Rita Levi-Montalcini: the neurologist who challenged fascism / Rita Levi-Montalcini: a neurologista que desafiou o fascismo

Abstract Rita Levi-Montalcini was a researcher in the field of neuroscience, Italian and Jewish in origin, who discovered the nerve growth factor and rightfully earned the 1986 Nobel Prize in Physiology or Medicine, alongside her collaborator Stanley Cohen. She was persecuted by the fascist dictatorship of Benito Mussolini and experienced gender and religious discrimination throughout her entire life. Despite these obstacles, she carried out her activities with diligence and grace, becoming a role model in the field. This paper reviews the life and career of Rita Levi-Montalcini.

Resumo Rita Levi-Montalcini foi uma pesquisadora no campo das neurociências, de origem Italiana e Judia, que descobriu o fator de crescimento neural e merecidamente recebeu o Prêmio Nobel de Fisiologia ou Medicina de 1986, em conjunto ao seu colaborador Stanley Cohen. Ela foi perseguida pela ditadura fascista de Benito Mussolini, e sofreu discriminação de gênero e religião durante sua vida inteira. A despeito desses obstáculos, sempre exerceu suas atividades com diligência e graça, tornando-se um exemplo nesse campo de estudo. O presente artigo faz uma revisão sobre a vida e carreira de Rita Levi-Montalcini.

Factor de crecimiento nervioso en neuropatía óptica traumática

La neuropatía óptica traumática (TON) es una entidad asociada al trauma facial y craneal, y constituye una causa importante para el desarrollo de la ceguera; es una complicación grave del trauma craneofacial que daña directa (dTON) o indirectamente (iTON) el nervio óptico (ON), cuya incidencia global de TON es de 0,7 a 2,5 %. El objetivo del presente estudio es presentar el caso de un paciente que padecía de TON y a la vez de una afección bilateral asimétrica, y que fue tratado con el factor de crecimiento nervioso mNGF. Este medicamento fue el primero que se descubrió y demostró eficacia en mantener la supervivencia de las neuronas centrales y periféricas y facilitar su crecimiento, diferenciación y regeneración. Se trata de un paciente de 13 años, sexo masculino, quien acude a la emergencia del Instituto Nacional de Ciencias Neurológicas y, posteriormente, su seguimiento clínico es por consultorio de Neuroftalmología, con un cuadro de amaurosis traumática, producto de un traumatismo encéfalo craneano con hematoma epidural, que recibió dos ciclos de tratamiento con factor de crecimiento nervioso. Luego del primer ciclo de tratamiento, se evidenció hiporreactividad de ambos ojos; al finalizar el segundo ciclo de tratamiento, se observó un aumento considerable de la agudeza visual. El mNGF está aprobado y comercializado en China desde el año 2015 y es un producto que ha demostrado su eficacia y seguridad en varios ensayos clínicos. Por ello, el presente estudio pretende convertir al factor de crecimiento nervioso como el tratamiento prometedor de iTON; en ese sentido, se necesita de amplias investigaciones clínicas en este caso en particular.

Traumatic optic neuropathy (TON) is an entity associated with facial and cranial trauma, and a leading cause of blindness. It is a severe complication of craniofacial trauma that directly (DTON) or indirectly (ITON) damages the optic nerve (ON) and whose global incidence is 0.7 to 2.5 %. The objective of this study is to present the case of a patient who suffered from TON and, at the same time, an asymmetrical bilateral condition, and was treated with nerve growth factor (NGF). This drug was the first to be discovered and demonstrate efficacy in maintaining the survival of central and peripheral neurons and facilitating their growth, differentiation and regeneration. A 13-year-old male patient attended the emergency room of Instituto Nacional de Ciencias Neurológicas and was later followed up at the Neuro-Ophthalmology Service. He was diagnosed with post-traumatic amaurosis caused by traumatic brain injury and epidural hematoma, and received two treatment cycles of NGF. After the first treatment cycle, hyporeactivity of both eyes occurred. And, at the end of the second treatment cycle, visual acuity improved significantly. NGF has been approved and marketed in China since 2015 and is a product that has demonstrated its efficacy and safety in several clinical trials. Therefore, this study aims to make NGF a promising ITON treatment; in that sense, further clinical research is needed in this particular case.

Perivascular Innervation in the Nasal Mucosa and Clinical Findings in Patients with Allergic Rhinitis and Idiopathic Rhinitis

Abstract Introduction The nonspecific hyperreactivity of rhinitis has been attributed to neurotrophins activating sensory nerves and inflammatory cells. The relationship between these markers and the intensity of the symptoms is not well established and few studies have evaluated individuals with idiopathic rhinitis. Objective The present study aims to evaluate whether perivascular innervation and nerve growth factor (NGF) are related to the intensity of the clinical conditions in allergic rhinitis (AR) and idiopathic rhinitis (IR). Methods A total of 15 patients with AR and 15 patients with IR with the indication for inferior turbinectomy (associated or not with septoplasty) were selected. The patients received a score according to their signs and symptoms. After the surgery, we quantified eosinophils, mast cells, NGF, and nerve fibers in the nasal turbinate. Results The score of the signs and symptoms was higher in the AR group. Nerve growth factor was found in the cytoplasm of inflammatory cells in the submucosa in greater quantity in the AR group. The nerve fibers were distributed throughout the tissue, mainly in the subepithelial, glandular, and vascular regions, and there was no difference between the groups. Greater perivascular innervation was associated with a higher signs and symptoms score. Conclusions We concluded that these findings suggest that the NGF produced by submucosal inflammatory cells stimulates increased perivascular innervation in rhinitis, thus directly reflecting in more intense clinical conditions, especially in AR.

Mechanism of anterior cingulate cortex in modulating pain and anxiety-like behavior in chronic non-specific low back pain model rats / 中华行为医学与脑科学杂志

Objective:To explore the potential mechanisms of anterior cingulate cortex (ACC) in modulating pain behavior and anxiety-like behavior of rats with chronic non-specific low back pain induced by nerve growth factor (NGF).Methods:Ninety-six male SPF grade SD rats aged 8 weeks were randomly divided into four groups according the random number table method: control group, model group, control+ D-2-amino-5-phosphonopentanoate (D-AP5) group (control+ D-AP5 group) and model+ D-AP5 group, with 24 rats in each group.Low back pain model of rat was established by injection of NGF into multifidus muscle (left side) of the low backs of rats(two times with a five-day interval). Five days after modeling, rats in model+ D-AP5 group and control+ D-AP5 group were injected with the N-methyl-D-aspartate (NMDA) receptor antagonist D-AP5(2 μg, 0.3 μL) at the right side of the ACC once a day for consecutive 3 days, and rats in control group and model group were injected with the same amount of 0.9% sodium chloride solution. Seven days after modeling, the pain threshold of rats was evaluated by mechanical stimulation test and hot and cold plate test.The anxiety-like behavior was tested by open field test.The density of glial fibrillary acidic protein (GFAP) positive cells and c-Fos(a kind of immediate early gene) positive cells of the spinal cord were observed by immunofluorescence. The expression of GFAP, c-Fos, phosphorylated-c-Jun N-terminal kinases (p-JNK), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-X-C motif) ligand 1 (CXCL-1) proteins in the L2 segment of the spinal cord were detected by Western blot. SPSS 23.0 software was used for statistical analysis. One-way ANOVA was used to analyze normal distribution measurement data for comparison among multiple groups, and Tukey test was used for further pairwise comparisons. The Kruakal-Wallis H test was used for non-normal distribution measurement data, and Mann-Whitney U test was used for further pairwise comparisons with Bonferroni-corrected P-values. Results:In the experiments measuring pressure pain threshold (PPT) and paw withdrawal threshold (PWT), there were statistically significant differences in the PPT and PWT of rats among the four groups ( F=53.498, 41.939, both P<0.001). Seven days after modeling, PPT ((418.5±46.9) g) and PWT ( (55.6±7.1) g) in the ipsilateral side of the rats in model+ D-AP5 group were higher than those in model group ((290.0±32.0) g, (30.5±7.5) g) (both P<0.001). In the open field test, there were statistically significant differences in percentage of the inner zone distance ( H=11.922, P<0.01) and the percentage of inner zone time ( H=21.614, P<0.001) of rats among the four groups. The percentage of inner zone time in model+ D-AP5 group was higher than that in model group (5.6(4.3, 7.9) %, 3.1(2.1, 3.8) %) ( P<0.01). The results of immunofluorescence showed that there were statistically significant differences in the density of GFAP positive cells and c-Fos positive cells at the ipsilateral side of the superficial laminae of rats among the four groups ( H=49.085, F=18.120, both P<0.001). The density of GFAP positive cells (34.3(21.1, 47.5) cells/mm 2) and c-Fos positive cells ((52.7±39.4) cells/mm 2) at the ipsilateral side of the superficial laminae in model+ D-AP5 group were less than those in model group (76.5(68.6, 94.9) cells/mm 2, (112.4±63.7) cells/mm 2) (both P<0.001). The Western blot results showed that there were statistically significant differences in the protein expression of GFAP, c-Fos, p-JNK, MCP-1 and CXCL-1 in the L2 segment of rats among the four groups ( F=49.413, 38.437, 41.867, 36.735, 130.951, all P<0.001). The protein expression of GFAP (1.7±0.5), c-Fos (1.1±0.1), p-JNK (1.7±0.3), MCP-1 (1.0±0.4) and CXCL-1 (0.8±0.1) in the L2 segment in model+ D-AP5 group were lower than those in model group ((4.3±0.7), (2.6±0.5), (2.8±0.4), (2.9±0.4), (3.5±0.4)) (all P<0.01). Conclusion:ACC modulates mechanical hyperalgesia and anxiety-like behavior in chronic non-specific low back pain rats, which might be associated with the involvement of spinal astrocytes, p-JNK signal pathway and chemokines such as MCP-1 and CXCL-1.

Effects of tandospirone combined with venlafaxine on neurotransmitters and related factors in patients with comorbid anxiety and depression / 中国基层医药

Objective:To investigate the efficacy of tandospirone combined with venlafaxine in the treatment of comorbid anxiety and depression and its effects on neurotransmitters and related factors.Methods:A total of 92 patients with comorbid anxiety and depression who received treatment in the Second People's Hospital of Lishui between June 2019 and June 2020 were included in this study. They were randomly divided into an observation group and a control group ( n = 46/group). The control group was treated with venlafaxine, while the observation group was treated with tandospirone and venlafaxine. Before and after treatment, the scores of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), the levels of 5-hydroxytryptamine, brain-derived neurotrophic factor, nerve growth factor, and adverse drug reactions were compared between the two groups. Results:At 4 and 8 weeks after treatment, HAMA scores in the observation group were (11.39 ± 3.11) points and (8.26 ± 2.18) points, respectively, which were significantly lower than (14.72 ± 3.57) points and (10.46 ± 2.37) points in the control group ( t = 4.77, 4.63, both P < 0.05). At 4 and 8 weeks after treatment, HAMD scores in the observation group were (15.95 ± 2.90) points and (9.33 ± 1.54) points, respectively, which were significantly lower than (17.43 ± 2.87) points and (13.28 ± 2.65) points in the control group ( t = 2.46, 8.74, both P < 0.05). After treatment, 5-hydroxytryptamine, nerve growth factor, and brain-derived neurotrophic factor levels in the observation group were (154.59 ± 45.26) μg/L, (13.62 ± 1.16) ng/L, (28.54 ± 2.33) ng/L, respectively, which were significantly higher than (129.99 ± 48.31) μg/L, (11.98 ± 1.04) ng/L, and (25.69 ± 2.51) ng/L in the control group ( t = 2.52, 7.14, 5.64, all P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( χ2 = 0.81, P = 0.369). Conclusion:The adjuvant treatment with tandospirone can markedly improve anxiety and depression and protect neurological function of patients with comorbid anxiety and depression, and is highly safe.

Evaluation of alprostadil combined with different doses of mouse nerve growth factor in diabetic peripheral neuropathy / 中国医师进修杂志

Objective:To investigate the application of alprostadil combined with different doses of mouse nerve growth factor in diabetic peripheral neuropathy (DPN) and its effect on motor and sensory nerve conduction and inflammatory factors.Methods:One hundred and fiftypatients with DPN treated in Beihai People′s Hospital from June 2018 to March 2020 were randomly divided into low-dose group and high-dose group, with 75 cases in each group. On the basis of routine treatment, the low-dose group was given alprostadil + mouse nerve growth factor 18 μg/time, once a day. The high-dose group was given alprostadil+mouse nerve growth factor 30 μg/time, once a day, both two groups were treated for 3 weeks. The curative effect, motor and sensory nerve conduction velocity and inflammatory index tumor necrosis factor-α(TNF-α)interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC) and cost-effectiveness analysis, adverse reactions between the two groups were compared.Results:There was no significant difference in the total effective rate between the low dose group and the high dose group ( P>0.05). After 1 and 3 weeks of treatment, the levels ofmotor and sensory nerve conduction velocity and TNF-α, IL-6, hs-CRP and WBC in the two groups has no significant differences ( P>0.05). The cost of each unit effect in the low-dose group was 43.11 Yuan, and the cost of each unit effect in the high-dose group was 57.58 Yuan. The high-dose group was higher than that in the low-dose group, and the high-dose group paid 572.56 Yuan more than the low-dose group for each additional unit effect. There was no significant difference in the total incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Alprostadil combined with 18 μg mouse nerve growth factor in the treatment of DPN has a similar improvement effect on clinical symptoms, motor and sensory nerve conduction and inflammatory factors, and has advantages in cost-effectiveness.

Effects of granulocyte macrophage colony-stimulating factor, nerve growth factor and interleukin-17 on autoimmune prostatitis / 现代泌尿外科杂志

【Objective】 To investigate the significance of granulocyte macrophage colony-stimulating factor (GM-CSF), nerve growth factor (NGF) and interleukin-17 (IL-17) in the prostate tissue of rats with experimental autoimmune prostatitis(EAP). 【Methods】 EAP rat models were established and divided into control group, EAP group, anti-GM-CSF group (blocking control group) and anti-GM-CSFEAP group (blocking EAP group). Pain behaviors were tested. The pathological changes were observed with HE staining. The mRNA and protein expressions of GM-CSF, NGF and IL-17 were detected with RT-PCR and Western blot. 【Results】 Pain test showed the anti-GM-CSF group had less chronic pelvic pain than the EAP group. HE staining showed the anti-GM-CSF group had less tissue inflammatory response. The EAP inflammation score was higher in the control group than in the anti-GM-CSF group. Immunohistochemistry showed GM-CSF was positive in the EAP group (mainly in the nucleus). RT-PCR and Western blot results showed the mRNA and protein expressions of IL-17 and NGF significantly decreased 50 days after EAP in the anti-GM-CSF group. 【Conclusion】 Increased expressions of GM-CSF, NGF and IL-17 in prostate tissue of EAP rats may be important inflammatory mediators of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS);decreased expressions of NGF and IL-17 after resistance against GM-CSF indicate that GM-CSF may be a potential therapeutic target for CP/CPPS.

Efficacy of mouse nerve growth factor combined with edaravone in the treatment of carbon monoxide poisoning and its influence on oxygen free radical-related indicators / 中国医师进修杂志

Objective:To investigate the therapeutic effect of the combination of mouse nerve growth factor and edaravone in the treatment of carbon monoxide poisoning and its effect on patients′ cognitive function, lactic acid clearance rate, and related indicators of oxygen free radicals.Methods:A selection of 158 patients with carbon monoxide poisoning in the Huxi Hospital Affilliated Jining Medical College from May 2017 to June 2020 were divided into study group (80 cases) and control group (78 cases) according to the treatment plan. Both groups were given conventional treatment. On this basis, the control group was given edaravone, and the study group was given mouse nerve growth factor combined with edaravone, both of which were treated for 2 weeks. The clinical efficacy of the two groups was compared with those before treatment and 1 week and 2 weeks after treatment. Neurological impairment score (NIHSS), disease severity score (APACHE Ⅱ), cognitive function score (MMSE), serum inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP)], oxygen free radical related indicators [lipid peroxide (LPO), superoxide dismutase (SOD), gluten Glutathione peroxidase (GSH-PX), malondialdehyde (MDA)] levels, blood lactic acid levels before treatment and lactic acid clearance rates after 12 h, 24 h, 72 h treatment, and statistics of adverse reactions and 30-day mortality.Results:The total effective rate of the study group was higher than that of the control group after 2 weeks of treatment [95.00% (76/80) vs. 78.21% (61/78)] ( P<0.05); NIHSS and APACHEⅡ scores of the study group after 1 week and 2 weeks of treatment Lower than the control group: (6.08 ± 1.15) points vs. (8.94 ± 1.71) points, (4.58 ± 0.74) points vs. (6.32 ± 0.93) points and (6.79 ± 1.03) points vs. (8.02 ± 1.47) points, (5.94 ± 1.47) points vs. (7.25 ± 0.94) points, the MMSE score was higher than that of the control group: (22.09 ± 4.35) points vs. (19.34 ± 5.32) points, (26.05 ± 2.37) points vs. (22.47 ± 4.64) points ( P<0.05) After 1 and 2 weeks of treatment, the serum TNF-α, IL-6, CRP, LPO and MDA levels in the study group were lower than those in the control group: (22.62 ± 4.12) ng/L vs. (29.43 ± 4.68) ng/L and (18.21 ± 2.09) ng/L vs. (24.37 ± 3.16) ng/L, (39.67 ± 4.35) ng/L vs. (52.14 ± 5.48) ng/L and (34.83 ± 3.75) ng/L vs. (41.07 ± 4.09) ng/L, (12.63 ± 1.85) mg/L vs. (17.02 ± 2.47) mg/L and (8.27 ± 1.16) mg/L vs. (11.05 ± 1.62) mg/L, (11.06 ± 1.28) μmol/L vs. (15.97 ± 1.85) μmol/L and (8.24 ± 1.12) μmol/L vs. (12.97 ± 1.40) μmol/L, (7.15 ± 1.16) μmol/L vs. (9.02 ± 1.47) μmol/L and (6.12 ± 0.96) μmol/L vs. (7.84 ± 1.25) μmol/L, the levels of SOD and GSH-PX were higher than those in the control group ( P<0.05); the lactate clearance rate in the study group was higher than that in the control group after 12, 24 and 72 h of treatment: (18.49 ± 3.63)% vs. (14.62 ± 2.95)%, (23.19 ± 4.20)% vs. (17.42 ± 3.57)%, (29.86 ± 6.37)% vs. (25.38 ± 5.21)% ( P<0.05); the incidence of adverse reactions in the study group during treatment Compared with the control group, there was no significant difference ( P>0.05); there was no significant difference in the 30-day mortality between the study group and the control group ( P>0.05). Conclusions:The combination of mouse nerve growth factor and edaravone in the treatment of carbon monoxide poisoning can reduce the severity of disease and neurological deficits, improve cognitive function and lactate clearance rate, reduce inflammation and oxidative stress, improve efficacy, and have good safety.

Effects of Cistanches Herba polysaccharides on rats with constipation-predominant irritable bowel syndrome / 中国药房

OBJECTIVE To investigate the effects of Cistanches Herba polysaccharides （abbreviated as CDPS） on rats with constipation-predominant irritable bowel syndrome （IBS-C）. METHODS SD rats were divided into control group （20 rats） and modeling group. The modeling group was given 2 mL of normal saline at 0-4 ℃ intragastrically （once a day， for 14 consecutive days） to induce IBS-C model. After modeling， model rats were grouped into model group， positive control group （mosapride citrate， 1.35 mg/kg）， CDPS low-dose group （50 mg/kg） and CDPS high-dose group （100 mg/kg）， with 20 rats in each group. Administration groups were given corresponding drug solution intragastrically， and control group and model group were given a constant volume of water intragastrically， once a day， for 28 consecutive days. The fecal water content， serum content of 5-hydroxytryptamine （5-HT）， and charcoal powder propulsion rate of rats were determined in each group；the pathological morphology of colon tissue was observed， and mRNA and protein expressions of nerve growth factor （NGF） and tropomyosin receptor kinase A （TrkA） in colon tissue were detected. RESULTS Compared with control group， the fecal water content and carbon powder propulsion rate in the model group were decreased significantly （P＜0.05）； the rupture of mucosal muscle layer in colon tissue， significant infiltration of inflammatory cells and cellular edema were observed； the content of 5-HT in serum， and relative mRNA and protein expressions of NGF and TrkA were increased significantly （P＜0.05）. Compared with model group， the fecal water content and carbon powder propulsion rate of rats were increased significantly in administration groups （P＜0.05）， and pathological changes of colon tissue were relieved significantly， while the content of 5-HT in serum， the mRNA and protein expressions of NGF and TrkA in colon tissue were decreased significantly （P＜0.05）； among them， the above indicators inthe positive control group and CDPS high-dose group were generally close to those in the control group （P＞0.05）. CONCLUSIONS CDPS can alleviate the symptoms of IBS-C rats， which may be related to the inhibition of NGF/TrkA signaling pathway.

MASH1 induces neuron transdifferentiation of adrenal medulla chromaffin cells / 中南大学学报(医学版)

OBJECTIVES@#Nerve growth factor (NGF) induces neuron transdifferentiation of adrenal medulla chromaffin cells (AMCCs) and consequently downregulates the secretion of epinephrine (EPI), which may be involved in the pathogenesis of bronchial asthma. Mammalian achaete scute-homologous 1 (MASH1), a key regulator of neurogenesis in the nervous system, has been proved to be elevated in AMCCs with neuron transdifferentiation in vivo. This study aims to explore the role of MASH1 in the process of neuron transdifferentiation of AMCCs and the mechanisms.@*METHODS@#Rat AMCCs were isolated and cultured. AMCCs were transfected with siMASH1 or MASH1 overexpression plasmid, then were stimulated with NGF and/or dexamethasone, PD98059 (a MAPK kinase-1 inhibitor) for 48 hours. Morphological changes were observed using light and electron microscope. Phenylethanolamine-N-methyltransferase (PNMT, the key enzyme for epinephrine synthesis) and tyrosine hydroxylase were detected by immunofluorescence. Western blotting was used to test the protein levels of PNMT, MASH1, peripherin (neuronal markers), extracellular regulated protein kinases (ERK), phosphorylated extracellular regulated protein kinases (pERK), and JMJD3. Real-time RT-PCR was applied to analyze the mRNA levels of MASH1 and JMJD3. EPI levels in the cellular supernatant were measured using ELISA.@*RESULTS@#Cells with both tyrosine hydroxylase and PNMT positive by immunofluorescence were proved to be AMCCs. Exposure to NGF, AMCCs exhibited neurite-like processes concomitant with increases in pERK/ERK, peripherin, and MASH1 levels (all P<0.05). Additionally, impairment of endocrine phenotype was proved by a signifcant decrease in the PNMT level and the secretion of EPI from AMCCs (all P<0.01). MASH1 interference reversed the effect of NGF, causing increases in the levels of PNMT and EPI, conversely reduced the peripherin level and cell processes (all P<0.01). MASH1 overexpression significantly increased the number of cell processes and peripherin level, while decreased the levels of PNMT and EPI (all P<0.01). Compared with the NGF group, the levels of MASH1, JMJD3 protein and mRNA in AMCCs in the NGF+PD98059 group were decreased (all P<0.05). After treatment with PD98059 and dexamethasone, the effect of NGF on promoting the transdifferentiation of AMCCs was inhibited, and the number of cell processes and EPI levels were decreased (both P<0.05). In addition, the activity of the pERK/MASH1 pathway activated by NGF was also inhibited.@*CONCLUSIONS@#MASH1 is the key factor in neuron transdifferentiation of AMCCs. NGF-induced neuron transdifferentiation is probably mediated via pERK/MASH1 signaling.

Effects of Qingre Huoxue Jiedu Formula on Nerve Growth Factor-Induced Psoriasis / 中国结合医学杂志

OBJECTIVE@#To elucidate the mechanisms of 4 effective components from a Chinese medicine formula, namely Qingre Huoxue Jiedu Formula (QHJ heat- and toxin-clearing and blood-activating formula), in the treatment of nerve growth factor (NGF)-induced psoriasis.@*METHODS@#Keratinocyte proliferation and T cell proliferation models were developed using NGF. An NGF solution (NGF+DMEM, 100 ng/mL) was added to all induced groups and treated groups and were cultured for 24 h, while a solution with NTRK1 antagonist (K252a+DEME, 300 nmol/L) was added and cultured for 1 h. The models were used to evaluate the effects of the treatment with each of the 4 components of QHJ, namely shikonin, paeonol, astilbin and ursolic acid. Cell apoptosis and proliferation were measured by flow cytometry analysis and CCK8 assay, respectively. The mRNA expression levels of Bax, Bcl-xl, and NGF receptor (NGFR) were assessed by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively.@*RESULTS@#(1) All QHJ-treated groups showed significantly increased cell apoptosis and inhibition of cell proliferation compared with the NGF-induced groups (P<0.05). In addition, treatment with QHJ plus NTRK1 significantly enhanced cell apoptosis and inhibition of cell proliferation compared with cells treated with QHJ only (P<0.05), particularly in cells treated with ursolic acid. (2) QHJ-treated groups showed higher protein expression levels of Bax, Bcl-xl compared with other groups (P<0.05). Additionally, treatment with QHJ plus NTRK1 significantly increased the protein expression levels of Bax, Bcl-xl and NGFR compared with those treated with QHJ only (all P<0.05), especially in those treated with shikonin.@*CONCLUSION@#The action mechanism of QHJ on psoriasis might be through enhancing cell apoptosis and inhibition of cell proliferation, and upregulating the expression level of Bax, Bcl-xl and NGFR.

Treatment of infraorbital nerve injury after orbital fracture with Triamcinolone acetonide combined with rat nerve growth factor / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the clinical efficacy of local application of triamcinolone acetonide combined with mouse nerve growth factor in the treatment of infraorbital nerve injury after infraorbital wall fracture.METHODS: Forty-three patients(43 eyes)with infraorbital wall fractures who underwent infraorbital wall fracture revision from April 2020 to February 2021 at the Affiliated Eye Hospital of Nanchang University were prospectively analyzed. Patients were randomly divided into two groups, in which 20 patients(20 eyes)in the experimental group had gelatin sponges infiltrated with triamcinolone acetonide and mouse nerve growth factor placed on the nerve injury intraoperatively; 23 patients(23 eyes)in the control group had no special treatment intraoperatively. At 6mo postoperative follow-up, the results of quantitative sensory testing(two-point localization, nociception, and touch)were compared between the affected and healthy lower lid areas, and the results were reported in an asymmetry index(AI).RESULTS: Baseline results showed no significant differences between the two groups in terms of gender, age, time of injury, and preoperative sensory testing between the two groups(all <i>P</i>>0.05). The AI values of two-point localization sensation, tactile sensation, and pain sensation in both groups were higher at 1wk after surgery than before surgery(all <i>P</i><0.05), and the symptoms of sensory impairment were aggravated, with different degrees of improvement at 1mo after surgery and statistically significant differences in pain sensation at 3mo after surgery(<i>P</i><0.05), and two-point localization sensation, tactile sensation, and pain sensation were significantly improved at 6mo after surgery than before treatment(all <i>P</i><0.01). At 1mo after surgery, the differences in two-point localization sensation and pain sensation in the test group were statistically significant compared with the control group(<i>t</i>=-2.082,-2.143; <i>P</i>=0.044, 0.038). At 3mo after surgery, there was a statistically significant difference in nociception in the test group compared to the control group(<i>t</i>=-2.118, <i>P</i>=0.04). At 6mo after surgery, there was no statistically significant difference in quantitative sensory testing between the two groups(<i>P </i>>0.05).CONCLUSION: Local application of triamcinolone acetonide combined with mouse nerve growth factor for the treatment of infraorbital nerve injury after infraorbital wall fracture was effective in early internal recovery and superior to the group without special intraoperative treatment.

Effect of pediatric Tuina combined with nerve growth factor therapy on neural function of children with acute ischemic hypoxic encephalopathy / 国际中医中药杂志

Objective:To explore the effect of pediatric massage combined with nerve growth factor treatment on the neurological function of children with acute ischemic hypoxic encephalopathy (HIS).Methods:A total of 96 children with HIS who were treated in Hubei Maternal and Child Health Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from February 2017 to October 2019 were selected for the study. The children were divided into 2 groups using a random number table method, with 48 cases in each group. The control group was treated with nerve growth factor on the basis of conventional treatment, and the observation group was treated with pediatric massage on the basis of the control group. The clinical efficacy, neurobehavior, intelligence index, EEG index, cerebral blood flow and hematology index were compared between the two groups.Results:The total effective rate of the observation group was 95.84%, which was higher than 81.25% of the control group, and the difference between the two groups was statistically significant ( χ2=5.03, P=0.025). The 28-day NBNA score ( t=-2.55, P=0.012) and three-month MDI and PDI of the observation group were significantly higher than those of the control group ( t values were -3.43, -2.65, all Ps<0.01). After treatment, the EEG spike wave amplitude of the two groups of children decreased significantly, and the decrease was greater in the observation group[(35.02 ± 4.16) mV vs. (46.92±5.81)mV, t=11.54]. After treatment, the cerebral blood flow of the two groups of children increased significantly, and the increase was more significant in the observation group [(179.36 ± 22.25) ml/(100 g?min) vs. (158.30±14.92) ml/(100 g?min), t=-5.45]. After treatment, the levels of MBP, NSE and VEGF in the two groups of children decreased significantly, but the decrease in the observation group was greater ( t values were 3.29, 4.07, 8.17, all Ps<0.01). Conclusion:Pediatric massage combined with nerve growth factor alone can improve the curative effect of children with HIS, improve neurobehavioral and intelligent indicators, increase cerebral blood flow, and reduce EEG spike wave amplitude and MBP, NSE and VEGF levels.

The healing effect of paeoniflorin on the wound and regulation of NGF/Akt/GSK3β pathway on rats with diabetic foot / 国际中医中药杂志

Objective:To analyze the healing effect of paeoniflorin on the wound of rats and regulation of NGF/Akt/GSK3β pathway on rats with diabetic foot.Methods:60 rats were randomly divided into normal control group, model group, low, medium and high dose paeoniflorin groups, 12 rats in each group. Diabetic foot model was established by intraperitoneal injection of streptozotocin (STZ) and electrothermal scald. Paeoniflorin groups were injected intraperitoneally with 20 mg/kg, 40 mg/kg and 80 mg/kg paeoniflorin, once a day for 21 days. The wound healing rate of the rats was measured. The fasting blood glucose was measured by blood glucose meter, HbAlc, TC, LDL-C and TG were measured by automatic biochemical analyzer. Serum CRP, IL-6, IL-1β and TNF-α were measured by ELISA. The histopathological changes of the wound were examined by HE staining, the levels of NGF, Akt and GSK3 β mRNA in skin tissue were measured by real-time quantitative polymerase chain reaction (RTq-PCR), the protein and phosphorylation levels of NGF, Akt and GSK3 β were determined by Western blot.Results:Compared with the model group, the healing rate the rats' wounded surface in the low, medium and high dose groups of paeoniflorin was increased ( P<0.05). The levels of fasting blood glucose, HbAlc, TC, LDL-C, TG levels and serum CRP, IL-6, IL-1β, TNF-α was decreased ( P<0.05). The expression of rat skin tissue NGF mRNA (0.83±0.12, 3.17±0.11, 4.54±0.25 vs. 0.31±0.06), Akt mRNA (1.71±0.14, 2.96±0.27, 4.10±0.34 vs. 0.97±0.20) increased ( P<0.05), expression of GSK3β mRNA (4.28±0.35, 2.82±0.14, 1.22±0.33 vs. 7.62±0.43) decreased ( P<0.05), expression of NGF (0.46±0.02, 0.70±0.04, 0.87±0.04 vs. 0.30±0.06), Akt (0.51±0.09, 0.63±0.03, 0.79±0.06 vs.0.41±0.05),p-NGF/NGF (0.47±0.06, 0.61±0.04, 0.83±0.07 vs. 0.25±0.03), p-Akt/Akt(0.54±0.08, 0.83±0.11,0.96±0.07 vs. 0.13±0.05) was increased( P<0.05), the expression of GSK3β (0.67±0.05, 0.54±0.04,0.45±0.03 vs. 0.86±0.05), and the ratio of p-GSK3β/GSK3β (0.78±0.09, 0.64±0.07, 0.42±0.07 vs. 0.97±0.05) was decreased ( P<0.05), and the changes of each index were dependent on the dose of paeoniflorin. Conclusion:Paeoniflorin can regulate the level of blood glucose and blood lipid, inhibit the level of serum inflammatory factors and promote the healing of the wound in diabetic foot rats, and its mechanism may be related to the regulation of NGF/Akt/GSK3β pathway.

Adipose-derived stem cell transplantation for the treatment of peripheral nerve injury induced by 1-bromopropane in rats / 中国职业医学

@#Abstract: Methods - （ ） To investigate the repairing effect of adipose derived stem cells ADSCs transplantation in - - Methods 1 bromopropane induced peripheral nerve injury in rats. A total of 45 specific pathogen free male SD rats were （ ） （ ） randomly assigned to the control group 15 rats and exposure group 30 rats . The rats in the exposure group were gavaged with - ， ， 1 bromopropane at a dose of 800 mg/kg body weight while the control group were given with equal volume of corn oil once a ， - day five days per week for eight weeks. The rat model of peripheral nerve injury induced by 1 bromopropane was established - ， - and was randomly assigned to the self recovery group and ADSCs group 12 rats in each group. ADSCs group and self recovery （ 6 ） ， group were injected with 0.5 mL contains 1×10 cells ADSCs or 0.5 mL phosphate buffer solution respectively by tail vein once a week for four weeks. The control group was not administered any treatment. The rats in each group were assessed using - - （ ） ， ， inclined plane test and Basso Beattie Bresnahan BBB score on the first day before treatment as well as 7 14 21 and 28 day ， after treatment. At the end of treatment the sciatic nerve was isolated for histopathological examination. The oxidative stress - indexes in the cerebral motor cortex were detected by colorimetric analysis. The levels of brain derived neurotrophic factor （ ） （ ） - Results BDNF and nerve growth factor NGF in the sciatic nerve were detected by enzyme linked immunosorbent assay. The - maximum tilt angle of the inclined plate and the BBB score were lower in self recovery group at the five time points of treatment （ P< ） all 0.05 compared with the control group. The maximum tilt angle of the inclined plate test was higher in ADSCs group at 21 （ P< ）， ， ， （ P< ）， and 28 days of treatment all 0.05 and the BBB score was higher at 7 14 21 and 28 days of treatment all 0.05 - （ ） when compared with the self recovery group. The level of malondialdehyde MDA in the cerebral motor cortex increased （P< ）， （ ） （ ） （ P< ）， 0.05 while the superoxide dismutase SOD activity and glutathione GSH level decreased all 0.05 and the levels （ P< ） - of BDNF and NGF in the sciatic nerve decreased all 0.05 in self recovery group compared with the control group. There was ， ， no significant difference in SOD activity and MDA GSH BDNF and NGF levels between ADSCs group and control group （ P> ） （P< ）， （ all 0.05 . The level of MDA in cerebral motor cortex decreased 0.05 the SOD activity and GSH level increased all P< ）， （P< ） - 0.05 and the level of BDNF in sciatic nerve increased 0.05 in ADSCs group compared with the self recovery group. Conclusion - - ADSCs transplantation can repair peripheral nerve injury induced by 1 bromopropane via anti oxidative stress and regulating the secretion of neurotrophic factors.

Effect of electroacupuncture at "Zusanli" (ST 36) on duodenal mast cells, NGF and NTRK1 in rats with functional dyspepsia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) on duodenal mast cells, nerve growth factor (NGF) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), and to explore the mechanism of electroacupuncture at Zusanli (ST 36) on functional dyspepsia (FD).@*METHODS@#Sixty SPF-grade 10-day-old SD rats were randomly divided into a normal group, a model group, a ketotifen group and an EA group, 15 rats in each group. The FD model was prepared by iodoacetamide combined with rat tail clamping method in the model group, the ketotifen group and the EA group. The rats in the ketotifen group were injected intraperitoneally with ketotifen (1 mg•kg-1•d-1) for 7 days; the rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), with disperse-dense wave, frequency of 2 Hz/50 Hz and intensity of 0.5 mA, 20 min each time, once a day for 14 days. The gastric emptying rate and small intestinal propulsion rate in each group were observed; the morphology of duodenal mucosa was observed by HE staining; the toluidine blue staining was used to observe the number and degranulation of mast cells in duodenal mucosa; the protein and mRNA expressions of NGF, NTRK1 in duodenum were detected by Western blot and real-time PCR; the level of interleukin-1β (IL-1β) in duodenum was measured by ELISA.@*RESULTS@#Compared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were decreased (P<0.01); compared with the model group, the gastric emptying rate and small intestinal propulsion rate in the ketotifen group and the EA group were increased (P<0.01); the small intestinal propulsion rate in the EA group was higher than that in the ketotifen group (P<0.01). In the model group, local defects in duodenal mucosa were observed with a small amount of inflammatory cell infiltration; no obvious abnormality was found in duodenal mucosa of the other groups. Compared with the normal group, the mast cells of duodenal mucosa in the model group were increased significantly with significant degranulation; compared with the model group, the mast cells of duodenal mucosa in the ketotifen group and the EA group were decreased significantly, and the degranulation was not obvious. Compared with the normal group, the protein and mRNA expressions of NGF, NTRK1 as well as the level of IL-1β in duodenum in the model group were increased (P<0.01); compared with the model group, the protein and mRNA expressions of NGF, NTRK1 as well as the levels of IL-1β in duodenum in the ketotifen group and the EA group were decreased (P<0.01, P<0.05); compared with the ketotifen group, the mRNA expression of NGF, as well as the protein and mRNA expressions of NTRK1 in duodenum in the EA group were decreased (P<0.05, P<0.01).@*CONCLUSION@#EA at "Zusanli" (ST 36) could inhibit the activation of duodenal mast cells and regulate the expressions of NGF and its receptor to improve the low-grade inflammatory response of duodenum, resulting in treatment effect on FD.

Efficacy of internal limiting membrane peeling combined with vitreous injection of mouse nerve growth factor for the treatment of macular hole in high myopia / 中华眼底病杂志

Objective:To observe the efficacy of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) peeling and vitreous injection of mouse never growth factor (mNGF) in the high myopia macular hole (HMMH).Methods:A prospective study. Thirty-one patients (33 eyes) with HMMH diagnosed in Affiliated Eye Hospital of Nanchang University from August 2020 and February 2021 were selected. Before surgery, all included patients were subjected to a complete ophthalmologic evaluation including best corrected visual acuity (BCVA), optical coherence tomography (OCT), macular microperimetry and axial length measurement. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into logarithm of minimum resolution angle (logMAR) visual acuity during statistics. The included subjects were accepted the treatment of PPV combined with ILM peeling and vitreous injection of mNGF (combined group) or PPV united with ILM peeling (simple group), 15 cases with 16 eyes, 16 cases with 17 eyes, respectively. There were no significant differences in logMAR BCVA ( t=0.836), macular hole (MH) diameter (t=0.657), visual acuity (VA) ( t=0.176), the missing length of external limting membrane (ELM) and ellipsoid zone (EZ) ( t=1.255, 0.966) between two groups ( P>0.05). The follow-up time was at least 6 months. The BCVA, closure rate of MH, integrity of ELM and EZ and recovery of VA in macular area were compared and observed between the two groups after surgery. The logMAR BCVA, VA, the deficient lengths of ELM and EZ at different time points were compared by independent-samples t-test between two groups and analysis of variance was used to compare the repeated measurement data of each group. Fisher test was performed for comparison of count data. Results:Six months after surgery, MH closure rates in the simple group and the combined group were 88.24% (15/17) and 93.75% (15/16), respectively, with no significant difference ( P=0.523). At 3 and 6 months after surgery, the integrity recovery of ELM in the combined group was better than that in the simple group, and the difference was statistically significant ( t=2.282, 3.101; P<0.05). At 1, 3 and 6 months after surgery, EZ deletion length in the combined group was lower than that in the simple group, and the difference was statistically significant ( t=1.815, 2.302, 2.784; P<0.05). Compared with 1 week after surgery, VA in macular area of the combined group increased at 1, 3 and 6 months, and the difference was statistically significant ( P=0.007, <0.001, <0.001). At 3 and 6 months after surgery, VA in macular area of affected eyes in the combined group was higher than that in the simple group, and the difference was statistically significant ( t=1.897, 2.250; P<0.05). There was an interaction effect between the surgical method and the follow-up time. The postoperative time was prolonged, and the VA in macular area was decreased in the simple group and increased in the combined group, with statistical significance ( F=12.963, P<0.001). The BCVA and BCVA changes in the two groups increased with the extension of postoperative time. The improvement of BCVA and the difference of BCVA changes in the combined group were significantly higher than those in the simple group at different time points after surgery, with statistically significant differences ( F=12.374, 21.807, 5.695, 4.095; P<0.05). Conclusion:PPV combined with ILM peeling and vitreous injection of mNGF is more effective than PPV with ILM peeling for HMMH, improving both anatomical and functional outcomes.

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.

Effects of aerobic physical exercise on neuroplasticity after stroke: systematic review / Efeitos do exercício físico aeróbico na neuroplasticidade após o acidente vascular cerebral: revisão sistemática de literatura

ABSTRACT Background: Stroke is among the leading causes of death and disability worldwide. Interventions for stroke rehabilitation aim to minimize sequelae, promote individuals' independence and potentially recover functional damage. The role of aerobic exercise as a facilitator of post-stroke neuroplasticity in humans is still questionable. Objective: To investigate the impact of aerobic exercise on neuroplasticity in patients with stroke sequelae. Methods: A systematic review of randomized clinical trials and crossover studies was performed, with searches for human studies in the following databases: PUBMED, EMBASE, LILACS and PeDRO, only in English, following the PRISMA protocol. The keywords used for selecting articles were defined based on the PICO strategy. Results: This systematic review evaluated the impacts of aerobic exercise on neuroplasticity through assessment of neural networks and neuronal excitability, neurotrophic factors, or cognitive and functional assessment. Studies that evaluated the effects of aerobic exercise on neuroplasticity after stroke measured through functional resonance (fMRI) or cortical excitability have shown divergent results, but aerobic exercise potentially can modify the neural network, as measured through fMRI. Additionally, aerobic exercise combined with cognitive training improves certain cognitive domains linked to motor learning. Studies that involved analysis of neurotrophic factors to assess neuroplasticity had conflicting results. Conclusions: Physical exercise is a therapeutic intervention in rehabilitation programs that, beyond the known benefits relating to physical conditioning, functionality, mood and cardiovascular health, may also potentiate the neuroplasticity process. Neuroplasticity responses seem more robust in moderate to high-intensity exercise training programs, but dose-response heterogeneity and non-uniform neuroplasticity assessments limit generalizability.

RESUMO Antecedentes: O acidente vascular cerebral (AVC) é a segunda causa principal de morte no mundo. Intervenções para reabilitação dos pacientes com AVC visam minimizar sequelas, promover sua independência e potencialmente recuperar danos funcionais. O papel do exercício aeróbico como facilitador da neuroplasticidade pós-AVC em humanos ainda é questionável. Objetivo: Investigar o impacto do exercício aeróbico na neuroplasticidade em pacientes com sequelas de AVC. Métodos: Foi realizada revisão sistemática de literatura, pesquisando nas seguintes bases de dados: PUBMED, EMBASE, LILACS e PeDRO. Foram selecionados trabalhos em língua inglesa, realizados apenas com humanos, seguindo o protocolo PRISMA. As palavras-chave utilizadas para a seleção de artigos foram definidas com base na estratégia PICO. Resultados: Esta revisão sistemática avaliou os impactos do exercício aeróbico na neuroplasticidade através da avaliação das redes neurais e da excitabilidade neuronal, por meio de fatores neurotróficos, por meio da avaliação cognitiva e funcional. Estudos que avaliaram os efeitos do exercício aeróbico sobre neuroplasticidade após o AVC medido através de ressonância funcional ou excitabilidade cortical, são controversos, mas há dados sugerindo uma modificação da rede neural na ressonância funcional após o exercício aeróbico. Há evidências de que, associar exercício aeróbico com treinamento cognitivo melhora certos domínios cognitivos ligados à aprendizagem motora. Estudos que envolveram a análise de fatores neurotróficos, como avaliação da neuroplasticidade, tiveram resultados conflitantes. Conclusões: Exercício aeróbico é uma intervenção terapêutica em programas de reabilitação, pois, além de proporcionar os benefícios no condicionamento físico, funcionalidade, humor e saúde cardiovascular, pode potencializar a neuroplasticidade.

Transcranial direct current stimulation did not revert the increased central and peripheral NGF levels induced by neuropathic pain in rats / Tratamento com estimulação transcraniana por corrente contínua não reverteu o aumento de NGF induzido por modelo de dor neuropática em ratos

ABSTRACT BACKGROUND AND OBJECTIVES: The expression of nerve growth factor (NGF) in the large-size neurons may represent a key role in the neuronal synaptic plasticity and re-organization of neuronal function after a nerve injury. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising tool to pain management since it promotes neuroplasticity in the central system, and it can be combined with other interventions. The aim was to investigate the effects of tDCS in the NGF levels in central and peripheral nervous system structures of rats submitted to a neuropathic pain (NP) model. METHODS: The chronic constriction injury (CCI) of sciatic nerve was used for the induction of NP. For sham surgery, the sciatic nerve was exposed, but without any ligation. The control group did not undergo surgical procedure. After the establishment of NP, treated groups were subjected to tDCS treatment 0.5 mA/20min/day/8 days. NGF levels in cerebral cortex, spinal cord and sciatic nerve were determined by sandwich-ELISA at 48 hours and 7 days after the end of treatment. RESULTS: The CCI model increased NGF levels in all three structures analyzed at long-lasting time, evidencing the importance of this neurotrophin in neuropathic pain condition. On the other hand, there was no tDCS effect in the central and peripheral NGF levels discarding the participation of this neurotrophin in the analgesic tDCS effect. CONCLUSION: tDCS modulation effects of nociceptive pathways seem not to be linked to the NGF signaling in this chronic pain model.

RESUMO JUSTIFICATIVA E OBJETIVOS: A expressão do fator de crescimento neural (NGF) em neurônios de diâmetro largo pode representar um papel importante na plasticidade sináptica neuronal e na reorganização da função neuronal após lesão neural. A estimulação transcraniana por corrente contínua (ETCC) é um método não invasivo de estimulação cerebral e representa uma ferramenta promissora para o manejo da dor, pois promove neuroplasticidade no sistema central, podendo ser combinada com outras intervenções. O objetivo foi investigar os efeitos da ETCC nos níveis de NGF em estruturas do sistema nervoso central e periférico de ratos submetidos a um modelo de dor neuropática (DN). MÉTODOS: A constrição crônica (CCI) do nervo isquiático foi utilizada para indução do modelo de DN. Na cirurgia sham, o nervo foi exposto, no entanto não houve constrição do nervo. O grupo controle não foi submetido ao procedimento cirúrgico. Após estabelecimento da DN, os grupos tratados foram submetidos a ETCC 0,5 mA/20min/dia/8 dias. Os níveis de NGF no córtex cerebral, medula espinal e nervo isquiático foram mensurados pela técnica de ELISA 48 horas e 7 dias após o final do tratamento. RESULTADOS: O modelo de dor CCI aumentou os níveis de NGF nas três estruturas analisadas, evidenciando a importância desta neurotrofina na dor neuropática. Por outro lado, não houve efeito da ETCC nos níveis de NGF central e periférico, descartando o papel desta neurotrofina no efeito analgésico da ETCC. CONCLUSÃO: Efeitos da ETCC sobre vias nociceptivas não estão diretamente relacionados com a sinalização do NGF neste modelo de dor crônica.