Elsevier

NeuroImage

Volume 25, Issue 4, 1 May 2005, Pages 1161-1167
NeuroImage

Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture

https://doi.org/10.1016/j.neuroimage.2005.01.016Get rights and content

Abstract

Both specific and non-specific factors may play a role in acupuncture therapy for pain. We explored the cerebral consequences of needling and expectation with real acupuncture, placebo acupuncture and skin-prick, using a single-blind, randomized crossover design with 14 patients suffering from painful osteoarthritis, who were scanned with positron emission tomography (PET). The three interventions, all of which were sub-optimal acupuncture treatment, did not modify the patient's pain. The insula ipsilateral to the site of needling was activated to a greater extent during real acupuncture than during the placebo intervention. Real acupuncture and placebo (with the same expectation of effect as real acupuncture) caused greater activation than skin prick (no expectation of a therapeutic effect) in the right dorsolateral prefrontal cortex, anterior cingulate cortex, and midbrain. These results suggest that real acupuncture has a specific physiological effect and that patients' expectation and belief regarding a potentially beneficial treatment modulate activity in component areas of the reward system.

Introduction

Many acupuncture trials demonstrate no efficacy or minimal superiority over placebo/control despite clinical effectiveness. Little is understood about the complexities of the interaction between acupuncture, placebo, patient, and practitioner. This relative ignorance may be responsible for the confusing results of acupuncture trials (Birch et al., 1996) and the lack of clarity emerging from the subsequent systematic reviews (White et al., 2002).

Cho et al., in a neuroimaging study, showed that stimulation of specific acupuncture points on the foot, traditionally used to treat the eye, causes activation of the visual cortical areas in the same way as direct stimulation of the eye by light (Cho et al., 1998). Alimi et al. found that stimulation of an auricular acupuncture point representing the hand causes a cerebral response similar to direct stimulation of the hand, but this effect is not consistent (Alimi et al., 2002). Wu et al. report a differential brain response to acupuncture and penetrating sham acupuncture (Wu et al., 1999a, Wu et al., 1999b). While Cho suggests that both acupuncture and sham acupuncture reduce activation of areas associated with pain perception (Cho et al., 2002). Hsieh noted differential patterns of brain activation with needling at the same site to produce pain and ‘deqi’ (the specific needling sensation associated with acupuncture) (Hsieh et al., 2001). Hui et al. suggest that subject expectation may influence anterior cingulate activity and this pattern of activation is not modified by previous experience of acupuncture (Hui et al., 2002). However, it may be difficult to generalize about the clinical effects of acupuncture from these studies, as they were carried out in pain-free healthy volunteers.

The placebo (Streitberger) needle (SN) (Streitberger and Kleinhenz, 1998) gives the impression of skin penetration without piercing the skin, it acts like a stage dagger with the needle disappearing into the needle shaft. The belief that real acupuncture (RA) has occurred has been confirmed (Kleinhenz et al., 1999), but we have no understanding of the physiological effect of SN. Non-specific placebo effects include the natural history of illness, the therapeutic relationship, the process and rituals involved in treatment, patient expectation, suggestibility, and conditioning (Araujo, 1998, Peck and Coleman, 1991, Sheppeard and Wigley, 1984). We have defined these effect sizes clinically and suggest that the non-specific effects are 3 or 4 times greater than the specific effects of acupuncture in a randomized, controlled, single blind assessment of acupuncture for chronic mechanical neck pain (White et al. submitted for publication). This is a similar ratio of specific to non-specific effect sizes to that found with pharmacological treatment of depression (Kirsch et al., 2002), reinforcing the impact and importance of belief and expectancy on outcome in chronic benign conditions.

Procedurally, we defined overt placebo (OP) as a skin prick with a blunt needle with patients aware that they were being given an ‘inert’ intervention. We manipulated belief by using the SN which gives the same physical sensation as the blunt needle but in the consistent and reliable expectation of positive therapeutic benefit. We argued that if expectation is of minor therapeutic importance, overt placebo and the Streitberger needles would show similar cerebral effects, especially if both were different to real acupuncture. On the other hand, differential cerebral responses to all three types of stimulation would suggest that both expectation and a specific acupuncture effect may both be important for effective therapy.

Section snippets

Patients

Patients were recruited from Southampton General Hospital orthopedic department. All patients were diagnosed with 1st metacarpophalangeal (MCP) osteoarthritis (OA) pain. This pain is known to respond to acupuncture (Dickens and Lewith, 1989). Patients abstained from normal analgesia or alcohol for a day prior to scanning and were otherwise without pain. No patient had a history of neurological or psychiatric illness and all gave written informed consent to the study. The study was approved by

Results

14 right-handed patients (11 females and 3 males), aged between 48 and 63 (mean age 59.4, SD = 5.7), were recruited. Six patients had first MCP joint osteoarthritis (OA) of the right and 8 of the left thumb. Four subjects had previously been treated with acupuncture, 10 were acupuncture naive.

Discussion

We investigated the effect of three acupuncture-related interventions: RA, SN, and OP. RA elicited a specific relative activation of the ipsilateral insula to needling that was not correlated with the sensation of being needled. When patients expected a “real treatment” (RA and SN), activations were found in the DLPFC, in the rACC, and in the midbrain. These areas have together been linked to pain modulation (Rainville et al., 1999, Wager et al., 2004) and reward expectation (Schultz, 2002).

Acknowledgments

We would like to thank Peter Belward from the Physiotherapy Department and Mrs. D. Warwick and D. Hargreaves from the Orthopaedic and Trauma Department at Southampton General Hospital for their help with recruitment. Dr. Lewith's post is funded by a grant from the Maurice Laing Foundation. Dr. White is a Department of Health CAM post-doctoral research fellow. RSJF is funded by a Wellcome Trust program grant and JP by the French Foreign Office (Bourse Lavoisier).

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