program. We evaluated ITB tightness with the Ober test and an inclinometer, pressure pain threshold, using an algometer, and we evaluated muscle strength with the Cybex Norm Isokinetic device. RESULTS: We found that all 3 groups exhibited an increase in the Ober inclination angle after the interventions (P = .001), but the increase was greater for participants in the IASTM and FR groups, compared with exercise alone. Additionally, both the IASTM and FR groups displayed an increased pressure pain threshold (P = .001), whereas there was no change in the control group. Moreover, while all 3 groups experienced an increase in hip muscle strength (P = .001), the IASTM and FR groups exhibited a greater increase compared with exercise alone (P = .001). CONCLUSIONS: Based on these findings, exercise improves pain, range of motion, and muscle strength in athletes with ITB tightness, and IASTM, and FR techniques enhanced exercise effects but did not differ from one another. While our study demonstrated that both IASTM and FR techniques significantly enhance the benefits of exercise for athletes with ITB tightness, further research could delve into the long-term effects of these interventions.
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Fuerza Muscular , Rango del Movimiento Articular , Humanos , Masculino , Rango del Movimiento Articular/fisiología , Fuerza Muscular/fisiología , Adulto Joven , Adolescente , Fútbol/fisiología , Atletas , Umbral del Dolor/fisiologíaRESUMEN
BACKGROUND: Migraine is a neurological disorder characterized by complex, widespread, and sudden attacks with an unclear pathogenesis, particularly in chronic migraine (CM). Specific brain regions, including the insula, amygdala, thalamus, and cingulate, medial prefrontal, and anterior cingulate cortex, are commonly activated by pain stimuli in patients with CM and animal models. This study employs fluorescence microscopy optical sectioning tomography (fMOST) technology and AAV-PHP.eB whole-brain expression to map activation patterns of brain regions in CM mice, thus enhancing the understanding of CM pathogenesis and suggesting potential treatment targets. METHODS: By repeatedly administering nitroglycerin (NTG) to induce migraine-like pain in mice, a chronic migraine model (CMM) was established. Olcegepant (OLC) was then used as treatment and its effects on mechanical pain hypersensitivity and brain region activation were observed. All mice underwent mechanical withdrawal threshold, light-aversive, and elevated plus maze tests. Viral injections were administered to the mice one month prior to modelling, and brain samples were collected 2 h after the final NTG/vehicle control injection for whole-brain imaging using fMOST. RESULTS: In the NTG-induced CMM, mechanical pain threshold decreased, photophobia, and anxiety-like behavior were observed, and OLC was found to improve these manifestations. fMOST whole-brain imaging results suggest that the isocortex-cerebral cortex plate region, including somatomotor areas (MO), somatosensory areas (SS), and main olfactory bulb (MOB), appears to be the most sensitive area of activation in CM (P < 0.05). Other brain regions such as the inferior colliculus (IC) and intermediate reticular nucleus (IRN) were also exhibited significant activation (P < 0.05). The improvement in migraine-like symptoms observed with OLC treatment may be related to its effects on these brain regions, particularly SS, MO, ansiform lobule (AN), IC, spinal nucleus of the trigeminal, caudal part (Sp5c), IRN, and parvicellular reticular nucleus (PARN) (P < 0.05). CONCLUSIONS: fMOST whole-brain imaging reveals c-Fos + cells in numerous brain regions. OLC improves migraine-like symptoms by modulating brain activity in some brain regions. This study demonstrates the activation of the specific brain areas in NTG-induced CMM and suggests some regions as a potential treatment mechanism according to OLC.