Is acupuncture effective in the treatment of pain in endometriosis?

INTRODUCTION: Endometriosis is a multifactorial, estrogen-dependent, inflammatory gynecological condition - often with long-lasting visceral pelvic pain of different origin, and infertility among women. Current management options for patients' are often inadequate, with side effects for many for whom acupuncture techniques could be an alternative. Earlier studies have discussed the efficacy of acupuncture, but not its methodological aspects. OBJECTIVES: To summarize the documented clinical effects of acupuncture on rated visceral pelvic endometriosis-related pain, and associated variables among individuals, within and between studied groups, and to discuss the methodological treatment aspects. METHODS: Published full text clinical studies, case reports, and observational studies with abstracts written in English were searched by using the keywords "Acupuncture and Endometriosis" in databases such as PubMed, Web of Science, and CINAHL. The reporting guidelines, Standards for Reporting Interventions in Clinical Trials of Acupuncture was used for the methodological report. RESULTS: Three studies were found including 99 women, 13-40 years old, with diagnosed endometriosis. The studies were different in research design, needle stimulation techniques, and evaluation instruments. Methodological similarities were seven to12 needle insertions per subject/session, and 15-25 minutes of needle retention time. The needles were placed in lower back/pelvic-abdominal area, in the shank, feet, and hands. Treatment numbers varied from nine to 16 and patients received one to two treatments per week. Similarity in reported treatment effects in the quoted studies, irrespective of research design or treatment technique, was reported decrease of rated pain intensity. DISCUSSION: Meta-analysis is the standard procedure for the evaluation of evidence of treatment effects, ie, on a group level, usually without analysis of the individual responses even with obvious spread in the results leading to lack of guidance for treatment of the individual patient. By conceptualizing pain as subjective, the individual aspect should serve as the basis for the analysis to allow clinical recommendations. From a physiological and a western medical perspective, acupuncture can be regarded as a type of sensory stimulation that induces changes in the function of the central nervous system that partly can explain the decrease of perceived pain in response to acupuncture treatment irrespective of the technique. CONCLUSION: Endometriosis is often painful, although with various origin, where standard treatments may be insufficient or involve side effects. Based on the reported studies, acupuncture could be tried as a complement as it is an overall safe treatment. In the future, studies designed for evaluating effectiveness between treatment strategies rather than efficacy design would be preferred as the analyses of treatment effects in the individual patients.

Immediate effect of three different electroacupuncture protocols on fasting blood glucose in obese patients: a pilot study.

BACKGROUND: Obesity is an increasing global health problem, and current methods of management are limited. Preliminary research data suggest that acupuncture may have an influence on metabolic parameters related to obesity. OBJECTIVE: To determine the electroacupuncture (EA) protocol to be used in a future clinical trial examining the effect of acupuncture on metabolic parameters related to obesity and to examine whether a single EA treatment can change fasting blood glucose in obese subjects. METHODS: 16 obese women aged 30-52 years with body mass index >30 kg/m(2) were assigned consecutively into three groups and their fasting blood glucose was measured before and after administering a single session, lasting 30 min, of one of three EA treatment protocols. The Dorsal group received EA to dorsal segmental acupuncture points BL18-23 bilaterally (corresponding to the segmental levels innervating the pancreas); the Ear group received EA to ear points in the cavum conchae; and the Limb group received EA to points in the arms and legs (LI10-LI11, ST36-Zongping). RESULTS: After a single session of EA there was a statistically significant decrease in fasting blood glucose in the Dorsal and Limb groups, but there was no change and even a trend towards an increase in the glucose level in the Ear group. CONCLUSIONS: The findings of this small pilot study suggest that EA to either dorsal segmental points corresponding to the pancreas or to muscle points in all four limbs may exert a beneficial effect on glucose metabolism in obese women.

Differential brain effects of laser and needle acupuncture at LR8 using functional MRI.

OBJECTIVE: While needle acupuncture is a well-accepted technique, laser acupuncture is being increasingly used in clinical practice. The differential effects of the two techniques are of interest. We examine this in relation to brain effects of activation of LR8, a putative acupuncture point for depression, using functional MRI (fMRI). METHODS: Sixteen healthy participants were randomised to receive low intensity laser acupuncture to LR8 on one side and needle acupuncture to the contralateral LR8. Stimulation was in an on-off block design and brain patterns were recorded under fMRI. RESULTS: Significant activation occurred in the left precuneus during laser acupuncture compared with needle acupuncture and significant activation occurred in the left precentral gyrus during needle acupuncture compared with laser acupuncture. CONCLUSIONS: Laser and needle acupuncture at LR8 in healthy participants produced different brain patterns. Laser acupuncture activated the precuneus relevant to mood in the posterior default mode network while needle acupuncture activated the parietal cortical region associated with the primary motor cortex. Further investigations are warranted to evaluate the clinical relevance of these effects.

A promise in the treatment of endometriosis: an observational cohort study on ovarian endometrioma reduction by N-acetylcysteine.

Urged by the unmet medical needs in endometriosis treatment, often with undesirable side effects, and encouraged by N-acetylcysteine (NAC) efficacy in an animal model of endometriosis and by the virtual absence of toxicity of this natural compound, we performed an observational cohort study on ovarian endometriosis. NAC treatment or no treatment was offered to 92 consecutive Italian women referred to our university hospital with ultrasound confirmed diagnosis of ovarian endometriosis and scheduled to undergo laparoscopy 3 months later. According to patients acceptance or refusal, NAC-treated and untreated groups finally comprised 73 and 72 endometriomas, respectively. After 3 months, within NAC-treated patients cyst mean diameter was slightly reduced (-1.5 mm) versus a significant increase (+6.6 mm) in untreated patients (P = 0.001). Particularly, during NAC treatment, more cysts reduced and fewer cysts increased their size. Our results are better than those reported after hormonal treatments. Twenty-four NAC-treated patients-versus 1 within controls-cancelled scheduled laparoscopy due to cysts decrease/disappearance and/or relevant pain reduction (21 cases) or pregnancy (1 case). Eight pregnancies occurred in NAC-treated patients and 6 in untreated patients. We can conclude that NAC actually represents a simple effective treatment for endometriosis, without side effects, and a suitable approach for women desiring a pregnancy.

Gastrointestinal symptoms of infantile colic and their change after light needling of acupuncture: a case series study of 913 infants.

BACKGROUND: Infantile colic is a common painful clinical condition associated with signs of distended intestines and an increase in colon peristalsis. However, clinical documentation of observed gastrointestinal functions in the condition is still lacking. Even though the ailment is common, no clear treatment guidelines exist. While acupuncture with minimal stimulation has been shown to be effective in reducing crying behaviour of infants suffering from colic, the documented effect of acupuncture on gastrointestinal function in children with infantile colic is scarce. This case series study aims to document the symptoms of routinely rated gastrointestinal function and the changes in these symptoms after minimal acupuncture in a larger group of children with infantile colic. METHODS: This study included 913 infants with normal weights, and lengths at birth. The infants' mean age was 5.4 weeks when the observations started, and had colic symptoms since two weeks after birth. Light needling stimulation of the acupuncture point LI4 was performed for 10-20 seconds bilaterally on a daily basis for a mean of 6.2 consecutive days. A questionnaire with verbal rating scales for the parents' evaluation was used before and after the treatment period. RESULTS: Before treatment the infants were assessed by the parents in terms of 'often have inflated stomachs' (99%) and 'seldom drool' (76%), 'regurgitate' (53%) and 'belch' (62%). Moreover, the reported frequency of defecation was 5-8 times per day (64%), with a yellowish-green colour (61%) and with a water-thin consistency (74%). After treatment, the variables of inflated stomachs, drooling and regurgitating were systematically changed, and rated by the parents as occurring 'sometimes' while belching was rated as occurring 'often' and the frequency of defecation was reduced to 1-4 times/day with a mustard yellow colour and a gruel-like consistency. The parents also rated their impression of the infants' general colic symptoms including crying behaviour as much ameliorated in 76% of the cases. CONCLUSION: The results of the present study show that minimal acupuncture at LI4 in infantile colic is an effective and easy treatment procedure that, furthermore, is reported to be without serious side effects.

Acupuncture and massage therapy for neuropathic pain following spinal cord injury: an exploratory study.

OBJECTIVE: The study sought to explore the possibility of using acupuncture and massage therapy for relieving neuropathic pain following spinal cord injury (SCI). DESIGN: 30 individuals with SCI and neuropathic pain were assigned to treatment of either massage or acupuncture, with 15 individuals in each group. Both groups received treatment twice weekly for 6 weeks. Treatments were evaluated at the end of treatment and 2 months later (follow-up). RESULTS: Data were analysed on an intention-to-treat basis. Within the groups, ratings of present pain, general pain, pain unpleasantness and coping improved significantly at the end of treatment after acupuncture compared to baseline values, and following massage therapy ratings of pain interference on the Multidimensional Pain Inventory improved. At follow-up no significant improvements were seen. Between-group differences were seen regarding ratings of worst pain intensity at the end of treatment, and regarding pain unpleasantness and coping with pain at follow-up, both in favour of acupuncture. At the end of treatment, eight of the 15 individuals receiving acupuncture and nine receiving massage reported an improvement on the Patient Global Impression of Change Scale, and at follow-up six patients in the acupuncture group and one patient in the massage group still reported a favourable effect from the treatment. Few side effects were reported and neither dropout from the study did this due to adverse events. CONCLUSION: Neuropathic pain following SCI is often only partially responsive to most interventions. Results from this study indicate, however, that both acupuncture and massage therapy may relieve SCI neuropathic pain. For this reason, larger randomised controlled trials are warranted for assessing the long-term effects of these treatments.

Is placebo acupuncture what it is intended to be?

Randomized, placebo-controlled clinical trials are recommended for evaluation of a treatment's efficacy with the goal of separating the specific effects (verum) from the non-specific ones (placebo). In order to be able to carry out placebo-controlled acupuncture trials, minimal/sham acupuncture procedures and a sham acupuncture needle has been used with the intention of being inert. However, clinical and experimental results suggest that sham/minimal acupuncture is not inert since it is reported that both verum acupuncture and sham/minimal acupuncture induce a significant alleviation of pain. This alleviation is as pronounced as the alleviation obtained with standard treatment and more obvious than the one obtained with placebo medication or by the use of waiting list controls. These results also suggest that sham acupuncture needles evoke a physiological response. In healthy individuals sham acupuncture results in activation of limbic structures, whereas a deactivation is seen in patients with pain, i.e. results from healthy individuals do not reflect what is seen in clinical conditions. Also, depending on the etiology of pain (or any under clinical condition under investigation), the response to sham acupuncture is varying. The acupuncture ritual may also be seen as an emotional focused therapy allowing for psychological re-orientation. Sham needling in such context may be as powerful as verum acupuncture. We recommend that the evaluated effects of acupuncture could be compared with those of standard treatment, also taking the individual response into consideration, before its use or non-use is established.

On the threshold - evaluation of variability in effects of acupuncture in a gender perspective.

Variable results of pain alleviation in response to acupuncture have been reported, complicating its interpretation. Sources of variability are probably multi-factorial, including the contribution of gender related effects. Gender related variation in perceived pain has been discussed frequently, but documented effects of acupuncture referring to gender are sparse. Furthermore, factors such as operationalisation of the outcome variable and the statistical method for evaluation could also be sources of variability. When pain is regarded as subjective, the produced data should be treated as ordinal. The rank-based method by Svensson, taking the non-metric qualities of the ordinal data into account as well as the variability at the group and the individual level, is therefore an alternative. The present commentary aims to (1) evaluate changes in electrical sensory thresholds and electrical pain thresholds after low frequency electro-acupuncture separately in healthy women and men; (2) introduce and exemplify the method by Svensson in a user-friendly approach. To analyze the systematic patterns of change in thresholds, indicating evidence of treatment on a group level, the relative position (RP) and relative concentration (RC), were measured. The variation related to the individual, the relative rank variation (RV) was also measured. The results were divergent between women (n = 23) and men (n = 22), i.e. unchanged sensory threshold after acupuncture at the group level in women while changed in men. The assessed pain threshold after acupuncture on the other hand was changed towards higher levels in women and unchanged in men. The individual variation was apparent in both women and men but larger in women. For statistical analysis of the variability for both group and individual related effects, the rank-based method by Svensson could be used. The present study indicates that evaluation of sensory and pain threshold response should be analysed separately in women and men.

More than antioxidant: N-acetyl-L-cysteine in a murine model of endometriosis.

N-acetyl-L-cysteine exerts a complex action on endometrial cells, involving regulation of gene expression and protein activity and location, all converging into a decreased proliferation and a switch toward a differentiating, less invasive, and less inflammatory phenotype. Also considering the lack of undesired side effects, including unaffected fertility potential, this suggests a beneficial use of NAC in endometriosis clinical treatment.

Thiol redox transitions in cell signaling: a lesson from N-acetylcysteine.

The functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox switches play a fundamental role that is just beginning to be understood. The maintenance of the redox status is, indeed, crucial for cellular homeostasis and its dysregulation towards a more oxidized intracellular environment is associated with aberrant proliferation, ultimately related to diseases such as cancer, cardiovascular disease, and diabetes. Redox transitions occur in sensitive cysteine residues of regulatory proteins relevant to signaling, their evolution to metastable disulfides accounting for the functional redox switch. N-acetylcysteine (NAC) is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling. We here review the redox chemistry of NAC, then screen possible mechanisms to explain the effects observed in NAC-treated normal and cancer cells; such effects involve a modification of global gene expression, thus of functions and morphology, with a leitmotif of a switch from proliferation to terminal differentiation. The regulation of thiol redox transitions in cell signaling is, therefore, proposed as a new tool, holding promise not only for a deeper explanation of mechanisms, but indeed for innovative pharmacological interventions.

Tramadol in neuropathic pain after spinal cord injury: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and safety of tramadol for relieving neuropathic pain after spinal cord injury (SCI). METHODS: Thirty-six patients with SCI and neuropathic pain were enrolled in a randomized, double-blind, placebo-controlled trial, and 35 patients were included in the intention-to-treat analysis based on all patients taking at least 1 dose of study medication. Of the intention-to-treat population, 23 were randomized to treatment with tramadol and 12 to placebo. Patients were given study medication for 4 weeks, starting with 3 times 50 mg tramadol daily or 3 times 1 tablet of placebo. RESULTS: At evaluation, 4 weeks after the treatment initiation, ratings of pain intensity were lower in those randomized to tramadol compared with those on placebo. Pain severity scores on the Multidimensional Pain Inventory had also decreased in patients on tramadol. No between-group differences in pain affect were observed. Adverse events were substantial and caused 43% of those on tramadol and 17% on placebo to withdraw from the study. DISCUSSION: Tramadol might be tried for neuropathic pain after SCI after the use of gabapentin/pregabalin, and tricyclic antidepressants have been found to be insufficient. Titration should be slow and individual, to minimize the risk of adverse events.

Treatment recommendations should take account of individual patient variation not just group responses.

Recommendations for treatment are commonly based on results evaluating variation in systematic effects (group responses) from randomised controlled trials without taking the individual patient's variation into account. In the evaluation of acupuncture-related treatment effects, the trial design and statistical analysis used are a challenge since the assessed variables commonly have subjective properties and are based on the person's own self-report. Thus, the results that are seen are often varied, most likely due to inter-individual variation in rating of the actual variable such that the treatment effects are expressed more (or less) in some individuals than in others. The basis for the individual variation is probably multi-modal and could be related to the individuals' expectation, gender, genetic polymorphisms and the aetiology of the condition. The assessment methods used should preferably have proven useful in controlled trials, and the methods for statistical analysis should consider the non-metric properties of the variable and the contribution of the individuals' variation in the results. In order to evaluate the treatment effects more properly and increase the possibility of detecting any effectiveness, it is therefore important to assess the level of perceived dysfunction or symptom, taking into account the individual variation as well as the systematic effects (the effects of the group). In the evaluation of acupuncture effects, both systematic and individual variation should be reported allowing for the detection of subgroup effects and thereby leading to treatment recommendations that are more likely to be based on each individual's specific needs.

Minimal acupuncture is not a valid placebo control in randomised controlled trials of acupuncture: a physiologist's perspective.

Placebo-control of acupuncture is used to evaluate and distinguish between the specific effects and the non-specific ones. During 'true' acupuncture treatment in general, the needles are inserted into acupoints and stimulated until deqi is evoked. In contrast, during placebo acupuncture, the needles are inserted into non-acupoints and/or superficially (so-called minimal acupuncture). A sham acupuncture needle with a blunt tip may be used in placebo acupuncture. Both minimal acupuncture and the placebo acupuncture with the sham acupuncture needle touching the skin would evoke activity in cutaneous afferent nerves. This afferent nerve activity has pronounced effects on the functional connectivity in the brain resulting in a 'limbic touch response'. Clinical studies showed that both acupuncture and minimal acupuncture procedures induced significant alleviation of migraine and that both procedures were equally effective. In other conditions such as low back pain and knee osteoarthritis, acupuncture was found to be more potent than minimal acupuncture and conventional non-acupuncture treatment. It is probable that the responses to 'true' acupuncture and minimal acupuncture are dependent on the aetiology of the pain. Furthermore, patients and healthy individuals may have different responses. In this paper, we argue that minimal acupuncture is not valid as an inert placebo-control despite its conceptual brilliance.

Tail skin temperatures reflect coping styles in rats.

This study was carried out to elucidate the predictive value of tail skin temperatures (TSTs) assessed in naïve rats as a non-invasive pre-experimental method of classification of coping style. Male Lewis rats were classified according to tail skin temperatures (TST), and relative size within cage-groups. TSTs were monitored over two-hour periods following exposure to physical and emotional stressors. Bodyweight-shifts associated to the experiments were analysed. Six organs of neuroendocrine relevance to allostasis were weighed. Challenge-specific TST-profiles were size-related and consistent with proactive or reactive coping. Pro-active (A) rats showed a more pronounced TST-response to unknown conspecifics, but reactive (B) rats to environmental novelties. B-rats showed challenge-specific weight-losses while A-rats gained more after experiments. Second size males showed rapidly decreased TSTs (vasoconstriction) after nociceptive stimulation. Males that showed the highest basal TSTs and weight-loss in emotionality tests had lost a first rank position during a pre-experimental period, suggesting long-lasting effects of social defeat. Pre-experimental growth correlated positively to adiposisity post-experimentally, but negatively to testes relative weight in B-rats. Scaling effects explained heart-size in B-rats and pituitary-size in A-rats. The overall patterns that emerged, in factor analyses including organ sizes, were consistent with pro-active coping in A-rats and reactive in B-rats. Our results, controlling for rank-effects, suggest that non-invasively assessed TSTs may predict individual stress-coping phenotypes pre-experimentally in rats housed in groups.

Acupuncture for preconditioning of expectancy and/or Pavlovian extinction.

Both specific and non-specific factors, as well as the therapist, may play a role in acupuncture therapy. Recent results suggest that verum acupuncture has specific physiological effects and that patients expectations and belief regarding a potentially beneficial treatment modulate activity in the reward and self-appraisal systems in the brain. We suggest that acupuncture treatment may partly be regarded and used as an intervention that preconditions expectancy, which results in both conditional reflexes and conditioning of expected reward and self-appraisal. If so, acupuncture should preferably be applied before the start of the specific treatment (drug or behavioural intervention which is given with the intention of achieving a specific outcome) to enhance the specific and non-specific effects. This hypothesis is further supported by the suggestions that acupuncture may be viewed as a neural stimulus that triggers Pavlovian extinction. If this is the case, acupuncture should preferably be applied repeatedly (ie in a learning process) before the start of the specific treatment to initiate the extinction of previous unpleasant associations like pain or anxiety. Our clinical data suggest that acupuncture may precondition expectancy and conditional reflexes as well as induce Pavlovian extinction. Based on the above we suggest that acupuncture should be tried (as an adjunct) before any specific therapy.