Placebo effect 'starts in the spine'

“Research suggests that the placebo effect works, in part, by blocking pain signals in the spinal cord from arriving at the brain in the first place,” The Times reported. The newspaper said the spinal cords of 15 healthy volunteers had been scanned while they received laser 'pinpricks' to their hands.

An inactive cream was applied to both hands, but sometimes the subjects were told it was analgesic. The volunteers told they had been given a pain relief cream reported feeling 25% less pain and showed “significantly reduced activity in the spinal cord pathway that processes pain”.

This interesting, small study highlights the powerful 'placebo effect' of suggestion. The 25% improvement in pain scores seen from the placebo effect is similar to the response seen in other studies on active versus placebo pills. This suggests that at least part of the effect can be explained by a neurological mechanism that is prompted by a belief in the effectiveness of a treatment.

The interest for scientists here is the imaging technique that made high resolution scans of this hard-to-reach area of the brain possible, and the confirmation that some sort of messaging from the brain to the spinal cord plays a role in pain control.

Where did the story come from?

This research was carried out by Dr Falk Eippert and colleagues from the Department of Systems Neuroscience at the University Medical Center Hamburg-Eppendorf in Germany. Funding for this study is not reported. The study was published in the peer-reviewed journal Science .

What kind of scientific study was this?

This experimental study investigated the theory that a measure of spinal cord blood flow and metabolism (known as the blood oxygen level dependent (BOLD) response), which is increased following painful heat stimulation, could be affected by placebo analgesia (the placebo effect).

The researchers explain that the placebo effect is an example of how psychological factors can influence the feeling of pain. They defined placebo analgesia as the administration of an inactive treatment that has a pain-relieving effect under the assumption that it is because of the belief in the effectiveness of the treatment.

The researchers enrolled 15 healthy men between the ages of 21 and 30 (average age 25). All subjects had taken part in a placebo analgesia study around seven months earlier that investigated brain responses during placebo analgesia. Subjects were only debriefed after participating in this current study, meaning they did not know that the first study had been looking at a placebo effect until after the second study.

Firstly, the researchers determined the temperatures that produced pain by applying heat to the forearms of the subjects with a laser up to the point that the volunteer said it had reached 80 out of a pain scale of 100. They then treated the subjects with two identical, pharmacologically inactive creams. Both creams were presented in professionally labelled tubes, one branded “lidocaine cream” (an anaesthetic) while the other was branded a “control cream”. Both creams were applied under a patch.

The subjects were told that the study was investigating the effect of an analgesic cream on spinal cord responses to painful stimulation. They were actually deceived in two ways. Firstly, they were told that the inactive cream was a highly effective pain reliever. Secondly, they went through a manipulation phase where the laser that was applied to the forearm after treatment with the placebo patch (labelled anaesthetic) was surreptitiously lowered at repeat testing. This gave the subject the sense of reducing pain and so created an expectation that this was an active patch that would later relieve pain when they were tested in the MRI scanner.

The patches were applied, one to each arm, and then the volunteers were given painful stimuli with the laser while in the MRI scanner, recording the amount of pain they felt on the 100 point scale.

Data from two of the 15 subjects were discarded because of either excessive movement during the test or technical failure.

What were the results of the study?

When the researchers tested for the effect of the painful stimulation with fMRI scans of the spinal cord, they found that the strongest blood flow changes (BOLD responses) were in an area of the spinal cord called the dorsal horn (part of the spinal cord where sensory nerves from the stimulated areas go into the spine). There were also differences between the left and right sides, despite the fact that both arms had been given the same level of painful heat stimulus. This indicates that the anaesthetic placebo was having an effect at the spinal cord level.

The pain ratings were significantly lower when the placebo cream was used compared with the control cream. On the 100-point pain scale, the pain rating with the placebo cream was 52.3, compared to 71.1 with the control cream. This gives a 26% reduction P = 0.002.

What interpretations did the researchers draw from these results?

The researchers say that their data "provide direct evidence that psychological factors can influence pain processing at the earliest stage of the central nervous system", which is the point at which the nerve fibres enter the spinal cord at the dorsal horn.

What does the NHS Knowledge Service make of this study?

The researchers discuss how placebo analgesia may work in terms of accepted theories of pain control, particularly the gate-control theory which was described in the 1960s. That theory suggests that the sensation of physical pain is not a direct result of pain receptors in the skin sending messages up to the brain, but instead is an interaction between different neurons, both pain-transmitting and non-pain-transmitting, working both up and down the spinal cord. The activation of nerves coming down from the brain, and pain-relieving chemicals released by nerves, are then thought to open or shut an imaginary gate that can either inhibit an individual's perception of pain or let that perception pass through to the brain.

The researchers note that:

• This study cannot demonstrate the exact mechanism of spinal inhibition, because the researchers did not measure the detail of what was happening between single nerves or neurons.
• It is not possible to be sure that the effects seen in the spinal cord were due to pain rather than some other sensation (touch for example) as the researchers did not test the responses to non-painful stimuli.

As a small study, this demonstration of the placebo effect improves the understanding of how pain is perceived and it is likely that it will lead to further similar studies.