The sensation of perceiving the physical “evil” more in some moments is not the result of suggestion, but of a complex alternation of the production of hormones and inflammatory molecules during the 24-hour period
If we have pain somewhere, at night it still seems to us less bearable compared to the day. And it’s not just a sensation: perception really changes in 24 hours because there is a biological clock for pain too, to which we are most sensitive between three and four in the morning. The suspicion that this was the case was from animal studies, but Claude Gronfier del Neuroscience Research Centre of Lyon, France, demonstrated this on 12 volunteers who underwent the so-called constant routine protocol, a very difficult condition to bear because everything is designed so that the participants never know what time it is: light and temperature are always equal, you can only eat small snacks every hour, you can’t sleep or get up to go to the bathroom. In this way all the biological changes recorded depend on the internal circadian rhythm and not on the environment.
Life “suspended”
The volunteers stayed in this one “suspended life” for 34 hours and every 2 hours they were subjected to a test to assess the pain threshold: an instrument with increasing heat was brought close to their skin, which they had to ask to move away when they started to feel bad. A “cycle of pain” clearly emerged, with a maximum of sensitivity in the early morning hours and a minimum 12 hours later, between 3 and 4 in the afternoon; the cycle concerns only the pain, because the reaction to a heat on the skin that is not painful does not have the same trend. The researchers then evaluated whether the pain perceived more intensely at night was all the fault of the sleep deprivation to which the volunteers were subjected: the detailed analysis of the phenomenon through mathematical models confirmed that the course of the pain is 80 percent dependent on the
internal circadian rhythm and only 20 percent of the quantity and quality of sleep. “The authors were amazed, but it is a reasonable proportion considering that it is emerging that many immune mediators or even pain receptors are controlled by circadian rhythms through clock genes,” comments Roberto Manfredini, chronobiologist at the University of Ferrara.
The role of melatonin
Manfredini continues: «Certainly, then, the sleep deprivation can make things worse: the melatoninsleep hormone, is a powerful anti-inflammatory and has an action on pain pathways, if we don’t sleep, therefore we miss the period of the day in which its concentration is high and cortisol, the stress hormone, rises instead, so the pain is perceived even more intensely. Demonstrating the cyclic nature of pain is complicated, also because it is a signal of various types and nature that can emerge from multiple organs and systems; however these data, together with many others collected in recent years, clearly indicate that pain also has a cyclical pattern». They have it heachachemigraine, the pain after dental procedures, sciatica or rheumatoid arthritis, which occurs mainly in the morning as a result of an increase in the production of inflammatory cytokines between 2 and 4 in the night. “In rheumatic diseases the cyclical nature of pain is such a consolidated fact that it has changed therapies: for the most complicated cases, in which taking the drugs upon waking means having to wait too long for them to take effect, controlled-release steroids can be used. They are taken in the evening and work best between 2 and 4 in the morning, reducing the pain upon awakening», says Manfredini.
Chronotherapy
«In the future – continues Manfredini – also for other types of pain it will be possible to have a more adequate chronotherapy. For example, the action of non-steroidal anti-inflammatory drugs varies over time used in postoperative pain, as well as the intensity of the pain itself and the inflammatory mediators associated with wound healing: in certain hours of the day, giving the anti-inflammatory can even be counterproductive, because it contrasts with the production of mediators that favor recovery». For each type of pain it will therefore be advisable to understand its rhythm and the best time to take the analgesic. This is not always the case today, on the contrary: a recent research by the Cincinnati Children’s Hospital has shown that in hospitals there is a “cycle” in painkiller prescriptions but that these still they do not take into account the real needs of the patients and are more numerous in the morningalthough many report the pain especially at night.
Shifts can affect back pain
Circadian rhythms impact many organs, tissues and systems, as well as the harmful consequences of their alteration. “Night shift work in healthy people increases the risk of developing painful symptoms, in those who already have pain it is more likely to increase its intensity”, explains Roberto Manfredini. The alteration of circadian rhythms it could then favor back pain, because the age-related degeneration of the intervertebral discs, the bearings between vertebrae which, by thinning, favor pain, are accentuated if the functionality of some genes-clock is altered: over 600 genes are involved in pathways essential to the physiology of the discs, which therefore are not only mechanical shock absorbers, but have their own rhythm not to disturb. Pain perception has a 24-hour rhythm; there are differences depending on the type of pain and the organs involved, but sensitivity is often greater at night. This happens, for example, with headaches and postoperative pain, while rheumatic pain and migraine peak more towards the morning. Knowing the pace of pain will help take pain relievers at the right time or with controlled release formulations, creating a real chronotherapy to keep the symptom under control over the course of 24 hours.
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March 6, 2023 (change March 6, 2023 | 16:25)
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