RESUMO
Surgical pain is associated with delirium in patients, and acupuncture can treat pain. However, whether electroacupuncture can attenuate the surgical pain-associated delirium via the gut-brain axis remains unknown. Leveraging a mouse model of foot incision-induced surgical pain and delirium-like behavior, we found that electroacupuncture stimulation at specific acupoints (e.g., DU20+KI1) attenuated both surgical pain and delirium-like behavior in mice. Mechanistically, mice with incision-induced surgical pain and delirium-like behavior showed gut microbiota imbalance, microglia activation in the spinal cord, somatosensory cortex, and hippocampus, as well as an enhanced dendritic spine elimination in cortex revealed by two-photon imaging. The electroacupuncture regimen that alleviated surgical pain and delirium-like behavior in mice also effectively restored the gut microbiota balance, prevented the microglia activation, and reversed the dendritic spine elimination. These data demonstrated a potentially important gut-brain interactive mechanism underlying the surgical pain-induced delirium in mice. Pending further studies, these findings revealed a possible therapeutic approach in preventing and/or treating postoperative delirium by using perioperative electroacupuncture stimulation in patients.
Assuntos
Delírio , Eletroacupuntura , Microbioma Gastrointestinal , Animais , Espinhas Dendríticas , Eletroacupuntura/métodos , Camundongos , DorRESUMO
BACKGROUND: We examined whether the effect of true electroacupuncture on pain and functionality in chronic pain participants can be differentiated from that of medication (gabapentin) by analyzing quantitative sensory testing (QST). METHODS: We recruited chronic back and neck pain participants who received six sessions (twice weekly) of true electroacupuncture versus sham electroacupuncture or 3 weeks of gabapentin versus placebo treatment. QST profiles, pain scores, and functionality profile were obtained at baseline (visit 1) and after three sessions (visit 4) or six sessions (visit 7) of acupuncture or 3 weeks of gabapentin or placebo. RESULTS: A total of 50 participants were analyzed. We found no differences in QST profile changes (p = 0.892), pain reduction (p = 0.222), or functionality (p = 0.254) between the four groups. A major limitation of this pilot study was the limited number of study participants in each group. CONCLUSION: This pilot study suggests that a large-scale clinical study with an adequate sample size would be warranted to compare acupuncture and medication therapy for chronic pain management. TRIAL REGISTRATION NUMBER: NCT01678586 (ClinicalTrials.gov).
Assuntos
Analgésicos/administração & dosagem , Dor Crônica/terapia , Eletroacupuntura , Gabapentina/administração & dosagem , Adulto , Idoso , Dor Crônica/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do TratamentoRESUMO
In this randomized clinical trial, we examined whether the effect of true acupuncture can be differentiated from sham acupuncture (pain and functionality) by analyzing quantitative sensory testing (QST) profiles in chronic pain participants. We recruited 254 healthy or chronic back and neck pain participants. Healthy subjects were included to control for a possible effect of acupuncture on baseline QST changes. Study participants received 6 sessions (twice weekly) of true acupuncture, sham acupuncture, or no acupuncture treatment (routine care). Quantitative sensory testing profiles, pain scores, and functionality profile were obtained at baseline (visit 1) and after 3 (visit 4) or 6 sessions (visit 7). A total of 204 participants were analyzed. We found no QST profile changes among 3 groups (P = 0.533 and P = 0.549, likelihood ratio tests) in either healthy or chronic pain participants. In chronic back and neck pain participants, true acupuncture reduced pain (visit 4: difference in mean [DIM] = -0.8, 95% confidence interval [CI]: -1.4 to -0.1, adjusted P = 0.168; visit 7: DIM = -1.0, 95% CI: -1.7 to -0.3, adjusted P = 0.021) and improved functional status including physical functioning (DIM = 14.21, 95% CI: 5.84-22.58, adjusted P = 0.003) and energy/fatigue (DIM = 12.28, 95% CI: 3.46-21.11, adjusted P = 0.021) as compared to routine care. Our results indicate that QST was not helpful to differentiate between true acupuncture and sham acupuncture (primary outcome) in this study, although true acupuncture reduced pain and improved functionality (secondary outcomes) when compared with routine care.
Assuntos
Terapia por Acupuntura , Dor Crônica/terapia , Cervicalgia/terapia , Sensação/fisiologia , Terapia por Acupuntura/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Resultado do TratamentoRESUMO
INTRODUCTION: The aim of this study was to examine the effect of electroacupuncture (EA) on trigeminal neuropathic pain in rats and explore the potential mechanism underlying the putative therapeutic effect of EA. METHODS: Trigeminal neuropathic pain behavior was induced in rats by unilateral chronic constriction injury of the distal infraorbital nerve (dIoN-CCI). EA was administered at ST2 (Sibai) and Jiachengjiang. A total of 60 Sprague Dawley rats were divided into the following four groups (n = 15 per group) to examine the behavioral outcomes after surgery and/or EA treatment: sham (no ligation); dIoN-CCI (received isoflurane only, without EA treatment); dIoN-CCI+EA-7d (received EA treatment for 7 days); and dIoN-CCI+EA-14d (received EA treatment for 14 days). Both evoked and spontaneous nociceptive behaviors were measured. Of these, 12 rats (n = 4 from sham, dIoN-CCI, and dIoN-CCI+EA-14d groups, respectively) were used to analyze protein expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel in the Gasserian ganglion (GG) by immunohistochemistry. RESULTS: dIoN-CCI rats exhibited mechanical allodynia and increased face-grooming activity that lasted at least 35 days. EA treatment reduced mechanical allodynia and face-grooming in dIoN-CCI rats. Overall, 14 days of EA treatment produced a prolonged anti-nociceptive effect as compared to 7-day EA treatment. The counts of HCN1 and HCN2 immunopositive puncta were increased in the ipsilateral GG in dIoN-CCI rats and were reduced by 14 days of EA treatment. DISCUSSION: EA treatment relieved trigeminal neuropathic pain in dIoN-CCI rats, and this effect was dependent on the duration of EA treatment. The downregulation of HCN expression may contribute to the anti-nociceptive effect of EA in this rat model of trigeminal neuropathic pain.
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Eletroacupuntura , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Gânglio Trigeminal/metabolismo , Neuralgia do Trigêmeo/terapia , Animais , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Masculino , Ratos , Ratos Sprague-Dawley , Neuralgia do Trigêmeo/genética , Neuralgia do Trigêmeo/metabolismoRESUMO
Acupuncture can provide therapeutic analgesic benefits but is limited by its cost and scheduling difficulties. Guided imagery is a commonly used method for treating many disorders, such as chronic pain. The present study examined a novel intervention for pain relief that integrates acupuncture with imagery called video-guided acupuncture imagery treatment (VGAIT). A total of 27 healthy subjects were recruited for a crossover-design study that included 5 sessions administered in a randomized order (i.e., baseline and 4 different interventions). We investigated changes in pain threshold and fMRI signals modulated by: 1) VGAIT, watching a video of acupuncture previously administered on the participant's own body at baseline while imagining it being concurrently applied; 2) a VGAIT control condition, watching a video of a cotton swab touching the skin; 3) real acupuncture; and 4) sham acupuncture. Results demonstrated that real acupuncture and VGAIT significantly increased pain threshold compared with respective control groups. Imaging showed that real acupuncture produced greater activation of the insula compared with VGAIT. VGAIT produced greater deactivation at the rostral anterior cingulate cortex. Our findings demonstrate that VGAIT holds potential clinical value for pain management.
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Analgesia por Acupuntura/métodos , Encéfalo/diagnóstico por imagem , Dor Crônica/terapia , Imagens, Psicoterapia/métodos , Limiar da Dor , Gravação em Vídeo , Adulto , Encéfalo/fisiologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Estudos Cross-Over , Feminino , Neuroimagem Funcional , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Masculino , Placebos , Adulto JovemRESUMO
Objective: Correlation between radiologic structural abnormalities and clinical symptoms in low back pain patients is poor. There is an unmet clinical need to image inflammation in pain conditions to aid diagnosis and guide treatment. Ferumoxytol, an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle, is clinically used to treat iron deficiency anemia and showed promise in imaging tissue inflammation in human. We explored whether ferumoxytol can be used to identify tissue and nerve inflammation in pain conditions in animals and humans. Methods: Complete Freud's adjuvant (CFA) or saline was injected into mice hind paws to establish an inflammatory pain model. Ferumoxytol (20 mg/kg) was injected intravenously. Magnetic resonance imaging (MRI) was performed prior to injection and 72 hours postinjection. The changes in the transverse relaxation time (T2) before and after ferumoxytol injection were compared between mice that received CFA vs saline injection. In the human study, we administered ferumoxytol (4 mg/kg) to a human subject with clinical symptoms of lumbar radiculopathy and compared the patient with a healthy subject. Results: Mice that received CFA exhibited tissue inflammation and pain behaviors. The changes in T2 before and after ferumoxytol injection were significantly higher in mice that received CFA vs saline (20.8 ± 3.6 vs 2.2 ± 2.5, P = 0.005). In the human study, ferumoxytol-enhanced MRI identified the nerve root corresponding to the patient's symptoms, but the nerve root was not impinged by structural abnormalities, suggesting the potential superiority of this approach over conventional structural imaging techniques. Conclusions: Ferumoxytol-enhanced MRI can identify tissue and nerve inflammation and may provide a promising diagnostic tool in assessing pain conditions in humans.
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Meios de Contraste , Diagnóstico por Imagem/métodos , Óxido Ferroso-Férrico , Inflamação/diagnóstico por imagem , Dor/diagnóstico por imagem , Radiculopatia/diagnóstico por imagem , Adulto , Animais , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Nanopartículas Metálicas , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-IdadeRESUMO
Complementary and integrative medicine (CIM) encompasses both Western-style medicine and complementary health approaches as a new combined approach to treat a variety of clinical conditions. Chronic pain is the leading indication for use of CIM, and about 33% of adults and 12% of children in the US have used it in this context. Although advances have been made in treatments for chronic pain, it remains inadequately controlled for many people. Adverse effects and complications of analgesic drugs, such as addiction, kidney failure, and gastrointestinal bleeding, also limit their use. CIM offers a multimodality treatment approach that can tackle the multidimensional nature of pain with fewer or no serious adverse effects. This review focuses on the use of CIM in three conditions with a high incidence of chronic pain: back pain, neck pain, and rheumatoid arthritis. It summarizes research on the mechanisms of action and clinical studies on the efficacy of commonly used CIM modalities such as acupuncture, mind-body system, dietary interventions and fasting, and herbal medicine and nutrients.
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Dor Crônica/terapia , Terapias Complementares , Medicina Integrativa , Animais , Artrite Reumatoide/terapia , Dor nas Costas/terapia , Terapias Complementares/efeitos adversos , Humanos , Cervicalgia/terapiaRESUMO
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability in both peripheral and central nerve systems. Emerging evidence indicates that HCN channels are involved in the development and maintenance of chronic pain. However, the impact of HCN channel activity in the thalamus on chronic pain has not been examined. In this report, we evaluated the effect on nociceptive behaviors after infusion of a HCN channel blocker ZD7288 into the ventral posterolateral (VPL) nucleus of the thalamus in rats with neuropathic pain or monoarthritis. We show that ZD7288 dose-dependently attenuated mechanical allodynia and thermal hyperalgesia in rats with chronic pain. In the thalamus, immunoreactivity of both HCN1 and HCN2 subunits was increased in both rat models. These results suggest that the increased HCN channel activity in the thalamus of the ascending nociceptive pathway contributes to both chronic neuropathic and inflammatory pain conditions.
Assuntos
Dor Crônica/fisiopatologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/fisiologia , Nociceptividade/fisiologia , Canais de Potássio/fisiologia , Tálamo/fisiopatologia , Animais , Artrite Experimental/fisiopatologia , Adjuvante de Freund , Hiperalgesia/fisiopatologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/antagonistas & inibidores , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Masculino , Neuralgia/fisiopatologia , Canais de Potássio/metabolismo , Pirimidinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Tálamo/metabolismoAssuntos
Encéfalo/fisiologia , Temperatura Alta , Dor Lombar/terapia , Moxibustão/métodos , Sensação/fisiologia , Feminino , Humanos , MasculinoRESUMO
Despite the subjective nature of pain experience with cognitive and affective dimensions, preclinical pain research has largely focused on its sensory dimension. Here, we examined the relationship between learning/memory and nociceptive behavior in rats with combined learning impairment and persistent nociception. Learning impairment was induced by bilateral hippocampal injection of a mixed Aß solution, whereas persistent nociception produced in these rats by complete Freund's adjuvant-induced ankle inflammation. Those rats with learning impairment showed a diminished development of thermal hyperalgesia and mechanical allodynia and a shorter time course of nociceptive behavior without alteration of their baseline nociceptive threshold. In rats with pre-established hyperalgesia and allodynia due to ankle inflammation, bilateral intra-hippocampal injection of cycloheximide (a protein synthesis inhibitor) promoted the earlier recovery of nociceptive behavior. Moreover, expression of Aß, NR1 subunit of the N-methyl-D-aspartate receptor, and protein kinase Cγ was upregulated, whereas the choline acetyl transferase expression was downregulated, in the hippocampus, thalamus, amygdala, and/or spinal cord of rats with combined learning impairment and persistent nociception. The data indicate that learning impairment could disrupt the response to a state of persistent nociception, suggesting an important role for cognitive maladaptation in the mechanisms of chronic pain. These results also suggest that a preclinical model of combined learning impairment and persistent nociception may be useful to explore the brain mechanisms underlying the transition from acute to chronic pain.
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Transtornos Cognitivos/fisiopatologia , Hiperalgesia/fisiopatologia , Aprendizagem , Nociceptividade , Limiar da Dor/fisiologia , Dor/fisiopatologia , Peptídeos beta-Amiloides/administração & dosagem , Animais , Tornozelo/fisiopatologia , Comportamento Animal , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/metabolismo , Cicloeximida/administração & dosagem , Adjuvante de Freund/administração & dosagem , Expressão Gênica , Temperatura Alta , Hiperalgesia/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/fisiopatologia , Masculino , Dor/metabolismo , Medição da Dor , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
Free radicals have long been studied as a contributor to aging and disease processes. Endogenous production of radicals from cellular metabolism and exogenous sources from ultraviolet radiation and pollution can damage the skin on the cellular and tissue levels. Although the body possesses an elegant defense system to prevent radical damage, this innate system can be overwhelmed and lead to a state of oxidative stress or immunosuppression, and can even trigger carcinogenesis. Topical supplementation of antioxidants can provide additional protection to neutralize reactive oxygen species from both endogenous and exogenous sources. This review will discuss our current understanding of the mechanisms of free radical damage and evaluate the potential benefit of topical antioxidants in sunscreens and skin care products.
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Antioxidantes/fisiologia , Envelhecimento da Pele/fisiologia , Luz Solar , Animais , Ácido Ascórbico/fisiologia , Radicais Livres/metabolismo , Humanos , Terapia de Imunossupressão , Peroxidação de Lipídeos , Mitocôndrias/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Luz Solar/efeitos adversos , Vitamina E/fisiologiaRESUMO
OBJECTIVES: To collect information on the role of acupuncture in pain management from pain physicians and referral physicians who manage clinical pain conditions. METHODS: The survey was conducted between 2007 and 2008 through nationwide direct mail or e-mail to 1083 physicians who are currently practicing in the United States. We divided our 16 survey questions into five categories: 1) physician's attitude toward acupuncture as a modality of pain management; 2) physician's preference or belief with regard to the type of pain condition suitable for acupuncture referrals; 3) timing for making acupuncture referrals (e.g., acupuncture as a first line pain treatment option or a last approach after failed conventional pain management); 4) clinical assessment criteria for the effectiveness of acupuncture therapy; and 5) barriers to making acupuncture referrals (e.g., physician's personal view, insurance issues, patient refusal, etc.). The survey results were calculated and interpreted as the percentage rate of response. RESULT: The results indicate that an overwhelming majority of survey responders have a positive attitude and favorable experience with using acupuncture as an alternative modality for chronic pain management. However, our survey responders are mostly from teaching hospitals, suggesting a possible gap between teaching hospitals and other medical facilities (private practice and community hospitals) in utilizing acupuncture for pain management. The lack of insurance coverage and facility for acupuncture treatment are two primary barriers to making acupuncture referrals. CONCLUSIONS: The survey results indicate that acupuncture is considered by many physicians to be a useful alternative modality for chronic pain management.