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A lack of scientific studies to prove or disprove the claimed effects of acupuncture has led to its rejection by many of the western scientific community. Now that many effects of acupuncture can be explained in terms of endogenous physiological mechanisms, and that these effects are reported as similar or sometimes superior to established treatments with a very low incidence of side effects, the integration of acupuncture with conventional medicine may be possible. Some of these aspects will be presented in this condensed overview.

Introduction Clinical guidelines depend on the analysis of randomised controlled trials in systematic reviews. How to interpret the results of acupuncture vs. sham–placebo procedures is a controversial aspect of the evidence base for acupuncture. Two inferences can be drawn from the acupuncture vs. sham–placebo randomised controlled trials. The first is whether acupuncture has a physiological basis. The second is whether there is any validity in traditional concepts of acupuncture practice. The degree to which sham acupuncture controls can physiologically be considered placebo controls has been challenged. However, whether these procedures should be considered ‘inert’ in terms of Chinese medicine theory has yet to be fully examined. This review aims to evaluate the extent to which sham–placebo procedures used in randomised controlled trials should be considered inert, with particular reference to traditional Chinese medicine theories. It also considers sham–placebo controls from a biomedical perspective. Methods Sham–placebo procedures were identified through reviews examining acupuncture controls. Results Four main types of sham–placebo control were identified. The procedures are heterogeneous and should not necessarily be considered as equivalent within systematic reviews. Conclusion These procedures cannot be considered as inert controls from either a Chinese medicine or biomedical perspective. There is a need to develop appropriate Acupuncture Control Assessment Guidelines to assess the risk of bias from sham–placebo controls when undertaking systematic reviews. The terminology used to describe control procedures needs to be developed and standardised. This article belongs to the Special Issue: Clinical Guidelines for Integrated Practice.

Increasing evidences attribute a central role to oxidation/reduction (redox) homeostasis in controlling cell physiology, with redox transitions of glutathione and sensitive cysteines in protein constituting the major players. Thiol redox control of protein activity and gene expression ultimately extends to the proliferation/differentiation switch. Several diseases, including the highest causes of mortality, have been attributed to a shift toward a more oxidized environment. Interfering with thiol redox transitions in diseases therefore appears a major clinical objective, N-acetyl-cysteine (NAC) being the most obvious candidate drug. Targets comprise diseases related to altered control of proliferation/differentiation, adhesion, inflammation. To quote a few benign disorders, gynecological diseases can include endometriosis, polycystic ovary syndrome, sterility originating from defective embryo implantation; dermatological diseases can include acne, alopecia, psoriasis, and vitiligo. We review here our journey with NAC, from mechanisms identified in cells, though an animal model and finally to the clinic where cases of successful patient's treatment are reported, some unpublished before. NAC effect was eventually enhanced by a combination with melatonin and selenium, both involved in the pathway of redox regulation. Further studies can well extend NAC use to several other diseases, while providing better treatment modalities and helping in identifying further specifically targeted compounds.

Pain is a vital sign in infants and children and is essential for survival. Pain is subjective and it is only the individual who can describe the pain or the anticipation of pain. In infants, observation of behaviors that suggests pain, physiological and biological markers are used in the clinical assessment. It is well established that infants from the gestational age of about 20 weeks have a functional pain system, even if immature, which can perceive and respond to tissue injury. Prolonged or repetitive nociceptive input and stress is harmful to the nervous system especially in the neonatal period of life. The nervous system shows a high degree of plasticity and untreated pain can lead to long-term undesired changes. Preventing or treating pain is therefore a primary goal in infants and children. Over the last decades, the practice of pediatric pain management has advanced rapidly. Pain management includes analgesics as well as non-pharmacological approaches. A multimodal strategy is often advocated. Among the non-pharmacological methods medical acupuncture has emerged as an alternative in its own right in for example baby colic.

Baby colic or infantile colic is a condition in which an otherise healthy baby cries or displays symptoms of distress (periods of ntense, unexplained fussing/crying lasting more than 3 h a day, more han 3 days a week for more than 3 weeks) without any discernible eason. The condition typically appears within the first month of life nd often disappears rather suddenly, before the baby is three to our months old, but can last up to one year. Persistent infant crying s much more than a parenting nuisance. Crying and the exhaustion ssociated with it can trigger serious problems, such as relationship tress, breastfeeding failure, excess visits to the doctor/emergency oom and even automobile accidents.

Study design:International validation study using self-administered surveys.Objectives:To investigate the utility and reliability of the International Spinal Cord Injury Pain (ISCIP) Classification as used by clinicians.Methods:Seventy-five clinical vignettes (case histories) were prepared by the members of the ISCIP Classification group and assigned to a category by consensus. Vignettes were incorporated into an Internet survey distributed to clinicians. Clinicians were asked, for each vignette, to decide on the number of pain components present and to classify each using the ISCIP Classification.Results:The average respondent had 86% of the questions on the number of pain components correct. The overall correctness in determining whether pain was nociceptive was 79%, whereas the correctness in determining whether pain was neuropathic was 77%. Correctness in determining if pain was musculoskeletal was 84%, whereas for visceral pain, neuropathic at-level spinal cord injury (SCI) and below-level SCI pain it was 85%, 57% and 73%, respectively. Using strict criteria, the overall correctness in determining pain type was 68% (versus an expected 95%), but with maximally relaxed criteria, it increased to 85%.Conclusions:The reliability of use of the ISCIP Classification by clinicians (who received minimal training in its use) using a clinical vignette approach is moderate. Some subtypes of pain proved challenging to classify. The ISCIP should be tested for reliability by applying it to real persons with pain after SCI. Based on the results of this validation process, the instructions accompanying the ISCIP Classification for classifying subtypes of pain have been clarified.Spinal Cord advance online publication, 7 February 2012; doi:10.1038/sc.2012.2.

Acupuncture is widely used for the treatment of chronic (long-term) pain. In a recent study, Vickers et al. characterized the analgesic effect of acupuncture in four different chronic pain conditions, back and neck pain, osteoarthritis, headache, and shoulder pain, and concluded that acupuncture is an effective type of treatment for these chronic pain states. Significant differences between true and sham acupuncture indicate that acupuncture induces superior effects. However, these differences were reported to be relatively modest, suggesting that non-specific effects, in addition to the specific effects of the needle stimulation, are important contributors to the therapeutic effects of acupuncture. It has been demonstrated that two factors that are seen as non-specific are related to individual therapists’ interaction with the patient and the patients’ positive expectation of the treatment effect. The therapist–patient interaction has been shown to be unrelated to empathy but may be attributable to the ability to express compassion. Compassion implies being attuned to undeserved suffering, but it is also a signaling behavior related to care giving that has physiological responses that orient the individual to social interaction. It is possible that therapists that report good treatment outcomes are more compassionate in their interaction with their patient compared to the therapist reporting poor outcomes.

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.

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.

To assess the efficacy and safety of tramadol for relieving neuropathic pain after spinal cord injury (SCI).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.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.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.

BackgroundColic causes crying in 10–30% of infants and is one of the primary reasons parents seek health care. Treatments are generally not totally effective and some cause side effects. In this study we aimed to test the effect of light needling (minimal acupuncture) on crying.MethodsForty children (median six weeks of age) with excessive crying unresponsive to conventional therapies, were recruited from 21 Child Welfare Clinics within an area of western Sweden, and quasi-randomised to control or light needling treatment. Parents were unaware of which group their child was assigned to. Children were given light needling acupuncture on one point (LI4) on both hands for approximately 20 seconds on four occasions, or received the same care except needling. Parental assessment questionnaires were used pre- and post-treatment to assess crying intensity, frequency, duration of crying and pain related behaviour throughout the day in six hour periods.ResultsLight needling resulted in a significant reduction in the rated crying intensity (assessed by a numeric rating scale, 0 to 10). For example, during the morning time period 0600–1200 hours, the median (range) rated crying intensity changed from 6 (1 to 9) pre-treatment to 2 (0 to 5) post-treatment (P=0.002), in the light needling group. The corresponding ratings for the children in the control group was 6 (0 to 10) and 5 (0 to 10) respectively. The difference between the groups was significant (P=0.016). There were also significant differences between the groups for the afternoon (1200–1800 hours), and evening (1800–midnight) time periods. Pain related behaviour like facial expression, was also significantly less pronounced in the light needling group as compared to the control group post-treatment, (P=0.027). The parents rated the light needling as more effective in improving symptoms than the control group (PConclusionFour treatments with light needling on one point in the hand may alleviate crying and pain related behaviour without any noted side effects.

Many different styles of acupuncture practice exist, and lack of agreement on the optimal acupuncture treatment for any particular condition may mean that some patients do not receive the best treatment. This uncertainty also makes the negative results of sham controlled trials difficult to interpret. Unless we can be sure that both adequate acupuncture and an inactive sham were used in a particular trial, then that trial should not be interpreted as dismissing acupuncture for that condition. Acupuncture practice clearly involves much more than needling procedures, but there is a strong argument for elucidating the role of those needling procedure first. The components of acupuncture needling procedures have been described in the STRICTA document, but it is also clear that the patient's perception of needling is relevant for the outcome of treatment. We therefore recommend the concept of ‘dose’ of acupuncture needling, which should include both the stimulus given to the patient, and certain aspects of the patient's perceptions and response that are known to be linked to the subsequent therapeutic response. We propose the following definition of dose: the physical procedures applied in each session, using one or more needles, taking account of the patient's resulting perception (sensory, affective and cognitive) and other responses (including motor). The dose may be affected by the state of the patient (eg nervous, immune and endocrine systems); different doses may be required for different conditions. The constituents of an adequate dose can be established initially by clinical opinion and subsequently by empirical evidence from experimental studies, which may be either clinical or basic research studies. Systematic reviews which do not consider the adequacy of the acupuncture treatment may have unreliable conclusions. Out of 47 recent systematic reviews, only six have applied some criteria for adequacy. Five used a rating system or conducted a subgroup analysis, and one excluded studies from the analysis altogether if they did not meet criteria for adequacy. Research into what constitutes an adequate dose of acupuncture has long been neglected and is now urgent. Clinical studies that compare the effects of different treatment protocols are probably the most reliable source of evidence, and may also demonstrate a dose-response relationship.

Pain is a unique personal experience showing variability where gender and sex related effects might contribute. The mechanisms underlying the differences between women and men are currently unknown but are likely to be complex and involving interactions between biological, sociocultural and psychological aspects. In women, painful experimental stimuli are generally reported to produce a greater intensity of pain than in men. Clinical pain is often reported with higher severity and frequency, longer duration, and present in a greater number of body regions in women than in men. Women are also more likely to experience a number of painful conditions such as fibromyalgia, temporomandibular dysfunction, migraine, rheumatoid arthritis and irritable bowel syndrome. With regard to biological factors, quantitative as well as qualitative differences in the endogenous pain inhibitory systems have been implicated, as well as an influence of gonadal hormones. Psychosocial factors like sex role beliefs, pain coping strategies, and pain related expectancies may also contribute to the differences. Being exposed to repeated painful visceral events (eg menses, labour) during life may contribute to an increased sensitivity to, and greater prevalence of, pain among women. When assessing the outcome of pharmacological and non-pharmacological therapies in pain treatment, the factors of gender and sex should be taken into account as the response to an intervention may differ. Preferably, treatment recommendations should be based on studies using both women and men as the norm. Due to variability in results, findings from animal studies and experiments in healthy subjects should be interpreted with care.

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterised by central sensitisation resulting in hypersentivity of the skin and deeper tissues as well as fatigue. Possibly the princess in Hans Christian Andersen's ‘The Princess and the Pea’ suffered from FMS since chronic sleep disturbances are typical in FMS. These sleep disturbances have been attributed to a dysfunction in the systems regulating sleep and wakefulness resulting in loss of deep sleep. In addition, many patients with FMS experience cognitive dysfunction, characterised by impaired concentration and short term memory consolidation, a complaint also commonly reported in other sleep disorders. In recent reviews evaluating the efficacy of acupuncture in FMS it has been concluded that acupuncture has no specific effect. A prerequisite for this conclusion is that all the major symptoms in the syndrome have been assessed. However, previous studies have generally focused on the pain alleviating effect of acupuncture in FMS. We have observed that not only pain but also sleep and cognitive dysfunction may be ameliorated in response to acupuncture, suggesting that these variables should be taken into account when evaluating the effects of acupuncture in FMS. Furthermore, the results demonstrated great individual variability apart from the systematic effects related to the group, indicating that individually performed treatment strategies are required. Our suggestion is supported by experimental and clinical studies showing that acupuncture may affect in somnia and alertness, and that there may be neurophysiologic bases for these specific effects.

Pain is a personal subjective multidimensional experience influenced by a number of factors with different origin like biological and socio-cultural. In women, painful experimental stimuli are generally reported to have a greater intensity in comparison with men. Clinical pain is often reported with higher severity and frequency, longer duration, and present in a greater number of body regions in women as compared to men. Women are also more frequently represented in a number of pain conditions such as fibromyalgia, temporo mandibular dysfunction, migraine, rheumatoid arthritis and irritable bowl syndrome. The mechanisms underlying these differences are still unclear but factors ranging from biological to psychosocial could all contribute. Relating to the biological factors, quantitative as well as qualitative differences in the endogenous pain inhibitory systems as well as the influence of gonadal hormones have been implicated. Psycho-social factors like sex role beliefs, pain coping strategies, and pain related expectancies may also contribute. Taken together the above findings suggest that gender aspects should be taken into consideration when designing and assessing the effects of acupuncture treatments.

In recent reviews regarding the efficacy of acupuncture in fibromyalgia syndrome (FMS) it has been concluded that acupuncture has no specific effect since the control procedure (superficial needling and/or needling away from ‘specific’ points) had similar effects. These conclusions may be questioned since superficial needling and/or needling away from specific trigger points is not inert. Also, manual acupuncture or mild electroacupuncture (EA) may not be sufficient to activate the endogenous pain inhibiting system.Patients with FMS suffer from allodynia, fatigue and muscle ache, which is partly explained by peripheral and central sensitisation. Sensitisation results in augmented and altered stimulus responses whereby light stimulation of the skin has as strong an effect as regular needling on the pain inhibitory system in FMS.Central sensitisation in FMS is also associated with expanded receptive fields of central neurons resulting in a larger topographic distribution of the pain. This would suggest that control procedures using needling away from the ‘specific site’ might have as strong an effect as needling within the most painful area. Also, repeated nociceptive input from muscles (as obtained by de qi) results in expansion of receptive fields which in turn may result in activation of descending pain inhibition outside the stimulated myotome.Sensitisation to pain, such as in FMS, may also be related to abnormalities in descending efferent pathways. As there is likely to be an imbalance between excitatory and inhibitory systems in FMS, stronger stimulation may therefore be needed to activate the descending pain inhibitory system. In studies using mild manual acupuncture or weak EA stimulation optimal pain inhibition may therefore not have been obtained.When conducting studies on acupuncture, the clinical condition or syndrome needs to be taken into account and the control procedure designed accordingly.

Background/Objectives: To examine the reliability, validity, sensitivity, and practicality of various outcome measures for pain after spinal cord injury (SCI), and to provide recommendations for sp...

Acupuncture is an ancient therapy with a variety of different explanatory models. A cascade of physiologic effects has been reported, both in the peripheral and the central nervous system, following the insertion of a needle. Clinical trials testing the specific claims of acupuncture have generally tried to focus on testing the efficacy of applying specific techniques and/or specified points. However, different conditions may respond differently to different modes of stimulation. Also, insertion of needles into the body can stimulate effects not dependent on the locations of stimulation. Recently, it was demonstrated that both superficial and deep needling (with de qi/Hibiki) resulted in amelioration of patellofemoral pain and an increased feeling of wellbeing. One area in the brain that is affected by acupuncture stimulation is the limbic system. The limbic system consists of a group of brain structures, including the hippocampus, amygdala, and their interconnections, and connections with the hypothalamus, septal area, and portions of the tegmentum. It contains many of the centres related to emotion and reward. The pleasurable aspect of the acupuncture experience has largely been ignored as it has been considered to be part of its antinociceptive effects. It has previously been reported that physical exercise and electroacupuncture in animals result in modulation of the peptidergic content in limbic structures. These results are supported by recent animal studies in Japan that have clearly demonstrated that acupuncture results in the activation of the reward system. These findings are supported by positron emission tomography studies in patients, which showed that the insula ipsilateral to the site of needling was activated, as well as the dorsolateral prefrontal cortex, the anterior cingulate and the midbrain. Taken together, these results suggest that acupuncture, as well as the patient's expectation and belief regarding a potentially beneficial treatment, modulate activity in the reward system.

Pain is a major clinical problem that causes great suffering for the individual and incurs costs for society. Accurate assessment and evaluation of perceived pain is necessary for diagnosis, for choice of treatment, and for the evaluation of treatment efficacy. The assessment of an individual's pain is a challenge since pain is a subjective, multidimensional experience, and assessment is based on the person's own self-report. The results are often varied, possibly due to inter-individual variation, but also in relation to gender and aetiology. A gold standard for pain assessment is still lacking, but rating scales, questionnaires, and methods derived from psychophysical concepts, such as threshold assessments and perceptual matching, are used. In the evaluation of pain and associated variables, both systematic and individual variation should be taken into account, as should pain-associated symptoms. Recommendations for pain treatment should be based on the patient's specific needs. Therefore, it is important to assess the level of perceived pain taking individual variation into account. The methods used should preferably have proved to be useful in randomised controlled trials, and analysis of pain assessment should consider its non-metric properties. In the future, the use of studies with a naturalistic protocol together with individual assessment of individual pain responses could increase the internal and external validity.

The purpose of this preliminary study was to evaluate the relationship between a possible biochemical marker of stress, 24-h urinary concentrations of Corticotropin Releasing Factor-Like Immunoreactivity (CRF-LI), and ratings of stress-related symptoms like depression and anxiety, as well as to evaluate pain and emotional reactions in patients with fibromyalgia (FM). Another purpose was to study the effects of massage and guided relaxation, with respect to change in the same variables. Urine sampling and ratings were performed before treatments, after and 1 month after completed treatments. Concentrations of CRF-LI was analysed with radioimmnoassay technique. For the assessment of depression, anxiety and pain the CPRS-A questionnaire was used and for rated pain and emotional reactions the NHP questionnaire was used. The 24-h urinary concentration of the CRF-LI was found to be related to depression, mood and inability to take initiative. After treatment the urinary CRF-LI concentrations and the rated levels of pain and emotional reactions were found to have decreased. In conclusion, the 24-h urinary CRF-LI concentration may be used as a biochemical marker of stress-related symptoms such as depression in patients with FM and possibly also other conditions characterized by chronic pain. Therapies such as massage and guided relaxation may be tried for the amelioration of pain and stress but further studies are required.

Objective: To assess whether a comprehensive multidisciplinary pain management programme could contribute to improvement regarding sleep quality, mood, life satisfaction, health-related quality of life, sense of coherence and pain for patients with a spinal cord injury and neuropathic pain. Design: A prospective intervention study. Patients: Twenty-seven patients with spinal cord injury and neuropathic pain participated in a pain management programme in parallel with 11 patients in a control group. Methods: A comprehensive pain management programme comprising educational, cognitive, and behavioural interventions was created for patients with spinal cord injury and neuropathic pain. The pain management programme consisted of 20 sessions over a 10-week period and included educational sessions, behavioural therapy, relaxation, stretching, light exercise and body awareness training. All patients were followed-up 3, 6 and 12 months after completion of the programme. Results: At the 12-month follow-up, levels of anxiety and depression in the treatment group decreased compared with baseline values, and a tendency towards better quality of sleep was seen. In comparison with the control group, patients in the treatment group improved regarding sense of coherence and depression. Conclusion: This study implies that a multidimensional pain management programme can be a valuable complement in the treatment of spinal cord injured patients with neuropathic pain.

Patellofemoral pain syndrome (PFPS) is one of the most common musculoskeletal disorders. However, no consensus on the definition, classification, assessment, diagnosis, or management has been reached. We evaluated symptoms and clinical findings in subgroups of individuals with PFPS, classified on the basis of the findings in radiological examinations and compared the findings with knee-healthy subjects. An orthopedic surgeon and a physical therapist consecutively examined 80 patients clinically diagnosed as having PFPS and referred for physical therapy. The examination consisted of taking a case history and clinical tests. Radiography revealed pathology in 15 patients, and scintigraphic examination revealed focal uptake in 2 patients indicating pathology (group C). Diffusely increased uptake was present in 29 patients (group B). In the remaining 29 patients radiographic and scintigraphic examinations were normal (group A). Knee-healthy controls (group D) reported no clinical symptoms. No symptom could be statistically demonstrated to differ between the three patient groups. Knee-healthy subjects differed significantly from the three patient groups in all clinical tests measuring pain in response to the provocations; compression test, medial and lateral tenderness, passive gliding of the patella, but they also differed in Q angle. Differences in clinical tests between the patient groups were nonsignificant. The main finding in our study on patients clinically diagnosed with PFPS is that possible pathologies cannot be detected from the patient's history or from commonly used clinical tests.

Objectives:Painful disorders of the patellofemoral joint are one of the most frequent complaints in orthopaedic and sports medicine. The aims of this study were to determine whether bone scintigrams of patients suffering from patellofemoral pain syndrome (PFPS) show diffuse uptake and in what bony compartment of the knee uptake, if any, was localised.Methods:Fifty eight patients with chronic PFPS were examined. All patients underwent a detailed clinical history and a thorough physical examination of the knee. Anterior and lateral static images of both knees were made using a gamma camera 3 h after injection of 550 MBq of99mTc-HMDP. Two experienced radiologists visually evaluated the scans blindly and separately. As 51 patients had bilateral pain, 109 painful knees are included in the results.Results:Diffuse uptake on bone scintigrams was found in 48 knees in 30 of the patients. In 33 knees the uptake was localised to only one bone compartment, in 10 knees diffuse uptake was found in two of the bones forming the knee joint, and in six knees all three bone compartments (the distal femur, the patella, and the proximal tibia) exhibited diffuse uptake.Conclusions:Scintigrams of approximately half of the patients with PFPS will show diffuse uptake in one or more of the bony compartments of the knee joint and radioactive tracer accumulation will occur as often in the proximal tibia as in the patella.

Gender differences in pain perception have been frequently discussed, but the documented gender-related pain-alleviating effects of nonpharmacological methods are sparse. In this study we aimed to investigate changes in electrical sensory thresholds and electrical pain thresholds, in response to high frequency transcutaneous electrical nerve stimulation, TENS, for 20 min in healthy women (n = 29) and men (n = 29). The thresholds were assessed pre-, during-, and post-TENS. The pattern of change in thresholds was evaluated with a rank-based statistical method regarding the level of systematic change, expressed as relative position (RP) and additional individual changes, expressed as relative rank variance (RV), with its 95% confidence intervals. Equal levels of systematic changes towards increased electrical sensory thresholds were seen in women and men post-TENS (RP, 0.35; 95% CI, 0.07, 0.63, and RP, 0.36; 95% CI, 0.17, 0.53, respectively). At the same point of time, systematic changes towards increased electrical pain thresholds were only seen in women (RP, 0.43; 95% CI, 0.27, 0.60), while they were unchanged in men (RP, −0.01; 95% CI, −0.13, 0.10). Significant additional individual variations were found in the women’s responses of assessed electrical sensory and pain thresholds but not in the men’s. It is concluded that both women and men responded with a significant increase of the electrical sensory threshold to high frequency TENS, but only women responded with increase of the electrical pain thresholds. The individual variation of the responses was greater in the women than in the men. © 2004 Elsevier Ireland Ltd. All rights reserved.

Assessed sensory and pain thresholds can change consequently to disturbances associated with ongoing pain. Such assessments could be an additional method in the daily clinical evaluation of perceived pain. To study the test-retest variability within-day and between-day of such procedures a newly developed instrument producing electrocutaneous stimulation, PainMatcher (PM), was used to assess the electrical sensory thresholds (EST) and pain thresholds (EPT) in healthy volunteers and in patients with pain. The produced data were considered ordinal and analyzed with rank-invariant statistics with properties of analyzing systematic disagreement, bias, and individual variations. The percentage agreements within +/- 1PM value for EST were in the two groups of healthy volunteers and patients in pain 94% and 92%, and for EPT assessments 49% and 78%, respectively. The variability in the EST assessments is possibly explained by a slight bias while the individual variations were negligible between the two occasions. The assessed EPT were unbiased in both groups while individual variations were significant among the healthy volunteers but negligible among the patients in pain. The EST was found to be increased in pain patients compared to healthy volunteers, p0.03, and the EPT decreased in pain patients compared to healthy volunteers, p0.001. The results in this study indicate stable and reliable assessments of EST and EPT except for a possible bias. The threshold assessment procedure followed in this study may be a valuable tool in the clinical evaluation of sensory and pain assessments in pain patients.

To assess the non-pharmacological treatments used and preferred by patients with spinal cord injury and pain.A cross-sectional descriptive study.One hundred and twenty three patients with spinal cord injury, matched for gender, age, level of lesion and completeness of injury were assessed in 1999 at the Spinalis SCI unit, Stockholm, Sweden and followed-up in a mailed survey 3 years later. In total, 82.1% of the questionnaires (n=101) were returned. Ninety of these patients still suffered pain and were thus included in the study.Pain questionnaires, visual analogue scale (VAS), Hospital Anxiety and Depression Scale and Life Satisfaction instrument.63.3% of the patients had tried non-pharmacological treatments, where acupuncture, massage and transcutaneous electrical nerve stimulation (TENS) were the most commonly tried. Predictive for having tried non-pharmacological treatment were high ratings of pain intensity, presence of aching pain, and cutting/stabbing pain.Massage, and heat were the non-pharmacological treatments reported to result in the best pain alleviation. Results from our study suggest that we need to (re)evaluate the treatments offered to patients with spinal cord injury and pain and combine non-pharmacological and pharmacological treatments.

Aim: To evaluate the effects of acupuncture in patients with keratoconjunctivitis sicca (KCS). Material and Methods: Twenty-five patients (20 women, five men) with KCS were randomly assigned to an acupuncture treatment group or a control group. The effects of acupuncture were evaluated by a questionnaire on symptoms, visual analogue scale recordings, registration of drop frequency, and dry eye tests. Ten acupuncture sessions were given. Follow-up was carried out after 2–3 weeks and again after a mean period of 8 months. Results: Patients receiving acupuncture felt better at the first follow-up compared with the control group (p = 0.036). However, no statistical significance could be found concerning any change, or difference, in the total number of subjective symptoms, dosage frequency or, as indicated by the dry eye tests, tear quality, tear secretion and ocular surface disease. Conclusion: The results indicate that acupuncture has subjective beneficial effects in patients with KCS and could therefore be tried as a complement to ordinary treatment.

The aims of the present study were to investigate, in rats, the behavioral effects of substance P (SP) microinjected into the ventrolateral periaqueductal gray (PAG) and the effects of the neurokinin 1 (NK-1) receptor antagonist [ d -Arg1, d -Trp7, 9, Leu11]-substance P (Spantide). The effect of morphine administration on the release of SP in the ventrolateral PAG was also investigated using microdialysis in awake rats. SP microinjected into the ventrolateral part of the PAG induced significant increases in the hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulation as an antinociceptive response. The NK-1 receptor antagonist blocked these effects but exhibited no antinociceptive effect alone. Subcutaneous administration of morphine increased basal SP-like immunoreactivity (SP-LI) release in the microdialysate obtained from the ventrolateral PAG of freely moving rats. Our results demonstrate that SP injected into the ventrolateral PAG induces an antinociceptive effect via activation of NK-1 receptors. Morphine administered systemically induces the release of SP in the ventrolateral PAG. We suggest that an increased release of SP in the PAG may contribute to opioid antinociception.

Nerve regeneration and the occurrence of three neuropeptides; i.e. substance P (SP), calcitonin gene related peptide (CGRP) and galanin (GAL), were studied during healing of tendon rupture in the rat by semi-quantitative immunohistochemistry. The neuronal findings were related to nociception as assessed by hindpaw withdrawal latencies at thermal and mechanical tests. Experimental rupture of rat Achilles tendon--normally devoid of nerves--elicited extensive nerve ingrowth into the rupture site in the early phase of healing followed by almost complete fiber disappearance (weeks 12-16). The ingrowth of SP and CGRP positive fibers, seen already at weeks 1-2, was associated with increased nociception. Subsequently, the occurrence of GAL positive fibers at weeks 4-6 was associated with decreased nociception. An even stronger relationship to nociception during healing was observed when the rate of change in neuropeptide expression instead of the expression in absolute terms was considered, according to the "cascade" formula of SP(')+CGRP(')-GAL(').It may prove that the observed temporal occurrence of different neuropeptides reflects a role of the peripheral nervous system in regulating synchronously nociception and healing.

We have previously reported that the level of 5-HT in the masseter muscle is increased in patients with fibromyalgia as compared with healthy subjects and that high intramuscular level of 5-HT is associated with muscle pain. We have also reported that injection of the 5-HT3 receptor antagonist granisetron (GRA) into the masseter muscle of healthy subjects reduced pain induced by 5-HT and abolished allodynia/hyperalgesia. The aim of this study was to investigate whether GRA can influence pain and allodynia/hyperalgesia of the masseter muscle in patients with fibromyalgia. Eighteen female patients who met the criteria of fibromyalgia according to the American College of Rheumatology participated in the study. They were examined regarding pain intensity and pressure pain threshold (PPT) over the masseter muscle. One milliliter of GRA (1 mg/ml) was injected into the masseter muscle on one side and 1 ml of isotonic saline on the other side in a randomized and double-blind manner. After the injections, the pain intensity and PPT were recorded during 30 min. The pain intensity increased after injection of saline and to a lower degree after injection of GRA. The PPT increased after injection of GRA, while no such change was observed after saline. The difference between GRA and saline was, however, not significant. Eight of the patients responded to the GRA injection by an increase of PPT during the experimental period that differed from saline. They also showed a tendency to a lower increase of pain intensity after injection of GRA when compared to saline. In conclusion, the results of this study do not prove that injection of the 5-HT3-antagonist GRA into the masseter muscle influences local pain and allodynia/hyperalgesia in patients with fibromyalgia.

Study design: Out of a population of 456 patients with spinal cord injuries (SCI), 130 having pain were selected after matching, based on gender, age, American Spinal Injury Association (ASIA) impairment grade and level of lesion. Objective: To investigate whether gender differences with regard to pain perception and prevalence exist in a population of patients following spinal cord injury. Setting: Spinalis SCI Unit (out-patient clinic), Stockholm, Sweden. Method: 130 patients suffering from pain were assessed over a 12-month period in a yearly health control. Results: SCI women had a higher prevalence of nociceptive pain than men and their use of analgesics was greater. However, no differences between the sexes could be seen regarding pain and localization, onset, distribution, factors affecting pain, number of painful body regions, pain descriptors, ratings of pain intensities or in pain and life satisfaction. Conclusion: This study showed that SCI men and women describe their pain very similarly. However, SCI women had a higher prevalence of nociceptive pain than men and their use of opiates and non-steroid anti-inflammatory drugs (NSAIDs) was greater.

Acupuncture is a complex intervention, and there are both specific and non-specific influences associated with its therapeutic benefit. Although large randomized controlled trials (RCT) and systematic reviews have demonstrated the efficacy of acupuncture, the conclusions are controversial due to the lack of a significant difference in the results between real and sham acupuncture. This similarity may be due to the omission of important components of the acupuncture treatment itself, such as the needling sensation. The needling sensation is considered to represent an important component of acupuncture. Despite this importance, several RCTs have lacked data on whether the needling sensation has been achieved. From a Traditional Chinese Medicine (TCM) perspective, the needling sensation, deQi, is a combination of unique sensations that are interpreted as the flow of Qi, or “vital energy.” Furthermore, acupuncture is believed to be successful only upon the arrival of “vital energy,” Qi. This state is suggested to be essential to the specific therapeutic effect of acupuncture. From a biomedical perspective, acupuncture excites sensory receptors and nerve fibers in the stimulated tissue, resulting in a needling sensation. Moreover, acupuncture induces both the deactivation of a limbic–paralimbic–neocortical network in the brain (the default mode network and the anti-correlated task-positive network) and the activation of somatosensory regions. A distinct needling sensation is associated with a marked deactivation of these brain networks, whereas the lack of a needling sensation (as during sham needling) is associated with significantly less deactivation. Conversely, when acupuncture induces sharp pain sensations, there is an activation of these networks instead. In a clinical context, this difference means that the therapist needs to identify a stimulation intensity that is scaled to the needling response of each patient, i.e., a sharp uncomfortable pain sensation during the needle stimulation should be avoided. Both the empirical bases of TCM and biomedical acupuncture research suggest that the therapist should strive for a needling sensation during an acupuncture treatment. If such a sensation is not achieved, are the specific effects of acupuncture likely smaller? This conclusion suggests that deQi is part of a proper acupuncture treatment and that the experience of a needling sensation should universally be assessed and reported in all types of clinical and experimental trials.

A randomized controlled study was conducted to evaluate the effect of acupuncture treatment in idiopathic anterior knee pain, a pain syndrome without known aetiology. Fifty-eight patients, clinically and radiologically examined, were randomly assigned to either deep or minimal superficial acupuncture treatment. The patients were treated twice weekly for a total of 15 treatments. The main outcome measurements were one leg vertical jump, functional score, daily VAS recording and skin temperature. Fifty-seven patients completed the study. Pain measurements on VAS decreased significantly within both groups; in the deep acupuncture group from 25 before treatments to 10 afterwards, and in the superficial (placebo) acupuncture group from 30 to 10. There was no significant difference between the groups. The improvement on the VAS recordings remained significant even after 3 and 6 months. Even though the pain decreased after sensory stimulation, neither the ability to jump on one leg, the functional score nor the skin temperature changed. This study shows that patients with idiopathic anterior knee pain benefit from both electroacupuncture treatment and subcutaneous needling. The pain-relieving effect remains for at least 6 months. Central pain inhibition, caused by either afferent stimulation or by non-specific therapeutic (placebo) effects, is a plausible explanation behind the treatment effects.

We previously found stress-reduction in rats exposed to an oxytocin-injected cage-mate. Olfactory impairment and oxytocin antagonist treatment blocked the effect. Here, we investigated effects of social stress on the exposure-induced response and exposure on amygdaloid oxytocin concentrations. CT concentrations in exposed olfactorily impaired, CT antagonist-treated and saline-injected unexposed rats were reduced, compared to the significantly higher level in untreated and exposed saline-injected rats. Saline injections and group mixing enhanced heat dissipation. Exposure abolished the injection-induced, but not mixing-induced stress response, most likely via a social stress induced effect on the oxytocin-injected rat. The difference in exposure responsivity may relate to recognition, stress type and intensity affecting different stress-response systems. The mechanism could reinforce social attachment.

Acupuncture is part of Traditional Chinese Medicine (TCM), a system with an empirical basis that has been used in the treatment of pain for centuries. Its use for pain relief is supported by clinical trials and this has facilitated its acceptance in pain clinics in most countries. Acupuncture effects on pain must devolve from physiological and/or psychological mechanisms with biological foundations. Acupuncture and some other forms of sensory stimulation elicit similar effects in man and other mammals, suggesting that they bring about fundamental physiological changes. Acupuncture excites receptors or nerve fibres in the stimulated tissue which are also physiologically activated by strong muscle contractions, and the effects on certain organ functions are similar to those obtained by protracted exercise. Both exercise and acupuncture produce rhythmic discharges in nerve fibres, and cause the release of endogenous neurotransmitters including opioids, monoamines, oxytocin and other neuropeptides (SP, CGRP, GAL, CRF, NPY), important in the control of both sensory, affective and cognitive elements of pain. Over the past 10 years, there has been a growing awareness that pain is due not simply to the activation of peripheral nociceptors, as in nociceptive pain, but to multiple factors, and is therefore susceptible to various modes of acupuncture treatments. Depending on the etiology, pain may be classified into several categories, such as nociceptive, neurogenic, chronic pain syndrome and psychogenic pain. Musculoskeletal and visceral pain states, both nociceptive, are characterized by hyperalgesia. However, despite belonging to a similar category, the pain is triggered by different mechanisms. Neurogenic pain is caused by injury or dysfunction in the nervous system and is often severe and intractable and may not respond to even powerful opiates. Recent studies suggest that there is a third pain category, distinct from the neurogenic and nociceptive, where pain is related to a sickness response that occurs with exposure to chemical compounds and infectious agents and the associated central changes produce heightened pain sensitivity (“hurting all over”), termed chronic pain syndrome. In clinical trials, acupuncture or low-frequency electroacupuncture have shown to be effective in some nociceptive pain states, whereas high-frequency stimulation is more effective in neurogenic pain. In chronic pain syndrome patients with high anxiety, acupuncture is generally inefficient. It is possible that part of the lack of effect in chronic pain syndromes can be attributed to high levels of the opioid-antagonist cholecystokinin (CCK) in the brain. Acupuncture may be effective in some categories of pain but the mode of stimulation should be adjusted to the etiology of pain. In addition, patients are likely to respond better if they are not stressed (anxious).

Massage-like stroking induces acute antinociceptive effects that can be reversed by an oxytocin antagonist, indicating activation of oxytocin on endogenous pain controlling systems. We now demonstrate an increase in hindpaw withdrawal latencies (HWLs), in response to thermal and mechanical stimuli, which was present after six treatments of massage-like stroking every other day and which continued to increase through the remaining seven treatments. Repeated massage-like stroking also resulted in increased oxytocin-like immunoreactivity (oxytocin-LI) levels in plasma and periaquaductal grey matter (PAG). Furthermore, increases in HWLs were also present after injections of oxytocin into the PAG (0.1, 0.5 and 1.0 nmol). Intra-PAG oxytocin injection of 1 nmol followed by 1 or 20 nmol of naloxone attenuated the increments in HWL. Also, there was a dose-dependent attenuation of the oxytocin-induced antinociceptive effects following intra-PAG injection of the m-opioid antagonist bfunaltrexamine (b-FNA) and the k-opioid antagonist nor-binaltorphimine (nor-BNI) but not the d-antagonist naltrindole. The longterm antinociceptive effects of massage-like stroking may be attributed, at least partly, to the oxytocinergic system and its interaction with the opioid system, especially the m- and the k-receptors in the PAG.

An experimental model of acute arterial thrombosis was developed in a rat groin flap model. Electrical stimulation was delivered to the flap artery while measuring blood flow in the artery and in the flap microcirculation using a laser Doppler system. Electrical stimulation produced an occlusive thrombosis in 10 rats within 68.1 ± 19.26 (mean ± SE) min. Thrombosis formation produced a rapid decrease of the LDF readings in the artery (90%) and in the flap (70%), the decrease being fairly parallel. Following the spontaneous thrombolysis, the artery perfusion recovered to baseline level but the flap blood flow only recovered by 10–20%. During electrical stimulation there was no change of the systemic blood pressure. The dynamic course of thrombus formation was documented on a videotape recorder through a microscope-mounted video camera and monitored on a television screen. Segments of the artery were obtained during and at the end of the experiments. The histological examination revealed arterial thrombosis composed of red blood cells, fibrin, and white blood cells, without any significant architectural and endothelial changes in the vessel walls. The study suggests that this model using electric vessel stimulation is effective for inducing arterial thrombosis and provides a simple method for recording the dynamic course of thrombus formation.

Intra-periaqueductal grey (PAG) injection of 1 nmol of oxytocin induced significant increases in hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats. The anti-nociceptive effect of oxytocin was attenuated significantly by subsequent intra-PAG injection of the mu opioid antagonist beta-funaltrexamine (beta-FNA) and the kappa opioid antagonist nor-binaltorphimine (nor-BNI), but not by the delta antagonist naltrindole. The results demonstrated that mu and kappa opioid receptors, not delta receptors, were involved in the oxytocin-induced anti-nociception in PAG of rats.

The present study was performed to explore the effect of calcitonin gene-related peptide (CGRP) and its antagonist CGRP8–37 on the evoked discharge frequency of wide dynamic range (WDR) neurons in the dorsal horn of the spinal cord in rats. Recording was performed with a multibarrelled glass micropipette and the chemicals were delivered by iontophoresis. The discharge of WDR neurons was evoked by transdermic electrical stimulation applied on the ipsilateral hindpaw. (1) Iontophoretic application of CGRP at an ejection current of 100 nA increased the discharge frequency of WDR neurons significantly. (2) Iontophoretic application of CGRP8–37 at an ejection current of 80 or 160 nA induced significant decreases in the discharge frequency of WDR neurons, but not at 40 nA. (3) Iontophoretic application of CGRP8–37 not only antagonized the CGRP-induced increase in the evoked discharge frequency of WDR neurons but also induced a significant decrease in the evoked discharge frequency of WDR neurons compared to basal levels. The results indicate that CGRP and its receptors play a facilitary role on the transmission and/or modulation of nociceptive information in the dorsal horn of the spinal cord in rats.

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/m2 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.

The present study investigated the effect of intraperiaqueductal grey injection of nociceptin/orphanin FQ (N/OFQ) and an antagonist (Nphe(1))nociceptin(1-13)NH(2) on the hindpaw withdrawal response to thermal and mechanical stimulation in rats. N/OFQ (5 nmol) significantly decreased the nociceptive thresholds in both tests and 1, 5 and 10 nmol of (Nphe(1))nociceptin(1-13)NH(2) significantly reversed this effect in a dose dependent way. Our results demonstrate, that N/OFQ has a nociceptive action, possibly through inhibition of PAG neurons. This effect is blocked by the antagonist (Nphe(1))nociceptin(1-13)NH(2) probably via ORL1 receptors in the periaqueductal grey.

An island groin flap based on the inferior epigastric vessels was raised in 10 rats in order to monitor simultaneous ischemic changes in arterial blood flow and skin microcirculation induced by electrical stimulation of the feeding artery. A modified laser Doppler perfusion system recorded blood flow in the epigastric artery and in the skin microcirculation of the flap before and for 40 min after the experimentally induced ischemia. Sections of the stimulated segment of the vessel were obtained at the end of the experimental procedure for histological analysis to determine the extent of endothelial changes, if any. Artery blood flow and the flap microcirculation decreased significantly immediately after stimulation, both slowly increasing to prestimulation levels after 30 min. Artery perfusion was quicker than microcirculation to recover to the baseline value, indicating that reperfusion of larger vessels could involve mechanisms fundamentally different from those active in the resolution of ischemia at the capillary level. Histological artery examination revealed no significant endothelial damage at the stimulation site, thus demonstrating that electrical stimulation induces reproducible ischemia without visible endothelial damage. The differential effects on the feeding artery and on capillary perfusion indicate recruitment of several different mechanisms.

Experimental inflammation was induced by subcutaneous injection of carrageenan into the left hindpaw of rats. Intra-periaqueductal grey (PAG) injection of 0.02 or 0.1 nmol of neuropeptide Y (NPY), but not 0.004 nmol, induced significant increases in hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats with inflammation. Furthermore, the anti-nociceptive effect of NPY was blocked partly by following intra-PAG injection of the Y1 receptor antagonist NPY28-36. The results demonstrated that NPY plays an anti-nociceptive role in PAG in rats with inflammation, in which Y1 receptor is involved.

Interleukin-1beta (IL-1beta) is an important mediator of fever and illness. Recent studies have demonstrated that IL-1beta (2 microg kg(-1)) increases gastric vagal afferent activity. The peripheral mechanisms of the action of lower doses were studied by recording the mass efferent and afferent activity of the gastric branch of the ventral vagal nerve in anesthetized rats. Twenty min after i.v. administration of IL-1beta (1 microg kg(-1)) the efferent activity of the vagal nerve was decreased to 62+/-6% in totally but not in partly vagotomized rats. Preadministration of indomethacin (5 mg kg(-1)) 30 min before IL-1beta blocked this reduction. Administration of 1 microg kg(-1) of IL-1beta had no effect on the afferent activity of the gastric branch of the vagal nerve. The present results suggest that the subdiaphragmatic vagal afferents modulate the parasympathetic efferent outflow in response to IL-1beta partly through prostaglandin dependent mechanisms and that supradiaphragmatic afferents or central sites are more sensitive to the low doses of IL-1beta which becomes evident after elimination of the subdiaphragmatic vagal input.

The levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in brain and periphery are susceptible to changes during development and as result of different physiopathological conditions, such as stress and aging and during the onset and progression of neurological and autoimmune diseases. Despite the sensitive methods for measurement of neurotrophin protein levels in different tissues, no easily applicable methods to evaluate changes in the level of NGF and BDNF mRNA expression within physiological range have been described. This study reports the development of a reproducible and simple procedure for measurement of neurotrophin mRNA expression in brain and peripheral tissues based upon an enzyme linked immunosorbent assay (ELISA) detection system of reverse transcriptase-polymerase chain reaction (RT-PCR) products. The major advantages of this RT-PCR ELISA procedure is to allow the co-amplification of diverse mRNAs starting from small amounts of tissues; to contemporaneously test a large number of samples; to be rapid and to use only commercial reagents and widely available equipment. The procedure could also be useful in studies addressed to measure the pattern of expression of molecules involved in the pathogenesis of neurodegenerative and inflammatory diseases, such as neuropeptides and cytokines.

Despite extensive research on the pathogenesis of polycystic ovary syndrome (PCOS), there is still disagreement on the underlying mechanisms. The rat model for experimentally induced polycystic ovaries (PCO)—produced by a single injection of estradiol valerate—has similarities with human PCOS, and both are associated with hyperactivity in the sympathetic nervous system. Nerve growth factor (NGF) is known to serve as a neurotrophin for both the sympathetic and the sensory nervous systems and to enhance the activity of catecholaminergic and possibly other neuron types. Electro-acupuncture (EA) is known to reduce hyperactivity in the sympathetic nervous system. For these reasons, the model was used in the present study to investigate the effects of EA (12 treatments, approximately 25 min each, over 30 days) by analyzing NGF in the central nervous system and the endocrine organs, including the ovaries. The main findings in the present study were first, that significantly higher concentrations of NGF were found in the ovaries and the adrenal glands in the rats in the PCO model than in the control rats that were only injected with the vehicle (oil or NaCl). Second, that repeated EA treatments in PCO rats resulted in concentrations of NGF in the ovaries that were significantly lower than those in non-EA-treated PCO rats but were within a normal range that did not differ from those in the untreated oil and NaCl control groups. The results in the present study provide support for the theory that EA inhibits hyperactivity in the sympathetic nervous system. adrenal, central nervous system, follicular development, hypothalamus, ovary, ovulation, pituitary, stress