Should we recruit patients or healthy volunteers for acupuncture studies of chronic pain?

OBJECTIVE: The aim of this study was to compare the results of healthy volunteers with patients in chronic pain, in terms of acupuncture needle sensation. The search for a credible mechanism that underpins the effect of acupuncture in pain has recently involved the use of brain imaging techniques in an attempt to identify the neural correlates involved in pain control. Such studies have usually enrolled healthy participants rather than patients. This practice might be inappropriate as we are unsure if we can generalize from healthy volunteers to patients in chronic pain. METHOD: This paper describes a comparison of data obtained from 2 small randomized controlled studies, 1 involving patients with chronic pain and the other which recruited healthy volunteers. Both studies used real acupuncture and a nonpenetrating "placebo" needle in a crossover design. The outcome studied in this paper was a comprehensive needling sensation questionnaire. RESULTS: There was a difference in the sensations experienced by patients as compared with healthy volunteers. Patients tended to feel much stronger sensation. Neither group differed in distinguishing between real and placebo needling. However, patients were more likely to state that both needles were real, whereas healthy participants were more likely to suggest that neither were real. DISCUSSION: It is concluded that if the nature of the sensation felt is of importance, then it might be inappropriate to recruit healthy volunteers in lieu of patients and a larger study is required to clarify this.     

The effect of real and sham acupuncture on thermal sensation and thermal pain thresholds

OBJECTIVE: To compare the effect of real and sham acupuncture and a control intervention on thermal sensation and thermal pain thresholds. DESIGN: Single-blind, randomized controlled, repeated-measures trial. SETTING: Laboratory. PARTICIPANTS: Eighteen acupuncture-naive, healthy subjects with no history of upper-limb pathology or acupuncture contraindications. INTERVENTION: Subjects were randomly assigned (blind card allocation) to 1 of 6 possible orders of application of the interventions, which consisted of 25 minutes each of control, real, and sham acupuncture. MAIN OUTCOME MEASURES: Thermal sensation and thermal pain thresholds measured with a thermal sensory analyzer before and after each intervention. RESULTS: There were increases in cold and hot pain and cold sensation thresholds with real acupuncture. The level of increase did not differ significantly from the changes that occurred with sham acupuncture and control interventions. CONCLUSIONS: Although we observed a trend toward a decreased sensitivity to thermal pain and thermal sensation with real acupuncture, this trend did not differ significantly from the changes with control or sham interventions. Therefore, no support was provided for analgesic or placebo effects of acupuncture. The trend, combined with the relatively low power of the inferential tests applied does, however, suggest that further research is merited.     

The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI

Clinical and experimental data indicate that most acupuncture clinical results are mediated by the central nervous system, but the specific effects of acupuncture on the human brain remain unclear. Even less is known about its effects on the cerebellum. This fMRI study demonstrated that manual acupuncture at ST 36 (Stomach 36, Zusanli), a main acupoint on the leg, modulated neural activity at multiple levels of the cerebro-cerebellar and limbic systems. The pattern of hemodynamic response depended on the psychophysical response to needle manipulation. Acupuncture stimulation typically elicited a composite of sensations termed deqi that is related to clinical efficacy according to traditional Chinese medicine. The limbic and paralimbic structures of cortical and subcortical regions in the telencephalon, diencephalon, brainstem and cerebellum demonstrated a concerted attenuation of signal intensity when the subjects experienced deqi. When deqi was mixed with sharp pain, the hemodynamic response was mixed, showing a predominance of signal increases instead. Tactile stimulation as control also elicited a predominance of signal increase in a subset of these regions. The study provides preliminary evidence for an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 that correlates with the psychophysical response.     

Perception of bodily sensation as a predictor of treatment response to acupuncture for postoperative nausea and vomiting prophylaxis

OBJECTIVES: Conditions associated with the response to acupuncture treatment remain widely elusive. This study aimed to identify predictors of treatment response in patients undergoing acupuncture treatment for prevention of postoperative nausea and vomiting (PONV). An intervention-specific questionnaire was developed to assess perception of bodily sensations (PBS) in patients undergoing acupuncture treatment. DESIGN: Exploratory study in addition to an observer-blinded randomized controlled trial. SETTINGS/LOCATION: The departments of anesthesiology and of gynecology, University of Heidelberg, Germany. SUBJECTS: Two hundred and twenty (220) female patients scheduled for breast or gynecologic surgery. INTERVENTIONS: True acupuncture on point P6 (Neiguan) or placebo/sham acupuncture on a virtual point 1 cm proximal and lateral to P6. OUTCOME MEASURES: Of 220 female patients scheduled for breast or gynecologic surgery who were included in the trial, 202 completed the newly developed PBS questionnaire before the intervention. The main outcome was incidence of PONV in relationship with PBS and the kind of acupuncture applied. Logistic regression analyses were performed to identify predictors of treatment response for those receiving surgery (n = 195). RESULTS: High PBS predicted low treatment response in patients receiving breast surgery (odds ratio [OR] = 1.6; p = 0.039 for each 10-point increase). The PBS questionnaire showed good item difficulty, internal consistency, and divergent validity. Treatment response in patients receiving gynecologic surgery was predicted by the kind of acupuncture applied (OR = 0.4; p = 0.027), whereas PBS played no role in this group. CONCLUSIONS: The incidence of PONV after breast surgery seems to be influenced by some psychological mechanisms. In this group of patients, acupuncture might be more effective in patients who have low PBS.     

Studies of heat pain sensation in man: perception thresholds, rate of stimulus rise and reaction time

Afferent impulse frequency, one of the determinants of subjective magnitude of sensation, varies with the rate of rise of stimulus intensity: the faster the increase in stimulus energy, the higher the frequency of firing for a given amount of energy. This predicts that the steeper the stimulus ramp the lower will be the threshold for perception. While such inverse relation holds for myelinated fibre mediated cold sensation and mechanical pressure sensation, the opposite has been reported for unmyelinated fibre mediated heat pain and cold pain sensations. These paradoxical results intuitively suggest possible reaction time artefact. Indeed, a fixed time interval that includes conduction of the impulses to the brain, central processing and efferent conduction, intervenes between sufficient peripheral stimulus and the voluntary signal in reaction to subjective experience. As stimulus temperature continues to rise along this time, an artefactually high threshold reading results: the steeper the temperature rise, the larger will be the artefact, particularly for submodalities with longer reaction time. The present study compared heat pain threshold, obtained through a method that involves reaction time participation, with heat pain thresholds obtained bypassing reaction time. It was found in 16 volunteers that: (a) Heat pain thresholds decreased as the rate of temperature rise increased when reaction time was not a factor (P less than 0.001). (b) Heat pain thresholds determined through the method involving reaction time participation were significantly higher than those obtained bypassing reaction time (P less than 0.01). Such difference increased with increasing rates of temperature rise. (c) Peripheral conduction velocity calculated from average reaction time was found to be approximately 0.6 m/sec.(ABSTRACT TRUNCATED AT 250 WORDS)     

The placebo needle, is it a valid and convincing placebo for use in acupuncture trials? A randomised, single-blind, cross-over pilot trial

The issue of what constitutes an effective and realistic acupuncture placebo control has been a continuing problem for acupuncture research. In order to provide an effective placebo, the control procedure must be convincing, visible and should mimic, in all respects, apart from a physiological effect, the real active treatment. The 'Streitberger' needle might fulfil these criteria and this paper reports on a validation study. This was a single-blind, randomised, cross-over pilot study. Patients were drawn from the orthopaedic hip and knee, joint replacement waiting list. Intervention consisted of either 2 weeks of treatment with real acupuncture followed by 2 weeks on placebo, or vice versa. The prime outcome was a needle sensation questionnaire and there was a range of secondary outcomes. Thirty-seven patients were randomised and completed treatment. Groups were well balanced at baseline. No significant differences between groups or needle types were found for any of the sensations measured. Most patients were unable to discriminate between the needles by penetration; however, nearly 40% were able to detect a difference in treatment type between needles. No major differences in outcome between real and placebo needling could be found. The fact that nearly 40% of subjects did not find that the two interventions were similar, however, raises some concerns with regard to the wholesale adoption of this instrument as a standard acupuncture placebo. Further work on inter-tester reliability and standardisation of technique is highly recommended before we can be confident about using this needle in further studies.     

Ultrasound measurements of the distance between acupuncture needle tip at P6 and the median nerve

BACKGROUND: Pericard 6 (P6) is one of the most frequently used acupuncture points, especially in preventing nausea and vomiting. At this point, the median nerve is located very superficially. OBJECTIVES: To investigate the distance between the needle tip and the median nerve during acupuncture at P6, we conducted a prospective observational ultrasound (US) imaging study. We tested the hypothesis that de qi (a sensation that is typical of acupuncture needling) is evoked when the needle comes into contact with the epineural tissue and thereby prevents nerve penetration. SETTINGS/LOCATION: The outpatient pain clinic of the Medical University of Vienna, Austria. SUBJECTS: Fifty (50) patients receiving acupuncture treatment including P6 bilaterally. INTERVENTIONS: Patients were examined at both forearms using US (a 10-MHz linear transducer) after insertion of the needle at P6. OUTCOME MEASURES: The distance between the needle tip and the median nerve, the number of nerve contacts and nerve penetrations, as well as the number of successfully elicited de qi sensations were recorded. RESULTS: Complete data could be obtained from 97 cases. The mean distance from the needle tip to the nerve was 1.8 mm (standard deviation 2.2; range 0-11.3). Nerve contacts were recorded in 52 cases, in 14 of which the nerve was penetrated by the needle. De qi was elicited in 85 cases. We found no association between the number of nerve contacts and de qi. The 1-week follow-up showed no complications or neurologic problems. CONCLUSIONS: This is the first investigation demonstrating the relationship between acupuncture needle placement and adjacent neural structures using US technology. The rate of median nerve penetrations by the acupuncture needle at P6 was surprisingly high, but these seemed to carry no risk of neurologic sequelae. De qi at P6 does not depend on median nerve contact, nor does it prevent median nerve penetration.     

脑卒中肩手综合征患者感觉障碍的定量分析

背景脑卒中偏瘫后肩手综合征(shoulder-hand syndrome,SHS)患者感觉减退已被证实,而感觉障碍的评估多用问卷式调查或仅为粗略临床检查来完成,难以精确评估.目的运用定量感觉检查技术(quantitative sensorytesting,QST)检查脑卒中后肩手综合征观察组和脑卒中对照组各15例患者的温度觉及振动觉,并进行定量分析,以了解小纤维神经功能状态及其与肩手综合征的关系.设计病例对照研究(case-control study).地点和对象研究地点为中南大学湘雅三医院,对象涉及2000-06/2001-04湘雅三医院门诊及住院脑卒中后瘫痪病例.方法用界限法分别检查观察组与对照组偏瘫侧上肢大鱼际掌侧温度觉阈值与拇指掌侧振动觉阈值.检查温度觉时,使用一个小的与检测区皮肤接触的热电极探头,探头温度以1℃/s速度递增(热觉、热痛觉)或递减(冷觉、冷痛觉),直至受检者产生感觉的那一刻由受检者本人按下按钮停止刺激.得到一个温度觉阈值,探头温度恢复到预置温度准备下一次刺激.重复4次得到平均温度觉阈值.在检测振动觉时,振动器的刺激强度以0.1～12 μm/s的速度递增,重复检测6次.主要观察指标感觉障碍发生率,温度觉、痛觉及振动觉的数据.结果SHS组中感觉障碍发生率为67%较对照组27%显著增高(P＜0.05).SHS组与对照组定量感觉比较,主要表现为冷觉阈值降低(分别为26.73±4.48,29.89±1 57,P＜0.05),热觉阈值增高(分别为36.83±1.90,35.40±0.89,P＜0.05).冷痛觉阈值、热痛觉阈值与振动觉阈值之间的差异无显著性意义.冷痛觉阈值与冷觉阈值的差值(P＜0.01)及热痛觉阈值与热觉阈值之间差值(P＜0.01)差异有显著性意义.结论脑卒中偏瘫后SHS患者感觉障碍发生率显著增高.主要形式为温度觉减退和痛觉过敏.C类和Aδ类神经纤维功能障碍可能在SHS发病中起重要作用.     

Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson's disease

Patients with Parkinson’s disease (PD) reportedly show deficits in sensory processing in addition to motor symptoms. However, little is known about the effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on temperature sensation as measured by quantitative sensory testing (QST). This study was designed to quantitatively evaluate the effects of STN-DBS on temperature sensation and pain in PD patients. We conducted a QST study comparing the effects of STN-DBS on cold sense thresholds (CSTs) and warm sense thresholds (WSTs) as well as on cold-induced and heat-induced pain thresholds (CPT and HPT) in 17 PD patients and 14 healthy control subjects. The CSTs and WSTs of patients were significantly smaller during the DBS-on mode when compared with the DBS-off mode (P < .001), whereas the CSTs and WSTs of patients in the DBS-off mode were significantly greater than those of healthy control subjects (P < .02). The CPTs and HPTs in PD patients were significantly larger on the more affected side than on the less affected side (P < .02). Because elevations in thermal sense and pain thresholds of QST are reportedly almost compatible with decreases in sensation, our findings confirm that temperature sensations may be disturbed in PD patients when compared with healthy persons and that STN-DBS can be used to improve temperature sensation in these patients. The mechanisms underlying our findings are not well understood, but improvement in temperature sensation appears to be a sign of modulation of disease-related brain network abnormalities.     

Traces: making sense of urodynamics testing--Part 8: Evaluating sensations of bladder filling

The "Traces" series discusses how the urodynamic clinician generates usable data from a filling cystometrogram (CMG). Part 8 focuses on the question, "What are the sensations of bladder filling?" Recent research suggests that sensations of bladder filling wax and wane from consciousness in healthy persons free of bothersome lower urinary tract symptoms. Because of its invasive and atypical nature when compared to daily life, multichannel urodynamics testing cannot reproduce the numerous and complex variables that influence bladder sensation in the healthy individual, making the evaluation of sensations of bladder filling a particularly challenging component of the filling CMG. Routine assessment of bladder sensations focuses on identification of three landmarks--first sensation of bladder filling, first desire to void, and a strong desire to void. A fourth sensation, bladder fullness or a compelling desire to void, is recommended. In addition to assessing these sensations, the urodynamic clinician must assess sensations indicating associated disease or disorders affecting lower urinary tract function, including urgency, pain, and atypical sensations. This assessment should be completed in the context of the results of one or more validated instruments used to measure bladder sensations.     

Factors that influence the applicability of sham needle in acupuncture trials: two randomized, single-blind, crossover trials with acupuncture-experienced subjects

OBJECTIVES: In recent years the retractable type of sham needle has been anticipated to be a possible solution for masking patients in acupuncture research. However, this needle has been intended mainly for acupuncture-na?ve subjects. The authors' goal in this study was to assess the validity of the retractable type of sham needle. METHODS: The authors conducted two randomized, single-blind, crossover trials with acupuncture-experienced subjects. Different acupuncture points were used in each trial (a LI-4 trial and a BL-23 trial). The subjects received two sessions of different stimulations in each trial. A Park Sham Needle was used in one session, a genuine acupuncture needle in the other. RESULTS: In the LI-4 trial, all of the 21 subjects (100%) felt penetration with the genuine needle, but only 7 of the 20 subjects (35%) felt a similar sensation with the sham needle (P=0.0002). Fifteen of the 21 subjects (71%) felt a dull sensation with the genuine needle, but only 4 of the 20 subjects (20%) felt a similar sensation with the sham needle (P=0.01). In the BL-23 trial, 14 of the 20 subjects (70%) felt penetration with the genuine needle and 10 of the 20 subjects (50%) felt "penetration" with the sham needle (P=0.39). Eight of the 20 subjects (40%) felt a dull sensation with the genuine needle and 2 of the 20 subjects (10%) did with the sham needle (P=0.109). CONCLUSIONS: Potential factors that influence the applicability of "placebo" needling include not only inter-tester variability but also the patient's knowledge and experience of acupuncture, acupuncture point selection, the visual impact of needling, and so on.     

Neurology (48)

Phantom pain and phantom sensations in upper limb amputees: an epidemiological study. (University Hospital Groningen, Groningen, The Netherlands) Pain 2000;87:33–41.
This study determined the prevalence and factors associated with phantom pain and phantom sensations in upper limb amputees in The Netherlands. Additionally, the relationship between phantom pain, phantom sensations, and prosthesis use in upper limb amputees was investigated. One hundred twenty-four upper limb amputees participated in the study. Subjects were asked to fill out a self-developed questionnaire scoring the following items: date, side, level, and reason of amputation, duration of experienced pain before amputation, frequencies with which phantom sensations, phantom pain, and stump pain are experienced, amount of trouble and suffering experienced, respectively, related to these sensations, type of phantom sensations, medical treatment received for phantom pain and/or stump pain, and the effects of the treatment, self medication, and prosthesis use. The response rate was 80%. The prevalence of phantom pain was 51%, of phantom sensations 76%, and of stump pain 49%; 48% of the subjects experienced phantom pain a few times per day or more. Moderate to severe suffering from phantom pain was experienced by 64% of the respondents. A significant association was found between phantom pain and phantom sensations (relative risk 11.3) and between phantom pain and stump pain (relative risk 1.9). No other factors associated with phantom pain or phantom sensations could be determined. Only 4 patients received medical treatment for their phantom pain. Phantom pain is a common problem in upper limb amputees that causes considerable suffering for the subjects involved. Only a small number of subjects are treated for phantom pain. Conclude that further research is needed to determine factors associated with phantom pain.     

Developing a sensation information message for femoral arteriography

Sensation information is proposed as a way of decreasing the patient's distress during a threatening health care event. A first step in developing a sensation information message is to determine the content of the message. This study, using a systematic theory-based methodology, was conducted to describe and validate the common physical sensations experienced by patients undergoing the diagnostic procedure of femoral arteriography. (A conceptual framework based on how an individual perceives or senses a situation was used.) A three-stage survey design was used including: (1) tool development following observation of the procedure and pilot-testing of the interview schedule, (2) interview of patients who had undergone femoral arteriography about the sensations experienced during the procedure, and (3) validation of the responses. Twenty-one steps in the femoral arteriography procedure of which patients were aware were identified. Nine 'feeling' sensations commonly experienced during the procedure and the sights and sounds associated with the procedure were determined. The sequencing and duration of procedure steps were observed and the environment in which the procedure was performed was described.     

Phantom limb sensations in adolescents: a case study to illustrate the utility of sensation and pain logs in pediatric clinical practice.

Although the nature of pain following amputations has been well documented for adults, little research has been conducted to determine the incidence, prevalence, and nature of phantom limb sensations and pains in children and adolescents. This case study documents the nature of phantom limb sensation (intensity, quality, location, duration, and frequency) for a 15-yr-old adolescent after leg amputation. She completed a brief sensation/pain log, consisting of quantitative and qualitative scales, for 28 days after surgery. She experienced phantom limb sensations, which spread from her toes to encompass her entire leg by day 10 after surgery. The pattern of spread was not consistent throughout this period. The quality of sensations remained relatively constant and was described as itching and tingling. The phantom sensations were not experienced consistently throughout the day, but were experienced as discreet episodes. Both the duration and frequency of these episodes decreased throughout the 28 days. Similarly, the intensity of her phantom sensations decreased gradually throughout this period. This case study illustrates how it is possible to integrate research with health care delivery in a practical manner, to obtain prospective information about the nature of childhood sensory experiences.     

Psychophysical properties of female genital sensation

Provoked vestibulodynia (PVD) is characterized by the presence of vulvar touch and pain hypersensitivity. Pain with vaginal distension, which motivates treatment seeking and perpetuates distress, is frequently reported with PVD. However, the concordance between the perception of vulvar and vaginal sensation (ie, somatic and visceral genital sensations, respectively) remains unstudied in healthy women, as well as in clinical populations such as PVD. To evaluate the static and dynamic (time-varying) properties of somatic and visceral genital sensation, women with PVD (n = 14) and age- and contraceptive-matched healthy controls (n = 10) rated varying degrees of nonpainful and painful genital stimulation. Somatic (vulvar) mechanical sensitivity to nonpainul and painful degrees of force were compared to visceral (vaginal) sensitivity to nonpainful and painful distension volumes. Results indicated that healthy women showed substantial individual variation in and high discrimination of vulvar and vaginal sensation. In contrast, PVD was associated with vulvar allodynia and hyperalgesia, as well as vaginal allodynia. Modeling of dynamic perception revealed novel properties of abnormal PVD genital sensation, including temporal delays in vulvar touch perception and reduced perceptual thresholds for vaginal distension. The temporal properties and magnitude of PVD distension pain were indistinguishable from vaginal fullness in healthy controls. These results constitute the first empirical comparison of somatic and visceral genital sensation in healthy women. Findings provide novel insights into the sensory abnormalities that characterize PVD, including an experimental demonstration of visceral allodynia. This investigation challenges the prevailing diagnostic assessment of PVD and reconceptualizes PVD as a chronic somatic and visceral pain condition.     

Acupuncture treatment of phantom limb pain and phantom limb sensation in amputees

Three case histories are presented in which amputees with acute or chronic phantom limb pain and phantom limb sensation were treated with Western medical acupuncture, needling the asymptomatic intact limb. Two out of the three cases reported complete relief of their phantom limb pain and phantom limb sensation. Acupuncture was successful in treating phantom phenomena in two of these cases, but a larger cohort study would be needed to provide more evidence for the success rate of this treatment technique for this indication.     

Investigation of the paradoxical painful sensation ('illusion of pain') produced by a thermal grill

A paradoxical painful sensation can be elicited by the simultaneous application of innocuous warm and cold stimuli to the skin. In the present study, we analyzed the conditions of production of this unique experimental illusion of pain in 52 healthy volunteers (27 men, 25 women). The stimuli were produced by a thermode composed of six bars whose temperature was controlled by Peltier elements. The temperature of alternate (even- and odd-numbered) bars could be controlled independently to produce various patterns of the 'thermal grill'. After measuring the cold and heat pain thresholds, a series of combinations of warm and cold stimuli, whose distance to the thermal pain threshold was at least 4 degrees C, were applied on the palmar surface of the right hand during 30s. After each stimulus, the subjects had to describe and rate their sensations on visual analog scales. Paradoxical painful sensations, mostly described as burning, were reported by all the subjects but three. However, the phenomenon was less frequent in approximately one third of ('low responder') volunteers. The frequency and intensity of such painful sensations were directly related to the magnitude (i.e. 5-25 degrees C) of the difference of the temperature between the warm and cold bars of the grill. The combination of increasingly colder temperature to a given warm temperature induces similar effects as combining increasingly warmer temperature to a given cold temperature. These results suggest that pain can be the result of a simple addition of non-noxious warm and cold signals.