Panos Barlas

Gender differences in pressure pain threshold in healthy humans.

&NA; Aims of investigation: To quantify the magnitude of putative gender differences in experimental pressure pain threshold (PPT), and to establish the relevance of repeated measurements to any such differences. Methods: Two separate studies were undertaken. A pressure algometer was used in both studies to assess PPT in the first dorsal interosseous muscle. Force was increased at a rate of 5 N /s. In study 1, two measurements were taken from 240 healthy volunteers (120 males, 120 females; mean age 25 years) giving a power for statistical analysis of &bgr;=0.80 at &agr;=0.01. In study two, 30 subjects (15 males, 15 females mean age 28 years) were randomly selected from study one. Fourteen repeated PPT measurements were recorded at seven, 10 min intervals. Mean PPT data for gender groups, from both studies, were analysed using analysis of covariance with repeated measures, and age as the covariate. Results: The mean PPT for each of the two measurements in study one showed a difference between gender of 12.2 N (f=30.5 N, m=42.7 N) and 12.8 N (f=29.5 N, m=42.3 N), respectively, representing a difference of 28% with females exhibiting a lower threshold. In study two, the mean difference calculated from 14 PPT repeated measurements over a 1 h period was comparable to that in study one at 12.3 N (range 10.4–14.4 N) again females exhibited the lower threshold. The differences in mean PPT values between gender were found to be significant in both study one, at (P<0.0005, F=37.8, df=1) and study two (P=0.01, F=7.6, df=1). No significant differences were found in either study with repeated measurement (P=0.892 and P=0.280), or on the interaction of gender and repeated measurement after controlling for age (P=0.36 and P=0.62). Conclusion: Healthy females exhibited significantly lower mean PPTs in the first dorsal interosseous muscle than males, which was maintained for fourteen repeated measures within a 1 h period. This difference is likely to be above clinically relevant levels of change, and it has clear implications for the use of different gender subjects in laboratory based experimental designs utilising PPT as an outcome measure.

Acupuncture as an adjunct to exercise based physiotherapy for osteoarthritis of the knee: randomised controlled trial.

Objective To investigate the benefit of adding acupuncture to a course of advice and exercise delivered by physiotherapists for pain reduction in patients with osteoarthritis of the knee. Design Multicentre, randomised controlled trial. Setting 37 physiotherapy centres accepting primary care patients referred from general practitioners in the Midlands, United Kingdom. Participants 352 adults aged 50 or more with a clinical diagnosis of knee osteoarthritis. Interventions Advice and exercise (n=116), advice and exercise plus true acupuncture (n=117), and advice and exercise plus non-penetrating acupuncture (n=119). Main outcome measures The primary outcome was change in scores on the Western Ontario and McMaster Universities osteoarthritis index pain subscale at six months. Secondary outcomes included function, pain intensity, and unpleasantness of pain at two weeks, six weeks, six months, and 12 months. Results Follow-up rate at six months was 94%. The mean (SD) baseline pain score was 9.2 (3.8). At six months mean reductions in pain were 2.28 (3.8) for advice and exercise, 2.32 (3.6) for advice and exercise plus true acupuncture, and 2.53 (4.2) for advice and exercise plus non-penetrating acupuncture. Mean differences in change scores between advice and exercise alone and each acupuncture group were 0.08 (95% confidence interval −1.0 to 0.9) for advice and exercise plus true acupuncture and 0.25 (−0.8 to 1.3) for advice and exercise plus non-penetrating acupuncture. Similar non-significant differences were seen at other follow-up points. Compared with advice and exercise alone there were small, statistically significant improvements in pain intensity and unpleasantness at two and six weeks for true acupuncture and at all follow-up points for non-penetrating acupuncture. Conclusion The addition of acupuncture to a course of advice and exercise for osteoarthritis of the knee delivered by physiotherapists provided no additional improvement in pain scores. Small benefits in pain intensity and unpleasantness were observed in both acupuncture groups, making it unlikely that this was due to acupuncture needling effects. Trial registration Current Controlled Trials ISRCTN88597683.

Sensory stimulation (TENS): effects of parameter manipulation on mechanical pain thresholds in healthy human subjects

&NA; Transcutaneous electrical nerve stimulation (TENS) is a popular form of electrostimulation. Despite an extensive research base, there remains no consensus regarding the parameter selection required to achieve maximal hypoalgesic effects. The aim of this double blind, sham‐controlled study was to investigate the relative hypoalgesic effects of different TENS parameters (frequency, intensity and stimulation site) upon experimentally induced mechanical pain. Two hundred and forty participants were recruited in order to provide statistical analysis with 80% power at &agr;=0.05. Subjects were randomised to one of the six TENS groups, a control, and a sham TENS group (n=30, 15 males, 15 females, per group). TENS groups differed in their combinations of stimulation; frequency (4 or 110 Hz), intensity (‘to tolerance’ or ‘strong but comfortable’) and stimulation site (segmental–over the distribution of the radial nerve or, extrasegmental–over acupuncture point ‘gall bladder 34’, or a combination of both segmental and extrasegmental). Pulse duration was fixed at 200 &mgr;s. Stimulation was delivered for 30 min and subjects were then monitored for a further 30 min. Mechanical pain threshold (MPT) was measured using a pressure algometer and taken from the first dorsal interosseous muscle of the dominant hand, ipsilateral to the stimulation site. MPT measures were taken, at baseline, and at 10‐min intervals for 60 min. Difference scores were analysed using repeated measures and one‐way ANOVA and relevant post hoc tests. Low frequency, high intensity, extrasegmental stimulation produced a rapid onset hypoalgesic effect, which increased during the stimulation period (P<0.0005 control and sham) and was sustained for 30 min post‐stimulation (P<0.0005control, P=0.024sham). Whilst high frequency, ‘strong but comfortable’ intensity, segmental stimulation produced comparable hypoalgesic levels during stimulation, this effect was not sustained post‐stimulation. Stimulation at a combination of the two sites did not produce any greater hypoalgesic effects. These results may have implications for the clinical use of sensory stimulation.

Defining an adequate dose of acupuncture using a neurophysiological approach – a narrative review of the literature

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 patients 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 patients 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 patients 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.

Effects of intensity of electroacupuncture upon experimental pain in healthy human volunteers: A randomized, double-blind, placebo-controlled study

Abstract Electroacupuncture is commonly used for pain relief. Despite an extensive evidence‐base guiding the selection of stimulation parameters, little methodologically robust research exists regarding the level of intensity required to provide effective doses. This study investigated the hypoalgesic effects of two stimulation intensities compared to placebo on pressure pain thresholds (PPTs) in pain‐free humans. Forty‐eight acupuncture‐naïve volunteers (mean age 23), stratified by gender, were screened for relevant contraindications and randomly allocated to four groups: control, placebo, high‐intensity (“to tolerance but sub‐noxious”) or low‐intensity (“strong but comfortable”). True or placebo electroacupuncture, using the Streitberger placebo needle, was administered to acupoints on dominant forearm (LI10, TH5) and ipsilateral leg (GB34, ST38). True needles (30 mm long, 0.3 mm diameter) were inserted 20–25 mm and “de‐qi” was elicited from active groups, prior to administering 30 min of 4 Hz, 200 &mgr;s electroacupuncture. No electrical stimulation was performed on control and placebo groups, and placebo needles were used. After the intervention period, all needles were removed. Volunteers were monitored for 30 further minutes. Two PPT measurements were taken bilaterally from muscle bellies of first dorsal interosseous by an independent rater, at baseline and at six subsequent 10‐min intervals. Square‐root transformed data were analysed using repeated‐measures ANOVA, with baseline data as covariate. The high‐intensity group was significantly different from the placebo group for both measurement sites (p = .020, p = .033). The control group displayed stable PPT readings over time. No significant differences were observed between the placebo and control groups. These findings suggest that high‐intensity levels may be important in optimal dose selection.

Effects of simultaneous dual-site TENS stimulation on experimental pain

Transcutaneous electrical nerve stimulation (TENS) is commonly used for pain relief. However, little robust research exists regarding the combination of parameters required to provide effective doses. This study investigated the hypoalgesic effects of different parameter combinations, applied simultaneously at two sites (segmental and extrasegmental), on pressure pain threshold (PPT) in pain‐free humans. Two‐hundred and eight volunteers (median age 22 years, range 20–26) were randomized to eight groups: six active TENS groups, placebo and control. Parameter combinations were such that frequency always differed at each site (110Hz or 4Hz), but intensity could be either the same or different levels: high (to tolerance without pain) or low (strong but comfortable). TENS was administered to the forearm over the radial nerve and the ipsilateral leg below the fibular head for 30min with monitoring for 30 further minutes. PPT measurements were taken bilaterally from the mid‐point of first dorsal interosseous muscle, by an independent blinded rater, at baseline and at six subsequent 10‐min intervals. Log‐transformed data were analysed using repeated‐measures analysis of covariance (baseline values and gender as covariates). Those groups using high‐intensity stimulation at the segmental stimulation sites showed significantly greater hypoalgesia than placebo (p<0.025 in each case). The largest hypoalgesic effect was for simultaneous high‐intensity stimulation at segmental and extrasegmental sites, using different frequencies. These results reaffirm that high‐intensity stimulation (regardless of frequency) is of fundamental importance in effective dosage.

Dose-specific effects of transcutaneous electrical nerve stimulation (TENS) on experimental pain: a systematic review.

ObjectiveTo determine the hypoalgesic effects of transcutaneous electrical nerve stimulation (TENS) parameter combinations on experimental models in healthy humans. MethodsSearches were performed using the electronic databases Ovid MEDLINE, CINAHL, AMED, and Web of Science (from inception to December 2009). Manual searches of journals and reference lists of retrieved trials were also performed. Randomized controlled trials (RCTs) were included in the review if they compared the hypoalgesic effect of TENS relative with placebo and control, using an experimental pain model in healthy human participants. Two reviewers independently selected the trials, assessed their methodologic quality and extracted data. ResultsForty-three RCTs were eligible for inclusion. A best evidence synthesis revealed: Overall “conflicting” (inconsistent findings in multiple RCTs) evidence of TENS efficacy on experimental pain irrespective of TENS parameters used. Overall intense TENS has “moderate” evidence of efficacy (1 high-quality and 2 low-quality trials). Conventional TENS has overall conflicting evidence of efficacy, this is derived from “strong” evidence of efficacy (generally consistent findings in multiple high-quality RCTs) on pressure pain but strong evidence of inefficacy on other pain models. “Limited” evidence (positive findings from 1 RCT) of hypoalgesia exists for some novel parameters. Low-intensity, low-frequency, local TENS has strong evidence of inefficacy. Inappropriate TENS (using “barely perceptible” intensities) has moderate evidence of inefficacy. DiscussionThe level of hypoalgesic efficacy of TENS is clearly dependent on TENS parameter combination selection (defined in terms of intensity, frequency, and stimulation site) and experimental pain model. Future clinical RCTs may consider these TENS dose responses.

Is acupuncture a useful adjunct to physiotherapy for older adults with knee pain?: The "Acupuncture, Physiotherapy and Exercise" (APEX) study [ISRCTN88597683]

BackgroundAcupuncture is a popular non-pharmacological modality for treating musculoskeletal pain. Physiotherapists are one of the largest groups of acupuncture providers within the NHS, and they commonly use it alongside advice and exercise. Conclusive evidence of acupunctures clinical effectiveness and its superiority over sham interventions is lacking. The Arthritis Research Campaign (arc) has funded this randomised sham-controlled trial which addresses three important questions. Firstly, we will determine the additional benefit of true acupuncture when used by physiotherapists alongside advice and exercise for older people presenting to primary care with knee pain. Secondly, we will evaluate sham acupuncture in the same way. Thirdly, we will investigate the treatment preferences and expectations of both the participants and physiotherapists participating in the study, and explore the effect of these on clinical outcome. We will thus investigate whether acupuncture is a useful adjunct to advice and exercise for treating knee pain and gain insight into whether this effect is due to specific needling properties.Methods/DesignThis randomised clinical trial will recruit 350 participants with knee pain to three intervention arms. It is based in 43 community physiotherapy departments in 21 NHS Trusts in the West Midlands and Cheshire regions in England. Patients aged 50 years and over with knee pain will be recruited. Outcome data will be collected by self-complete questionnaires before randomisation, and 6 weeks, 6 months and 12 months after randomisation and by telephone interview 2 weeks after treatment commences. The questionnaires collect demographic details as well as information on knee-related pain, movement and function, pain intensity and affect, main functional problem, illness perceptions, self-efficacy, treatment preference and expectations, general health and quality of life. Participants are randomised to receive a package of advice and exercise; or this package plus real acupuncture; or this package plus sham acupuncture. Treatment details are being collected on a standard proforma. Interventions are delivered by experienced physiotherapists who have all received training in acupuncture to recognised national standards. The primary analysis will investigate the main treatment effects of real or sham acupuncture as an adjunct to advice and exercise.DiscussionThis paper presents detail on the rationale, design, methods, and operational aspects of the trial.

Critically Appraised Topics (CATs)

Summary A critically appraised topic (CAT) is a summary of the best available evidence, which answers a clinical question and includes a clinical ‘bottom-line’. A CAT is essentially patient-based, in that it begins with a clinical question generated from a specific patient situation or problem. As such, a CAT has direct relevance to clinicians, who may sometimes feel that the concepts of evidence-based medicine are idealistic and far removed from real clinical practice. This paper presents one method of helping to develop the skills of critical appraisal and present research findings in a clear and consistent manner, so that their clinical relevance may be understood and used to facilitate clinical decision-making. It discusses the essential steps in the formation of CATs and presents some examples, which were developed as part of a new module on evidence-based practice for physiotherapists. These examples are presented to show that the key components and uses of CATs are applicable to all physiotherapists, across all areas of practice. The use of CATs within physiotherapy practice offers a consistent method of critically appraising and summarising the results of research findings. Their formation, use and evaluation within the clinical environment offer one method of increasing confidence in understanding research as well as dissemination of important research findings within physiotherapy.

The effectiveness of acupuncture for osteoarthritis of the knee - a systematic review

Objective To determine the effectiveness of acupuncture treatment for pain and function of patients with osteoarthritis of the knee. Methods A systematic review of randomised controlled trials was performed, including a meta-analysis which combined the results of trials that used adequate acupuncture treatment and used WOMAC scores to measure the effect. The internal validity (quality) and heterogeneity of studies were taken into account. Results Thirteen studies were available, of which eight, involving 2362 patients, could be combined. For both reduction of pain and improvement of function, acupuncture was significantly superior to sham acupuncture (P<0.05 for all comparisons) in both the short term and the long term. Compared with no additional intervention (usual care), acupuncture was again significantly superior for pain and function. The treatment effects were maintained after taking account of quality and heterogeneity in sensitivity analyses. Conclusion Acupuncture is an effective treatment for osteoarthritis of the knee. Its overall effect size is 0.8, and it can be considered instead of non-steroidal anti-inflammatory drugs for patients whose symptoms are not controlled by education, exercise, weight loss if appropriate and simple analgesics. Further research is necessary into the most efficient way of delivering acupuncture, and its longer term benefits.