Nociceptors – What are they? Why are they important? And what this means for clinical practice.

Nociceptors – What are they? Why are they important? And what this means for clinical practice.

In my first pain specific blog I thought I would discuss the humble nociceptor. Understanding this very common nerve ending is incredibly important for anyone in pain management, not because we need an in-depth knowledge of neurophysiology to practice effectively, but because even the most cursory understanding has huge implications for the way we practice.

Let’s dive in!

 

What’s a nociceptor?

A nociceptor is a free nerve ending in our body which in the presence of a noxious stimulus (something harmful or unpleasant) fires in a process called nociception. This signal is sent to second order neurons in the spinal cord where most of these sites have an ascending pathway to the brain stem and brain.

Most nociceptors are polymodal meaning they can respond to noxious stimulus that is mechanical, thermal and/or chemical, rather than being specific to one. Their response to different stimulus can also change over time. For example, in the presence of a chemical stimulus such as inflammation, the mechanical sensitivity may increase. Nifty hey!

A great example of this would be sunburn, where the thermal and mechanical sensitivity increases dramatically in response to the changes in the skin. So in the presence of a normally non-noxious stimulus such as a warm shower, or in particularly bad burns (we’ve all been there), the pressure of a shirt against your skin, the sensitivity may be so high nociceptors fire, despite the stimulus being previously non-threatening.

 

Nociceptors aren’t pain sensors – nociception isn’t pain sensation

For many years nociceptors and the process of nociception was referred to as pain receptors and pain sensation respectively. This coming from the idea originally suggested by Decartes in 1664 that if the body operates like a machine, pain must be the indication of damage, therefore the signal that responds to a noxious stimulus must equate to the physical sensation of pain.

Decartes’ theory of pain sensation – the heat (A) causing a pain signal from the foot (B) which is transported along the nerve to the brain

This has lead to the dominant theory that pain is equal and proportionate to tissue damage.

However, we know this isn’t the case because as we discussed above nociceptors respond to noxious stimulus, which can include both harmful and non-harmful stimulus and can change their sensitivity depending on other stimulus, resulting in the process of nociception at even less harmful stimulus.

If we consider the sunburn example, when you experience pain from a warm shower, is the presence of pain indicating that tissue damage is occurring, or is nociception there to protect you against potentially threatening stimulus?

 

‘Nociception is neither sufficient or necessary for pain’

This famous phrase depicts the multidimensional nature of pain. While nociception can be a stimulus or contributor to a pain sensation or experience, there are many other factors that can contribute to an experience of pain. These include:

  • Attention
  • Expectation
  • Sensitisation of the nervous system
  • Beliefs
  • Previous experiences of pain
  • Visual information
  • Sounds
  • Stress
  • Synaptic imprecision, to just name a few.

What this combination of factors tell us is that pain is much more about the body making sense of an experience, than it is about responding to tissue damage. Therefore nociception fits in as a stimulus or information that can inform a pain experience, but is not analogous to one. We can explore this concept through a few examples.

There is a  famous case of a construction worker who accidentally jumped on a nail, having it pierce through his boot and presumably his foot. Reported in the BMJ, the authors reported when at hospital he had extreme pain which he required medication to ease before the doctors could remove his boot. When they did they found miraculously that the nail had in-fact based in-between his toes. He didn’t even have a scratch! The belief that the nail had gone through his foot and the visual information of the nail is his boot was enough information for his body to experience pain.

A picture of the nail having gone through the construction workers boot

Another case where nociception wasn’t required to produce pain and a reflex response is the rubber hand experiment. Have a look at the video below. Patients are setup so they have one hand hidden away, but a fake rubber hand and a mirror is present to create the illusion that the rubber hand is in fact their hand that they are seeing. Then both the rubber hand and the patient’s real hand are brushed gently and the same time in the same location to strengthen the brains interpretation that the rubber hand is in fact theirs. So much so, when there is any new stimulus that the patient observes being applied to the rubber hand, they feel and respond appropriately. Including a fork.

Not my other arm - GIF on Imgur
A video of The Rubber Hand Experiment, including bonus fork

We can also have many examples of no pain despite nociception, sometimes quite extreme levels. Many medics and field doctors as early as the 1800’s had noticed soldiers who has experienced extreme amounts of tissue damage (and therefore nociception) and experience no pain until they were safely in the hospital.

A more common example, the spice chilli is a known activator of nociceptors that respond to thermal stimulus, therefore creating a burning sensation when eaten. Despite fairly consistent activation of nociceptors everyone has an individual tolerance to the amount of chilli they can ingest. We all know someone who can barely tolerate any chilli (so small amounts of nociception creating a large experience of pain/burning) and people who piles on the hot sauce without breaking a sweat (so large amounts of nociception with a limited response in pain). We also know that this tolerance an change over time.

 

Understanding nociception in practice – a clinical example

The best example of putting pain science into practice (albeit often done inadvertently) is a grade 2 acute lateral ankle ligament injury (the common acute ankle inversion injury).

Within minutes to hours of the injury occurring the patient often feels quite intense amounts of pain with weightbearing, which can often be disproportionate to the injury that they have just sustained. This is caused by inflammation from the tissue injury increasing the sensitivity of nociceptors so they have a greater response to smaller stimulus, encouraging more protection of the injured area.

This makes pain severity a poor guide to whether a fracture, ligament or tendon injury has occurred and why we have developed toolkits such as the Ottawa ankle rules, a series of tests based on pain location and response to palpation and weightbearing, to be a much more accurate and reliable guide.

Within a few days to a week, the inflammation and swelling reduces which causes the pain to reduce quite significantly. We encourage the patient to walk to their pain tolerance, understanding that despite the experience of pain and likely tissue damage, it is beneficial to move as much as possible.

By week 3 most, if not all, rehabilitation programs have the patient back doing some form of strengthening and higher load exercises and by week 6, assuming there have been no complications, the patient starts returning to their sport. By this point pain has usually substantially reduced and the patient is able to move comfortably in many different situations such as change of direction drills and high load strength activities.

Despite the fact that we know that the ligament can take up to 6 months for the tissue to completely heal, at 6 weeks our patients are often feeling a lot less pain and moving comfortably. Without realizing it, our rehabilitation programs for an acute ankle sprain recognizes that nociception and a pain experience isn’t entirely mediated by tissue damage.

Image 1. Estimate Healing Times for Various Injuries Courtesy of Dr Caleb Burgess, DPT.
Estimate of Healing Times for Various Injuries – Image by Dr Caleb Burgess, DPT.

Early in the injury there is lots of pain, the area is very sensitive, reflecting a recent injury and a need for rest. However as well slowly start moving the affected area, we not only get the many benefits of movement, one of which is an anti-inflammatory effect, but we start to teach the body and the person it is safe to move and bear weight. So much so that we’ve got so much credible evidence that it is safe to move, pain reduces despite tissue damage/healing and therefore some level of nociception being present.

If pain returns after this point, we often don’t rush to conclusions such as we’ve re-injured the ligament or there may be further damage. We recognize that the area is still healing, that nociception is still present and that doing exercise that maybe was too intense, that doing too much exercise or movements that placed too much strain on the tissue, such as a small ankle inversion moment, may redraw the body’s attention to the underlying level of nociception temporarily. Management is often lowering the amount or intensity of an exercise and allowing the area and potential increased sensitivity to reduce while still doing a tolerable amount of exercise, not back to offloading.

 

Clinical implications and changing the way we view the body:

Many current theories and approaches to care base themselves on the idea that pain is proportional to tissue damage. From this brief understanding of nociceptors we understand that this can’t be true, as nociceptors respond to both harmful and non-harmful noxious stimulus as well as the amount of nociception can be increased or modulated, therefore creating a response that isn’t proportional to the stimulus.

We can also see that nociceptors aren’t the only factor that contribute to a pain experience, with many factors such as attention, expectation, visual information, beliefs and previous experiences all having an impact on a persons experience. In some cases, nociception isn’t required at all for a patient to experience pain.

This leads us to the conclusion that pain isn’t proportional to tissue damage.

What this tells us is in clinical practice, a patient’s pain as well as their recovery is unlikely to be explained solely by tissue damage and repair. For us this means we need to:

  • Rethink our clinical tests and what they mean. Does pain with palpation of an area indicate tissue damage or is it more likely to be tissue sensitivity? Does a painful squat or single leg calf raise indicate that the tissue is being damaged by movement or is incapable of this load, or is this mediated by other factors such as a increased tissue sensitivity, expectation of pain, the belief that their body is damaged and needs to be protected?
  • Do we always need to offload an injured area, or because we know that pain doesn’t equate to tissue damage, are there circumstances where we can we reload and strengthen a tissue despite pain, reaping the benefits of movement and teaching the patient it is safe to move?
  • When a patient experiences benefit from a foot orthoses, is this primarily due to the fact that we have unloaded the painful tissue in question or is the patient gaining other benefits? Examples of these effects could include manual feedback from a device, a change in expectation now that they believe their pain will reduce?
  • We also need to carefully consider how we educate patients on their condition. To explain to a patient that their pain is due to tissue damage, (especially those with long term pain), can go a long way in instilling the idea that the body is fragile and breaks easily. Potentially providing new contributors to a pain experience, or barriers to treatment such as a fear of pain (kinesiophobia), pain catastrophisation or simply changes to their belief and expectation.

When we consider these new questions we may also need to change the primary way we view the body. Instead of viewing each of these factors as separable factors and add together as the sum of their parts, for example, this person’s pain is 50% due to tissue damage, 25% due to their belief, 15% expectation and 10% visual information (with the conclusion being that if you got rid of a patients beliefs expectation and visual information you could reduce a patient’s pain by half), we may have to view these contributors as inseparable from one another. Meaning that the nociception that occurs with tissue damage may only be relevant or contribute to a pain experience because of the pattern of other factors present.

A great example being attention and visual information. How many times have you cut yourself and not experienced pain until you’ve realized you have a cut? The amount of nociception, beliefs, expectations didn’t change. But when we added attention and visual information, the way our body perceived all these other factors changed completely, also meaning that we couldn’t re-distract ourselves from the pain.

This is the same way we can view a patient’s pain experience as well as their treatment. We can’t separate the specific effects of an orthotics (i.e. kinetic and kinematic changes) from their non-specific effects (impact on beliefs, expectations etc.). So to consider that a portion of the benefit of a foot orthoses device may not be the tissue specific effects or reduction in nociception but due to the patient knowing they’re being treated with a foot orthoses and therefore having changes to their expectation and behavior isn’t saying that a foot orthoses ‘don’t work’.

In many patients we may not be able to separate the non-specific effects from the specific effects, simply because if we don’t have the specific effects, i.e. the changes to kinetics and kinematics, we may not be able to alter their expectations or beliefs without them. The factors are indivisible and together produce an effect greater that the sum of their parts.

(For a more comprehensive explanation of this shift in the way we can view the body, you can watch my free Complex Systems Webinar).

What this means is that there may be situations where the primary benefit of a treatment, such as foot orthoses, is the non-specific effect and therefore we should consider whether there are treatment options available that provide both specific and non-specific effects, are cheaper, or are more tailored to our patient’s specific situation. It also tells us that there may be more than one treatment option available that produces the same or similar benefits.

Who knew that knowing a little bit more about nociceptors could make us have to rethink so much!

 

 

Conclusions:

Nociceptors aren’t pain receptors, they are danger receptors that respond to both harmful and non-harmful noxious stimulus.

Pain isn’t proportional to tissue damage and therefore can’t be explained in such terms.

There are many other factors that can impact a patient’s sensation or experience of pain that we need to consider.

Because of these facts, we need to rethink the way view our patient’s pain/injuries and how they benefit from our current treatments.

Pain is complex. Don’t feel bad if you don’t understand it, no-one really does. However that doesn’t stop us from

 

 

References:

Wall, P. D., McMahon, S. B., & Koltzenburg, M. (2013). Wall and Melzack’s textbook of pain. Philadelphia: Elsevier/Churchill Livingstone.

 

Fisher JP, Hassan DT, O’Connor N, BMJ 1995; 310:70

 

Butler, D. S., Moseley, G. L., & Sunyata. (2019). Explain pain. Adelaide, Australia: Noigroup Publications.

 

Butler, D. S. & Mosley, G. L. (2017) Explain pain supercharged. Adelaide, Australia: Noigroup Publications.

 

Moseley, G. L. (2007). “Reconceptualising pain according to modern pain science.” Physical Therapy Reviews 12(3): 169-178.

 

Alex Murray Podiatrist

Alex Murray is a Podiatrist working in private practice and the founder of website Making Sense in Podiatry. He's passionate about helping other clinicians make sense of evidence and clinical practice with a core philosophy of exploring the complexity of human beings, embracing the uncertainty of clinical practice, and avoiding overly reductionist thinking. In addition to his undergraduate degree from La Trobe, he also holds a Post Graduate Diploma in Sports and Exercise Medicine from the University of Otago. He has experience with both national and international athletes and has recently transitioned to focusing primarily on helping the general population and local athletes manage their pain and achieve their goals.

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