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1.
Medicine (Baltimore) ; 99(8): e19325, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080151

RESUMO

Elucidation of epigenetic mechanisms correlating with neuropathic pain in humans is crucial for the prevention and treatment of this treatment-resistant pain state. In the present study, associations between neuropathic pain characteristics and DNA methylation of the transient receptor potential ankyrin 1 (TRPA1) gene were evaluated in chronic pain patients and preoperative patients. Pain and psychological states were prospectively assessed in patients who suffered chronic pain or were scheduled for thoracic surgery. Neuropathic characteristics were assessed using the Douleur Neuropathique 4 (DN4) questionnaire. DNA methylation levels of the CpG islands in the TRPA1 gene were examined using whole blood. Forty-eight adult patients were enrolled in this study. Increases in DNA methylation rates at CpG -51 showed positive correlations with increases in the DN4 score both in preoperative and chronic pain patients. Combined methylation rates at CpG -51 in these patients also significantly increased together with increase in DN4 scores. Neuropathic pain characteristics are likely associated with methylation rates at the promoter region of the TRPA1 gene in human peripheral blood.


Assuntos
Metilação de DNA , Neuralgia/genética , Canal de Cátion TRPA1/genética , Idoso , Dor Crônica/genética , Ilhas de CpG , Depressão/psicologia , Feminino , Humanos , Masculino , Neuralgia/psicologia , Medição da Dor , Regiões Promotoras Genéticas , Estudos Prospectivos
2.
Nat Neurosci ; 22(10): 1659-1668, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31501573

RESUMO

Neuropathic pain can be a debilitating condition with both sensory and affective components, the underlying brain circuitry of which remains poorly understood. In the present study, a basolateral amygdala (BLA)-prefrontal cortex (PFC)-periaqueductal gray (PAG)-spinal cord pathway was identified that is critical for the development of mechanical and thermal hypersensitivity after peripheral nerve injury. It was shown that nerve injury strengthens synaptic input from the BLA onto inhibitory interneurons located in the prelimbic medial PFC, by virtue of reduced endocannabinoid modulation. These augmented synaptic connections mediate a feedforward inhibition of projections from the PFC to the ventrolateral PAG region and its downstream targets. Optogenetic approaches combined with in vivo pharmacology reveal that these BLA-PFC-PAG connections alter pain behaviors by reducing descending noradrenergic and serotoninergic modulation of spinal pain signals. Thus, a long-range brain circuit was identified that is crucial for pain processing and that can potentially be exploited toward targeting neuropathic pain.


Assuntos
Vias Neurais/patologia , Neuralgia/patologia , Neurônios/patologia , Tonsila do Cerebelo/patologia , Animais , Comportamento Animal , Temperatura Alta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora , Neuralgia/psicologia , Optogenética , Substância Cinzenta Periaquedutal/patologia , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/psicologia , Estimulação Física , Córtex Pré-Frontal/patologia , Medula Espinal/patologia , Sinapses/patologia
3.
Medicine (Baltimore) ; 98(33): e16600, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415351

RESUMO

Severe persistent pain after groin hernia repair impairs quality-of-life. Prospective, consecutive cohort study including patients with pain-related impairment of physical and social life. Relevant surgical records were obtained, and examinations were by standardized clinical and neurophysiological tests. Patients demonstrating pain sensitivity to pressure algometry in the operated groin underwent re-surgery, while patients with neuropathic pain received pharmacotherapy. Questionnaires at baseline (Q0) and at the 5-year time point (Q5Y) were used in outcome analyses of pain intensity (numeric rating scale [NRS] 0-10) and pain-related effect on the activity-of-daily-living (Activities Assessment Scale [AAS]). Data are mean (95% CI).Analyses were made in 172/204 (84%) eligible patients. In 54/172 (31%) patients re-surgery (meshectomy/selective neurectomy) was performed, while the remaining 118/172 (69%) patients received pharmacotherapy. In the re-surgery group, activity-related, and average NRS-scores at Q0 were 6.6 (5.6-7.9) and 5.9 (5.6-5.9), respectively. Correspondingly, NRS-scores at Q5Y was 4.1 (3.3-5.1) and 3.1 (2.3-4.0; Q0 vs. Q5Y: P < .0005), respectively. Although both groups experienced a significant improvement in AAS-scores comparing Q0 vs. Q5Y (re-surgery group: 28% (4-43%; P < .0001); pharmacotherapy group: 5% (0-11%; P = .005)) the improvement was significantly larger in the re-surgery group (P = .02).This 5-year cohort study in patients with severe persistent pain after groin hernia repair signals that selection to re-surgery or pharmacotherapy, based on examination of pain sensitivity, is associated with significant improvement in outcome. Analyzing composite endpoints, combining pain and physical function, are novel in exploring interventional effects.ClinicalTrials.gov Identifier NCT03713047.


Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/efeitos adversos , Neuralgia/terapia , Manejo da Dor/métodos , Dor Pós-Operatória/terapia , Analgésicos/uso terapêutico , Feminino , Virilha/inervação , Virilha/cirurgia , Hérnia Inguinal/psicologia , Herniorrafia/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/etiologia , Neuralgia/psicologia , Medição da Dor , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/psicologia , Estudos Prospectivos , Qualidade de Vida , Reoperação/estatística & dados numéricos , Resultado do Tratamento
4.
Pain Res Manag ; 2019: 2091960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249636

RESUMO

Objective: Neuropathic pain is a common presenting complaint of patients with peripheral neuropathy (PN) and is considered one of the most disabling neuropathic symptoms, with detrimental effects on patients' quality of life (QoL). The aim of this review was to overview the current literature that focuses on QoL in painful PN of various aetiologies. We sought to clarify the direct effect of pain and its treatment on patients' QoL. Methodology: A systematic computer-based literature search was conducted using the PubMed database to search for papers on QoL in painful PN. Information was extracted regarding prevalence, demographics, and response to treatment where relevant. Results: We identified 66 articles eligible for inclusion. The vast majority of studies (n=47) focused on patients with diabetic PN. Other aetiologies of painful PN where QoL has been studied to date include gluten, immune-mediated, HIV, chemotherapy-induced, and chronic idiopathic axonal polyneuropathy. Pharmacological treatment is the mainstay in managing pain and has a direct positive and independent effect on the overall QoL. Other nonpharmacological approaches can also be of benefit, either alone or as adjuvant treatments, and are discussed. Conclusion: The findings demonstrate that QoL is impaired in painful PN and should not be neglected in clinical practice. Patients' pain management and subsequent impact on QoL should routinely be assessed and monitored.


Assuntos
Neuralgia/psicologia , Qualidade de Vida , Humanos , Manejo da Dor
6.
J Med Food ; 22(5): 460-468, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864870

RESUMO

Neuropathic pain (NP) is associated with chronic hyperglycemia and emotional disorders such as depression in diabetic patients, complicating the course of treatment. Drugs currently used to treat NP have undesirable side effects, so research on other natural sources has been required. ß-caryophyllene (BCP), a natural sesquiterpene found in some food condiments and considered an agonist to cannabinoid receptor type 2, could have potential therapeutic effects to treat conditions such as NP and emotional disorders. For this reason, we assessed whether BCP modulates nociception, anxiety, and depressive-like behavior in streptozotocin (STZ)-induced experimental diabetic BALB/c female mice. BCP was orally chronic administrated (10 mg/kg/60 µL). Pain developed with STZ was evaluated with von Frey filament test, SMALGO®, and hot plate test. Anxiety and depression-like behavior were assessed by marbles test, forced swim test, and tail suspension test. BCP significantly reduced glycemia in experimental diabetic mice. The pain was also mitigated by BCP administration. Depression-like behavior assessed with tail suspension test was attenuated with orally chronic BCP administration. Substance P and cytokines such as interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were also attenuated with BCP administration. NP was positively correlated with substance P and IL-6 and IL-1ß release. Our data using an orally chronic BCP administration in the STZ challenged mice to suggest that glycemia, diabetes-related NP, and depressive-like behavior could be prevented/reduced by dietary BCP.


Assuntos
Diabetes Mellitus Experimental/complicações , Neuralgia/tratamento farmacológico , Neuralgia/psicologia , Sesquiterpenos/administração & dosagem , Animais , Ansiedade , Comportamento Animal/efeitos dos fármacos , Depressão , Feminino , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Neuralgia/etiologia , Neuralgia/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
7.
Psychopharmacology (Berl) ; 236(7): 1999-2014, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30798405

RESUMO

Patients suffering from neuropathic pain have a higher incidence of depression and cognitive decline. Although environment enrichment (EE) may be effective in the treatment of neuropathic pain, the precise mechanisms underlying its actions remain determined. The aim of the study was to examine the molecular mechanisms underlying the EE's beneficial effects in mice with neuropathic pain. EE attenuated the pain threshold reduction, depression-like phenotype, and memory deficit in mice after chronic constriction injury (CCI). Furthermore, EE attenuated decreased neurogenesis and increased inflammation in the hippocampus of mice with neuropathic pain after CCI. Moreover, the suppression of adult hippocampal neurogenesis by temozolomide antagonized the beneficial effects of EE on depression-like phenotype and cognitive deficit in the mice with neuropathic pain. In addition, lipopolysaccharide-induced increase in tumor necrosis factor-α (TNF-α) in the hippocampus antagonized the beneficial effects of EE for these behavioral abnormalities in mice with neuropathic pain. Knock-down of NPAS4 (neuronal PAS domain protein 4) in the hippocampus by lentivirus targeting NPAS4 blocked these beneficial effects of EE in the mice with neuropathic pain. These all findings suggest that hippocampal NPAS4 plays a key role in the beneficial effects of EE on the pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain. Therefore, it is likely that NPAS4 would be a new therapeutic target for perceptional, affective, and cognitive dimensions in patients with chronic pain.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Depressão/metabolismo , Meio Ambiente , Transtornos da Memória/metabolismo , Neuralgia/metabolismo , Limiar da Dor/fisiologia , Animais , Depressão/psicologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/psicologia , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Limiar da Dor/psicologia , Fenótipo , Temozolomida/farmacologia
8.
Transl Psychiatry ; 9(1): 57, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30705252

RESUMO

Patients with chronic neuropathic pain frequently suffer from symptoms of anhedonia, which is a core symptom of depression. Accumulating studies suggest that gut microbiota may play a role in depression via gut-microbiota-brain axis. However, it is unknown whether gut microbiota plays a role in neuropathic pain-associated anhedonia. Here, we used a rat model of spared nerve injury (SNI). Hierarchical cluster analysis of sucrose preference test (SPT) results was used to classify the SNI rats with or without anhedonia-like phenotype. The 16S ribosomal RNA sequencing analysis showed abnormal composition of gut microbiota in the anhedonia susceptible compared to sham-operated rats and resilient rats. Furthermore, antibiotics-treated mice showed pain as well as depression-like and anhedonia-like phenotypes, suggesting a role of gut microbiota in these abnormal behaviors. Transplantation of fecal microbiota from anhedonia susceptible rats into antibiotics-treated pseudo-germ-free mice significantly exaggerated pain and depression-like phenotypes, including anhedonia. In contrast, transplantation of fecal microbiota from resilient rats into antibiotics-treated pseudo-germ-free mice significantly improved pain and depression-like phenotypes, including anhedonia. In conclusion, this study suggests that abnormal composition of gut microbiota may contribute to anhedonia susceptibility post SNI surgery, and that gut microbiota also plays a role in the pain as well as depression-like phenotypes. Interestingly, fecal microbiota transplantation from SNI rats with or without anhedonia can alter pain, depression-like and anhedonia-like phenotypes in the pseudo-germ-free mice. Therefore, it is likely that gut microbiota plays a key role in the pain as well as depression-like phenotypes including anhedonia in rodents with neuropathic pain.


Assuntos
Anedonia/fisiologia , Depressão/microbiologia , Microbioma Gastrointestinal , Neuralgia/microbiologia , Neuralgia/psicologia , Animais , Comportamento Animal , Depressão/complicações , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Neuralgia/complicações , Fenótipo , Ratos Sprague-Dawley , Nervo Isquiático/lesões
9.
Pain Physician ; 22(1): E37-E44, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30700077

RESUMO

BACKGROUND: Spinal cord stimulation (SCS) relieves pain by delivering doses of electric current to the dorsal column of the spinal cord and has been found to be most effective in the treatment of neuropathic pain. Psychological distress is a significant risk factor for the development of chronic pain and has been found to affect the outcome of SCS. Childhood trauma is a risk factor for chronic pain, but has not previously been studied in SCS patients. OBJECTIVES: The objective of this prospective registry-based study was to investigate the prevalence of 5 domains of childhood trauma (emotional neglect, emotional abuse, physical neglect, physical abuse, and sexual abuse) and their relationship with the outcome of spinal cord stimulation on patients suffering from treatment-resistant chronic pain. METHODS: SCS patients treated at Kuopio University Hospital between 1/1/2015 and 12/31/2016 were sent a survey in the mail, the Trauma and Distress Scale, assessing childhood trauma (n = 43). Neuropathic pain, disability, anxiety, and depression were measured in the patients pre-surgery and at 6 and 12 months post-surgery. The patients who provided their name on the questionnaire (n = 22) and had suffered from 3 or more domains of trauma were grouped as the high-trauma group (n = 13) and the rest as the low-trauma group (n = 9). RESULTS: The questionnaire was completed by 40 patients (93%). At least 1 domain of trauma was experienced by 35 (88%) patients, and at least 2 by 24 (60%). The low-trauma group displayed a statistically significant decrease in the mean PainDETECT score from 21.5 before SCS to 16.5 at 12 months post-surgery (Wilk's lambda = 0.297, F(2,9) = 10.6, P = 0.004), contrary to the high- trauma group (Wilk's lambda = 0.904, F(2,6) = 0.3, P = 0.739). LIMITATIONS: Only 22 of the 40 patients provided their name on the questionnaire, which decreased the sample size on follow-up. CONCLUSION: This was the first study to investigate childhood trauma in SCS patients. Patients who had experienced high amounts of childhood trauma did not experience any relief from neuropathic pain 12 months' post-SCS, contrary to the low-trauma group. Childhood trauma might be a factor worth screening in the preoperative evaluation and aftercare of SCS candidates. KEY WORDS: Spinal cord stimulation, the Trauma and Distress Scale, chronic pain, childhood trauma, childhood abuse, childhood neglect, chronic back pain, back pain, psychological distress, neuropathic pain.


Assuntos
Maus-Tratos Infantis/psicologia , Neuralgia/psicologia , Neuralgia/terapia , Estimulação da Medula Espinal , Adulto , Criança , Dor Crônica/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento
10.
Science ; 363(6424): 276-281, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30655440

RESUMO

Pain is an unpleasant experience. How the brain's affective neural circuits attribute this aversive quality to nociceptive information remains unknown. By means of time-lapse in vivo calcium imaging and neural activity manipulation in freely behaving mice encountering noxious stimuli, we identified a distinct neural ensemble in the basolateral amygdala that encodes the negative affective valence of pain. Silencing this nociceptive ensemble alleviated pain affective-motivational behaviors without altering the detection of noxious stimuli, withdrawal reflexes, anxiety, or reward. Following peripheral nerve injury, innocuous stimuli activated this nociceptive ensemble to drive dysfunctional perceptual changes associated with neuropathic pain, including pain aversion to light touch (allodynia). These results identify the amygdalar representations of noxious stimuli that are functionally required for the negative affective qualities of acute and chronic pain perception.


Assuntos
Afeto , Tonsila do Cerebelo/fisiologia , Dor Crônica/fisiopatologia , Hiperalgesia/fisiopatologia , Neuralgia/fisiopatologia , Animais , Ansiedade , Comportamento Animal , Cálcio/análise , Dor Crônica/psicologia , Hiperalgesia/psicologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia de Fluorescência , Motivação , Atividade Motora , Neuralgia/psicologia , Percepção da Dor
11.
Neuropharmacology ; 148: 291-304, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30668942

RESUMO

Neuropathic pain is a complex disorder associated with emotional and cognitive deficits that may impair nociceptive manifestations. There is high inter-individual variability in the manifestations of human neuropathic pain, which largely depends on personality traits. We aim to identify the influence of different behavioral traits in the inter-individual vulnerability to neuropathic pain manifestations using behavioral, electrophysiological and genetic approaches. We first selected mice with extreme social and emotional traits and look for correlation with the spontaneous neuronal activity in the central amygdala. Neuropathic pain was induced to these mice to evaluate the influence of behavioral traits on nociceptive manifestations and gene expression profiles in the amygdala. Our results show an association of the spontaneous central amygdala neuronal activity with the sociability behavior. We demonstrate that low sociable, high anxious and low depressive phenotypes develop enhanced nociceptive hypersensitivity after nerve injury. However, greater emotional alterations and cognitive impairment are observed in high sociable, anxious-like and depressive-like mice, indicating that nociceptive, emotional and cognitive manifestations of neuropathic pain do not correlate with each other. Gene analyses identify high Pdyn and Il6 levels in the amygdala as indicative of enhanced nociceptive hypersensitivity and reveal an association between high Gadd45 expression and attenuated emotional and cognitive manifestations of neuropathic pain.


Assuntos
Cognição/fisiologia , Emoções/fisiologia , Individualidade , Neuralgia/fisiopatologia , Neuralgia/psicologia , Dor Nociceptiva/psicologia , Animais , Comportamento Animal , Proteínas de Ciclo Celular/biossíntese , Núcleo Central da Amígdala/metabolismo , Núcleo Central da Amígdala/fisiologia , Encefalinas/metabolismo , Expressão Gênica , Interleucina-6/metabolismo , Masculino , Camundongos , Neuralgia/complicações , Dor Nociceptiva/complicações , Precursores de Proteínas/metabolismo , Comportamento Social
12.
Pain Med ; 20(1): 161-171, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29522115

RESUMO

Objective: To identify factors associated with pain severity and opioid consumption in the early perioperative period. Design: Prospective observational cohort study. Setting: Tertiary academic medical center. Subjects: Patients with osteoarthritis older than age 45 years undergoing primary total knee replacement at Brigham and Women's Hospital. A total of 126 patients enrolled. Methods: Preoperatively, pain questionnaires and quantitative sensory testing were performed on patients to develop a psychosocial and psychophysical profile. Postoperatively, pain scores and opioid consumption were measured as primary end points. Univariate and multiple linear regression analyses were performed to determine the predictive value of these characteristics on perioperative pain scores and opioid consumption. Results: Regression analysis revealed several predictors of acute postoperative pain scores including temporal summation of pain (TSP; P = 0.001), body mass index (BMI; P = 0.044), number of previous knee surgeries (P = 0.006), and female gender (P = 0.023). Similarly, predictors of opioid utilization included TSP (P = 0.011), BMI (P = 0.02), age (P = <0.001), and tourniquet time (P = 0.003). Conclusions: The only significant, unique predictors of both pain and opioid consumption were TSP, an index of central pain facilitatory processes, and BMI. Interestingly, psychosocial factors, such as catastrophizing and somatization, although correlated with postoperative pain scores and opioid consumption, generally did not independently explain substantial variance in these measures. This study suggests that BMI and quantitative sensory testing, specifically the temporal summation of pain, may provide value in the preoperative assessment of patients undergoing total knee arthroplasty and other surgeries via predicting their level of risk for adverse pain outcomes.


Assuntos
Analgésicos Opioides/uso terapêutico , Artroplastia do Joelho/psicologia , Dor Pós-Operatória/psicologia , Período Perioperatório/psicologia , Dor Aguda/tratamento farmacológico , Dor Aguda/psicologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Neuralgia/psicologia , Medição da Dor/psicologia , Dor Pós-Operatória/tratamento farmacológico
13.
Anesth Analg ; 129(2): 587-597, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-29863609

RESUMO

BACKGROUND: Neuropathic pain is often associated with depression. Enhancing endocannabinoids by fatty acid amide hydrolase (FAAH) inhibitors relieves neuropathic pain and stress-induced depressive-like behaviors in animal models. However, it is unclear whether FAAH inhibitor can relieve neuropathic pain-induced depression by or not by its antinociceptive effects. METHODS: Adult male Wistar rats with chronic constriction injury (CCI) to the sciatic nerve were treated with the systemic FAAH inhibitor URB597 (5.8 mg·kg·day, intraperitoneally) or peripherally acting FAAH inhibitor URB937 (1.6 mg·kg·d, intraperitoneally; n = 11-12). The treatment was applied from the 15th day after surgery and continued for 15 days. Mechanical withdrawal threshold was examined by Von Frey test before surgery and on the 28th day after CCI. Depressive-like behaviors were evaluated by forced swimming test (FST) and novelty-suppressed feeding (NSF) after 15-day treatment. The levels of anandamide and 2-arachidonoylglycerol in hippocampus were examined by liquid chromatography and mass spectrometry. Hippocampal neurogenesis including proliferation, differentiation, and survival of newborn cells was assessed by immunohistochemistry. RESULTS: After CCI injury, the rats developed significantly nociceptive and depressive-like behaviors, indicated by persistent mechanical hypersensitivity in Von Frey test, significantly prolonged immobility time in FST (sham: 84.2 ± 13.4 seconds versus CCI: 137.9 ± 18.8 seconds; P < .001), and protracted latency to feed in NSF (sham: 133.4 ± 19.4 seconds versus CCI: 234.9 ± 33.5 seconds; P < .001). For the CCI rats receiving treatment, compared to vehicle placebo group, pain threshold was increased by both URB597 (3.1 ± 1.0 vs 11.2 ± 1.2 g; P < .001) and URB937 (3.1 ± 1.0 vs 12.1 ± 1.3 g; P < .001). Immobility time of FST was reduced by URB597 (135.8 ± 16.6 vs 85.3 ± 17.2 seconds; P < .001) but not by URB937 (135.8 ± 16.6 vs 129.6 ± 17.8 seconds; P = .78). Latency to feed in NSF was also reduced by URB597 (235.9 ± 30.5 vs 131.8 ± 19.8 seconds; P < .001) but not by URB937 (235.9 ± 30.5 vs 232.2 ± 33.2 seconds; P = .72). Meanwhile, CCI decreased the number of proliferating cells and reduced survival of new mature neurons in hippocampus. URB597 but not URB937 treatment improved these cellular deficits. CONCLUSIONS: Inhibition of FAAH can improve depressive-like behaviors induced by neuropathic pain independent of its peripheral antinociceptive action. Enhanced neurogenesis in hippocampus might contribute to the antidepressive effects of URB597.


Assuntos
Amidoidrolases/antagonistas & inibidores , Comportamento Animal/efeitos dos fármacos , Benzamidas/farmacologia , Carbamatos/farmacologia , Depressão/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Hipocampo/efeitos dos fármacos , Neuralgia/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Amidoidrolases/metabolismo , Animais , Ácidos Araquidônicos/metabolismo , Depressão/enzimologia , Depressão/fisiopatologia , Modelos Animais de Doenças , Endocanabinoides/metabolismo , Comportamento Alimentar/efeitos dos fármacos , Glicerídeos/metabolismo , Hipocampo/enzimologia , Hipocampo/fisiopatologia , Locomoção/efeitos dos fármacos , Masculino , Neuralgia/enzimologia , Neuralgia/fisiopatologia , Neuralgia/psicologia , Neurogênese/efeitos dos fármacos , Alcamidas Poli-Insaturadas/metabolismo , Ratos Wistar , Receptor CB1 de Canabinoide/metabolismo , Transdução de Sinais , Natação
14.
Behav Brain Res ; 359: 942-949, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29935275

RESUMO

Psychological stresses such as social loss and separation during childhood induce hardship, referred to as emotional pain. These experiences are well-documented risk factors for the development of physical pain in adulthood. However, the underlying neuronal mechanisms of this exacerbation of pain are largely unknown, and consequently there is no effective pharmacotherapy. In this study, we sought to determine whether infant maternal separation (MS) contributes to aggravation of neuropathic pain in adult mice. MS increased anxiety- and depression-like behavioral responses to adult stress. In MS animals, chronic constriction injury (CCI) heightened the sensory dimension of chronic pain relative to that of control mice. However, MS mice treated with fluoxetine for 4 weeks after MS did not exhibit augmentation of allodynia, and their emotional response was attenuated. Microglia were more abundant in the spinal cord in MS/CCI mice than in control/CCI mice. These results suggest that emotional impairment is related to augmentation of neuropathic pain, and that dysfunction of microglial activation contributes to heightened pain sensitivity.


Assuntos
Privação Materna , Transtornos do Humor/etiologia , Neuralgia/complicações , Neuralgia/psicologia , Animais , Animais Recém-Nascidos , Antidepressivos de Segunda Geração/uso terapêutico , Proteínas de Ligação ao Cálcio , Modelos Animais de Doenças , Fluoxetina/uso terapêutico , Preferências Alimentares/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Proteínas dos Microfilamentos , Microglia/metabolismo , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/patologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Sacarose/administração & dosagem , Natação/psicologia
15.
Patient Educ Couns ; 102(1): 134-138, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30131265

RESUMO

OBJECTIVE: The adequate treatment of chronic pain also calls for measuring its quality not only its intensity. For this reason, this pilot study investigated the non-verbal description of pain quality based on tones, distinguishing between nociceptive and neuropathic pain. METHODS: A nociceptive and a neuropathic pain stimulus were applied to 80 chronic pain patients and 80 healthy subjects. Using a tone generator, all participants matched both pain stimuli to an appropriate tone (in Hz). The stimulus intensity was measured using the NRS-scale, and the PainDETECT questionnaire was completed. RESULTS: Both groups matched a significantly higher tone to the neuropathic than to the nociceptive pain stimulus. Compared to healthy participants, chronic pain patients allocated higher tones to both pain stimuli. Higher values were also shown for the neuropathic pain stimulus, and chronic pain patients indicated an overall higher intensity of pain as healthy participants. CONCLUSIONS: It is possible to differentiate pain stimuli non-verbally through tones, however, whether quality or intensity, was the key factor remains unknown. Future studies could investigate the influence of additional factors. PRACTICAL IMPLICATIONS: A practical tool using tones should be developed to detect pain quality in patients - without verbal descriptions - quickly and more precisely.


Assuntos
Dor Crônica/psicologia , Neuralgia/psicologia , Dor Nociceptiva/psicologia , Comunicação não Verbal , Medição da Dor/métodos , Som , Adulto , Estudos de Casos e Controles , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Inquéritos e Questionários
16.
Eur J Pain ; 23(2): 285-306, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30098102

RESUMO

BACKGROUND: Chronic pain is often accompanied by comorbidities like anxiety and depression. The temporal correlations, as well as the underlying mechanisms of these reciprocal correlations, are unclear. Moreover, preclinical studies examining emotional behaviour are very controversial, and a chronological analysis of anxiety-like behaviour in mouse pain models considering both genders has not been performed so far. METHODS: We used several behavioural tests to assess and validate anxiety-like behaviour in complete Freund's adjuvant (CFA) and spared nerve injury (SNI) pain models in C57BL/6 mice. Among these were the elevated plus maze test, open field test, hole-board test and light-dark test. Additionally, we included a late stage analysis of depression-like behaviour using the forced swim test. All tests were applied once for each cohort of mice. Importantly, we used C57BL/6N mice of both genders; we investigated the effect of social isolation, the impact of pain induction to either the right or left hind limb and also investigated C57BL/6J mice. RESULTS: The validity of test conditions was confirmed using the anxiogenic drugs Yohimbine and Pentylenetetrazol. Anxiety-like behaviour was analysed throughout the time period when mice exhibited hypersensitivity to mechanical stimuli. We did not observe any consistent alteration in anxiety-like behaviour at any of the investigated time points between 1 and 14 days following CFA-induced inflammation or 3 and 84 days following SNI surgery using different behavioural tests. CONCLUSIONS: Inflammatory and neuropathic pain conditions do not primarily evoke anxiety- and depression-like behavioural alterations within the herein investigated time period. SIGNIFICANCE: Anxiety-like behaviour is not primarily altered following CFA and SNI in C57BL6 mice, irrespective of the gender, mouse sub-strain, housing conditions or affected body side within the herein investigated time period.


Assuntos
Ansiedade/etiologia , Dor Crônica/psicologia , Depressão/etiologia , Neuralgia/psicologia , Animais , Modelos Animais de Doenças , Emoções , Feminino , Adjuvante de Freund , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL
17.
Int J Neurosci ; 129(2): 146-154, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30118368

RESUMO

Purpose/Aim of the study In this study, we sought to observe the effects of Ca2+/calmodulin-dependent protein kinase II (CaMKII) on neuropathic pain and fear memory in a rat model of chronic constriction injury (CCI). Materials and methods Rats were randomly divided into the Sham, Control, CCI and m-AIP groups. In the m-AIP group, an intrathecal injection of m-AIP, the specific antagonist of CaMKII, was given either pretreatment or posttreatment in rats. Mechanical allodynia and thermal hyperalgesia tests were used to test pain behavior, and the passive avoidance test was used to measure fear memory in rats. Results The right side of hippocampus tissues were taken at varying time points. The expression levels of CaMKII-α, pCaMKII-α, CaMKII-ß, pCaMKII-ß, NR2A, pNR2A, NR2B and pNR2B were detected by Western blot analysis. Significant pain behaviors and impaired cognitive function were shown after CCI surgery, accompanied by the upregulation of proteins in the hippocampus. Pretreatment with m-AIP appeared to provide a temporary improvement in pain and fear memory and decreased the expression of the above proteins in the hippocampus seven days after surgery. Furthermore, postoperative treatment with m-AIP provided relief for pain behavior and protein expression but did not affect fear memory. Conclusions These data suggested that CaMKII played an important role in the crosstalk between neuropathic pain and fear memory, indicating that CaMKII may be a potential therapeutic target for neuropathic pain treatment.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Medo/fisiologia , Hipocampo/metabolismo , Memória/fisiologia , Neuralgia/metabolismo , Animais , Constrição , Hiperalgesia/metabolismo , Masculino , Neuralgia/psicologia , Fosforilação , Ratos Sprague-Dawley , Nervo Isquiático/lesões
18.
Arch Phys Med Rehabil ; 100(1): 17-25, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30268806

RESUMO

OBJECTIVES: To explore the feasibility and efficacy of web-based mindfulness training for carers of people with spinal cord injury (SCI). DESIGN: Randomized controlled feasibility study with 3-month follow-up. SETTING: Community setting. PARTICIPANTS: Spouses or family caregivers (N=55) of people with SCI and chronic neuropathic pain were recruited via the direct care team and advertisements. Participants were older than 18 years (no upper age limit), with Internet access for the duration of the study. Participants were randomly allocated to an 8-week online mindfulness training intervention (n=28), or to receive 8 weeks of psychoeducational materials on SCI and chronic pain (n=27). INTERVENTIONS: An established web-based, mindfulness training course was delivered over 8 weeks. Participants completed 10 minutes of mindfulness practices, twice per day, 6 days per week, totaling 960 minutes. The control group received a weekly e-mail with psychoeducational materials (based on the established elements) on SCI and pain for 8 weeks. MAIN OUTCOME MEASURE: Depression severity. RESULTS: Mindfulness reduced depression severity more than psychoeducation at T2 (mean difference= -.891; 95% confidence interval,-1.48 to -.30) and T3 (mean difference=-1.96; 95% confidence interval, -2.94 to -.97). Mindfulness training also reduced anxiety at T2 (mean difference=-.888; 95% confidence interval, -1.40 to -.38) and T3 (mean difference=-2.44; 95% confidence interval, -3.20 to -1.69). CONCLUSIONS: Results indicate that Internet-delivered mindfulness training offers unique benefits and is viable for caregivers of people with SCI and chronic neuropathic pain. Further work should explore the feasibility of combined education and mindfulness training incorporating both patient and caregiver, for optimum benefit.


Assuntos
Ansiedade/terapia , Cuidadores/psicologia , Depressão/terapia , Atenção Plena/métodos , Educação de Pacientes como Assunto/métodos , Adulto , Ansiedade/psicologia , Dor Crônica/psicologia , Depressão/psicologia , Estudos de Viabilidade , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Neuralgia/psicologia , Traumatismos da Medula Espinal/psicologia , Telemedicina/métodos , Resultado do Tratamento
19.
Pain Pract ; 19(2): 183-195, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30269431

RESUMO

INTRODUCTION: The differentiation between acute and chronic pain can be insufficient for appropriate pain management. The aim of this study was to evaluate the prevalence of the predominant pain type (nociceptive, neuropathic, or central sensitization [CS] pain) in breast cancer survivors (BCS) with chronic pain. The secondary aims were to examine (1) differences in health-related quality of life (HRQoL) between the different pain groups; and (2) the associations between patient-, disease-, and treatment-related factors and the different pain types. METHODS: To determine the prevalence of the predominant type of pain, a recently proposed classification system was used. BCS were asked to complete the VAS for pain, Douleur Neuropathique 4 Questionnaire, Margolis Pain Diagram, Central Sensitization Inventory, and Short Form 36 (SF-36). RESULTS: Ninety-one BCS participated, among whom 25.3% presented neuropathic pain, 18.7% nociceptive pain, and 15.4% CS pain. Mixed pain was found in 40.6%. A significant intergroup difference in HRQoL was found for SF-36 "general health" (P = 0.04). The odds for the presence of CS rather than nociceptive pain are 26 times higher in patients exposed to hormone therapy in comparison to the nonexposed (odds ratio 25.95, 95% confidence interval 1.33 to 504.37, P = 0.03). CONCLUSION: Neuropathic pain is most frequent in BCS. Strong associations were found between CS pain and hormone therapy.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Sensibilização do Sistema Nervoso Central , Dor Crônica/epidemiologia , Neuralgia/epidemiologia , Dor Nociceptiva/epidemiologia , Adulto , Idoso , Dor Crônica/etiologia , Dor Crônica/psicologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Neuralgia/etiologia , Neuralgia/psicologia , Dor Nociceptiva/etiologia , Dor Nociceptiva/psicologia , Prevalência , Qualidade de Vida , Inquéritos e Questionários
20.
Ann Phys Rehabil Med ; 62(1): 49-57, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30312665

RESUMO

BACKGROUND: Treatment of spinal cord injury (SCI)-associated neuropathic pain is challenging, with limited efficacy and no definitive options, and SCI patients often show resistance to pharmacologic treatment. Virtual reality (VR) therapy is a non-invasive, non-pharmacologic alternative with minimal adverse effects. OBJECTIVE: To investigate the effect of VR therapy on SCI-associated neuropathic pain in a systematic review. METHODS: Articles needed to 1) be written in English; 2) include adult subjects, with at least half the study population with a SCI diagnosis; 3) involve any form of VR therapy; and 4) assess neuropathic pain by quantitative outcome measures. Articles were searched in MEDLINE/PubMed, CINAHL®, EMBASE, and PsycINFO up to April 2018. Reference lists of retrieved articles were hand-searched. Methodologic quality was assessed by the Physiotherapy Evidence Database Score (PEDro) for randomized controlled trials and Modified Downs and Black Tool (D&B) for all other studies. Level of evidence was determined by using a modified Sackett scale. RESULTS: Among 333 studies identified, 9 included in this review (n=150 participants) evaluated 4 methods of VR therapy (virtual walking, VR-augmented training, virtual illusion, and VR hypnosis) for treating neuropathic pain in SCI patients. Each VR method reduced neuropathic pain: 4 studies supported virtual walking, and the other 3 VR methods were each supported by a different study. Combined treatment with virtual walking and transcranial direct current stimulation was the most effective. The quality of studies was a major limitation. CONCLUSION: VR therapy could reduce SCI-associated neuropathic pain, although the clinical significance of this analgesic effect is unclear. Clinical trials evaluating VR therapy as standalone and/or adjunct therapy for neuropathic pain in SCI patients are warranted.


Assuntos
Neuralgia/reabilitação , Traumatismos da Medula Espinal/complicações , Terapia de Exposição à Realidade Virtual/métodos , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Neuralgia/etiologia , Neuralgia/psicologia , Traumatismos da Medula Espinal/psicologia , Estimulação Transcraniana por Corrente Contínua/métodos , Resultado do Tratamento
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