Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture
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).
References (47)
- et al.
Is acupuncture effective for the treatment of chronic pain? A systematic review
Pain
(2000) - et al.
Activation of the hypothalamus characterizes the acupuncture stimulation at the analgesic point in human: a positron emission tomography study
Neurosci. Lett.
(2001) - et al.
Randomised clinical trial comparing the effects of acupuncture and a newly designed placebo needle in rotator cuff tendinitis
Pain
(1999) - et al.
The mechanism of placebo analgesia
Lancet
(1978) - et al.
Decreased heart rate by acupuncture stimulation in humans via facilitation of cardiac vagal activity and suppression of cardiac sympathetic nerve
Neurosci. Lett.
(1997) - et al.
Neural responses during anticipation of a primary taste reward
Neuron
(2002) - et al.
Imaging cognitive modulation of pain processing
Pain
(2002) - et al.
Functional imaging of brain responses to pain. A review and meta-analysis (2000)
Neurophysiol. Clin.
(2000) Getting formal with dopamine and reward
Neuron
(2002)- et al.
Introducing a placebo needle into acupuncture research
Lancet
(1998)
The placebo needle, is it a valid and convincing placebo for use in acupuncture trials. A randomised, single blind, cross-over trial
Pain
Relations between brain network activation and analgesic effect induced by low vs. high frequency electrical acupoint stimulation in different subjects: a functional magnetic resonance imaging study
Brain Res.
Auricular acupuncture stimulation measured on fMRI
Med. Acupunct.
Does the choice of placebo determine the results of clinical studies on acupuncture
Res. Complement. Med.
Somatotopic activation of opioid systems by target-directed expectations of analgesia
J. Neurosci.
Acupuncture in the treatment of pain
J. Altern. Complement. Med.
New findings of the correlation between acupoints and corresponding brain cortices using functional MRI
Proc. Natl. Acad. Sci.
Acupuncture: the search for biologic evidence with fMRI and PET techniques
J. Altern. Complement. Med.
Interoception: the sense of the physiological condition of the body
Curr. Opin. Neurobiol.
Single-blind, controlled and randomised clinical trial to evaluate the effect of acupuncture in the treatment of trapezio-metacarpal osteoarthritis
Comp. Med. Res.
Complementary medicine: attitudes and expectations, a scale for evaluation
Comp. Med. Res.
Modified activation of somatosensory cortical network in patients with right-hemisphere stroke
Brain
Human brain function
Cited by (318)
Acupuncture for endometriosis-associated infertility: Study protocol for a randomized controlled trial
2024, World Journal of Acupuncture - MoxibustionRandomized, sham-controlled trial of acupuncture for post-cataract surgery dry eye disease
2022, Complementary Therapies in Clinical PracticeInfralimbic medial prefrontal cortex alters electroacupuncture effect in animals with neuropathic chronic pain
2022, Behavioural Brain ResearchAnalysis of the traditional characters of deqi and proposal for a biocircuit based on the general systems theory
2021, Revista Internacional de AcupunturaRole of acupuncture in the treatment of insulin resistance: A systematic review and meta-analysis
2019, Complementary Therapies in Clinical Practice