An unexpected injury to the body triggers three responses simultaneously:

- an alertness response that involves adjusting the posture and turning the head and eyes to examine the injured area;

- an autonomic nervous system response that involves secreting substances such as norepinephrine, adrenalin, ACTH and/or cortisol, as well as phenomena such as vasoconstriction and piloerection (”goosebumps”);

- a more elaborate behavioural response, which may include expressing the pain verbally, moaning, shouting, crying, or complaining. This response may also include typical facial expressions, rubbing the affected area to reduce the pain, adopting a body posture that reduces the intensity of the pain, reducing movement and activity in general, and so on.

The description that 19th-century Scottish explorer David Livingstone gives of his being attacked by a lion provides eloquent evidence that pain is not always proportional to the seriousness of the injury:

”Growling horribly close to my ear, he shook me as a terrier dog does a rat. The shock produced … a sort of dreaminess, in which there was no sense of pain nor feeling of terror, though quite conscious of all that was happening. It was like what patients … under the influence of chloroform describe, who see all the operation, but feel not the knife… The shake annihilated fear, and allowed no sense of horror in looking round at the beast. This peculiar state is probably produced in all animals killed by the carnivora…”.

- David Livingstone, Missionary Travels and Researches in South Africa, 1857

A very small number of people are born with a complete inability to sense pain. They don’t try to protect themselves when they get hurt (which happens frequently), and they generally die fairly young. These people are said to have a congenital insensitivity to pain or congenital analgesia.

Because of this condition, these people are in constant danger and must rely on learned rules of behaviour to try to avoid being injured. But rules such as “try not to bump too hard into stationary objects” and “keep away from things that are hot” are still just intellectual constructs with none of the edifying power of pain to repel one’s body from sources of danger. And these rules are even harder to apply when these people are still children; as a result, such children often succumb to injuries or internal bleeding that go unnoticed—a simple attack of appendicitis, for example, can prove fatal.

When these children do survive, they often suffer injuries to their mouth (because they bite their tongue without feeling it) or to their eyes (because they fail to remove foreign particles soon enough). They also commonly experience problems with their joints, as well as multiple broken bones. Even during sleep, the lack of nociception can lead to injuries caused by staying in uncomfortable positions for too long.

One good example of this condition is the case of a Canadian woman who was born with an indifference to pain stimuli but with no other sensory deficits, and who was highly intelligent. Even though she learned early in life to avoid any situations that might hurt her, she developed a progressive degeneration of her joints and vertebrae, which rapidly led to a major deformation of her skeleton and an infection that ended her life at age 28.

The existence of such individuals also confirms that pain is different from the other senses, and that it does not result from an excess of any one of them, because the people in question do not have any somatic sensory disorders other than their nociception deficit.

This deficit may have many different causes. Some people with this condition appear to have excessively high levels of endorphins. The administration of endorphin-blocking substances reduces the intensity of the stimulus needed for such individuals to experience pain.

Other people with this condition seem to have a problem with their nociceptive sensory fibres, and in particular the C fibres, as well as with the corresponding peripheral nociceptors. A mutation in gene SCN9A, which encodes a voltage-gated sodium channel, might prevent this channel from working and hence greatly disrupt the transmission of nerve impulses in these neurons.

Lastly, malfunctions in the areas of the brain that are involved in processing nociceptive information may also cause a deficit in the perception of pain messages.

This deficit occurs most often in homogeneous societies where recessive genes, such as the one for congenital analgesia, can be expressed more readily. For example, in the village of Gällivare, in northern Sweden, some 40 cases have been reported.

The intensity of pain is not always correlated with the severity of the injury. A given pain stimulus will not always produce the same reaction in two different people, and the same person may even react very differently to the same pain stimulus from one day, month, or year to the next. The reason that our subjective experience of pain varies so greatly is that so many different sets of factors influence the way that we perceive it.

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One such set consists of biological or genetic factors, such as a person’s sex, or the levels of certain hormones in his or her body, or his or her ability to respond to stress.

For example, the thresholds at which women begin to feel pain have been shown to vary with their menstrual cycle. Several studies have also shown that women’s pain tolerance levels are lower than men’s. Published studies provide anatomical data to support this finding: the density of nerve fibres is almost two times higher in women’s skin than in men’s. Hence it is no surprise that women feel pain more quickly than men do.

In addition, the male hormone testosterone helps to mask the discomfort associated with pain. Many researchers believe that from an evolutionary perspective, selection would have favoured those males who had higher testosterone levels and hence could tolerate pain from their injuries longer when fighting other males in competition for females.

But things aren’t all that simple. In a study published in the April 2004 edition of the journal Pain, researchers from McGill University showed that sustained low-level pain might produce more anxiety in men than in women, even if women feel pain more intensely than men.

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The perception of pain is also influenced by cultural factors. For example, if people have philosophical or religious beliefs that pain represents a test, a punishment, a necessary evil, or something unavoidable, those beliefs will definitely affect the way that those people experience pain. Thus, people who are raised in families or cultures where they are taught to endure pain stoically will show less discomfort than people who focus their attention on their pain. For example, cases have been documented in East Africa where people underwent brain surgery without anesthesia, in the middle of the bush, without showing any signs of pain.

Another extreme example of cultural factors’ influencing the perception of pain comes from the Tamil community of Malaysia, which celebrates the festival of Thaipusam every year. As part of the celebrations, some participants compete in acts of self-mutilation, during which their faces betray no signs of pain.

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The subjective perception of pain is also greatly influenced by a multitude of cognitive or psychological factors. Some of these factors, such as stress and depression, increase our perception of pain, while others, such as a calm, optimistic attitude, decrease it.

Distress and anxiety are two of the cognitive factors that most often amplify pain. In a 1985 study, British psychologist Gerry Kent noted that people who regarded themselves as anxious were the ones who reported the highest levels of pain immediately following a visit to the dentist. Three months later, these people evaluated the level of pain that they had experienced during that visit as four times higher than than they had initially. In contrast, the subjects who considered themselves less anxious reported levels half as high as they had initially.

Other studies have shown that another factor that can greatly increase pain is simply how much attention is paid to it by the individuals experiencing it, or by the people close to them. For example, if the parents of children with a disease that makes their skin itch express sympathy when their children scratch the itch (even though they have been told not to), those children will scratch themselves more than children whose parents do not pay such attention. Similarly, in experiments where men were interviewed about their sensations of pain, those men who knew that their sympathetic wives were listening behind a two-way mirror evaluated their pain as more intense than those men who did not have this sympathetic ear.

Among those cognitive factors that can reduce our perception of pain, simple distraction has proven its effectiveness many times over. Experiments have shown that simply listening to sounds while receiving a painful stimulus reduces the subjective perception of pain. This finding has also been confirmed by brain-imaging studies showing that the areas of the brain that are involved in processing pain become less active when sounds are played.

In ordinary life, too, there are myriad examples of distractions’ attenuating pain. Haven’t you ever cut yourself and not even noticed, because you were so wrapped up in the task you were working on? And yet, if someone else cut you the same way while you had to watch, you would feel a sharp pain and probably cry out.

There are also many examples where athletes have sustained heavy blows in the course of a game and continued playing until the end, only then to discover that they had broken a finger or an ankle.

There are many other reported cases of soldiers who have been seriously injured on the battlefield but experienced minimal pain. The positive emotions associated with the knowledge that for them, the war was over, must surely have had something to do with these spectacular examples of the descending control of pain.

This phenomenon has been investigated more systematically in studies comparing civilians and military personnel who had received similar injuries. The civilians demanded medication more often and complained much more intensely than the military personnel. One can also speculate that for for the civilians, such injuries represented not a welcome respite from adversity, but a prolonged inability to work, loss of income, loss of mobility, and so on.

The meaning that people ascribe to their pain can thus also influence its perceived intensity. If someone is stuck at home with a painful illness or injury but sees it in a positive light—for example, as a chance to think about the meaning of life, or to get some writing done, or to spend time with his or her children—that will have beneficial effects on his or her perception of the pain’s intensity.

Besides inflammation, muscle spasm is another aspect of the healing process that can cause pain. Unlike a cramp, which is a painful, involuntary muscle contraction of short duration, a muscle spasm is a cramp that can last for days and days, or even years.

Muscle spasms originate in a protective mechanism: after someone sustains a blow or suffers a fall, or injures themselves by failing to warm up properly before engaging in some physical activity that they are unused to, one of their muscles may contract to immobilize the injured part of the body and thus act as a natural splint or cast. But if the contraction persists, it can become harmful instead of helpful. When a muscle fails to relax normally, the results are poor blood circulation and painful congestion. These in turn make the muscle contract even more tightly and painfully, and the vicious cycle of muscle spasm is then established.

A stiff neck is a classic example of a muscle spasm. This spasm in the broad muscles of the neck usually affects one side more than the other, forcing the person to keep his or her head facing in one particular direction. Most muscle spasms occur in the back, between the base of the neck and the lumbar region.

”Physician communication with patients is the closest thing to magic. It gets communicated in incredibly subtle ways—a flash in the eye, a smile, a spring in the step.” - Daniel Moerman

A pure placebo is a pharmacologically inert substance prescribed in a therapeutic context— generally, lactose in a gel capsule, for oral administration, or normal saline solution, for injection. By extension, the term “placebo” is also used in expressions such as “placebo surgery” (which consists solely of making incisions in the skin) and “placebo therapies” (such as simulated acupuncture treatments).

An impure placebo is a medication that is marketed for a given condition but is being used for another for which its therapeutic effectiveness has not been demonstrated—in other words, a drug that is intended for a specific condition but is diverted to another use. Vitamin C, for instance, is unquestionably effective for treating scurvy (which results from a deficiency of this vitamin), but has no proven effects on flu, fatigue, or colds, much less any proven ability to prevent cancer, even though people sometimes take it for these purposes.

The “double-blind” is a procedure used in clinical drug trials to overcome the influence that doctors might have on their patients —sometimes even unconsciously—if the doctors knew whether the substance that they were giving them was actually an active medication or only a placebo. A double-blind can be achieved in a variety of ways, such as by having someone other than the doctors determine which subjects receive what and by keeping this information hidden from the doctors for the duration of the protocol.

In this way, not only do the patients not know what they are receiving, but the doctors do not know what they are giving, so that they cannot influence their patients in any way. The information on who receives the placebo also remains hidden throughout all the procedures for measuring physiological effects, and is disclosed only at the end of the trial, when the results are analyzed.

For ethical reasons, patients who participate in double-blind drug trials are told in advance that they may receive a placebo instead of a medication.

In clinical drug trials, the undesirable side effects of the medication being tested may sometimes give the researchers some indications as to which patients have received the actual medication rather than the placebo. These indications can thus invalidate the double-blind control (see preceding sidebar).

To avoid this kind of bias, researchers sometimes use what is known as an active placebo: a substance that produces the same undesirable effects as the medication being tested, but without containing the same active molecule. It thus becomes much harder to detect which patients have received the placebo.

Atropine is an example of a substance that is used as an active placebo. It is a molecule that binds to muscarinic acetylcholine receptors, causing symptoms such as dry mouth, constipation, and elevated body temperature.

The proportion of patients who show a placebo effect varies greatly with the nature of the illness being treated. This proportion ranges from virtually 0 to 100%, with about 33% often cited as the average.

For example, in one study of a tranquilizer, 10 to 20% of the patients who had received only a placebo experienced negative side effects. (Such “nocebo effects” are the reverse of the placebo effect but arise from the same belief that one has received an actual medication.) In another study, of a new chemotherapy drug, 30% of the individuals who received the placebo lost their hair.

But the percentage response to a placebo often exceeds one-third. For example, in one study, an analgesic effect was observed in 39% of the people who had received a placebo after having their wisdom teeth extracted. In another study, such an effect was seen in 56% of the people who had had a potentially painful amount of heat applied to the skin of their left hand. In people with severe depression, the placebo response rate is about 30%, but it can be as high as 70% in people whose depression is slight. Lastly, in a study of how the analgesic effects of a placebo pill varied according to what the subjects were told that it cost, 61% of the subjects who were told a lower price said that the pill reduced their pain, while among the subjects who were given a higher price, the figure was 85%. These results clearly show the sensitivity of the placebo effect to certain factors.

As regards the percentage of the effects of active medications that a placebo generally achieves, the average figure is about 55% for the effects of analgesics such as aspirin or morphine. In treatment for depression, numerous studies on tricyclic antidepressants have shown that the placebo was about 59% as effective as the actual medication. The percentages when placebos are used in place of insomnia medications also range from 55 to 60%.

One last example with the two types of statistics: in a study on the analgesic effect of morphine, 75% of the patients who received morphine reported experiencing a 50% reduction in their pain, whereas 36% of those who had received a placebo said that they had experienced a reduction in pain that they too estimated at 50%.

These results demonstrate an important fact: not everyone responds to the placebo effect, but not everyone responds to the active medication either! The human body is a very complex thing.

In a 1972 study that has since become a classic, medical researcher Barry Blackwell showed that the placebo effect can be clearly observed in healthy subjects—in this case, in 56 medical students who agreed to participate in what they were told was an experiment on the effects of taking a single dose of a stimulant or a sedative drug.

The students were divided into four groups. The first group were asked to take one blue sedative pill, the second two blue sedative pills, the third one pink stimulant pill, and the fourth two pink stimulant pills. What the students did not know was that all of these pills were actually placebos that contained nothing but inert ingredients.

Of the students who had been told that they were receiving sedatives, more than two-thirds reported feeling sleepy, and the students who had taken two of these blue “sedative” pills felt sleepier than those who had taken only one. Likewise, a large proportion of the students who had been told that they were receiving stimulants reported feeling less tired.

Moreover, about a third of the 56 participants complained of side effects such as headaches and dizziness. And here too, the effect felt was proportional to the dose of placebo received: in other words, more severe side effects were reported by the students who had received two pills. Only 3 of the 56 students said that they had experienced no noticeable effects after taking the pills.