Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 488
Filtrar
1.
Schmerz ; 34(1): 79-83, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31741064

RESUMO

This article describes the case of a female patient with symptoms of complex regional pain syndrome (CRPS) of the right wrist and forearm. Ergotherapy of the affected hand (unilateral desensitization) showed little success and became impossible with increasing environmental temperature due to excessive pain. A physiological feedback via simultaneous treatment of the unaffected healthy arm (bilateral treatment approach) ultimately led to a clear decline of all CRPS symptoms.


Assuntos
Biorretroalimentação Psicológica , Síndromes da Dor Regional Complexa , Hiperalgesia , Síndromes da Dor Regional Complexa/terapia , Feminino , Mãos , Humanos , Hiperalgesia/terapia , Dor
2.
Acupunct Med ; 37(6): 356-364, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31517506

RESUMO

BACKGROUND: Inflammatory pain occurs when local tissue injury activates macrophages and neutrophils, hence increasing pro-inflammatory cytokine and chemokine levels. Toll-like receptor 2 (TLR2) antagonism reportedly suppresses neuropathic and inflammatory pain. AIMS: In the present study, we investigated the effect of electroacupuncture (EA) on TLR2 and related signalling molecules in a complete Freund's adjuvant (CFA)-induced mouse model of inflammatory pain to determine whether EA can attenuate inflammatory pain via the TLR2 signalling pathway. METHODS: EA significantly reduced mechanical and thermal hyperalgesia in the animal model. A similar effect was produced by TLR2 antagonism induced by CU-CPT22 injection. RESULTS: TLR2 expression in the dorsal root ganglia, spinal cord and thalamus increased following induction of inflammation. Expression levels of downstream molecules such as pPI3K, pAkt and pmTOR also increased, as did those of MAPK subfamily members such as pERK, pp38 and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were also involved. CONCLUSION: Increased expression of the above molecules was attenuated by both EA and TLR2 antagonism. Our results show that EA attenuates inflammatory pain via TLR2 signalling.


Assuntos
Analgesia por Acupuntura , Eletroacupuntura , Hiperalgesia/terapia , Receptor 2 Toll-Like/imunologia , Animais , Modelos Animais de Doenças , Humanos , Hiperalgesia/genética , Hiperalgesia/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Manejo da Dor , Receptor 2 Toll-Like/genética
3.
Neuropeptides ; 77: 101957, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31400959

RESUMO

Irritable bowel syndrome patients frequently complain of pain in body regions somatotopically distinct from the gut, suggesting the involvement of an exaggerated signaling process in both visceral and somatic sensory pathways. Increasing evidence has shown that sprouting of tyrosine hydroxylase immunoreactive (TH-IR) fibers toward sensory neurons in dorsal root ganglia maintains and exacerbates the neuropathic and inflammatory pain, as well as colonic inflammation. The aim of the present study was to determine whether electroacupuncture could alleviate the visceral and secondary somatic hyperalgesia in colitis rats by suppressing the TH-IR expression in related dorsal root ganglia. After trinitrobenzene sulfonic acid irritation, rats developed inflammatory tissue damage in the distal colon, which was accompanied by visceral hypersensitivity and secondary hind paw hyperalgesia, as indicated by enhanced visceromotor response to colorectal distension and decreased mechanical and thermal withdrawal latency of the hind paw. Additionally, excessive TH-IR fibers sprouted toward calcitonin gene-related peptide immunoreactive sensory neurons, and TH-IR neurons also increased in the sixth lumbar dorsal root ganglia of colitis rats. Both electroacupuncture and guanethidine attenuated visceral and referred hind paw hyperalgesia by inhibiting the over-expression of TH-IR neurons and fibers in the sixth lumbar dorsal root ganglia. Moreover local inflammatory damage in the distal colon was restored after 7 days of electroacupuncture intervention. These results suggest that electroacupuncture relieved visceral and referred hind paw hypersensitivity in colitis rats by inhibiting TH expression in the sixth lumbar dorsal root ganglia.


Assuntos
Colite/complicações , Gânglios Espinais/metabolismo , Hiperalgesia/terapia , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Colite/metabolismo , Modelos Animais de Doenças , Eletroacupuntura , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Masculino , Medição da Dor , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/metabolismo
4.
J Zhejiang Univ Sci B ; 20(8): 628-636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273960

RESUMO

It is commonly accepted that females and males differ in their experience of pain. Gender differences have been found in the prevalence and severity of pain in both clinical and animal studies. Sex-related hormones are found to be involved in pain transmission and have critical effects on visceral pain sensitivity. Studies have pointed out the idea that serum estrogen is closely related to visceral nociceptive sensitivity. This review aims to summarize the literature relating to the role of estrogen in modulating visceral pain with emphasis on deciphering the potential central and peripheral mechanisms.


Assuntos
Estrogênios/metabolismo , Hiperalgesia/terapia , Dor Visceral/terapia , Animais , Feminino , Humanos , Sistema Imunitário , Masculino , Nociceptores , Ovariectomia , Manejo da Dor , Limiar da Dor , Fatores Sexuais
5.
Mol Med Rep ; 20(2): 1113-1120, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173210

RESUMO

Electroacupuncture (EA), a traditional Chinese therapeutic technique, is considered an effective method for treating certain painful neuropathies induced by various neuropathological damage. The current study investigated the effect of EA on intrathecal (IT) morphine­induced hyperalgesia (MIH) and examined the hypothesis that activation of cannabinoid receptor 1 (CB1) could enhance the antinociceptive effect of EA on MIH via regulation of the extracellular signal­regulated kinase 1/2 (ERK1/2) signaling pathway. Using a rat model of IT MIH, mechanical and thermal hyperalgesia were evaluated by an electronic von Frey filament and hotplate at baseline (1 day before IT administration) and at days 1, 3, 5 and 7 after IT administration. Rats received IT normal saline, IT morphine or IT morphine + EA at ST36­GB34. The protein levels of ERK1/2, phosphorylated (p)­ERK1/2 and CB1 in the spinal cord were assayed by western blotting. Furthermore, the effect of IT injection of the CB1 agonist WIN 55,212­2 and the CB1 antagonist SR141716 on the antinociceptive effect of EA in rats with MIH was investigated. Nociceptive behavior and ERK1/2, phosphorylated (p)­ERK1/2 and CB1 protein levels were evaluated as mentioned above. The results revealed that chronic IT injections of morphine induced a significant decrease in mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) accompanied with remarkable upregulation of p­ERK1/2 in the spinal cord, which could be attenuated by EA at the ST36­GB34 acupoints. In the rat model of MIH, IT injection of WIN 55,212­2 combined with EA induced a significant increase in MWT and TWL accompanied with a significant decrease in p­ERK1/2 and a significant increase in CB1 protein level compared with EA alone, while SR141716 induced the opposite results. The present study suggests that EA alleviates hyperalgesia induced by IT injection of morphine partially through the inhibition of ERK1/2 activation. Activation of the CB1 receptor enhances the antinociceptive effect of EA in rats with MIH partly through the regulation of the spinal CB1­ERK1/2 signaling pathway.


Assuntos
Eletroacupuntura , Hiperalgesia/terapia , Sistema de Sinalização das MAP Quinases , Morfina/efeitos adversos , Receptor CB1 de Canabinoide/genética , Medula Espinal/metabolismo , Animais , Regulação da Expressão Gênica , Hiperalgesia/induzido quimicamente , Hiperalgesia/genética , Hiperalgesia/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
6.
Phys Ther ; 99(9): 1211-1223, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158282

RESUMO

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is commonly used for pain control. However, the effects of TENS on osteoarthritis (OA) pain and potential underlying mechanisms remain unclear. OBJECTIVE: The objective of this study was to investigate the effect of TENS on OA pain treatment and underlying mechanisms related to glial cell inhibition. DESIGN: This was an experimental study. METHODS: OA was induced by injection of monosodium iodoacetate into the synovial space of the right knee joint of rats. High-frequency (HF) TENS (100 Hz), low-frequency (LF) TENS (4 Hz), or sham TENS was applied to the ipsilateral knee joint for 20 minutes. Paw withdrawal threshold (PWT), weight bearing, and knee bend score (KBS) were measured. Immunohistochemistry for microglia and astrocytes was performed with L3 to L5 spinal segment samples. To investigate the effects of glial inhibition on OA pain, minocycline, l-α-aminoadipate, or artificial cerebrospinal fluid was injected intrathecally, and PWT and KBS were measured. RESULTS: Compared with sham TENS, both HF TENS and LF TENS significantly increased PWT, decreased KBS, and inhibited activated microglia in the L3 to L5 segments but did not decrease the total number of microglia, except in the L4 segment (HF TENS). Astrocyte expression was significantly decreased in the L3 to L5 segments following LF TENS and in the L3 segment following HF TENS. Compared with artificial cerebrospinal fluid, both minocycline and l-α-aminoadipate increased PWT and decreased KBS. LIMITATIONS: These results cannot be generalized to humans. CONCLUSIONS: TENS alleviates OA pain in rats by inhibiting activated microglia and reducing astrocyte expression in the spinal cord. Although these results may not be generalizable to chronic pain in patients with OA, within the limitation of the experimental animal model used in the present study, they suggest a possible mechanism and preclinical evidence supporting further experimentation or clinical use of TENS in humans.


Assuntos
Artralgia/terapia , Neuroglia/citologia , Osteoartrite do Joelho/terapia , Medula Espinal/citologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Animais , Astrócitos/citologia , Contagem de Células , Hiperalgesia/induzido quimicamente , Hiperalgesia/terapia , Ácido Iodoacético , Articulação do Joelho , Masculino , Osteoartrite do Joelho/induzido quimicamente , Medição da Dor/métodos , Ratos , Ratos Sprague-Dawley , Suporte de Carga
7.
J Orthop Res ; 37(10): 2258-2263, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31115924

RESUMO

Autologous vein wrapping is used to treat recurrent chronic constriction neuropathy and traumatic peripheral nerve injury. However, its use is restricted due to the inability to obtain sufficiently long veins for larger grafts. We previously reported that vein-derived basic fibroblast growth factor (bFGF) promotes heme oxygenase-1 (HO-1), which reduces allodynia via its anti-inflammatory properties. To mimic vein wrapping, we developed a collagen sheet impregnated with bFGF. Chronic constriction injury (CCI) was induced in male Wistar rats as a model of sciatic nerve injury, and the rats were divided into three groups: (i) untreated after CCI surgery (control group), (ii) treated with a collagen sheet wrap impregnated with phosphate-buffered saline (PBS/CS group), and (iii) treated with a collagen sheet wrap impregnated with bFGF (bFGF/CS group). Pain behavior (von Frey test) was evaluated on postoperative days (PODs) 1, 5, 7, and 14. Quantitative polymerase chain reaction was conducted on sciatic nerve RNA to quantify HO-1 gene, Hmox1, expression. Enzyme-linked immunosorbent assay were used to determine HO-1 protein levels on POD 1. von Frey testing showed significantly greater pain hypersensitivity in the control and PBS/CS groups than the bFGF/CS group. In the bFGF/CS group, Hmox1 messenger RNA and HO-1 protein levels were significantly increased in the sciatic nerve compared with the control and PBS/CS groups on PODs 1 and 5 and POD 1, respectively. The bFGF/CS group showed decreased allodynia and HO-1 induction, as observed with vein wrapping. Therefore, local application of bFGF may be an alternative treatment strategy for compressive neuropathy and peripheral nerve trauma in clinical settings. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2258-2263, 2019.


Assuntos
Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Hiperalgesia/terapia , Traumatismos dos Nervos Periféricos/terapia , Neuropatia Ciática/terapia , Animais , Colágeno , Portadores de Fármacos , Avaliação Pré-Clínica de Medicamentos , Heme Oxigenase (Desciclizante)/metabolismo , Distribuição Aleatória , Ratos , Nervo Isquiático/metabolismo , Suínos
8.
Neurosci Lett ; 706: 18-23, 2019 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-31026533

RESUMO

We examined the effect of immobilization, low-intensity muscle contraction exercise, and transcutaneous electrical nerve stimulation (TENS) on tissue inflammation and acute pain following the onset of arthritis in a rat model. Sixty Wistar rats were divided into five groups: (1) Arthritis group, (2) arthritis and immobilization (Immobilization group), (3) arthritis and low intensity muscle contraction (Exercise group), (4) arthritis and TENS (TENS group), and (5) sham arthritis (Sham group). Arthritis was induced in the right knee joints by single injection of 3% kaolin and carrageenan. Immobilization of the right hindlimb was conducted by full extension of the right knee joints and full plantar flexion of the ankle joints using a plaster cast for 7 days after injection. The right quadriceps muscles were subjected to electrical stimulation (frequency: 50 Hz; intensity: 2-3 mA) for 20 min/day as contraction exercise for one week. TENS was delivered at 20 min/day for one week (frequency: 50 Hz; intensity: 1 mA). The pressure pain threshold (PPT) and paw withdrawal response (PWR) were evaluated at 1 and 7 days after injection. We also analyzed the number of CD68-positive cells in the synovium by immunohistochemistry and determined the expression level of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn with immunofluorescence. Improvements of both PPT and PWR were observed in the Exercise group at 7 days after injection compared to those of the Arthritis and Immobilization groups, although only improvement of PPT was observed in the TENS group. The number of CD68-positive cells in the synovium and CGRP expression in the dorsal horn decreased only in the Exercise group. These results suggested that low-intensity muscle contraction exercise might be a better treatment for reduction of arthritis-induced inflammation and acute pain compared to immobilization and TENS.


Assuntos
Artrite Experimental/terapia , Sensibilização do Sistema Nervoso Central/fisiologia , Terapia por Exercício/métodos , Hiperalgesia/terapia , Inflamação/terapia , Contração Muscular/fisiologia , Medula Espinal/fisiopatologia , Animais , Artrite Experimental/fisiopatologia , Hiperalgesia/fisiopatologia , Inflamação/fisiopatologia , Músculo Esquelético/fisiopatologia , Medição da Dor , Limiar da Dor/fisiologia , Ratos , Ratos Wistar , Estimulação Elétrica Nervosa Transcutânea
9.
Mol Pain ; 15: 1744806919845739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31012383

RESUMO

Effective pharmacological treatment options for chronic pain remain very limited, and continued reliance on opioid analgesics has contributed to an epidemic in the United States. On the other hand, nonpharmacologic neuromodulatory interventions provide a promising avenue for relief of chronic pain without the complications of dependence and addiction. An especially attractive neuromodulation strategy is to optimize endogenous pain regulatory circuits. The prefrontal cortex is known to provide top-down control of pain, and hence neuromodulation methods that selectively enhance the activities in this brain region during pain episodes have the potential to provide analgesia. In this study, we designed a low-frequency (2 Hz) electrical stimulation protocol to provide temporally and spatially specific enhancement of the prefrontal control of pain in rats. We showed that low-frequency electrical stimulation of the prelimbic region of the prefrontal cortex relieved both sensory and affective responses to acute pain in naive rats. Furthermore, we found that low-frequency electrical stimulation of the prefrontal cortex also attenuated mechanical allodynia in a rat model of chronic pain. Together, our findings demonstrated that low-frequency electrical stimulation of the prefrontal cortex represents a promising new method of neuromodulation to inhibit pain.


Assuntos
Dor Aguda/terapia , Dor Crônica/terapia , Córtex Pré-Frontal/metabolismo , Analgesia/métodos , Animais , Estimulação Elétrica , Hiperalgesia/terapia , Masculino , Córtex Pré-Frontal/efeitos da radiação , Ratos , Ratos Sprague-Dawley
10.
Pain ; 160(5): 1059-1069, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31008815

RESUMO

The taste of sucrose is commonly used to provide pain relief in newborn humans and is innately analgesic to neonatal rodents. In adulthood, sucrose remains a strong motivator to feed, even in potentially hazardous circumstances (ie, threat of tissue damage). However, the neurobiological mechanisms of this endogenous reward-pain interaction are unclear. We have developed a simple model of sucrose drinking-induced analgesia in Sprague-Dawley rats (6-10 weeks old) and have undertaken a behavioral and pharmacological characterization using the Hargreaves' test of hind-paw thermal sensitivity. Our results reveal an acute, potent, and robust inhibitory effect of sucrose drinking on thermal nociceptive behaviour that unlike the phenomenon in neonates is independent of endogenous opioid signalling and does not seem to operate through classical descending inhibition of the spinal cord circuitry. Experience of sucrose drinking had a conditioning effect whereby the apparent expectancy of sucrose enabled water alone (in euvolemic animals) to elicit a short-lasting placebo-like analgesia. Sweet taste alone, however, was insufficient to elicit analgesia in adult rats intraorally perfused with sucrose. Instead, the sucrose analgesia phenomenon only appeared after conditioning by oral perfusion in chronically cannulated animals. This sucrose analgesia was completely prevented by systemic dosing of the endocannabinoid CB1 receptor antagonist rimonabant. These results indicate the presence of an endogenous supraspinal analgesic circuit that is recruited by the context of rewarding drinking and is dependent on endocannabinoid signalling. We propose that this hedonic sucrose-drinking model may be useful for further investigation of the supraspinal control of pain by appetite and reward.


Assuntos
Hiperalgesia/terapia , Limiar da Dor/efeitos dos fármacos , Medula Espinal/fisiologia , Sacarose/uso terapêutico , Edulcorantes/uso terapêutico , Animais , Antagonistas de Receptores de Canabinoides/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Adjuvante de Freund/toxicidade , Temperatura Alta/efeitos adversos , Hiperalgesia/induzido quimicamente , Injeções Espinhais/métodos , Masculino , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Rimonabanto/farmacologia , Medula Espinal/efeitos dos fármacos , Privação de Água/fisiologia
11.
Reg Anesth Pain Med ; 44(5): 604-608, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30902913

RESUMO

BACKGROUND: Therapeutic ultrasound (TU) alleviates nerve injury-associated pain, while the molecular mechanisms are less clear. This is an investigator-initiated experimental study to evaluate the mechanisms and effects of ultrasound on prolonged post-thoracotomy pain in a rodent model. METHODS: The rats were randomly separated into four groups (n=8 per group): sham-operation (sham; group 1), thoracotomy and rib retraction (TRR; group 2), and TRR procedure followed by TU (TRR+TU-3; group 3) or TU with the ultrasound power turned off (TRR+TU-0; group 4). TU was delivered daily, beginning on postoperative day 11 (POD 11) for the next 2 weeks. Mechanical sensitivity, subcutaneous tissue temperature, and spinal substance P and interleukin-1 beta (IL-1ß) were evaluated on PODs 11 and 23. RESULTS: Group 3, which received ultrasound treatment (3 MHz; 1.0 W/cm2) for 5 min each day, demonstrated higher mechanical withdrawal thresholds when compared with the group without ultrasound intervention (group 2) or sham ultrasound (group 4). Ultrasound treatment also inhibited the upregulation of spinal substance P and IL-1ß measured from spinal cord dorsal horns extract and increased subcutaneous temperature. CONCLUSIONS: The results of this study suggest an increase in mechanical withdrawal thresholds and subcutaneous temperature, as well as a downregulation of spinal substance P and IL-1ß, in the group which received ultrasound treatment. The regulation of spinal substance P and IL-1ß may mediate potential effects of this non-invasive treatment.


Assuntos
Hiperalgesia/metabolismo , Medição da Dor/métodos , Dor Pós-Operatória/metabolismo , Substância P/biossíntese , Toracotomia/efeitos adversos , Terapia por Ultrassom/métodos , Animais , Expressão Gênica , Hiperalgesia/terapia , Masculino , Medição da Dor/tendências , Dor Pós-Operatória/genética , Dor Pós-Operatória/terapia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Substância P/genética , Toracotomia/tendências , Terapia por Ultrassom/tendências
12.
PLoS One ; 14(2): e0211824, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30785911

RESUMO

The objective of this study was to verify the effects of aerobic exercise associated with tryptophan (TRP) supplementation on hyperalgesia, as well as on cortisol, IL-6 and TNF concentrations in female rats with experimental fibromyalgia (FM). Female Wistar rats (initial body weight: ~ 350 g; age: 12 months) were randomly divided into 5 groups: CON (Control); F (Fibromyalgia induced); FE (Fibromyalgia induced plus exercise); FES (Fibromyalgia induced plus exercise and TRP supplementation) and FS (Fibromyalgia induced plus TRP supplementation). Fibromyalgia was induced with two injections (20 µL) of acidic saline (pH 4.0) into the right gastrocnemius muscle with a 3-day interval. Control animals received the same doses of neutral saline (pH 7.4). The exercised animals underwent progressive low-intensity aerobic exercise (LIAE) on a treadmill (10-12 m/min, 30-45 min/day, 5 days/week) for three weeks. During this period, the supplemented animals received a TRP supplemented diet (210 g/week), while the others received a control diet. Mechanical hyperalgesia was evaluated weekly and serum cortisol and muscle IL-6 and TNF concentrations were assessed after three weeks of interventions. Experimental FM caused bilateral hind paw hyperalgesia and augmented serum cortisol and muscle IL-6 concentrations. After 3 weeks of interventions, LIAE alone reduced hyperalgesia (151%) and reduced serum cortisol concentrations (72%). Tryptophan supplementation itself diminished hyperalgesia (57%) and reduced serum cortisol concentrations (67%). Adding TRP supplementation to LIAE did not further reduce hyperalgesia significantly (11%), which was followed by an important decrease in muscle IL-6 concentrations (68%), though reduction in serum cortisol pulled back to 45%. Muscle TNF concentrations were not affected. In conclusion, the association of TRP supplementation to LIAE does not potentiate significantly the reduction of bilateral mechanical hyperalgesia promoted by LIAE in female rats with experimental FM, however an important decrease in IL-6 is evident.


Assuntos
Fibromialgia , Hiperalgesia , Interleucina-6/sangue , Condicionamento Físico Animal , Triptofano/farmacologia , Fator de Necrose Tumoral alfa/sangue , Animais , Modelos Animais de Doenças , Feminino , Fibromialgia/sangue , Fibromialgia/fisiopatologia , Fibromialgia/terapia , Hiperalgesia/sangue , Hiperalgesia/fisiopatologia , Hiperalgesia/terapia , Inflamação/sangue , Inflamação/fisiopatologia , Inflamação/terapia , Ratos , Ratos Wistar
13.
Neuromodulation ; 22(5): 509-518, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30786105

RESUMO

OBJECTIVES: We aimed to investigate if different protocols of electrical stimulation following nerve injury might improve neuropathic pain outcomes and modify associated plastic changes at the spinal cord level. MATERIALS AND METHODS: Adult rats were subjected to sciatic nerve transection and repair, and distributed in four groups: untreated (SNTR, n = 12), repeated acute electrical stimulation (rAES, 50 Hz, one hour, n = 12), chronic electrical stimulation (CES, 50 Hz, one hour, n = 12), and increasing-frequency chronic electrical stimulation (iCES, one hour, n = 12) delivered during two weeks following the lesion. The threshold of nociceptive withdrawal to mechanical stimuli was evaluated by means of a Von Frey algesimeter during three weeks postlesion. Spinal cord samples were processed by immunohistochemistry for labeling glial cells, adrenergic receptors, K+ -Cl- cotransporter 2 (KCC2) and GABA. RESULTS: Acute electrical stimulation (50 Hz, one hour) delivered at 3, 7, and 14 days induced an immediate increase of mechanical pain threshold that disappeared after a few days. Chronic electrical stimulation given daily reduced mechanical hyperalgesia until the end of follow-up, being more sustained with the iCES than with constant 50 Hz stimulation (CES). Chronic stimulation protocols restored the expression of ß2 adrenergic receptor and of KCC2 in the dorsal horn, which were significantly reduced by nerve injury. These treatments decreased also the activation of microglia and astrocytes in the dorsal horn. CONCLUSION: Daily electrical stimulation, especially if frequency-patterned, was effective in ameliorating hyperalgesia after nerve injury, and partially preventing the proinflammatory and hyperalgesic changes in the dorsal horn associated to neuropathic pain.


Assuntos
Terapia por Estimulação Elétrica/métodos , Hiperalgesia/terapia , Neuralgia/terapia , Traumatismos dos Nervos Periféricos/terapia , Células do Corno Posterior , Animais , Feminino , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Neuralgia/etiologia , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/metabolismo , Células do Corno Posterior/metabolismo , Ratos , Ratos Sprague-Dawley
14.
Oral Dis ; 25(3): 888-897, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30636099

RESUMO

OBJECTIVE: Our objective was to evaluate the Transcranial direct current stimulation (tDCS) effect on facial allodynia induced by chronic constriction of the infraorbital nerve (CCI-ION) and on the brainstem levels of TNF-α, NGF, IL-10, and serum LDH in rats. METHODS: Rats were exposed to the CCI-ION model. Facial allodynia was assessed by von Frey filaments test at baseline, 3, 7, 10, and 14 days postsurgery and 24 hr and 7 days after the bimodal tDCS sessions for 20 min/day/8 days. RESULTS: Chronic constriction of the infraorbital nerve induced a significant decrease in the mechanical threshold 14 days after surgery. This effect was reversed by tDCS treatment, with the mechanical threshold returning to basal levels at 24 hr after the end of the treatment and it persisted for 7 days after the end of the treatment. tDCS also decreased LDH serum levels compared to those in the control group. There was an interaction between pain and treatment with respect to brainstem levels of NGF, TNF-α, and IL-10. CONCLUSION: Chronic constriction of the infraorbital nerve model was effective in establishing trigeminal neuropathic pain on 14 days after surgery, and tDCS reduced allodynia and LDH serum levels and promoted alterations in NGF, TNF-α, and IL-10 brainstem levels. Thus, we suggest that tDCS may be a potential therapy in the trigeminal pain treatment.


Assuntos
Dor Facial/terapia , Hiperalgesia/terapia , Neuralgia/terapia , Estimulação Transcraniana por Corrente Contínua , Nervo Trigêmeo , Animais , Tronco Encefálico/metabolismo , Constrição , Modelos Animais de Doenças , Dor Facial/etiologia , Hiperalgesia/etiologia , Interleucina-10/metabolismo , Lactato Desidrogenases/sangue , Masculino , Fator de Crescimento Neural/metabolismo , Neuralgia/etiologia , Limiar da Dor , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
15.
J Oral Rehabil ; 46(1): 40-50, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30281821

RESUMO

BACKGROUND: Transcranial direct-current stimulation (tDCS) is a noninvasive method of brain stimulation suggested as a therapeutic tool for pain and is related to the reversal of maladaptive plasticity associated with chronic pain. OBJECTIVES: This study investigated the effect of tDCS, a non-pharmacological therapy, on local mechanical hyperalgesia, and remote thermal hyperalgesia in rats submitted to orofacial inflammatory pain model, by facial von Frey and hot plate tests, respectively. In addition, we evaluated levels of BDNF, NGF, IL-10 and IL-6 in the brainstem and blood serum of these animals at 24 hours and 7 days after the end of tDCS treatment. METHODS: Rats were subjected to temporomandibular joint pain and treated with tDCS. The animals were divided into control, pain and pain + treatment groups. Mechanical and thermal hyperalgesia were evaluated at baseline, 7 days after administration of complete Freund's adjuvant, and immediately, 24 hours, and 7 days after the tDCS treatment. Neuroimmunomodulators levels were determined by ELISA. Statistical analyses were performed by (GEE)/Bonferroni (behavioural tests), three-way ANOVA/SNK (neurochemical tests) and Kruskal-Wallis (histological analysis). RESULTS: Transcranial direct-current stimulation reduced mechanical and thermal hyperalgesia (P < 0.01). We observed interaction between factors (pain and treatment) increasing brainstem BDNF (P < 0.01) and NGF (P < 0.05) levels. Furthermore, we found an increase in IL-6 and IL-10 levels in the brainstem at 24 hours and 7 days after tDCS, respectively. CONCLUSION: We showed that tDCS reduces thermal and mechanical hyperalgesia induced by orofacial pain until 7 days after treatment. These findings demonstrate that tDCS was effective in the control of orofacial inflammatory pain.


Assuntos
Dor Facial/terapia , Hiperalgesia/terapia , Neuroimunomodulação/fisiologia , Nociceptividade/fisiologia , Estimulação Transcraniana por Corrente Contínua , Animais , Modelos Animais de Doenças , Dor Facial/fisiopatologia , Hiperalgesia/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley
16.
Disabil Rehabil ; 41(8): 991-993, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29216768

RESUMO

PURPOSE: To describe the clinical manifestation and the treatment of complex regional pain syndrome type II in childhood. METHODS: Using information on the symptoms, diagnosis, rehabilitation and outcome of a young patient with complex regional pain syndrome type II. RESULTS: A 9-year -old girl had severe pain in the region of the left foot, signs of a common fibular nerve entrapment, hyperalgesia not limited to the distribution of the injured nerve, weakness and temperature asymmetry unknown origin. She consulted few doctor's before she was given the right diagnosis of complex regional pain syndrome type II. Following the diagnosis the treatment started, it included intensive physiotherapy, electrical therapy and also supportive psychological therapy. Half a year later, the patient was free of the daily pain and returned to all physical activity without any restrictions. CONCLUSIONS: The case report illustrates that peripheral nerve compression or injuries specifically, complex regional pain syndrome type II, should be taken into consideration when evaluating children with weakness and pain of the lower or upper limb. Implication of rehabilitation Raising the awareness of complex regional pain syndrome in the childhood is essential for an early diagnosis and appropriate treatment. The treatment options include early and adequate pain management inclusive electrical therapy and physiotherapy. Psychological therapy helps to avoid psychological stress reaction and the disease negative impact on the child's education and sports and the family social life.


Assuntos
Síndromes da Dor Regional Complexa , Terapia por Estimulação Elétrica/métodos , , Modalidades de Fisioterapia , Técnicas Psicológicas , Criança , Síndromes da Dor Regional Complexa/diagnóstico , Síndromes da Dor Regional Complexa/fisiopatologia , Síndromes da Dor Regional Complexa/psicologia , Síndromes da Dor Regional Complexa/reabilitação , Exercício , Feminino , Pé/inervação , Pé/fisiopatologia , Humanos , Hiperalgesia/diagnóstico , Hiperalgesia/etiologia , Hiperalgesia/terapia , Síndromes de Compressão Nervosa/diagnóstico , Síndromes de Compressão Nervosa/fisiopatologia , Síndromes de Compressão Nervosa/terapia , Medição da Dor/métodos , Resultado do Tratamento
17.
Neuromodulation ; 22(5): 597-606, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30117624

RESUMO

OBJECTIVES: Kilohertz high-frequency alternating current (KHFAC) electrical nerve stimulation produces a reversible nerve block in peripheral nerves in human patients with chronic pain pathologies. Although this stimulation methodology has been verified with nonselective extrafascicular electrodes, the effectiveness of producing a selective nerve block with more-selective intrafascicular electrodes has not been well documented. The objective of this study was to examine whether intrafascicular electrodes can block painful stimuli while preserving conduction of other neural activity within the implanted nerve. MATERIALS AND METHODS: We analyzed the effects of various stimulation waveforms delivered through Utah Slanted Electrode Arrays (USEAs) implanted in the median nerve of a male human subject with a left brachial plexus injury. We compared KHFAC stimulation with a sham control. RESULTS: KHFAC stimulation through USEA electrodes produced a reduction in pain sensitivity in the palmar aspect of the left middle finger. KHFAC had limited effects on the patient's ability to feel tactile probing in the same area or move the digits of his left hand. Other tested stimulation parameters either increased or showed no reduction in pain. CONCLUSIONS: KHFAC stimulation in peripheral nerves through intrafascicular electrodes demonstrated a selective reduction in pain sensitivity while preserving other nerve functions. This treatment may benefit patient populations who have chronic pain originating from peripheral nerves, but who do not want to block whole-nerve function in order to preserve sensory and motor function reliant on the implanted nerve. Furthermore, KHFAC may benefit patients who respond negatively to other forms of peripheral nerve stimulation therapy.


Assuntos
Plexo Braquial/lesões , Plexo Braquial/fisiologia , Eletrodos Implantados , Hiperalgesia/terapia , Nervo Mediano/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Idoso , Humanos , Hiperalgesia/diagnóstico por imagem , Hiperalgesia/fisiopatologia , Masculino , Nervos Periféricos/fisiologia , Estimulação Elétrica Nervosa Transcutânea/instrumentação
18.
Pain ; 160(1): 136-150, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30157131

RESUMO

Clinical studies indicate that cannabidiol (CBD), the primary nonaddictive component of cannabis that interacts with the serotonin (5-HT)1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact on models of neuropathic pain are unknown. First, using in vivo single-unit extracellular recordings in rats, we demonstrated that acute intravenous (i.v.) increasing doses of CBD (0.1-1.0 mg/kg) decreased the firing rate of 5-HT neurons in the dorsal raphe nucleus, which was prevented by administration of the 5-HT1A antagonist WAY 100635 (0.3 mg/kg, i.v.) and the TRPV1 antagonist capsazepine (1 mg/kg, i.v.) but not by the CB1 receptor antagonist AM 251 (1 mg/kg, i.v.). Repeated treatment with CBD (5 mg/kg/day, subcutaneously [s.c.], for 7 days) increased 5-HT firing through desensitization of 5-HT1A receptors. Rats subjected to the spared nerve injury model for 24 days showed decreased 5-HT firing activity, mechanical allodynia, and increased anxiety-like behavior in the elevated plus maze test, open-field test, and novelty-suppressed feeding test. Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Antiallodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), whereas the anxiolytic effect was blocked only by WAY. Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.


Assuntos
Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Canabidiol/uso terapêutico , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Neuralgia/complicações , Serotonina/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Gânglios Espinais/citologia , Hiperalgesia/terapia , Dietilamida do Ácido Lisérgico/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Neuralgia/patologia , Piperazinas/uso terapêutico , Piperidinas/farmacologia , Pirazóis/farmacologia , Piridinas/uso terapêutico , Ratos , Ratos Wistar , Antagonistas da Serotonina/farmacologia , Natação
19.
Chin J Integr Med ; 25(6): 462-467, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30467696

RESUMO

OBJECTIVE: To study the effects of electroacupuncture (EA) in chronic constrictive injury (CCI) rat model and the expression of N-methyl-D-aspartate receptor type 2B (NR2B) in ipsilateral spinal dorsal horn in rats to explore the analgesic mechanisms of EA. METHODS: According to the random number table, totally 180 rats were evenly divided into a sham group, a CCI group, and an EA group. CCI model was conducted with four 4-0 chromic gut ligatures loosely ligated around the left sciatic nerve 1 cm above the trifurcation. Rats in the EA group received 2 Hz EA therapy bilaterally at acupoints of Zusanli (ST 36) and Sanyinjiao (SP 6) once daily (30 min/d) for 30 days after surgery. Paw withdrawal thresholds (PWTs) were measured on 0 (baseline), 1, 3, 7, 15, 30 days after surgery. Rats were sacrificed on 0, 1, 3, 7, 15 and 30 days after surgery, and the L4-5 segments of spinal cord were removed to detect the expression of NR2B by immunohistochemistry and quantitative polymerase chain reaction. RESULTS: PWTs in the CCI group were significantly lower than the sham group at Day 1-30 after surgery, and reached its lowest at Day 1 (P<0.01). After EA treatment, the PWTs recovered rapidly and were significantly higher than those in the CCI group on 3, 7, 15 and 30 days after surgery (P<0.01). The numbers of NR2B-immunoreactive cells of the CCI group significantly increased after CCI surgery compared with the sham group (P<0.01). Compared with the CCI group, stimulation of EA markedly decreased the numbers of NR2B-immunoreactive cells at Day 3, 7, 15 and 30 (P<0.05). In the sham group, NR2B mRNA was expressed at a low level. It increased after CCI surgery, which increased rapidly at Day 7 (P<0.01) and reached its peak value at Day 15 (P<0.01). After EA stimulation, relative quantity of NR2B mRNA expression was less than that in the CCI group at Day 15 and 30 (P<0.05). CONCLUSIONS: Low frequency of EA had antinociceptive effect in CCI rat model. The analgesic effects of EA might be through the inhibition of NR2B.


Assuntos
Eletroacupuntura , Hiperalgesia/etiologia , Hiperalgesia/terapia , Receptores de N-Metil-D-Aspartato/genética , Corno Dorsal da Medula Espinal/patologia , Regulação para Cima/genética , Animais , Comportamento Animal , Doença Crônica , Constrição Patológica , Ligadura , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Nervo Isquiático/lesões , Fatores de Tempo
20.
Behav Brain Res ; 360: 303-311, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30543902

RESUMO

Peripheral neuropathy is a common adverse effect observed during the use of paclitaxel (PTX) as chemotherapy. The present investigation was directed to estimate the modulatory effect of bone marrow derived mesenchymal stem cells (BM-MSCs) on pregabalin (PGB) treatment in PTX-induced peripheral neuropathy. Neuropathic pain was induced in rats by injecting PTX (2 mg/kg, i.p) 4 times every other day. Rats were then treated with PGB (30 mg/kg/day, p.o.) for 21 days with or without a single intravenous administration of BM-MSCs. At the end of experiment, behavioral and motor abnormalities were assessed. Animals were then sacrificed for measurement of total antioxidant capacity (TAC), nerve growth factor (NGF), nuclear factor kappa B p65 (NF-κB p65), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and active caspase-3 in the sciatic nerve. Moreover, protein expressions of Notch1 receptor, phosphorylated Janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK) were estimated. Finally, histological examinations were performed to assess severity of sciatic nerve damage and for estimation of BM-MSCs homing. Combined PGB/BM-MSCs therapy provided an additional improvement toward reducing PTX-induced oxidative stress, neuro-inflammation, and apoptotic markers. Interestingly, BM-MSCs therapy effectively prevented motor impairment observed by PGB treatment. Combined therapy also induced a significant increase in cell homing and prevented PTX-induced sciatic nerve damage in histological examination. The present study highlights a significant role for BM-MSCs in enhancing treatment potential of PGB and reducing its motor side effects when used as therapy in the management of peripheral neuropathy.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Terapia Baseada em Transplante de Células e Tecidos/métodos , Células-Tronco Mesenquimais/fisiologia , Transtornos Motores/etiologia , Transtornos Motores/terapia , Paclitaxel/toxicidade , Pregabalina/uso terapêutico , Receptor Notch1/metabolismo , Neuropatia Ciática , Acetona/toxicidade , Análise de Variância , Animais , Antioxidantes/metabolismo , Caspase 3/metabolismo , Modelos Animais de Doenças , Hiperalgesia/fisiopatologia , Hiperalgesia/terapia , Interleucina-6/metabolismo , Janus Quinases/metabolismo , Masculino , Fator de Crescimento Neural/metabolismo , Ratos , Ratos Wistar , Teste de Desempenho do Rota-Rod , Fatores de Transcrição STAT/metabolismo , Neuropatia Ciática/induzido quimicamente , Neuropatia Ciática/complicações , Neuropatia Ciática/terapia , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA