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Pain Really Is Worse At Night, And This Is Why

Discussion in 'Hospital' started by The Good Doctor, Sep 28, 2022.

  1. The Good Doctor

    The Good Doctor Golden Member

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    Have you ever wondered what pain actually is? The truth is much deeper than you might have realized.
    We can sometimes think of pain as a purely physical experience – the result of something going wrong or getting injured in your physical body. In fact, nothing could be further from the truth: pain is a physical sensation, but it’s also incredibly tied up with factors like our emotions and psychology.

    It’s also affected by things unrelated to us entirely – things like the weather, or the time of day. In fact, it’s an incredibly weird, hard-to-explain experience overall.

    But that doesn’t mean we can’t try.

    What is pain?

    Considering it’s felt by nearly everybody on the planet, pain is a surprisingly nebulous phenomenon to define.

    “Pain is what we call a biopsychosocial experience,” Rocío de la Vega, a psychology researcher at the Biomedical Research Institute of Málaga and University of Málaga in Spain, told IFLScience. In other words, she explained, “it has elements that have to do with our bodies, and our brains… and [there’s] also a social dimension.”

    It’s not that no objective definition exists – the International Association for the Study of Pain, or IASP, revised their definition of pain in 2020 to be “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.”

    However, as de la Vega pointed out, there are a few problems with that description. Some pain has no connection at all to tissue damage – in fact some pain can be felt in tissue that doesn’t even exist. Neuropathic pain is caused by nerve damage, and nociplastic pain isn’t fully understood at all yet; some pain is psychological; and chronic pain can sometimes be little more than a crapshoot.

    “[With] chronic pain… our brain keeps telling us something’s wrong,” de la Vega said, “but a lot of times there’s no tissue damage or there’s no danger.”

    It’s not that the pain isn’t legitimate: “it hurts, it’s real,” she stressed, but “other things are in play, and more complex, multidisciplinary therapies are needed to tackle it.”

    So, maybe the official definition isn’t super useful – but perhaps that’s not surprising. After all, pain is an intensely personal experience, and notoriously difficult to describe externally. “[That]’s the social dimension,” de la Vega explained. “People who are struggling to be believed that they have pain, [and] how we communicate our pain with one another.”

    Of course, there are observable physical reactions and processes that the body goes through to create what we experience as pain.

    That’s when “specialized pain receptors, called nociceptors… send an electrical signal to your spinal cord and up to your brain,” Jessi Cucinello-Ragland, who studies pain and addiction in Louisiana State University’s Department of Physiology, told IFLScience. "A bunch of different brain regions receive that signal and communicate to recognize that you’re experiencing pain.”

    But as we’ve seen, this pure sensory response to tissue damage, known as nociception, isn’t the whole story. “There are psychosocial contributors to pain… that shape every person’s individual subjective pain experience,” Cucinello-Ragland said. “Pain, then, is both your nervous system response and your subjective response,” they explained.

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    Why do we feel pain?

    Pain is, generally speaking, not a pleasant experience – and there’s a good reason for that.

    “Acute pain – so, pain that happens after say an accident, or a burn, or an injury – it’s an alarm signal from our brain,” de la Vega said.

    “Our brain is telling us, ‘hey, be careful – something is wrong, stop touching that, or stop walking, because you’re going to get hurt,’” she explained. “So it’s a really wise thing that nature has done for us – it’s telling us that we are in danger, so we need to listen to that pain.”

    At its core, then, pain is a survival mechanism – which explains why it’s so ubiquitous. Everything from bees to ‘bots can feel this facet of the experience, and if you really stretch the definition, it can even apply to some reactions seen within plant life.

    However, ask anybody with a chronic pain condition, and they’ll likely tell you: pain isn’t always such a helpful feeling. “Pain is like an alarm system for a car,” de la Vega explained. It’s there to alert you when something goes wrong, and when it works, it’s very useful – but, “haven’t you ever [heard] at night, when some car alarm is going on and on, and nothing is happening – nobody is trying to steal the car!”

    “Maybe it’s the wind, maybe the system has broken and become hypersensitive – that’s what’s happens when we have chronic pain,” she said. “Sometimes there’s no danger, and we’re not going to get hurt – but still, that alarm is sounding.”

    With chronic pain, then, the answer to “why am I in pain” is often a solid “not sure” – it could be nerve damage, some underlying long-term physical condition, or even a symptom of mental ill-health. “Stress is a really common emotional state that can contribute to pain perception,” pointed out Cucinello-Ragland.

    “A parent can lift a car off their child without feeling pain because stress is dampening our pain perception,” they said. “However, stress can also sensitize our nerves and cause our nociceptors to activate even when we’re not faced with a painful stimulus.”

    Meanwhile, “pain and depression are mutually comorbid,” de la Vega said. “One symptom of depression that people sometimes have is pain, and a very common symptom of people with chronic pain is depression.”

    In a way, that makes sense – after all, life in constant pain is unlikely to be a joyful experience. But it’s not that simple: there are actually specific mechanisms throughout the brain and body which link depression and chronic pain. “Regions in the brain’s limbic system, which controls emotions, are activated by that nociceptive signal to your brain,” Cucinello-Ragland said.

    Just as pain can trigger an emotional response, the same is true in the opposite direction. “In animal models, we know that administration of the stress hormone cortisol can increase or decrease nociception,” they explained. “There’s also human research out there showing that emotional states like sadness or anger actually increase pain in an experimental setting.”

    “Your emotions and pain perception are very tightly linked,” they added. “This is even why some people find pain pleasurable.”

    Is pain worse at different times of the day?

    “Because pain is an emotional and sensory experience, pretty much anything that happens to us can influence how we feel pain,” Cucinello-Ragland said.

    That could be our psychological state; our physical state; even weird things like whether we like to swear or the natural color of our hair can affect how loud that pain alarm sounds. But what about the time of day?

    “We… identified a circadian rhythm of pain sensitivity,” Inès Daguet, who studies pain perception and assessment at the French Institute of Health and Medical Research, told IFLScience. “In healthy humans… the worst times of day for pain are in the middle of the night (around 4 AM) and the best times are in the middle of the afternoon (around 4 PM).”

    It was an unexpected result – and the more the researchers looked for answers, the more intriguing things got. The natural explanation for the effect would be to relate it to sleep deprivation – it’s long been known that a lack of sleep increases pain, and a good night’s sleep can work wonders for aches and pains. In fact, Daguet and her colleagues discovered that sleep-related processes accounted for only one-fifth of the pain sensitivity effect over the 24-hour period – four times less than the effect from the circadian rhythm.

    “This proportion was very surprising,” explained Daguet, first author of the recently published study that discovered this daily cycle of pain perception. “Many previous studies had shown an impact of sleep on pain sensitivity, so we expected a strong sleep effect. On the [other] hand, the impact of the circadian system was rarely studied in the correct conditions and was therefore commonly underestimated.”

    It’s an understandable omission: proving links to the circadian rhythm like this is notoriously difficult. It requires study participants to be placed in a laboratory environment so highly-controlled that it’s impossible to know what time it is – meaning no changes to temperature or light; no movement, sleeping, or access to the world outside the lab; even standing up to go pee is verboten. Only then, once any influence from the natural day-night cycle has been removed – which necessarily takes more than 24 hours to achieve – can any biological process be attributed to the body’s internal rhythm rather than some external stimulus

    The experiment took 34 hours in total. “Every two hours, each participant received three two-second heat stimulations on the forearm at 42, 44 and 46 degrees, in a randomized order,” Daguet explained. “However, to avoid comparison between stimulations and therefore a possible placebo effect, the participants were told that these temperatures were different every time.”

    Why is pain worse at night?

    Finding evidence for an effect and explaining it are very different tasks, and the reasons behind a circadian rhythm of pain perception are not yet clear: “many hypotheses can be given,” Daguet said.

    “I personally believe that there could be a relationship with the fact that originally, we (as animals) needed to be more sensitive at night when we slept in order to wake up quickly in case of a danger,” she said.

    Ironically, this vagueness may in part be thanks to the very rigor that made the study possible at all. “I do sleep things too,” de la Vega, who was not involved in the study, said, “and [with] polysomnography and things like that… the results usually don’t translate [in real life].”

    That said, the results aren’t surprising, de la Vega said. “[Throughout] our circadian rhythm, several things happen to our body,” she explained. “One of them is the release of certain hormones at different times of the day – in the morning we have a peak of cortisol… and then at night we release melatonin, and that’s what makes us feel sleepy… That would be my wild guess.”

    Cucinello-Ragland had a similar explanation for the result. “It makes a lot of sense that pain can be controlled on a circadian cycle because cortisol is also circadian-regulated,” they said. “Patients often report worse pain at night, and part of this is because cortisol is lowest at nighttime.”

    “While cortisol is our go-to stress hormone, at normal levels it is also anti-inflammatory,” they explained, meaning that lower cortisol levels at night can worsen our pain simply because we aren’t able to reap the anti-inflammatory benefits of cortisol as well at night.”

    When it comes to explaining the real-world phenomenon, there’s a major factor that can’t be overlooked: our own tricksy brains.

    “At night is usually the perfect time [for] ruminating,” pointed out de la Vega. “We can feel like, ‘oh yeah, my knee is hurting – is that just because I turned a little bit, or is it because I have something bad on my knee? Oh my god, yeah, I remember my second cousin, we thought she was ok, and then she got this thing, and they had to do surgery, I’m going to google it,’ and then you google it, and then basically you’re dead already.”

    “You know, at night, in the darkness… the stimuli that we’re [usually] surrounded by are decreased, and if we have pain, that can become a more salient stimulus,” she said. “We pay more attention to it and feel it more.”

    Of course, she added, there’s one more potential explanation for why that headache or backache is throbbing so much more at the end of a busy day.

    “Sleep can be a big factor... to tackle pain” she pointed out. “Maybe you’re just tired.”

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