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Abstract Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that acts on the activity of the cerebral cortex employing electrical currents. Aim: The objective of this project is to evaluate the effectiveness of rTMS on pain and quality of life in patients with chemotherapy-induced peripheral neuropathic pain. Method: Ten patients with chemotherapy-induced peripheral neuropathic pain received 20 sessions of rTMS, consisting of 15 minutes of treatment repeated 5 times per week for four weeks (10 Hz, 20s, 30 trains with 81% intensity). Patients were evaluated using the Brief pain inventory (BPI) and the Functional Assessment of Cancer Therapy and neurotoxicity (FACT-GOG-NTX 13). Results: There were significant differences in BPI mean severity, interference score and FACT-GOG-NTX 13 (p<0,05). Conclusion: The pilot study results suggest that rTMS is potentially beneficial for the treatment of chemotherapy-induced peripheral neuropathy. rTMS over the M1 had an important reduction in pain severity, interference with daily activities, and quality of life scores. However, results should be taken with caution due to the small sample size, absence of a control group and short period of follow-up.
Resumen Antecedentes: La estimulación magnética transcraneal repetitiva (EMTr) es una técnica no invasiva que actúa sobre la actividad de la corteza cerebral, empleando corrientes eléctricas. Objetivo: El objetivo de este proyecto es evaluar la eficacia de la EMTr sobre el dolor y la calidad de vida en pacientes con dolor neuropático periférico inducido por quimioterapia. Métodos: Diez pacientes con dolor neuropático periférico inducido por quimioterapia recibieron 20 sesiones de EMTr que consistieron en un tratamiento de 15 minutos repetido 5 veces por semana durante cuatro semanas (10 Hz, 20 s, 30 trenes con 81 % de intensidad). Los pacientes fueron evaluados mediante el Inventario Breve de Dolor (BPI) y la Evaluación Funcional de la Terapia del Cáncer y la neurotoxicidad (FACT-GOG-NTX 13). Resultados: Hubo diferencias significativas en la severidad media del dolor del BPI, la puntuación de interferencia y el FACT-GOG-NTX 13 (p<0,05). Conclusión: Los resultados del estudio piloto sugieren que la rTMS es potencialmente beneficiosa para el tratamiento de la neuropatía periférica inducida por la quimioterapia. La rTMS sobre M1 tuvo una reducción importante de la severidad del dolor, la interferencia con las actividades diarias y las puntuaciones de calidad de vida. Sin embargo, los resultados deben tomarse con cautela debido al pequeño tamaño de la muestra, la ausencia de un grupo de control y el corto período de seguimiento.
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Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.
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Trigeminal neuralgia is a manifestation of orofacial neuropathic pain disorder,always deemed to be an insurmountable peak in the field of pain research and treatment.The pain is recurrent,abrupt in onset and termination similar to an electric shock or described as shooting.A poor quality of life has been attributed to trigeminal neuralgia,as the paroxysms of pain may be triggered by innocuous stimuli on the face or inside the oral cavity,such as talking,washing face,chewing and brushing teeth in daily life.The pathogenesis of trigeminal neuralgia has not been fully elucidated,although the microvascular compression in the trigeminal root entry zone is generally considered to be involved in the emergence and progression of the pain disorder.In addition,orofacial neuropathic pain restricted to one or more divisions of the trigeminal nerve might be secondary to peripheral nerve injury.Based on current hypotheses regarding the potential causes,a variety of animal models have been designed to simulate the pathogenesis of trigeminal neuralgia,including models of compression applied to the trigeminal nerve root or trigeminal ganglion,chronic peripheral nerve injury,peripheral inflammatory pain and center-induced pain.However,it has not yet been possible to determine which model can be perfectly employed to explain the mechanisms.The selection of appropriate animal models is of great significance for the study of trigeminal neuralgia.Therefore,it is necessary to discuss the characteristics of the animal models in terms of animal strains,materials,operation methods and behavior observation,in order to gain insight into the research progress in animal models of trigeminal neuralgia.In the future,animal models that closely resemble the features of human trigeminal neuralgia pathogenesis need to be developed,with the aim of making valuable contributions to the relevant basic and translational medical research.
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Neuropathic pain(NP)is caused by leision or disease of the somatic sensory nervous system,and its pathological mechanism is complex,mainly related to abnormal neural structure and function.It is hard for existing treatment methods to obtain satisfactory results.With the deepening of the study of peroxisome proliferate activation receptor-γ(PPAR-γ),its role in neuroinflammation,oxidative stress,ion channels,mitochondrial function,neuroprotection and other aspects have been discovered succes-sively,PPAR-γ may be one new target for pain prevention and treatment.This paper reviews the role of PPAR-γ in NP and related mechanisms,in order to provide new thinking for the clinical treatment of NP.
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Objective:To explore the feature of FOS expression in oxytocin-and vasopressin-positive neurons in the hypothalamic paraventricular nucleus(PVN)under different status of diabetes mellitus(DM).Methods:Intraperito-neal injection of vehicle or STZ in mice was conducted to establish control or diabetes model.Mechanical sensitivity was evaluated by von Frey filament tests to distinguish diabetic neuropathic pain(DNP)from without-pain group(DWP).The expression of FOS,oxytocin(OXT)-and vasopressin(VP)-positive neurons,as well as their double labeling was detected by immunohistochemical and immunofluorescent staining.Cell counting and comparison were made in groups.Results:FOS expression was easily detected in the PVN in the three groups(Control group,DNP group and DWP group)at 7 days,while that in DWP and DNP groups at 28 days was hardly detectable,with the number being signifi-cantly different from the 7 days group(P＜0.05 or 0.001).Likewise,compared with the control group,immunofluo-rescent signals for VP and OXT staining in the DNP and DWP groups also showed a trend of weakening as the modeling time increased(P＜0.05).The cell counting after double staining for VP or OXT with FOS showed that,in the DWP group at 7 days,the number of VP and FOS double-labeled neurons was 74.33±22.10,accounting for(56.64± 7.52)％of VP-positive cells,whereas the double labeling rate for OXT and FOS was only(10.44±3.14)％.In the DNP group at 7 days,the number of OXT and FOS double-labeled neurons was 51.00±31.80,accounting for(18.50 ±9.51)％of OXT-positive neurons,whereas the double labeling rate for VP and FOS was only(9.34±3.27)％.In contrast to these changes in 7 days group,the expression of FOS decreased sharply in the group of 28 days,thereby al-most no double-labeled neurons.Conclusion:The plasticity changes of oxytocin-and vasopressin-positive neurons in the PVN are different depending on the status of pain and non-pain,and the stage of disease progression.Understanding the changes is of great significance for unravelling the neural mechanism of diabetes and its complications.
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Objective:To study the regulatory mechanism of p38 MAPK signaling pathway participate in hyperalge-sia reaction in Parkinson's disease(PD)rats model induced by 6-hydroxy dopamine(6-OHDA).Methods:Forty male Sprague Dawley(SD)rats were randomly divided into four groups:Sham group(Sham),model group(6-OHDA),p38 MAPK inhibitor SB203580 treatment group(6-OHDA+SB203580)and p38 MAPK activator anisomycin(ANS)treatment group(6-OHDA+ANS).PD model was established by intra-striatal injection of 6-OHDA stereotactically.6-OHDA+SB203580 and 6-OHDA+ANS groups was injected with 6-OHDA to establish PD model,and treated with inhibitor SB203580 or activator ANS respectively.The von Frey hairs were applied to measure the mechanical paw with-draw threshold(PWT)of rats.Enzyme linked immunosorbent assay(ELISA)was used to detect the content of IL-6,IL-1β,and TNF-α in rat dorsal root ganglion(DRG).The mRNA levels of genes IL-6,IL-1β,TNF-α,and p38 MAPK in rat DRG was detected by real time RT-PCR.Results:In the DRG of 6-OHDA included PD rats,the expres-sion levels of IL-6,IL-1β,TNF-α,and p38 MAPK were significantly increased(P＜0.05),and the PWT of rats were significantly decreased(P＜0.05).The application of activator ANS further increased the expression levels of IL-6,IL-1β,TNF-α,and p38 MAPK,and the PWT of rats were decreased.After application of inhibitor SB203580,the ex-pression levels of IL-6,IL-1β,TNF-α and p38 MAPK were significantly decreased in the DRG of rats(P＜0.05),and the PWT were significantly increased in rats(P＜0.05).Conclusion:6-OHDA induces mechanical hyperalgesia reaction in rats,and the molecular mechanism is related to activation of the p38 MAPK signalling pathway.
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BACKGROUND:It has been reported that the application of biotic amniotic membrane and corneal bandage lens in pterygium surgery can significantly reduce the pain reaction after pterygium excision and promote the healing of corneal wounds. OBJECTIVE:To compare the efficacy of biotic amniotic membrane and corneal bandage lens on the repair of corneal wounds and neuropathic pain after pterygium surgery. METHODS:A total of 121 cases(142 eyes)of primary pterygium patients admitted to Nanyang Second People's Hospital from August 2020 to May 2022 were retrospectively selected.They all underwent pterygium excision combined with autogenous free conjunctival flap transplantation.Among them,63 cases(68 eyes)of pterygium postoperative wound repair with biotic amniotic membrane were classified as the amniotic membrane group,and 58 cases(74 eyes)of pterygium wound repair with corneal bandage lens were classified as the bandage lens group.Postoperative follow-up was conducted,and the corneal wound repair of the patients within 2 weeks after surgery was recorded.Neuropathic pain was quantified by Wong-Baker face on the day after surgery,1 day,and 2 weeks after surgery.The corneal topographic map indicating asymmetry index,best corrected visual acuity,corneal refractive index,and surface rule index were recorded before surgery,1 and 3 months after surgery. RESULTS AND CONCLUSION:(1)2 weeks after treatment,the wound repair rate in the bandage lens group was significantly higher than that in the amniotic membrane group(P<0.05).The wound healing time was shorter in the bandage lens group than that in the amniotic membrane group(P<0.01).(2)The degree of neuropathic pain in the bandage lens group was lower than that in the amniotic membrane group on the day and 1 day after surgery(P<0.001),and there was no significant difference between the two groups in neuropathic pain at 2 weeks after surgery(P>0.05).(3)The corneal topographic map indicating asymmetry index,best corrected visual acuity,corneal refractive index,and surface rule index were significantly improved in both groups 1 and 3 months after surgery(P<0.05).The corneal topographic map indicating asymmetry index,corneal refractive index,and surface rule index of the bandage lens group were lower than those of the amniotic membrane group 1 and 3 months after surgery(P<0.05).(4)Recurrence occurred in 1 eye(1.47%)in the amniotic membrane group and 3 eyes(4.05%)in the bandage lens group within 3 months after operation,and there was no significant difference between the groups(P>0.05).(5)These findings suggest that the corneal bandage lens is more effective than the biotic amniotic membrane in the repair of corneal wounds after pterygium surgery.
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Objective To observe the effects of wheat grain moxibustion for"Huantiao"on sciatic nerve function,pathological morphology of sciatic nerve stem and expressions of TLR4/MyD88/NF-κB signaling pathway expression in spinal cord tissue of rats with sciatic nerve injury(SNI);To explore the possible mechanism of wheat grain moxibustion for the treatment of SNI.Methods Totally 24 SD male rats were randomly divided into blank group,sham-operation group,model group and wheat grain moxibustion group,with 6 rats in each group.The model group and the wheat grain moxibustion group used a rat model with sciatic nerve clamping injury.From the 7th day after modeling,the rats were treated with moxibustion on the affected side of"Huantiao"for 6 strokes each time,once a day,for consecutive 10 days.The sciatic nerve function index(SFI)of rats on the 7th day after modeling and after intervention were observed,mechanical withdraw threshold(MWT)in rats were measured using a fiber optic pain gauge,ELISA was used to detect NO and iNOS content in spinal cord tissue,HE staining was used to observe the morphology of sciatic nerve stem,the expression of TLR4,NF-κBp65,p-NF-κBp65,MyD88,IκBα and p-IκBα in spinal cord tissue were detected by Western blot.Results Compared with the sham-operation group,the SFI and MWT of the rats in the model group significantly decreased(P<0.01),the arrangement of nerve fibers in sciatic nerve stem was disordered,with a significant increase in the number of Schwann cells and a large number of vacuolar degeneration,the content of NO,iNOS and the expression of TLR4,p-NF-κBp65,MyD88,p-IκBα protein in spinal cord tissue significantly increased(P<0.01).Compared with the model group,the SFI and MWT of the rats in the wheat grain moxibustion group increased significantly(P<0.01),the damage of sciatic nerve stem was reduced,with orderly cell arrangement,a decrease in the number of Schwann cells,and a decrease in axonal demyelination and cellular vacuolar degeneration,the content of NO,iNOS and the expression of TLR4,p-NF-κBp65,MyD88,p-IκBα in spinal cord tissue significantly decreased(P<0.05).Conclusion Wheat grain moxibustion for"Huantiao"can down-regulate TLR4,p-NF-κBp65,MyD88 and p-IκBα protein expressions in spinal cord tissue of SNI rats,reduce the secretion of NO and iNOS,thereby relieve pain and damaged nerve tissue inflammation response.
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Objective @#To evaluate the effect of melatonin on nocturnal exacerbation of neuropathic pain and to ex plore its mechanism through the specific silencing information regulator 1 ( SIRT1)-brain and muscle ARNT-like protein 1 ( BMAL1 ) pathway .@*Methods @# 96 SPF grade male C57/B6 mice were randomly divided into three groups : the sham operation (S) group , the neuropathic pain model (NP) group and the NP model + melatonin treatment (10 mg/kg) ( NP + M) group; preoperative experimental mice were placed in the environment of the specified light pattern; the environment of alternating 12 h light and 12 h darkness was used for at least two weeks , and natural time was converted into the time of the award (ZT) , and the starting point of the light was ZT0; only the sciatic nerve was isolated in the S group , and the mouse NP model was prepared using chronic constriction injury (CCI) of the sciatic nerve in the NP group and the NP + M group , and the NP + M group was inj ected with me latonin after the operation; the expression levels of SIRT1, BMAL1, and glutathione peroxidase 1 (Gpx1) were de tected in the spinal cord at each time point at 14 d postoperatively by Western blot. Postoperative co-staining of SIRT1 in the dorsal horn of the spinal cord with the spinal cord neuronal marker neuron specific nuclear protein (NeuN) , the microglial cell activation marker ion calcium binding adapter molecule 1 (iba-1) , and the astrocyte marker glial fibrillary acidic protein ( GFAP) was carried out by immunofluorescence and iba-1 was detected at each time point to determine the activation status of microglia.@*Results @#SIRT1 , BMAL1 and Gpx1 decreased in NP group mice at 14 d ZT22 postoperatively compared to ZT10 time point in NP group ( P < 0.05) ; SIRT1 and BMAL1 were elevated in NP + M group at ZT14 time point compared to ZT14 time point in NP group (P < 0.05) , whereas Gpx1 was elevated at ZT18 time point (P < 0.05) . SIRT1 was co expressed in the dorsal horn of the spinal cord and in microglia. C ompared with ZT10 time point , microglia expression decreased in NP group mice at ZT22 time point 14 d after surgery (P < 0.05) ; compared with ZT10 time point , there was no statistically significant difference in microglia expression in NP + M group mice at ZT22 time point 14 d after surgery .@*Conclusion@#Melatonin attenuates nocturnal exacerbation of neuropathic pain by a mechanism that may be related to activation of microglia SIRT1-BMAL1 pathway protein expression .
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Introduction: Intracranial tumors cause various neurological symptoms and neuropathic pain, which are often refractory to opioids. In some of these cases, the combination of Kampo medicines can be effective. Case: The case was a 44-year-old patient who underwent surgery for a suspected papilloma. After resection, pathological examination revealed squamous cell carcinoma, positive for margins, and then, the left intraorbital metastasis was observed. Due to the intracranial invasion of the tumor, he had pain in the second and third branches of the trigeminal nerve in the left face and paresthesia in the second branch of the trigeminal nerve bilaterally (Numerical Rating Scale: NRS 10/10). Hydromorphone was introduced, and the pain was relieved, but the paresthesia remained (NRS 8/10). Both paresthesia and pain worsened during the course of chemotherapy, but MRI showed no tumor progression, thus, the cause of symptom aggravation was diagnosed edema of the tissue around the tumor. Therefore, Goreisan was started, and both paresthesia and pain were relieved. Discussion: Goreisan has been shown to be effective in cerebral edema due to its water-regulating effect by inhibiting aquaporin. In the present case, the reduction of edema in peritumoral tissues by Goreisan may have contributed to the symptomatic relief.
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ObjectiveTo explore the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) in M1 region combined with dorsolateral prefrontal cortex (DLPFC) on electroencephalogram (EEG) θ frequency band amplitude of patients with neuropathic pain (NP) after spinal cord injury. MethodsFrom June, 2022 to June, 2023, 50 NP patients after SCI in Qingdao University Affiliated Hospital were included and divided into M1 region stimulation group (n = 25) and M1 region combined with DLPFC stimulation group (the combined stimulation group, n = 25). M1 region stimulation group received 10 Hz rTMS in the left M1 region, while the combined stimulation group received same stimulation in left M1 region combined with DLPFC, for three weeks. Before and after intervention, the pain was assessed with Short Form of McGill Pain Questionnaire (SF-MPQ), the depression and anxiety status were evaluated using Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), and the EEG θ frequency band amplitude was recorded to detect the changes of brain electrophysiological activity. ResultsFour cases in M1 region stimulation group, and two cases in the combined stimulation group were dropped. After intervention, the total score of SF-MPQ and the scores of the subscales, the scores of HMMD and HAMA decreased in both groups (|t| > 2.523, P < 0.05). The EEG θ frequency band amplitude significantly reduced in the prefrontal and frontal regions in M1 region stimulation group (|t| > 5.243, P < 0.001), and it also significantly reduced in the prefrontal, frontal regions, central and parietal regions in the combined stimulation group (|t| > 4.630, P < 0.001). All the scores were lower (|t| > 2.270, Z = -1.973, P < 0.05), and the EEG θ frequency band amplitude in the prefrontal, frontal regions, central and parietal regions were lower (P < 0.05) in the combined stimulation group than in M1 region stimulation group. ConclusionHigh frequency rTMS is an effective analgesic method on NP after SCI, which can improve their depression and anxiety symptoms and reduce the EEG θ frequency band amplitude. Compared with M1 region rTMS stimulation, the combination of M1 region and DLPFC rTMS is more effective.
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Objective To explore the effect and mechanism of C-C motif chemokine ligand 2(CCL2)/C-C chemokine receptor type 2(CCR2)signaling pathway mediated by ZXDC in spinal dorsal root ganglion(DRG)on neuropathic pain after chronic compressive injury.Methods A chronic compressive injury(CCI)mouse model was established.The expression of ZXDC and CCL2 in DRG was detected by immunofluorescence,Western blot,and real-time fluorescent quantitative PCR(RT-qPCR).The animals were divided in-to sham group,CCI+AAV-NC group,and CCI+AAV-ZXDC siRNA group.Western blot and immunofluorescence were employed to measure the expression of ZXDC,CCL2,and CCR2 in DRG after CCI,and the expression of pro-inflammatory factor TNF-α and IL-1β mRNA was evaluated by RT-qPCR.At last,the paw withdrawal threshold was used to evaluate the changes in neuropathic pain be-havior.Results ZXDC was localized in large,medium,and small DRG neurons.The expression of ZXDC and CCL2 protein and mRNA were significantly increased 1-3 days after CCI,and decreased 7days after CCI in DRG.The expression of ZXDC and CCL2mRNA was positively correlated(P＜0.05).3 days after CCI,compared with sham group,ZXDC,CCL2,CCR2 protein expression,TNF-α and IL-1 β mRNA in CCI+AAV-NC group and CCI+AAV-ZXDC siRNA group were significantly increased,and ZXDC,CCL2,CCR2 protein expression,TNF-α and IL-1 β mRNA in CCI+AAV-ZXDC siRNA group were significantly decreased than those in CCI+AAV-NC group(P＜0.05).Compared with sham group,the paw withdrawal threshold of CCI+AAV-ZXDC siRNA group and CCI+AAV-NC group were significantly decreased at various time points after CCI,and the withdrawal threshold in CCI+AAV-ZXDC siRNA group was significantly increased than that in CCI+AAV-NC group at 7days after CCI(P＜0.05).Conclusion Spinal dorsal root gan-glion ZXDC siRNA can inhibit neuropathic pain after CCI injury by downregulating CCL2/CCR2signaling axis.
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Objective To analyze and explore the analgesic effect of Angelica dahurica in neuropathic pain and its regulatory effect on the Mas-related G-protein coupled receptor member D(MrgprD)-transient receptor potential ankyrin 1(TRPA1)signaling pathway,using a mouse model of sciatic nerve chronic constriction injury(CCI).Methods A CCI mouse model was prepared by sterile surgical ligation and wrapping of the sciatic nerve in 30 mice.Pain-related behavioral changes induced by mechanical stimulation were detected by the VonFrey method,and the thermal hyperalgesic effects of Angelica dahurica were evaluated by thermal radiation experiments.The effects of Angelica dahurica on the protein expression levels MrgprD and TRPA1,the number of dorsal root ganglion(DRG)positive neurons,and mRNA levels of MrgprD and TRPA1 in mice were detected by Western Blot,immunofluorescence,and reverse transcription-polymerase chain reaction,respectively.Differences in fluorescence signal intensity in HEK293 cells after single transfection and co-transfection with MrgprD and TRPA1 plasmids,respectively,were analyzed by calcium imaging experiments.Results A total of 25 CCI mouse models were successfully prepared,with a modeling rate of 83.33％(25/30).The mechanical threshold and foot retraction latency were significantly higher in CCI mice treated with Angelica dahurica compared with the control group(P＜0.05).Expression levels of MrgprD and TRPA1 proteins were significantly lower in CCI mice treated with Angelica dahurica than in the control group(P＜0.05).The number of MrgprD-and TRPA1-positive neurons in the DRG was significantly lower group(P＜0.05)and the mRNA levels of MrgprD and TRPA1 were also significantly lower in CCI mice treated with Angelica dahurica than in the control group(P＜0.05).The fluorescence intensity was significantly higher in HEK293 cells co-transfected with MrgprD and TRPA1 plasmids than in single-transfected and blank control cells(P＜0.05).Conclusions This study demonstrated that the MrgprD-TRPA1 pathway is an important target for neuropathic pain,and indicated that Angelica dahurica can inhibit neuropathic pain by regulating this signal transduction pathway.These result provide a foundation for further research on the development of new clinical analgesic drugs and analgesic mechanisms.
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Background The activated microglia have been reported as pillar factors in neuropathic pain (NP) pathology, but the molecules driving pain-inducible microglial activation require further exploration. In this study, we investigated the effect of dorsal root ganglion (DRG)-derived exosomes (Exo) on microglial activation and the related mechanism. Methods A mouse model of NP was generated by spinal nerve ligation (SNL), and DRG-derived Exo were extracted. The effects of DRG-Exo on NP and microglial activation in SNL mice were evaluated using behavioral tests, HE staining, immunofluorescence, and western blot. Next, the differentially enriched microRNAs (miRNAs) in DRG-Exo-treated microglia were analyzed using microarrays. RT-qPCR, RNA pull-down, dual-luciferase reporter assay, and immunofluorescence were conducted to verify the binding relation between miR-16-5p and HECTD1. Finally, the effects of ubiquitination modification of HSP90 by HECTD1 on NP progression and microglial activation were investigated by Co-IP, western blot, immunofluorescence assays, and rescue experiments. Results DRG-Exo aggravated NP resulting from SNL in mice, promoted the activation of microglia in DRG, and increased neuroinflammation. miR-16-5p knockdown in DRG-Exo alleviated the stimulating effects of DRG-Exo on NP and microglial activation. DRG-Exo regulated the ubiquitination of HSP90 through the interaction between miR-16-5p and HECTD1. Ubiquitination alteration of HSP90 was involved in microglial activation during NP. Conclusions miR-16-5p shuttled by DRG-Exo regulated the ubiquitination of HSP90 by interacting with HECTD1, thereby contributing to the microglial activation in NP.
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Resumen: La diabetes mellitus, un padecimiento crónico y progresivo, ocupó el tercer lugar en defunciones durante el período comprendido de enero a junio de 2021 en México. Su complicación crónica más frecuente es la neuropatía diabética que tiene un impacto importante en el sistema nervioso. En la Ciudad de México se reunió un grupo multidisciplinario de expertos para establecer un algoritmo de tratamiento que considere los aspectos sintomáticos y etiopatogénicos de la neuropatía diabética. Se utilizó un método Delphi en tiempo real con dos rondas de preguntas interactivas. La implementación del algoritmo propuesto permitirá abordar de manera integral al paciente diabético con neuropatía dolorosa y no dolorosa, tanto en el terreno de los síntomas como en la etiopatogenia. Este abordaje brinda la oportunidad de mejorar la calidad de vida y lograr la reinserción a la vida familiar y laboral. El panel de expertos recomienda al ácido tióctico como tratamiento etiopatogénico de primera línea en la neuropatía diabética.
Abstract: Diabetes mellitus, a chronic and progressive condition, was the third most common cause of death in Mexico between January and June 2021. Its most frequent chronic complication is diabetic neuropathy, which has a major impact on the nervous system. A multidisciplinary group of experts met in Mexico City to establish a treatment algorithm considering the symptomatic and etiopathogenic aspects of diabetic neuropathy. A real-time Delphi method with two rounds of interative questions was used. The implementation of the proposed algorithm will allow a comprehensive approach to the diabetic patient with painful and non-painful neuropathy, both in terms of symptoms and etiopathogenesis. This approach provides the opportunity to improve quality of life and achieve reintegration into family and work life. The expert panel recommends thioctic acid as the first line etiopathogenic treatment for diabetic neuropathy.
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Mirogabaline besylate is a novel gabapentinoid approved for use in the treatment of diabetic neuropathic pain and postoperative neuralgia Further studies had explored the role of mirogabalin in chemotherapy- induced neuropathy, trigeminal trophic syndrome, chronic psychological stress, psychiatric disorders like anxiety-related behaviours and tactile allodynia and neuropathic pain of various etiologies. This review article is aimed to comtemplate all the studies on mirogabalin, its role, superiority over other gabapentanoids as well as to validate its efficacy and safety profile
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ABSTRACT BACKGROUND AND OBJECTIVES: Neuropathic pain is a chronic condition with a significant burden for patients, society, and healthcare systems. Due to neuropathic complexity, its management must be different than the one for nociceptive pain. First-line systemic treatments may be associated with dose-dependent adverse events and drug-drug interactions. On the other hand, topical treatments have less systemic adverse events, with the 5% lidocaine transdermal patch being recommended for firstor second line of treatment for neuropathic pain according to various international guidelines. The aim of this study is to present three cases of localized neuropathic pain due to nerve compression managed with 5% lidocaine transdermal patch. CASE REPORTS: The cases of three adult patients (>40 years old) with pain or tingling for a long period of time and their outcomes with treatment with 5% lidocaine transdermal patch for a prolonged duration were investigated. All three cases report a significant improvement in pain. CONCLUSION: The results of the reported cases revealed that a 5% lidocaine transdermal patch represents an effective, safe and tolerable and noninvasive option for the management of localized neuropathic pain due to peripheric nerve compression.
RESUMO JUSTIFICATIVA E OBJETIVOS: A dor neuropática é uma condição crônica com impactos significativos para o paciente, a sociedade e o sistema de saúde. Pela sua complexidade neuropática, a sua abordagem deve ser diferente da dor nociceptiva. Os tratamentos sistêmicos de primeira linha para a dor neuropática podem estar associados à incidência de eventos adversos dose-dependentes e interações farmacológicas. Por outro lado, os fármacos tópicos apresentam menor incidência de eventos adversos sistêmicos, sendo o emplastro de lidocaína a 5% recomendado como primeira ou segunda linha de tratamento para essa condição em diversos guidelines internacionais. O objetivo deste estudo foi apresentar três casos clínicos de dor neuropática localizada por compressão nervosa manejados com o emplastro de lidocaína a 5%. RELATO DOS CASOS: Três pacientes com idade superior a 40 anos e queixas de dor ou parestesia de longa duração foram manejados com emplastro de lidocaína a 5% em tratamento prolongado, com melhora da intensidade de dor expressiva. CONCLUSÃO: Os resultados dos casos reportados revelaram que o emplastro de lidocaína a 5% se apresentou como uma opção terapêutica eficaz, segura, bem tolerada e não invasiva no manejo da dor neuropática localizada por compressão nervosa periférica.
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Abstract Background Chronic spontaneous urticaria (CSU) is a condition that is associated with recurrent pruritic hives and/or angioedema lasting for more than 6 weeks and is known to affect 1% of the population. Neuropathic pain can be defined as abnormal pain in the peripheral or central nervous system following injury and results from dysfunctions in the peripheral or central nervous system without peripheral nociceptor stimulation. Histamine appears in the pathogenesis of both the CSU and diseases of the neuropathic pain spectrum. Objective To evaluate the symptoms of neuropathic pain in patients with CSU using scales. Method Fifty-one patients with CSU and 47 sex- and age-matched healthy controls were included in the study. Results The results of the short-form McGill Pain Questionnaire revealed the scores in the sensory and affective domains, Visual Analogue Scale (VAS) scores and pain indices to be significantly higher in the patient group (p < 0.05 for all cases), while the overall pain assessment and sensory assessment based on the Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) pain scale were also significantly higher in the patient group. Based on the assumption that scores of > 12 indicated neuropathy, 27 (53%) of the patients in the patient group and 8 (17%) in the control group were found to have neuropathy (p < 0.05). Study limitations Cross-sectional study, small patient sample and use of self-reported scales. Conclusion In addition to itching, patients with CSU should be aware of the potential for the association of neuropathic pain. In this chronic disease that is known to affect the quality of life, using an integrated approach with the patients and identifying accompanying problems are as important as treating the dermatological disorder.
ABSTRACT
Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. WLB-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive effect. Contrary to morphine and oxycodone, tolerance to its antinociceptive effect did not develop after repeated 4-week administration. Also, contrary to opioid comparators, WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy, and it was devoid of proemetic effect (retching and vomiting) in ferrets at potentially effective doses. WLB-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.
ABSTRACT
Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.