Iréne Lund

Are minimal, superficial or sham acupuncture procedures acceptable as inert placebo controls?

Most controlled trials of acupuncture have used minimal, superficial, sham, or ‘placebo’ acupuncture. It has recently been demonstrated that light touch of the skin stimulates mechanoreceptors coupled to slow conducting unmyelinated (C) afferents resulting in activity in the insular region, but not in the somatosensory cortex. Activity in these C tactile afferents has been suggested to induce a ‘limbic touch’ response resulting in emotional and hormonal reactions. It is likely that, in many acupuncture studies, control procedures that are meant to be inert are in fact activating these C tactile afferents and consequently result in the alleviation of the affective component of pain. This could explain why control interventions are equally effective as acupuncture in alleviating pain conditions that are predominantly associated with affective components such as migraine or low back pain, but not those with a more pronounced sensory component, such as osteoarthritis of the knee or lateral epicondylalgia.

RELIABILITY AND RESPONSIVENESS OF THREE DIFFERENT PAIN ASSESSMENTS

The visual analogue scale (VAS) and ordered categorical scales, i.e. numeric rating scales (NRS), are commonly used in the assessment of pain. However, these scales are bounded by fixed endpoints and thus the range of measurement is limited. The disparity in repeated assessments of perceived pain intensity with the VAS, NRS, and electrical stimulation applied as a matching stimulus was studied in 69 patients (48 women and 21 men, 19-72 years) with chronic nociceptive or neurogenic pain. Responsiveness with transcutaneous electrical nerve stimulation (TENS) using the same measurement procedures was evaluated in the same patients. Comparison of results from the three pain assessments showed that the painmatcher is at least as reliable and responsive as VAS and NRS. None of the three measurements showed evidence for systematic disagreement and had only significant random individual disagreement. They also showed evidence for responsiveness.

Repeated massage-like stimulation induces long-term effects on nociception: contribution of oxytocinergic mechanisms.

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 µ‐opioid antagonist β‐funaltrexamine (β‐FNA) and the κ‐opioid antagonist nor‐binaltorphimine (nor‐BNI) but not the δ‐antagonist naltrindole. The long‐term 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 µ‐ and the κ‐receptors in the PAG.

Lack of interchangeability between visual analogue and verbal rating pain scales: a cross sectional description of pain etiology groups

Background:Rating scales like the visual analogue scale, VAS, and the verbal rating scale, VRS, are often used for pain assessments both in clinical work and in research, despite the lack of a gold standard. Interchangeability of recorded pain intensity captured in the two scales has been discussed earlier, but not in conjunction with taking the influence of pain etiology into consideration.Methods:In this cross-sectional study, patients with their pain classified according to its etiology (chronic/idiopathic, nociceptive and neuropathic pain) were consecutively recruited for self-assessment of their actual pain intensity using a continuous VAS, 0–100, and a discrete five-category VRS. The data were analyzed with a non-parametric statistical method, suitable for comparison of scales with different numbers of response alternatives.Results:An overlapping of the VAS records relative the VRS categories was seen in all pain groups. Cut-off positions for the VAS records related to the VRS categories were found lower in patients with nociceptive pain relative patients suffering from chronic/idiopathic and neuropathic pain. When comparing the VAS records transformed into an equidistant five-category scale with the VRS records, systematic disagreements between the scales was shown in all groups. Furthermore, in the test-retest a low percentage of the patients agreed to the same pain level on the VAS while the opposite hold for the VRS.Conclusion:The pain intensity assessments on VAS and VRS are in this study, not interchangeable due to overlap of pain records between the two scales, systematic disagreements when comparing the two scales and a low percentage intra-scale agreement. Furthermore, the lower VAS cut-off positions relative the VRS labels indicate different meaning of the rated pain intensity depending on pain etiology. It is also indicated that the scales have non-linear properties and that the two scales probably have different interpretation. Our findings are in favor of using the VRS in pain intensity assessments but if still the VAS is preferred, the VAS data should be analyzed as continuous using statistical methods suitable for ordinal data. Furthermore, our findings indicate a risk to over or under estimate the patients perceived pain when interpreting condensed VAS data.

Is Placebo Acupuncture What It is Intended to Be

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

The Emperors sham – wrong assumption that sham needling is sham

During the last five years a large number of randomised controlled clinical trials (RCTs) have been published on the efficacy of acupuncture in different conditions. In most of these studies verum is compared with sham acupuncture. In general both verum and sham have been found to be effective, and often with little reported difference in outcome. This has repeatedly led to the conclusion that acupuncture is no more effective than placebo treatment. However, this conclusion is based on the assumption that sham acupuncture is inert. Since sham acupuncture evidently is merely another form of acupuncture from the physiological perspective, the assumption that sham is sham is incorrect and conclusions based on this assumption are therefore invalid. Clinical guidelines based on such conclusions may therefore exclude suffering patients from valuable treatments.

Substance P microinjected into the periaqueductal gray matter induces antinociception and is released following morphine administration

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.

Pain in a Swedish spinal cord injury population

Objective: To describe pain and associated variables in a prevalence group of persons with a sustained spinal cord injury (SCI) in the Swedish capital and its surroundings. Setting: Spinalis SCI Unit (outpatient clinic), Stockholm, Sweden. Design: Assessment over a 12-month period in a yearly health control. Subjects: Four hundred and fifty-six SCI patients. Results: Two hundred and ninety-one out of 456 SCI patients (63.7%) suffered from pain, and in 45.7% of these it was classified as being neurogenic. Aching pain was the most used descriptor (38.5%). The onset of pain was commonly within three months (73.5%). In 70.4% of patients pain occurred below the level of the lesion. Most patients identified pain as coming from one (55.0%) or two (28.2%) body regions. Rating of the general pain intensity on a visual analogue scale (VAS) was 46 out of 100 and rating of the worst pain intensity was 78 out of 100. Ninety-four out of 276 patients (32.3%) considered that their quality of life was significantly affected by pain. Conclusion: Pain was most common in patients with incomplete lesions (ASIA impairment grade D) and there was a correlation between pain and higher mean age at injury and between pain and female gender.

Decrease of pregnant women's pelvic pain after acupuncture: a randomized controlled single‐blind study

Background. The efficacy of acupuncture on low‐back and/or pelvic pain in late pregnancy is reviewed in few reports. Our aim was to evaluate the effects of two different acupuncture stimulation modes on pelvic pain intensity and some emotional symptoms due to the pain condition. Methods. In a prospective randomized controlled single‐blind study, pregnant women with pelvic pain, median gestational age 26 weeks (range 18–35), were given 10 acupuncture treatments. Needles were inserted subcutaneously over acupuncture points without further stimulation (superficial, n=22), or intramuscular and stimulated repeatedly until a perceived sensation of numbness, de qi, (deep, n=25). Self‐reported pain intensity at rest and during daily activities was assessed on a visual analog scale. The variables pain, emotional reactions, and loss of energy were assessed according to the Nottingham Health Profile questionnaire. Changes in assessed variables were analyzed with a nonparametric statistical method allowing for analysis of systematic group changes separated from additional individual changes. Results. After acupuncture stimulation, significant systematic group changes towards lower levels of pain intensity at rest and in daily activities as well as in rated emotional reaction and loss of energy were seen. The results also showed additional individual changes in most variables. In this study, no differences between the effects induced by the superficial and deep acupuncture stimulation modes were observed. Conclusion. Acupuncture stimulation that is individually designed may be a valuable treatment to ameliorate suffering in the condition of pelvic pain in late pregnancy.

Massage-like stroking of the abdomen lowers blood pressure in anesthetized rats: influence of oxytocin

The aim of this study was to determine how massage-like stroking of the abdomen in rats influences arterial blood pressure. The participation of oxytocinergic mechanisms in this effect was also investigated. The ventral and/or lateral sides of the abdomen were stroked at a speed of 20 cm/s with a frequency of 0.017-0.67 Hz in pentobarbital anesthetized, artificially ventilated rats. Arterial blood pressure was recorded with a pressure transducer via a catheter in the carotid artery. Stroking of the ventral, or both ventral and lateral sides of the abdomen for 1 min with a frequency of 0.67 Hz caused a marked decrease in arterial blood pressure (approx. 50 mmHg). After cessation of the stimulation blood pressure returned to the control level within 1 min. The maximum decrease in blood pressure was achieved at frequencies of 0.083 Hz or more. Stroking only the lateral sides of the abdomen elicited a significantly smaller decrease in blood pressure (approx. 30 mmHg decrease) than stroking the ventral side. The decrease in blood pressure caused by stroking was not altered by s.c. administration of an oxytocin antagonist (1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin, 1 mg/kg) directed against the uterine receptor. In contrast, the administration of 0.1 mg/kg of oxytocin diminished the effect, which was antagonized by a simultaneous injection of the oxytocin antagonist. These results indicate that the massage-like stroking of the abdomen decreases blood pressure in anesthetized rats. This effect does not involve intrinsic oxytocinergic transmission. However, since exogenously applied oxytocin was found to diminish the effect of stroking, oxytocin may exert an inhibitory modulatory effect on this reflex arc.