The efficacy and neural mechanism of acupuncture therapy in the treatment of visceral hypersensitivity in irritable bowel syndrome

Irritable Bowel Syndrome (IBS) is a complex functional gastrointestinal disorder primarily characterized by chronic abdominal pain, bloating, and altered bowel habits. Chronic abdominal pain caused by visceral Hypersensitivity (VH) is the main reason why patients with IBS seek medication. Significant research effort has been devoted to the efficacy of acupuncture as a non-drug alternative therapy for visceral-hyperalgesia-induced IBS. Herein, we examined the central and peripheral analgesic mechanisms of acupuncture in IBS treatment. Acupuncture can improve inflammation and relieve pain by reducing 5-hydroxytryptamine and 5-HT3A receptor expression and increasing 5-HT4 receptor expression in peripheral intestinal sensory endings. Moreover, acupuncture can also activate the transient receptor potential vanillin 1 channel, block the activity of intestinal glial cells, and reduce the secretion of local pain-related neurotransmitters, thereby weakening peripheral sensitization. Moreover, by inhibiting the activation of N-methyl-D-aspartate receptor ion channels in the dorsal horn of the spinal cord and anterior cingulate cortex or releasing opioids, acupuncture can block excessive stimulation of abnormal pain signals in the brain and spinal cord. It can also stimulate glial cells (through the P2X7 and prokinetic protein pathways) to block VH pain perception and cognition. Furthermore, acupuncture can regulate the emotional components of IBS by targeting hypothalamic-pituitary-adrenal axis-related hormones and neurotransmitters via relevant brain nuclei, hence improving the IBS-induced VH response. These findings provide a scientific basis for acupuncture as an effective clinical adjuvant therapy for IBS pain

Plasticity in descending modulation of pain : therapeutic effects of non-painful heating-needle stimulation and its potential mechanisms

In the present series of studies, contributions of descending pain facilitatory and inhibitory pathways to behavioral pain responses were assessed under physiological conditions in humans and rats, under a simulated weightlessness condition in rats, and in an experimental model of Parkinson’s disease (PD) in rats. A long-term activation of descending pain modulatory pathways was induced by noxious conditioning stimulation to allow determining whether the studied experimental procedures cause decreases or increases in the activity of descending pathways. Acute muscle nociception was induced by intramuscular injection of 5.8% hypertonic saline. Secondary mechanical hyperalgesia was used as an index of the magnitude of descending facilitation, and secondary heat hypoalgesia as an index of the magnitude of descending inhibition. To explore whether heating-needle stimulation (H.N.S.) can promote analgesia due to modulation of descending pain controls, the effect of H.N.S. on descending facilitation and inhibition was also determined in different experimental conditions of the present study. To study whether thalamic dopamine is involved in descending modulation of pain, the effects induced by microinjections of dopamine or dopamine D2 receptor antagonist into the thalamic mediodorsal (MD) / ventromedial (VM) nuclei on descending pain modulation were evaluated. Furthermore, expression of Fos, a marker of neuronal activation, was determined in the spinal cord dorsal horn to reveal a spinal neuronal correlate for descending pain modulation. In the current series of studies, simulated weightlessness and a partial depletion of dopamine in the striatum enhanced endogenous descending facilitation and depressed descending inhibition. In the spinal dorsal horn, changes in Fos expression in the superficial layers were associated with changes in descending facilitation and those in the middle/deep layers with changes in descending inhibition. Intramuscular (i.m.) H.N.S. at an innocuous temperature of 43 C triggered descending inhibition without concomitant activation of descending facilitation both in physiological conditions and in experimental model of PD. In the PD model, dopamine D2 receptors in the thalamic VM nucleus were involved in mediating the enhancement of descending pain inhibition induced by H.N.S. applied at the temperature of 43 C. In humans, i.m. H.N.S. applied at the non-painful temperature of 43 C enhanced selectively descending inhibition, and it may be explained by a difference in the density of capsaicin- and heat-sensitive fibers innervating these heating-needle stimulation targets. Injection of capsaicin that selectively activates C-fibers produced stronger pain in acupoints than in non-acupoints.Koe-eläimillä aikaansaatiin patofysiologinen tilanne joko painotonta olosuhdetta simuloivalla tilalla tai kemiallisesti aikaansaadulla kokeellisella Parkinsonin taudilla. Kaikissa olosuhteissa niin ihmisellä kuin koe-eläimillä aktivoitiin pitkäkestoisesti laskevat kivunmuuntelujärjestelmät antamalla toispuoleisesti raajan lihakseen hypertonista keittosuolaa. Kynnysmääritykset tehtiin ihoalueella, joka oli etäällä hypertonisella keittosuolalla käsitellystä lihaksesta, minkä vuoksi kynnysmuutokset kuvastavat keskushermostollisiin mekanismeihin perustuvaa sekundaarista hyperalgesiaa tai hypoalgesiaa. Työsarjassa selvitettiin myös kuumaneulastimulaation terapeuttista vaikutusta ja vaikutusmekanismia kivulle herkistymiseen. Mediaalisen talamuksen dopamiinihermotuksen merkitystä laskevan kivunmuuntelujärjestelmän toiminnan häiriölle tutkittiin annostelemalla mediaalisen talamuksen tumakkeisiin dopamiinia tai dopamiini D2 reseptorin antagonistia. Mediaalisessa talamuksessa tutkimuksen kohteena olivat mediodorsaalinen (MD) tumake ja ventromediaalinen (VM) tumake. Lisäksi tutkittiin selkäytimen takasarven eri solukerrosten osuutta laskevassa kivun muuntelussa käyttäen hermosolujen toiminnan mittarina c-FOS-merkkiaineen ilmentymistä. Painotonta olosuhdetta simuloiva tila sekä kokeellinen Parkinsonin tauti vahvistivat kivun laskevaa fasilitaatiota ja vaimensivat kivun laskevaa inhibitiota. Selkäytimen takasarvessa laskeva fasilitaatio korreloi hermosoluaktiviteetin muutoksiin selkäytimen takasarven pinnallisissa solukerroksissa, kun taas laskeva inhibitio korreloi muutoksiin takasarven syvempien solukerrosten hermosoluaktiviteetissa. Kivuton kuumaneulastimulaatio 43oC lämpötilassa olevilla neuloilla vahvisti selektiivisesti kivun laskevaa inhibitiota koe-eläimillä sekä fysiologissa oloissa että kokeellisessa Parkinsonin tautimallissa. Mediaalisen talamuksen VM-tumakkeen dopamiini 2-reseptori oli välittämässä kuumaneulastimulaation kipua inhiboivaa vaikutusta Parkinsonin tautimallissa. Myös ihmiskokeissa kivuton kuumaneulastimulaatio 43oC lämpötilassa olevilla neuloilla vahvisti selektiivisesti kivun laskevaa inhibitiota. Ihmiskoetulokset osoittivat, että ääreishermoista C-syyt ovat keskeisiä kuumaneulastimulaation vaikutuksen välittäjiä, koska kuumaneulastimulaation terapeuttinen vaikutus oli voimakkain, kun stimuloitiin ihoaluetta, jossa C-syitä selektiivisesti aktivoiva kemiallinen aine kapsaisiini aiheutti voimakkaimman poltteen

Acupuncture in Modern Medicine

This book contains four integrated sections: 1) Acupuncture Research; 2) New Developments in Acupuncture; 3) Acupuncture Therapy for Clinical Conditions and 4) Assessment and Accessibility in Acupuncture Therapy. Section 1 provides updates on acupuncture research. From acupuncture effects in modulation of immune system to the role of nitric oxide in acupuncture mechanisms, chapters in this section offer readers the newest trends in acupuncture research. Section 2 summarizes new developments in acupuncture. The included chapters discuss new tools and methods in acupuncture such as laser acupuncture, sham needles, and new technologies. Section 3 discusses acupuncture therapy for clinical conditions. The chapters in this section provide comprehensive and critical views of acupuncture therapy and its application in common clinical practice. Section 4 takes a new look at the issues related to assessment and accessibility in acupuncture therapy. These issues are central to developing new standards for outcome assessment and policies that will increase the accessibility to acupuncture therapy

Acupuncture as treatment for dogs suffering from chronic pain

Pain is an unpleasant feeling bound to affect us, both humans as animals, during our lifetimes. Thousands of people are suffering from chronic pain around the world, and chronic pain in animals and ways to treat it is rapidly gaining more and more interest. The pain network is a vastly intricate one, with complex interactions between a plethora of neurons and cells. Modern science has yet to shine a light on the complete process of pain sensation. Acupuncture has been used for thousands of years in treating pain amongst other problems and is today approved by the World Health Organization as a treatment for certain types of pain among other conditions. Wide research has been carried out during the last few decades as acupuncture is gaining ground in the Western world and while evidence of its analgesic effects and some mechanisms of action (e.g. endogenous opioid-release) have been found through studies, our understanding of the response elicited by acupuncture still remains incomplete. In the current study, material was gathered in form of questionnaires, which owners to dogs treated with acupuncture filled out. We then assessed the efficacy of acupuncture as a treatment method for dogs suffering from chronic pain by analysing improvements in mobility, quality of life and pain by means of the Helsinki Chronic Pain Index (HCPI), visual analogue scales (VAS) (n=5-9) and a comparative enquiry (n=85). Although no statistically significant differences were found, results were constantly indicative of improvement, and significant differences might have been found were it not for the small numbers of cases in the HCPI-and VAS-studies. While no conclusions can be drawn from the current study, the results may be guardedly interpreted as indicative of the analgesic abilities of acupuncture in treating chronic pain in dogs

Efeito antinociceptivo e anti-hiperalgésico da acupuntura no teste de formalina em ratos machos e fêmeas

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Florianópolis, 2011Os mecanismos fisiológicos da analgesia produzida pela acupuntura foram extensamente explorados nas últimas décadas e evidências mostram o envolvimento de opióides endógenos e seus receptores neste efeito analgésico. Em paralelo, estudos apontam dimorfismo sexual na sensibilidade a estímulos dolorosos e na resposta analgésica aos opióides. O objetivo deste estudo foi investigar se os efeitos antinociceptivos e anti-hiperalgésicos da acupuntura são sensíveis às diferenças sexuais. Foram utilizados 275 ratos Wistar adultos, fêmeas (200-250g) e machos (300-350g). Hiperalgesia e inflamação foram induzidos por 0,05ml de solução de 1,0% de formaldeído em salina (0,9%) (solução de formalina), injetada (sc) na superfície plantar da pata posterior direita. Para controle da solução de formalina, grupos de animais foram injetados (sc) somente com salina. Depois de injetados com salina ou formalina, os grupos de animais aguardavam por 10 min e eram submetidos aos seguintes procedimentos: contenção (controle) ou contenção + acupuntura no ponto análogo ST36 ou contenção + acupuntura no ponto sham. A acupuntura manual no ponto análogo ao ST36 ou no ponto sham foi realizada por 20 min e os animais permaneciam livres para se mover na caixa de observação. Os comportamentos nociceptivos induzidos pela solução de formalina foram avaliados, subseqüentemente, por 30 min e utilizados para o cálculo do índice de dor. O limiar de retirada da pata em resposta a estímulo mecânico (filamentos de Von Frey) e a latência de retirada da pata em resposta a estímulo térmico (calor radiante) foram determinados 90 min após a injeção de formalina ou salina. Não houve diferença no índice de dor entre ratos machos e fêmeas controles, injetados com formalina. O limiar basal de retirada da pata em resposta a estímulo mecânico foi menor em ratos fêmeas em estro quando comparados aos ratos machos e fêmeas em diestro e proestro, já a latência basal de retirada da pata foi maior em ratos machos quando comparados às fêmeas em qualquer fase do ciclo estral. No entanto, ratos machos e fêmeas controles não apresentaram diferença no limiar de retirada da pata em resposta a estímulo mecânico e na latência de retirada da pata em resposta a estímulo térmico quando avaliados 90 min após injeção de formalina. A acupuntura manual no ponto análogo ao ST36 não produziu efeito antinociceptivo no teste da formalina, porém produziu um aumento no limiar de retirada da pata em resposta a estímulo mecânico em ratos fêmeas em diestro e em estro e um aumento na latência de retirada da pata em resposta a estímulo térmico, somente em ratos machos, ambos avaliados 90 min pós-formalina. Este efeito não foi observado nos grupos submetidos à acupuntura manual no ponto sham, demonstrando ser específico à acupuntura manual no ponto análogo ao ST36. Estes resultados sugerem que os hormônios gonadais podem estar envolvidos na nocicepção e no aumento de limiares nocifensivos provocados pela acupuntura no ponto análogo ao ST36, porém estes efeitos parecem ser dependentes do teste nociceptivo utilizado

Effect of acupuncture on temporal summation of pain: a randomised, double-blind, sham-controlled study

BACKGROUND: The analgesic effects of manual acupuncture (MA) and electro-acupuncture (EA) have been studied in healthy humans and patients with pain. The advantage of studying pain in healthy humans is that the intensity of stimulation can be accurately controlled and thereby the analgesic effect can be quantitatively assessed. However, an important difference between experimentally induced pain and clinical pain is central sensitisation, that is, an enhanced activity of the central nervous system (CNS). Temporal summation (TS) of pain refers to pain induced by repeated stimulations at sub-threshold level. It is a central phenomenon that reflects the sensitivity of CNS. The electrical TS pain model has been validated and applied to quantitatively determine the levels of analgesia and the central inhibition effects of analgesic medications. OBJECTIVES: The present study aimed to: 1. systematically review available randomised, controlled trials (RCTs) of acupuncture on experimentally induced pain in healthy humans; 2. conduct a RCT to assess the effect of MA and EA on TS of pain and the spatial characteristics of this effect (i.e. the same and different dermatome segments to the acupuncture point), and the temporal factors (i.e. immediately after and 24-hours after intervention). METHODS: The systematic review was carried out in accordance with the requirements of a Cochrane Systematic Review. The methodological quality and quality of the acupuncture techniques of the included RCTs were assessed. The Review Management software (RevMan version 4.2, The Cochrane Library) was used for data extraction and data analysis. For the present experiment, 27 healthy volunteers were recruited and randomly assigned to either EA, MA or sham-acupuncture (SA) group, with nine volunteers in each group. The acupuncture sites were ST36 and ST40 on the dominant leg. Both the volunteers and the assessor were blinded to the treatment allocation. A second researcher, who was blinded to the outcome assessment processes, delivered all the interventions. Each treatment lasted for 25 minutes. To test pain thresholds, transcutaneous electrical stimulation was delivered to three sites: 1. the tibia anterior muscle along the sural nerve path of the treatment leg and parallel to the mid-point between ST36 and ST40; 2. the same area on the other leg; and 3. the dorsum of the non-dominant forearm along the median nerve path and 3 to 4 cm above the wrist crease. Pain thresholds to single electrical stimulation (SPT) and to TS stimulation (TST) were assessed before, 30-minutes after and 24-hours after the intervention. Ratings to supra-threshold stimulation at intensities of 1.2 and 1.4 times the TST were assessed with a visual analogue scale. The level of anxiety was assessed before and after acupuncture. Data on pain thresholds and anxiety scores were analysed with one-way analysis of variance (ANOVA) using Statistical Package for the Social Sciences (SPSS, Version 13.0) to detect between treatment group differences. Significance for each of the ANOVAs was assessed at α = 0.05 / 3 = 0.0167 (Bonferroni Correction). When a significant ANOVA was obtained, Bonferroni corrected post-hoc analyses were applied for multiple-comparisons. Equivalence of the groups on demographic variables was assessed by ANOVA and chi-square tests. Power analysis and sample size calculations were performed using MINITAB (Version 15.0). RESULTS: The literature search identified 605 papers, however, only nine papers met the inclusion criteria and thus included in this review. The methodological quality and quality of the acupuncture procedures were satisfactory. In these studies, the pain models and interventions varied substantially, therefore, meta-analysis was not practicable. Four studies employed both invasive and non-invasive controls with three of them reported that the invasive controls induced significantly stronger analgesia than the non-invasive controls. One study reported that there was no difference between EA and MA tested using a heat pain model. In the present RCT, baseline values were comparable among the three groups with respect of SPT and TST. Overall, the baseline values of TST were lower than those of SPT. Within group comparison, the level of anxiety did not change significantly after the inventions. Between group comparisons, when sufficient statistical power was demonstrated, indicated that EA significantly increased SPT and TST on the treatment leg 24-hour after the treatment when compared with SA. In addition, the EA effect was not found on the non-treatment leg or the forearm. For the delivery of the supra-threshold stimulation, 1.2 and 1.4 times of the TST of each time point, instead of baseline TST, was mistakenly applied. Data from this component of the study were not analysed, however presented in the thesis for information. As the first study in this field, the current findings provide the base for sample size calculation. For example, the sample sizes for EA and MA comparisons with 80% statistical power at a significance level of 0.05 will be 21 subjects in each group to detect the immediate effect of acupuncture on TST, ; and 11 to detect the effect of acupuncture after 24-hour. CONCLUSIONS: The systematic review showed that there has been only a small number of experimental RCTs. Comparing acupuncture with non-invasive control, significant acupuncture analgesia was reported. These studies also demonstrated that invasive controls produced analgesia. Thus, future studies should consider using non-invasive intervention as control. No conclusion could be drawn regarding the relative analgesic effect of EA versus MA. Consistent with previous studies, TS of pain can be successfully elicited in healthy humans with electrical stimulation. This study on TS demonstrated that the effect of EA was stronger than SA. The fact that such an effect increased within 24 hours after acupuncture might indicate the potential role of neurohumoral mechanisms in acupuncture analgesia. The spatial effect of acupuncture tended to be localised at the needling site. It is important to note that acupuncture increased both SPT and TST, which may suggest that both peripheral and central nervous systems mechanisms are involved in acupuncture analgesia

Resolving long-standing uncertainty about the clinical efficacy of transcutaneous electrical nerve stimulation (TENS) to relieve pain: A comprehensive review of factors influencing outcome

Pain is managed using a biopsychosocial approach and pharmacological and non-pharmacological treatments. Transcutaneous electrical nerve stimulation (TENS) is a technique whereby pulsed electrical currents are administered through the intact surface of the skin with the intention of alleviating pain, akin to ‘electrically rubbing pain away’. Despite over 50 years of published research, uncertainty about the clinical efficacy of TENS remains. The purpose of this comprehensive review is to critically appraise clinical research on TENS to inform future strategies to resolve the ‘efficacy-impasse’. The principles and practices of TENS are described to provide context for readers unfamiliar with TENS treatment. The findings of systematic reviews evaluating TENS are described from a historical perspective to provide context for a critical evaluation of factors influencing the outcomes of randomized controlled trials (RCTs); including sample populations, outcome measures, TENS techniques, and comparator interventions. Three possibilities are offered to resolve the impasse. Firstly, to conduct large multi-centered RCTs using an enriched enrolment with randomized withdrawal design, that incorporates a ‘run-in phase’ to screen for potential TENS responders and to optimise TENS treatment according to individual need. Secondly, to meta-analyze published RCT data, irrespective of type of pain, to determine whether TENS reduces the intensity of pain during stimulation, and to include a detailed assessment of levels of certainty and precision. Thirdly, to concede that it may be impossible to determine efficacy due to insurmountable methodological, logistical and financial challenges. The consequences to clinicians, policy makers and funders of this third scenario are discussed. I argue that patients will continue to use TENS irrespective of the views of clinicians, policy makers, funders or guideline panel recommendations, because TENS is readily available without prescription; TENS generates a pleasant sensory experience that is similar to easing pain using warming and cooling techniques; and technological developments such as smart wearable TENS devices will improve usability in the future. Thus, research is needed on how best to integrate TENS into existing pain management strategies by analyzing data of TENS usage by expert-patients in real-world settings

Does Acupuncture/Dry Needling Improve Pain and Itch in Abnormal Hypertrophic Scars

This research program investigated the use of acupuncture intervention as an adjunct for hypertrophic scar (HTS) management. Mechanistic evidence from ex vivo and animal studies suggests that acupuncture has the potential to modulate neurogenic inflammation to influence pain and itch associated with HTS. Further, acupuncture may mediate non-neuronal cells involved in the proliferation and remodelling stage of healing to promote scar maturation. Previous studies using acupuncture for scar management demonstrated positive outcomes, however low-quality clinical trials and case studies provide limited evidence for treatment benefit. A treatment protocol was designed to investigate the effects of locally applied acupuncture compared to distant acupuncture, combined with routine care scar massage therapy. The protocol was tested for feasibility on one participant with scarring post-burn injury and demonstrated reduced pain, and improved scar physical characteristics. Results from expanded testing of the research protocol in participants with surgical or linear scars are presented as a case series. Outcomes from the case series show improvement in scar symptoms for most participants, however no clear difference was seen between local and distant acupuncture outcomes. Finally, data analysis suggested one sub-group of hypersensitive participants (with high initial scores for both pain and itch) responded to acupuncture intervention possibly providing insight into treatment mechanisms and adding weight to recommendations for future research and clinical practice

Acupuncture and sports medicine : effects and application perspectives

Vor dem Hintergrund der gestiegenen medizinischen und sozioökonomischen Relevanz von Akupunktur und Laserakupunktur werden im Rahmen der vorliegenden Arbeit Anwendungsfelder und Forschungsperspektiven in der präventiven und rehabilitativen Sportmedizin skizziert. Hierzu zählen insbesondere die Therapie von Sportverletzungen und Sportschäden, die Steigerung der körperlichen Leistungsfähigkeit, die Unterstützung und Förderung der Regeneration sowie die Vorbeugung von belastungsinduziertem Asthma. Aufbauend auf den aktuellen Forschungsstand werden eigene Originalarbeiten vorgestellt, die sich mit der Evaluation spezifischer Effekte der Akupunktur und Laserakupunktur befassen.Against the background of the increasing medical and socioeconomic importance of acupuncture and laser acupuncture, the present work aims at outlining scientific and practical applications in fields related to preventive and rehabilitative sports medicine. These include, in particular, the treatment of acute and chronic sports injuries, the enhancement of physical performance, the promotion of recovery, as well as the prevention of exercise-induced asthma. Based on current research, the author presents his original investigations dealing with specific effects of acupuncture and laser acupuncture