In Sheather-Reid’s 1990s study on efficacy of pain relief agents, the agents used were opioids and non-opioid analgesics (such as nonsteroidal anti-inflammatory drugs and acetaminophen (paracetamol)) to examine the analgesic efficacy of the opioid agonist codeine versus the nonsteroidal anti-inflammatory drug ibuprofen in regional cervicobrachial pain using N-of–1 methodology. Analgesic effect was monitored by patients self-reporting of clinical effect. The study showed that there was no statistically significant difference between patients who used analgesics and those who took a placebo.

Similar results were reported in another study on N-of-1 methodology in 19 subjects (U.S. Cancer Pain Relief Committee, 1998) with neuropathic pain in which “no significant differences (were found) between placebo and dextromethorphan for any of the outcome measures, leading to the conclusion that dextromethorphan was ineffective in neuropathic pain.” (Sheather-Reid,1998)

Other studies point out that the variable effects of analgesia are dependent on the way it was administered. For example, experiments have shown that a given dose of morphine relieves post-surgical pain to a considerably greater extent when administered openly in a standard injection procedure, than when administered in a hidden fashion by means of a computerized infusion pump, without the patient knowing when it will be given. (Colloca et al., 2005, pp.545–552)

In addition, research shows that the placebo effect can be greatly increased if the patient’s expectations of the results are increased. For example, telling a patient in pain that he is about to receive a powerful painkiller can either produce or enhance analgesic responses. Abundant experimental evidence demonstrates that research subjects often experience substantial analgesic responses when they are administered a pain stimulus and then given an inert placebo intervention deceptively described as a powerful pain-relieving agent. (Colloca et al., 2005)

On the face of it, these diverse findings may seem confusing. Their significance though is easily explained. We’ll do just that in the next post.