Placebo: Mind over Matter in Modern Medicine. Dylan Evans

to indicate their level of pain on a line where one end was labelled ‘no pain’ and the other ‘unbearable pain’. Compared with the untreated control group, all those treated with the ultrasound machine reported a significant reduction in pain. Surprisingly, it didn’t seem to matter whether the machine had been switched on or not. Those who had been massaged with the machine while it was turned off showed the same level of pain reduction as those who had received the proper treatment. In fact, when the ultrasound machine was turned up high, it was actually reported as giving less pain relief than when it was switched off.

      We cannot be absolutely sure, even with this model study, that the greater relief experienced by those receiving the fake ultrasound, compared to those receiving no treatment, was due entirely to the placebo effect. Before the switched-off ultrasound machine was applied to the patient’s jaw, a coupling cream was rubbed on the skin around it, and this may have reduced the postoperative swelling by itself. Another study examined this possibility by including a control group of patients who were instructed to apply the facial massage, including the cream, to themselves.⁷ No reduction in the pain or swelling occurred in this group. The reduction in swelling could not, therefore, have been due to either the massage or the cream. It must have been due to the placebo effect.

      Another study to include a no-treatment group compared the placebo response with the powerful painkilling drug buprenorphine.⁸ Fifty-seven patients with lung cancer who had undergone the notoriously painful operation of thoracotomoy (surgical opening of the chest cavity) and lobectomy (removal of part of the lung) were given injections of buprenorphine at thirty-minute intervals until the pain was adequately reduced. The next day, when their pain had returned to a high level, some of the patients were injected with salt water, while the rest were given no treatment at all. Those who received the saline injection experienced a significant decrease in pain over the following hour, while the pain level of the no-treatment group actually increased during the same period. Once again, the body had been encouraged by a pharmacologically inert substance to suppress its own pain.

      KINDS OF PAIN

      To say that placebos can relieve pain is to make a very general claim. For the species of pain are as abundant as the flora and fauna in a tropical rainforest. Pain can be flickering, quivering, beating or pounding. It can be sharp and cutting or dull and throbbing. It can be caused by material objects such as stinging nettles and bullets, or by tension and worry. There are mild pains, annoying pains, and excruciating pains. And pain can strike anywhere in the body; there are headaches, stomachaches, swollen ankles, and backaches. It would be impressive indeed if placebos could affect all these different beasts.

      Without doing separate tests for each different kind of pain, we cannot be absolutely sure that placebos can relieve them all. However, nobody has yet identified a kind of pain that is completely unresponsive to placebos, which does suggest that they work across the board. The pain of a headache is typically very different to that experienced in the aftermath of a dental operation or chest surgery, yet headaches too are placebo-responsive. In one experiment, two British psychologists recruited over eight hundred female volunteers to take part in a study of headache pills.⁹ They gave the volunteers, at random, identical packets of pills, and told them to take two tablets for any headache they had during the following two weeks – and to note down how much relief they obtained. Half the tablets were placebos.

      This study did not include a no-treatment group, but it got round this problem in an ingenious way, by making half the packets identical in every way to those of a well-known painkiller, while the remaining packets were simply labelled ‘analgesic tablets’. This applied to both the placebo packets and the packets containing the active tablets, which were of the same well-known brand. There were, therefore, four groups in the study: two placebo groups (one of which was issued with the placebo tablets in a branded packet) and two nonplacebo groups (with the same division into branded and unbranded packets).

      By comparing the pain relief from all four groups, the experimenters were able to calculate the effects of branding itself on the treatment of headaches. The result was clear: within each group (placebo and nonplacebo), those taking branded tablets got more relief than those taking unbranded pills – though the branding effect was not as powerful as the effect of the active ingredient. Since branding must clearly act via a psychological route, this study supports the idea that headaches are no exception to the general rule that placebos can affect all sorts of pain.

      ALL IN THE MIND?

      Placebos are good at reducing pain. But if this were all they were good for, the placebo response could perhaps be dismissed as a mere figment of the patient’s imagination. Western medicine distinguishes between symptoms, which are subjective feelings reported by the patient, and signs, which are objective indications of disease detectable by the physician. Pain is, of course, a symptom and not a sign; it cannot be measured by any physical test. The only way, in fact, that we can tell how much pain someone feels is by asking them. All the studies that document placebo analgesia are constrained by this important limitation. They may use various different techniques to gauge the level of pain, from simple yes – no questions to numerical charts on which patients are asked to indicate their current degree of suffering on a scale of zero to ten, but they all have to take the patient’s word for it. Is the placebo response, then, just a private affair, dwelling entirely inside the patient’s mind?

      Some early studies appeared to suggest that this was in fact the case. Two of the most famous, both conducted in the late 1950s, were designed to investigate the effectiveness of an operation known as internal mammary ligation, which was widely practised at the time as a treatment for angina pectoris. Angina is characterised by a vice-like pain in the centre of the chest which tends to be brought on by exercise and goes away with rest. It is generally attributed to the clogging up of the coronary arteries, which reduces the amount of blood these arteries can then supply to the muscle in the heart wall. Internal mammary ligation involved, paradoxically, blocking some of the furred-up arteries completely – the rationale being that the blood would be forced to find alternative routes by sprouting new channels through the heart muscle. These new channels would be free of blockages, and so the circulation in the heart would improve – or so the surgeons hoped. Thousands of operations were carried out without any proof that the new channels did actually sprout, although thousands of patients reported that they felt much better after receiving the operation. Only when pathologists failed to detect any of the supposed new blood vessels in those who had received the operation did some doctors begin to wonder if it had the effect they thought it did.

      Two groups of doctors decided to investigate by carrying out controlled trials comparing internal mammary ligation with a placebo operation.¹⁰ This ‘sham surgery’ involved cutting into the chest and exposing the arteries, but not ligating them. Much to their surprise, the doctors found that patients receiving the dummy operation showed about the same level of improvement as those receiving the real one. The reaction of the medical community was depressingly predictable: instead of being struck by the power of the placebo response, doctors quickly dropped the operation of internal mammary ligation. Nobody paused to wonder how the mere belief that one had received a proper operation could be so effective at reducing chest pain.

      Of course, without a no-treatment control group, we cannot be sure that the improvement that occurred after these operations was the result of the placebo response, or whether it was simply the natural course of the disease. However, the success rates were high enough to suggest that the placebo response was playing an important role. Around three quarters of all patients reported significantly lower levels of pain, showed a great increase in their exercise tolerance, and decreased their consumption of vasodilating drugs. This is almost certainly a lot more improvement than doctors would expect in the absence of any treatment.

      It is important to note, however, that the placebo response – if such it was – did not, in this case, reverse the underlying pathology. No new arteries sprouted in either the experimental