Specific effects and expectation of acupuncture treatment. A trial utilising PET imaging Dr P White Dr G Lewith Dr J Pariente Prof R Frackowiac

Background Effectiveness vs Efficacy for acupuncture Often large treatment effects Neck pain trial –White, Lewith, Prescott (2004), Annals of internal Medicine

Neck pain - method Acupuncture versus MTNS Outcomes: -Pain (VAS) -Credibility (B & N) -QoL (general and disease specific) -A range of movement -Analgesic intake Baseline, treatment, short (3) and long (12) term follow- up.

Mean pain scores from baseline to week 12 Acupuncture versus MTNS, 12% difference P = 0.01, 95% confidence intervals, 3-21% Neck pain - results The specific effect of acupuncture is statistically significantly different to placebo This may be clinically significant but not in our study The specific effect of acupuncture is about 4 times smaller than the non-specific effect

Background Need to tease apart specific and non- specific effects Many different controls have been used ? Physiological effect of acupuncture

Possible specific effects on healthy subjects - stimulation of GB37 (leg) & GB43 (foot) causes activation of visual & auditory cortex (Cho 2000) (fMRI) Different areas become functional with ‘deqi’ vs needle stimulation in normal subjects (Hsieh 2001) (fMRI) Placebo and Expectation (Dopamine release) may influence experience of pain (Wager 2004) (Fuente-Fernandez 2002) Functional Imaging and Acupuncture

Placebo analgesia shares mechanisms with opioid analgesia (Petrovic 2002) PAG involved in higher cortical pain control (Tracey 2002) Acupuncture induces PAG activity (Liu 2004) and modulates limbic system (Hui 2000)

Questions Does real acupuncture have a specific effect? Is there a physiological/therapeutic response to the streitberger needle and how does this compare to that of real acupuncture? Is the observed therapeutic effect of acupuncture and placebo due to the patient’s belief that there will be an effect?

Method Single blind Crossover Randomised to order of treatment - Real acupuncture - Streitberger - Overt placebo Patients – OA first MCP joint, any age, no other major pain or illness.

Streitberger Needle

Outcomes Primary Comparison of brain activation maps Secondary Needle sensation (Jongbae Park 2002) Credibility (Borkevec and Nau 1972) HCAMQ (Hyland, Lewith, Westoby 2003) Pain (100mm VAS)

Consent, history/ assessment/ questionnaires, insert cannula, MRI scan Randomisation Real AcupunctureStreitberger PlaceboOvert Placebo Baseline PET scan Manipulate (4 mins) Manipulate and scan (8 mins) Apply needle (0 minutes) Scan only (16 mins) Remove needle (23.5 mins) Scan only (24 mins) Scan only (32 mins) Continues as per ‘Real acupuncture’ Apply needle (0 minutes) Insert needle (0 mins) Flow chart of PET procedure

Results 14 patients (F=11, M=3) Right handed 8= pain in left thumb Mean age=59 (S.D.=5.7) (Range 48-63) 4 patients had experience of acupuncture

Credibility (  2 p values) StreitbergerOvert Q1Q2Q1Q2 RA SN Real and Streitberger = similar credibility Real and Overt = significantly different Streitberger and Overt = ?different (less so)

Skin penetration –14 subjects for RA & SN, 1 subject for OP Was the treatment real –No sig diff for RA & SN, both were sig diff to OP Sensation –All 3 had similar sensations (although RA tended to elicit slightly stronger sensations followed by SN) Other confounders – HCAMQ –Experience –Order –Pain No effect on outcome

Hyperactivation of the insula ipsilateral to the intervention – not found on the other two interventions Real Acupuncture vs Streitberger needle (specific acupuncture effect).

Painful stimulus Area of activation in the contralateral insula

Real & Streitberger vs Overt placebo (Expectation) A – Rostral part of anterior cingulate cortex & midbrain periaqueductal gray; B - dorsolateral prefrontal cortex are both activated over and above OP. They are part of the expectation/reward system AB

Interpretation Acupuncture has a specific physiological effect – not linked to pain/ sensation of the procedure Expectation has a mediating effect on the physiological response to a physical stimulus Streitberger needle is fundamentally different from RA and might be an inert control (or at least a physiologically less effective treatment). It only affected sensory areas

The next phase? Further investigation of the physiological effect of skin prick – is it inert?