Plantar vein thrombosis: an uncommon cause of plantar foot pain / Trombose venosa plantar: uma causa incomum de dor em região plantar

INTRODUCTION: Plantar vein thrombosis is a rare condition that can lead to pain, edema, and walking difficulties. It presents a series of predisposing factors, such as recent surgeries, the use of oral contraceptives, and local trauma, among others. Imaging tests are essential for the right diagnosis, and ultrasonography is the modality of choice. As for treatment, there is no consensus in the literature. REPORT: Case of a 30-year-old patient who sought emergency medical care complaining of sudden severe pain in the plantar region of her right foot with walking difficulties. On physical examination, hyperalgesia was observed in the plantar region, irradiating to the calf, associated with swelling. Color Doppler imaging identified an acute thrombus in the medial plantar vein. Rivaroxaban was initially prescribed and replaced by acetylsalicylic acid after three months. The treatment was effective, and the patient was discharged after 11 months. CONCLUSION: Plantar vein thrombosis is a rare condition and has a wide range of differential diagnoses so physicians must maintain a high level of clinical suspicion. To improve diagnosis and treatment, it would be necessary to include plantar veins in the investigation protocols of patients suspected of having Deep Venous Thrombosis, besides additional clinical research for improving treatment.

INTRODUÇÃO: A trombose de veias plantares é uma condição rara que pode cursar com dor, edema e dificuldade na deambulação. Apresenta uma série de fatores predisponentes, como cirurgias recentes, uso de anticoncepcional oral, trauma local, entre outros. A realização de exame de imagem é essencial para o diagnóstico, sendo a ultrassonografia a modalidade de escolha. Quanto ao tratamento, não há consenso na literatura. RELATO: Relatamos o caso de uma paciente de 30 anos que procurou atendimento médico de urgência com queixa de dor de forte intensidade, súbita, em região plantar do pé direito com dificuldade de deambulação. Ao exame físico, observou-se hiperalgesia em região plantar com irradiação para panturrilha, associada a empastamento da mesma. O ecodoppler colorido identificou trombo agudo em veia plantar medial. Optou-se pela prescrição de rivaroxabana, a qual foi substituída por ácido acetilsalicílico após três meses. A paciente evoluiu bem e recebeu alta do tratamento após 11 meses. CONCLUSÃO: A trombose de veias plantares é rara e tem uma alta gama de diagnósticos diferenciais, de forma que o profissional médico deve manter um alto nível de suspeição clínica. Para aperfeiçoar seu diagnóstico e tratamento, seria necessária a inclusão das veias plantares aos protocolos de investigação de pacientes com suspeita de Trombose Venosa Profunda, e pesquisas clínicas que elucidassem os melhores métodos terapêuticos.

Ketamine pour la gestion de la douleur post hystérectomie au CHU Professeur Zafisaona Gabriel Mahajanga Madagascar / Ketamine for the management of post-hysterectomy pain at the Professor Zafisaona Gabriel University Hospital, Mahajanga, Madagascar

Une analgésie multimodale est incontournable pour la prise en charge de la douleur post opératoire. L'objectif de notre étude était de montrer l'intérêt de l'utilisation de la kétamine, avec son effet analgésique, parmi les différentes molécules disponibles. Méthodes : Il s'agit d'une étude prospective monocentrique en simple aveugle de 31 cas d'hystérectomie programmée sur une période de 6 mois (mai­octobre 2016) divisée en deux groupes soumis au même protocole anesthésique : un groupe recevant de la kétamine en bolus suivi d'une perfusion continue peropératoire et sur les premières 24 heures et un groupe contrôle sans kétamine. En période post opératoire les deux groupes bénéficient d'une analgésie multimodale. L'analyse statistique a été faite par le test de Student. Résultats : Les scores de douleur diffèrent peu en moyenne sur les 24 heures de surveillance, tandis qu'une épargne morphinique importante est notée dans le groupe kétamine de l'ordre de 50% avec une valeur de p<0,001 fortement significative. A côté nous n'avons constaté aucun effet indésirable notable. Conclusion : L'adjonction de kétamine même de brève durée dans la prise en charge de la douleur post opératoire a permis de baisser considérablement la consommation morphinique

Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain / 神经科学通报·英文版

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.

Allodynia in cervical polyradiculopathy due to low-voltage electrical burn injury: A case report

@#Neuropathic pain has been described following an electrical injury, whether as an immediate response or a late-onset sequela. There is much information on high-voltage injuries in literature due to its dramatic presentation, but limited studies on low-voltage injuries. However, low-voltage injuries can be as diverse and may have symptoms varying from minimal cutaneous involvement to full-thickness injury. Significant injuries may result from multiple factors, including prolonged duration of exposure and a higher amount of current transmitted. We illustrate an atypical presentation of a low-voltage injury in a 17-year-old female. The patient had a low voltage electrical injury with no cutaneous burn noted on the affected extremity. She initially presented with allodynia, which seemed disproportionate to the clinical findings expected in a low-voltage injury. The patient underwent an electrodiagnostic study, which showed cervical polyradiculopathy (C5, C6, C7 polyradiculopathy) and neuromusculoskeletal ultrasonology, which showed enlarged right C5 nerve root. Medical management, daily physical and occupational therapies, and psychological management, were instituted, which resulted in significant improvement of the patient’s pain level and functional status. We describe the importance of the multimodal approach (medical and rehabilitation) in managing this atypical case.

Comparative study of cold hyperalgesia and mechanical allodynia in two animal models of neuropathic pain: different etiologies and distinct pathophysiological mechanisms

Abstract Neuropathic pain (NP) affects more than 8% of the global population. The proposed action of the transient receptor potential ankyrin 1 (TRPA1) as a mechanosensor and the characterization of the transient receptor potential melastatin 8 (TRPM8) as a cold thermosensor raises the question of whether these receptors are implicated in NP. Our study aimed to evaluate the involvement of TRPA1 and TRPM8 in cold and mechanical signal transduction to obtain a comparative view in rat models of streptozotocin-induced diabetes (STZ) and chronic constriction injury of the sciatic nerve (CCI). The electronic von Frey test showed that STZ rats presented mechanical allodynia that was first evidenced on the 14th day after diabetes confirmation, and four days after CCI. This phenomenon was reduced by the intraplantar (ipl) administration of a TRPA1 receptor antagonist (HC-030031; 40 µL/300 µg/paw) in both NP models. Only CCI rats displayed cold hyperalgesia based on the cold plate test. The pharmacological blocking of TRPA1 through the injection of the antagonist attenuated cold hyperalgesia in this NP model. STZ animals showed a reduction in the number of flinches induced by the intraplantar injection of mustard oil (MO; TRPA1 agonist; 0.1%/50 µL/paw), or intraplantar injection of menthol (MT; TRPM8 agonist; 0.5% and 1%/50 µL/paw). The response induced by the ipl administration of MT (1%/50 µL/paw) was significantly different between the CCI and SHAM groups. Together, these data suggest a different pattern in nociceptive behavior associated with different models of NP, suggesting a variant involvement of TRPA1 and TRPM8 in both conditions

Alleviation of neuropathic pain by trazodone in rats

Abstract Neuropathic pain is generally characterised by an abnormal sensation (dysesthesia), an increased response to painful stimuli (hyperalgesia), and pain in response to a stimulus that does not normally provoke pain (allodynia). The present study was designed to investigate the effect of trazodone (5mg/kg and 10mg/kg) on peripheral neuropathic pain induced by partial sciatic nerve ligation in rats. Mechanical hyperalgesia, cold allodynia and thermal hyperalgesia were assessed by performing the pinprick, acetone, and hot plate tests, respectively. Biochemically, lipid peroxidation level and total calcium levels were measured. However, trazodone administration (5 and 10 mg/ kg i.p.) for 21days significantly diminished partial sciatic nerve ligation-induced neuropathic pain along with areduction in oxidative stress and calcium levels. The results of the present study suggest that trazodone is effective in attenuating partial sciatic nerve ligation-inducedpainful neuropathic states, which may be attributed to decreased oxidative stress and calcium levels.

Neuroprotective role of Tinospora cordifolia extract in streptozotocin induced neuropathic pain

Abstract Diabetic Neuropathy (DN) is one of the prevailing micro vascular complications of diabetes which can be characterized by neuropathic pain. Streptozotocin (STZ) induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy. STZ injection leads to neurotoxicity of peripheral nerves that leads to development of Peripheral Diabetic Neuropathy in rat model. The present study was aimed at exploring the protective role of Tinospora cordifolia extract in STZ induced neurotoxicity and evaluating mechanisms responsible for attenuating neuropathic pain. Neuropathic pain markers like hyperalgesia, allodynia and motor deficits were assessed before STZ injection and after the treatment with 250 mg/kg and 500 mg/kg dose of Tinospora cordifolia. Oxidative stress markers, NGF expression in sciatic nerve were observed after seven weeks treatment. Our results demonstrated that seven weeks treatment with Tinospora cordifolia leaf extract significantly relieved thermal hyperalgesia and allodynia by increasing the antioxidant enzyme levels, decreasing the lipid peroxidation and by increasing the Nerve growth factor (NGF) expression in diabetic rat sciatic nerves. Our findings highlighted the beneficial effects of oral administration of Tinospora cordifolia extract in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and by inducing NGF m RNA in sciatic nerves.

Protective Mechanism of Electroacupuncture on Peripheral Neurotoxicity Induced by Oxaliplatin in Rats / 中国结合医学杂志

OBJECTIVE@#To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats.@*METHODS@#Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot.@*RESULTS@#EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01).@*CONCLUSION@#EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

Behavioral-electrophysiological observation of the involvement of dopamine D1 receptor of the rat anterior cingulate cortex in the regulation of pain-related emotion / 生理学报

The present study was aimed to explore the involvement of dopamine D1 receptor of the anterior cingulate cortex (ACC) in the regulation of chronic inflammatory pain-related emotion. On the first day, the rats were acclimated to the environment and the baseline indices were measured. On the second day, the rats were administered with the dopamine D1 receptor antagonist SCH-23390 or agonist SKF38393 in the ACC, and then they were subcutaneously injected with complete Freund's adjuvant (CFA, 0.08 mL) in the left hind paw to establish conditioned place avoidance (CPA) response after pairing with specific environment. On the third day, the CPA response and the firing frequency of ACC neurons were observed synchronously, and the open-field behavior, mechanical pain behavior and paw withdrawal latency (PWL) tests were also observed subsequently. In other experiments, rats were given subcutaneous injection of normal saline (NS) on the left hind paw after SCH-23390 or SKF-38393 was administered in the ACC, and then the same observations were performed. The results showed that: (1) Compared with the control group, the PWL and mechanical pain thresholds of rats injected with CFA on the left hind paw were significantly decreased (P < 0.05); (2) The residence time of rats injected with CFA in the "pain environment" and open field center was significantly shortened (P < 0.05); (3) Pre-injection of antagonist SCH-23390 in ACC (10 μg) alleviated the anxiety-like negative behavior response induced by CFA (P < 0.05) and reversed CFA-induced increases of discharge frequency of ACC neurons (P < 0.05); (4) Pre-injection of agonist SKF-38393 in the ACC (10 μg) induced CPA-like behavioral response in rats injected with NS in the left hind paw, and increased the firing frequency of ACC neurons (P < 0.05); (5) Immunofluorescence detection showed that dopamine D1 receptor and NMDA receptor were co-expressed in the same neuron. These results suggest that inhibition of dopamine D1 receptor in ACC can alleviate the negative emotional response induced by persistent pain.

Referred Somatic Hyperalgesia Mediates Cardiac Regulation by the Activation of Sympathetic Nerves in a Rat Model of Myocardial Ischemia / 神经科学通报·英文版

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8-T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α2 adrenoceptor (α2AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α2AR-mediated sympathetic-sensory coupling.

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats / 神经科学通报·英文版

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.

Hippocampus is involved in 17β-estradiol exacerbating experimental occlusal inter- ference-induced chronic masseter hyperalgesia in ovariectomized rats / 北京大学学报(医学版)

OBJECTIVE@#To investigate the influence of chronic masseter hyperalgesia induced by 17β-estradiol (E2) and experimental occlusal interference (EOI) on underlying mechanism in hippocampus of ovariectomized (OVX) rats.@*METHODS@#In the study, 32 OVX rats were randomly divided into 4 groups (8 rats/group): The control group was OVX group, and 0 μg/d E2 (vehicle) injection was started 7 d after OVX without EOI; in the experimental group (1) OVX + E2 group, 80 μg/d E2 injection was started 7 d after OVX without EOI; in the experimental group (2) OVX + EOI group, vehicle injection was started 7 d after OVX and EOI was applied 17 d after OVX; in the experimental group (3) OVX + E2 + EOI group, 80 μg/d E2 injection was started 7 d after OVX and EOI was applied 17 d after OVX. Bilateral masseter muscle mechanical withdrawal thresholds were measured before OVX, 7 days after OVX (before E2 injection), 17 days after OVX (10 days after E2 injection and before EOI) and 24 days after OVX (7 days after EOI). Immunofluorescence staining was used to reveal phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2)-positive neurons in CA3 of hippocampus. The protein expression of p-ERK1/2 in hippocampus was detected using Western Blot.@*RESULTS@#Compared with the control group [left side: (135.3±8.5) g, right side: (135.4±10.8) g], bilateral masseter muscle mechanical withdrawal thresholds of OVX+E2 group [left side: (113.3±5.6) g, right side: (112.5 ± 5.6) g] and OVX+EOI group [left side: (93.3±5.4) g, right side: 90.8±5.5) g] were decreased (P < 0.01). Bilateral masseter muscle mechanical withdrawal thresholds were significantly lower in OVX+E2+EOI group [left side: (81.2±6.2) g, right side: 79.8±7.7) g] than in the control, OVX+E2 and OVX+EOI groups (P < 0.05). The proportion of p-ERK1/2 positive neurons in the CA3 region of the hippocampus was increased in the control, OVX+E2, OVX+EOI and OVX+E2+EOI groups in turn, and the difference between the groups was statistically significant (P < 0.05). p-ERK1/2 protein expression was increased in the control, OVX+E2 and OVX+EOI groups in turn, but the difference was not statistically significant (P>0.05). p-ERK1/2 expression was significantly higher in OVX+E2+EOI group than in the other three groups (P < 0.05).@*CONCLUSION@#High concentration of E2 could exacerbated EOI-induced chronic masseter hyperalgesia in ovariectomized rats, and its central mechanism may be related to the upregulation of the phosphorylation of ERK1/2 in hippocampus.

Beneficial effects of octreotide in alcohol-induced neuropathic pain. Role of H 2S, BDNF, TNF-α and Nrf2

ABSTRACT Purpose To explore the role and molecular mechanisms of neuroprotective effects of octreotide in alcohol-induced neuropathic pain. Methods Male Wistar rats were employed and were administered a chronic ethanol diet containing 5% v/v alcohol for 28 days. The development of neuropathic pain was assessed using von Frey hair (mechanical allodynia), pinprick (mechanical hyperalgesia) and cold acetone drop tests (cold allodynia). The antinociceptive effects of octreotide (20 and 40 µg·kg-1) were assessed by its administration for 28 days in ethanol-treated rats. ANA-12 (0.25 and 0.50 mg·kg-1), brain-derived neurotrophic factor (BDNF) receptor blocker, was coadministered with octreotide. The sciatic nerve was isolated to assess the biochemical changes including hydrogen sulfide (H2S), cystathionine β synthase (CBS), cystathionine γ lyase (CSE), tumor necrosis factor-α (TNF-α), BDNF and nuclear factor erythroid 2-related factor 2 (Nrf2). Results Octreotide significantly attenuated chronic ethanol-induced neuropathic pain and it also restored the levels of H2S, CBS, CSE, BDNF, Nrf2 and decreased TNF-α levels. ANA-12 abolished the effects of octreotide on pain, TNF-α, BDNF, Nrf2 without any significant effects on H2S, CBS, CSE. Conclusions Octreotide may attenuate the behavioral manifestations of alcoholic neuropathic pain, which may be due to an increase in H2S, CBS, CSE, BDNF, Nrf2 and a decrease in neuroinflammation.

Effects of vitamin D administration on nociception and spinal cord pro-oxidant and antioxidant markers in a rat model of neuropathic pain

Reactive oxygen species (ROS) are involved in neuropathic pain, a complicated condition after nerve tissue lesion. Vitamin D appears to improve symptoms of pain and exhibits antioxidant properties. We investigated the effects of oral administration of vitamin D3, the active form of vitamin D, on nociception, the sciatic functional index (SFI), and spinal cord pro-oxidant and antioxidant markers in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. Vitamin D3 (500 IU/kg per day) attenuated the CCI-induced decrease in mechanical withdrawal threshold and thermal withdrawal latency (indicators of antinociception) and SFI. The vitamin prevented increased lipid hydroperoxide levels in injured sciatic nerve without change to total antioxidant capacity (TAC). Vitamin D3 prevented increased lipid hydroperoxide, superoxide anion generation (SAG), and hydrogen peroxide (H2O2) levels in the spinal cord, which were found in rats without treatment at 7 and 28 days post-CCI. A significant negative correlation was found between mechanical threshold and SAG and between mechanical threshold and H2O2 at day 7. Vitamin D3 also prevented decreased spinal cord total thiols content. There was an increase in TAC in the spinal cord of vitamin-treated CCI rats, compared to CCI rats without treatment only at 28 days. No significant changes were found in body weight and blood parameters of hepatic and renal function. These findings demonstrated, for first time, that vitamin D modulated pro-oxidant and antioxidant markers in the spinal cord. Since antinociception occurred in parallel with oxidative changes in the spinal cord, the oxidative changes may have contributed to vitamin D-induced antinociception.

GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus mediates nerve injury-induced neuropathic pain in rats / 生理学报

The present study was aimed to investigate the role of GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus (CSF-CN) in neuropathic pain. Intra-lateral ventricle injection of cholera toxin subunit B conjugated with horseradish peroxidase (CBHRP) was used to label the CSF-CN. Double-labeled immunofluorescent staining and Western blot were used to observe the expression of GluN2B and BDNF in the CSF-CN. Chronic constriction injury of sciatic nerve (CCI) rat model was used to duplicate the neuropathic pain. Pain behavior was scored to determine the analgesic effects of GluN2B antagonist Ro 25-6981 and BDNF neutralizing antibody on CCI rats. GluN2B and BDNF were expressed in the CSF-CN and their expression was up-regulated in CCI rats. Intra-lateral ventricle injection of GluN2B antagonist Ro 25-6981 or BDNF neutralizing antibody notably alleviated thermal hyperalgesia and mechanical allodynia in CCI rats. Moreover, the increased expression of BDNF protein in CCI rats was reversed by intra-lateral ventricle injection of Ro 25-6981. These results suggest that GluN2B and BDNF are expressed in the CSF-CN and alteration of GluN2B-BDNF pathway in the CSF-CN is involved in the modulation of the peripheral neuropathic pain.

Elemene Emulsion Injection Administration Reduces Neuropathic Pain by Inhibiting Astrocytic NDRG2 Expression within Spinal Dorsal Horn / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanisms underlying elemene-induced analgesia in rats with spared nerve injury (SNI).@*METHODS@#Sixty-five rats were equally divided into 5 groups using a random number table: naive group, sham group, SNI group, SNI + elemene (40 mg·kg@*RESULTS@#The SNI rat model exhibited a significant decrease in paw withdrawal threshold and exploratory behaviour in the EPM (P<0.05). Consecutive administration of elemene alleviated SNI-induced mechanical allodynia and anxiety in rats (P<0.05). Immunohistochemical data showed that elemene decreased SNI-induced upregulation of NDRG2 within the SDH (P<0.05). Double immunofluorescent staining data further showed that elemene decreased SNI-induced upregulation of the number of GFAP immunoreactive (-ir), NDRG-ir, and GFAP/NDRG2 double-labelled cells within the SDH (P<0.05). Immunoblotting data showed that elemene decreased SNI-induced upregulation of GFAP and NDRG2 within the SDH (P<0.05).@*CONCLUSION@#Elemene possibly alleviated neuropathic pain by downregulating the expression of NDRG2 in spinal astrocytes in a rat model of SNI.

Intervenção baseada em mindfulness reduz parâmetros de sensibilidade em mulheres com DTM dolorosa crônica / Mindfulness-based intervention reduces sensitivity parameters in women with chronic painful TMD / La intervención basada en la atención plena reduce los parámetros de sensibilidad en mujeres con TMD dolorosa crónica

OBJETIVO: analisar parâmetros clínicos sugestivos de sensibilização central em mulheres com disfunção temporomandibular dolorosa crônica antes e após uma intervenção baseada em mindfulness. MÉTODO: onze mulheres com idade entre 27 e 44 anos (36,36 ± 5,61), com diagnóstico de disfunções temporomandibulares dolorosa crônica (Diagnostic Criteria for Temporomandibular Disorders), participaram do estudo. A hiperalgesia, a alodinia e o limiar de dor à pressão foram avaliados em pontos trigeminais e extra-trigeminais antes e após a intervenção baseada em mindfulness, bem como a aplicação do questionário Mindful Attention Awareness Scale. O programa de mindfulness de 8 semanas foi oferecido às participantes do estudo, com base no protocolo Mindfulness Trainings International, em sessões semanais de 2 horas e uma sessão de 4 horas. RESULTADOS: houve redução significativa da alodinia, da hiperalgesia e aumento do limiar de dor à pressão, além de aumento significativo do nível de atenção plena (p < 0,05) enquanto marcador de efetividade da intervenção baseada em mindfulness oferecida. CONCLUSÃO: índices mais saudáveis nos parâmetros clínicos sugestivos de sensibilização central investigados após a intervenção, representam melhora significativa na relação da pessoa com quadro de enfermidade crônica geradora de experiências desagradáveis contínuas como a disfunções temporomandibulares.

OBJECTIVE: manifestations of allodynia and hyperalgesia are commonly present in chronic painful temporomandibular disorder. Studies point to the benefits of people with chronic pain undergoing mindfulness-based interventions, by demonstrating brain, hormonal, and clinical changes. This study aimed to analyze clinical parameters suggestive of central sensitization (pressure pain threshold, allodynia, and hyperalgesia) in women with chronic painful temporomandibular disorder before and after a mindfulness-based intervention, through a before-and-after intervention study, longitudinal, uncontrolled. METHOD: the analysis included 11 women chosen at random from a total of 20, aged between 27 and 44 years (36.36 ± 5.61), diagnosed with chronic painful temporomandibular disorder according to the Diagnostic Criteria for Temporomandibular Disorders protocol and who completed the 8-week mindfulness-based intervention program. Hyperalgesia, allodynia, and pressure pain threshold were tested at trigeminal and extra-trigeminal points before and after the intervention as well as the application of the questionnaire to measure the level of mindfulness (Mindful Attention Awareness Scale). The 8-week mindfulness program was offered to the study participants, based on the Mindfulness Trainings International - protocol, in weekly 2-hour sessions and a 4-hour session (immersion). RESULTS: the results pointed to a reduction in allodynia, hyperalgesia and an increase in pressure pain threshold, with significant differences in several tested points (p <0.05). The changes identified were accompanied by a significant increase in the level of mindfulness (p < 0.05). CONCLUSION: healthier indexes in clinical parameters suggestive of central sensitization investigated after the intervention represent a significant improvement in the person's relationship with a chronic illness that generates continuous unpleasant experiences such as temporomandibular disorder. Thus, the practice of mindfulness represents an appropriate and particularly interesting care because it is a low-cost, non-invasive intervention with low evidence of adverse effects.

OBJETIVO: las manifestaciones de alodinia y hiperalgesia y están comúnmente presentes en lo trastorno temporomandibular doloroso crónico. Los estudios señalan los beneficios de las personas con dolor crónico que se someten a intervenciones basadas en la atención plena, al demostrar cambios cerebrales, hormonales y clínicos. El objetivo de este estudio fue analizar parámetros clínicos sugestivos de sensibilización central (umbral de dolor por presión, alodinia e hiperalgesia) en mujeres con trastorno temporomandibular doloroso crónico antes y después de una intervención basada en la atención plena, a través de un estudio de intervención antes y después, longitudinal, sin control. MÉTODO: el análisis incluyó a 11 mujeres elegidas al azar de un total de 20, con edades entre 27 y 44 años (36.36 ± 5.61), diagnosticadas con trastorno temporomandibular doloroso crónico de acuerdo con protocolo Criterios de diagnóstico para trastornos temporomandibulares y que completaron el 8- programa de intervención basado en mindfulness de una semana. La hiperalgesia, la alodinia y el umbral de dolor por presión se probaron en los puntos trigémino y extra-trigémino antes y después de la intervención, así como también en la aplicación del cuestionario para medir el nivel de atención plena (Escala de conciencia de atención plena). El programa de atención plena de 8 semanas se ofreció a los participantes del estudio, basado en el protocolo Mindfulness Trainings International, en sesiones semanales de 2 horas y una sesión de 4 horas (inmersión). RESULTADOS: los resultados apuntaron a una reducción en la alodinia, hiperalgesia y un aumento en la umbral de dolor por presión, con diferencias significativas en varios puntos probados (p <0.05). Los cambios identificados fueron acompañados por un aumento significativo en el nivel de atención plena (p <0.05), como un marcador de la efectividad de la capacitación ofrecida para la práctica de la atención plena. CONCLUSIÓN: los índices más saludables en los parámetros clínicos sugestivos de sensibilización central investigados después de la intervención, representan una mejora significativa en la relación de la persona con una enfermedad crónica que genera experiencias continuas desagradables como trastorno temporomandibular doloroso crónico. Por lo tanto, la práctica de la atención plena representa una atención aplicable y particularmente interesante porque es una intervención no invasiva de bajo costo con poca evidencia de efectos adversos.

High energy photobiomodulation therapy in the early days of injury improves sciatic nerve regeneration in mice / Aplicação de alta energia da terapia de fotobiomodulação nos primeiros dias de lesão otimiza a regeneração de nervo ciático em camundongos

INTRODUCTION: Different studies have evaluated the effects of electrophysical agents on regeneration after peripheral nerve injury. Among them, the most used in clinical and experimental research is photobiomodulation therapy (PBMT). OBJECTIVE: To analyze the effect of standard energy (16.8 J) of PBMT on peripheral nerve regeneration, applied at different periods after sciatic nerve injury in mice. METHODS: Thirty male Swiss mice were divided into six groups: naive; sham; control; LLLT-01 (660 nm, 16.8 J of total energy emitted in 1 day); LLLT-04 (660 nm, 4.2 J per day, 16.8 J of total energy emitted in 4 days); LLLT-28, (660 nm, 0.6 J per day, 16.8 J of total energy emitted over 28 days). The animals were evaluated using thermal hyperalgesia, Sciatic Functional Index (SFI), and Static Sciatic Index (SSI). Data were obtained at baseline and after 7, 14, 21, and 28 days after surgery. RESULTS: For the SFI and SSI, all groups showed significant differences compared to the control group, and the LLLT-04 group presented the best results among those receiving PBMT. In the assessment of thermal hyperalgesia, there was a significant difference in the 14th day of evaluation in the LLLT-04 group. CONCLUSION: The application of 16.8 J was useful in sciatic nerve regeneration with an improvement of hyperalgesia, with higher efficacy when applied in four days (4.2 J/day).

INTRODUÇÃO: Estudos avaliaram os efeitos de diferentes terapias aplicadas após lesão nervosa periférica, com o intuito de promover a regeneração local. Dentre elas, a mais utilizada em pesquisa clínica e experimental é a terapia de fotobiomodulação (TFBM). OBJETIVO: Analisar o efeito da fotobiomodulação (16,8 J) na regeneração nervosa periférica, aplicada em diferentes regimes após a lesão do nervo ciático em camundongos. MÉTODOS: Foram utilizados trinta camundongos machos (Swiss) divididos em: naive; sham; controle; LBI-01 (660 nm, 16,8 J de energia total emitida em 1 dia); LBI-04 (660 nm, 4,2 J por dia, 16,8 J de energia total emitida em 4 dias); LBI-28, (660 nm, 0,6 J por dia, 16,8 J de energia total emitida durante 28 dias). Os animais foram avaliados utilizando a hiperalgesia térmica, Índice Funcional do Ciático (IFC) e Índice estático do ciático (IEC). Os dados foram obtidos na linha de base e após 7, 14, 21, e 28 dias após a cirurgia. RESULTADOS: Para o IFC e IEC, todos os grupos mostraram um aumento no valor e diferenças significativas em relação ao grupo de controle, e o grupo LBI-04 apresentou os melhores resultados, alcançando valor basal no 21° dia dentre os que foram submetidos a TFBM. Na avaliação da hiperalgesia térmica, houve aumento do tempo de resposta com diferença significativa no 14° dia de avaliação no grupo LBI-04. CONCLUSÃO: A aplicação de 16,8 J foi eficaz na regeneração do nervo ciático quando distribuída ao longo dos 4 primeiros dias pós-lesão, com dose diária de 4,2 J/ponto.

Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

Altered thalamic neurotransmitters metabolism and functional connectivity during the development of chronic constriction injury induced neuropathic pain

BACKGROUND: To investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain. METHODS: The paw withdrawal threshold was measured by mechanical stimulation the right hind paw with the von frey hair in the rats of CCI-induced neuropathic pain. The N-acetylaspartate (NAA) and Glutamate (Glu) in thalamus were detected by magnetic resonance spectrum (MRS) process. The thalamic functional connectivity with other brain regions was scanned by functional magnetic resonance image (fMRI). RESULTS: The paw withdrawal threshold of the ipsilateral side showed a noticeable decline during the pathological process. Increased concentrations of Glu and decreased levels of NAA in the thalamus were significantly correlated with mechanical allodynia in the neuropathic pain states. The thalamic regional homogeneity (ReHo) decreased during the process of neuropathic pain. The functional connectivity among the thalamus with the insula and somatosensory cortex were significantly increased at different time points (7, 14, 21 days) after CCI surgery. CONCLUSION: Our study suggests that dynamic changes in thalamic NAA and Glu levels contribute to the thalamic functional connection hyper-excitation during CCI-induced neuropathic pain. Enhanced thalamus-insula functional connection might have a significant effect on the occurrence of neuropathic pain.