Oldies but Goodies – Everything you wanted to know about CENTRAL SENSITISATION

Over this holiday season we are posting the most read articles from the last five years.  The third is a BiM review of a J Pain paper by Alban Latremoliere and Clifford J. Woolf (AKA L&W)

Everything you wanted to know about CENTRAL SENSITISATION

By Kerwin Talbot & Lorimer Moseley

Another of our series on the Journal of Pain’s most downloaded articles – this one on central sensitisation. There is no doubt that central sensitisation has such a prominent role in our pain lexicon that it almost deserves upper case letters. This paper examines the role that CENTRAL SENSITISATION has in enhancing the function of the neurons and circuits in nociceptive pathways. CENTRAL SENSITISATION (OK – I will now leave the upper case thing alone) provides a physiological explanation for the many alterations in the temporal, spatial and threshold systems associated with persistent pain. This review is clearly a fan favourite and I can understand why – it is comprehensive in the extreme and to cover it here is a distant second to you getting a copy and reading it. There are heaps of pictures that are well captioned and the text is not intimidatingly jargonised.

I want to flag one important issue, but let’s first set the scene:

  • Central sensitisation, as it is discussed in this paper, concerns changes in the functional properties of spinal nociceptors in the dorsal horn.
  • Broadly speaking, there are two patterns of sensitisation – homosynaptic and heterosynaptic.
  • Homosynaptic refers to sensitisation of the spinal nociceptors that code for the tissue in which the primary nociceptor – the nociceptor that started it all – sits. Homosynaptic sensitisation leads to allodynia and hyperalgesia in the culprit area.
  • Heterosynaptic refers to sensitisation of nearby spinal nociceptors, which code for areas adjacent to those in which the primary nociceptor – the nociceptor that started it all – sits. Heterosynaptic sensitisation leads to secondary hyperalgesia and allodynia – when the pain and sensitivity to noxious stimuli spreads to adjacent body areas.

L&W take care to emphasise that central sensitization provides an explanation for the presence of ongoing pain in the absence of ongoing primary nociception, tissue damage or inflammation. They then hone in on the two ‘causes’ of central sensitisation – ongoing inflammation or peripheral nerve damage/dysfunction – and describe the differences in central sensitisation in these two situations. They stress that the multiple inputs to the spinal nociceptor is what determines central sensitisation although they do not seem to consider descending modulation as part of that mix. I am surprised at that, but it is very difficult to think of experiments that would successfully interrogate that in animals, or humans for that matter.

L&W instead attribute central sensitisation to these two processes – inflammation or nerve injury. In clinical terms, this is profound – central sensitisation applies to your patients who have an inflammatory disorder, for example rheumatoid arthritis and to those who have a peripheral nerve injury. What proportion of your patients is that?

Does this seem odd to you? I reckon it does and I think this is because the term central sensitisation is used to explain the pain of anyone with reduced pain thresholds away from the primary nociceptive site (if indeed a primary site can be identified). The review article itself even slips into this ambiguity by referring to central sensitisation in fibromyalgia, yet they cite papers that describe reduced pain thresholds and temporal wind-up of repeated stimuli at remote sites, and decreased conditioned pain modulation at remote sites, in people with fibromyalgia. As far as I can see from the L&W review, these phenomena are consistent with neither homosynaptic nor heterosynaptic mechanisms. I contend that they point to a different mechanism altogether. I concede that there are human studies, also cited by L&W, that show enhanced activation of cortical structures in states of central sensitisation, but that would make sense the spinal nociceptor is upregulated wouldn’t it?

Aside from offering a top shelf review of true central sensitisation, L&W present to us a challenging reality – that central sensitisation causes allodynia and hyperalgesia in the problem area (primary allodynia and hyperalgesia) and the surrounding tissue (secondary….), but it does not cause reduced pain thresholds, temporal wind-up or deficient conditioned pain modulation elsewhere; and central sensitisation is caused by ongoing inflammation or nerve damage, which means it does not explain the vast majority of the patients we see.

Clearly there is an alternate version of central sensitisation out there that is applied, more and more, to the people we do see. But where did this alternate central sensitisation come from? I wonder if it is another manifestation of the difficulty we have in separating pain from nociception. I think reduced pain thresholds at remote sites and dodgy conditioned pain modulation would be a very appropriate adaptation for an organism with good reason to be hyperprotective of their body, and I can see no other place this would happen than in the brain (not necessarily via neuronal mechanisms per se). However, to call it central sensitisation is a bit misleading. When I talk about this stuff to people in pain, or to clinicians who treat them, I refer to ‘facilitation of protective neurotags’ and it seems to work. I know that any self-respecting journal editor would feel nauseous at such a term, but it seems easy to grasp down here at the coalface.

There is no doubt that this is a fantastically comprehensive coverage of central sensitisation and I highly recommend it to anyone who really wants to understand AND who has the temperament to take on the gaggle of acronyms. I think you should read it and then decide if central sensitisation as L&W know it, is an explanation for widespread pain, for chronic non-specific low back pain that moves or swaps sides or just covers your whole back and legs, or spreads up to your neck, or for fibromyalgia or for CRPS or for whiplash associated disorder or for myofascial pain syndrome (whatever that is).

About Lorimer Moseley

Lorimer is NHMRC Senior Research Fellow with twenty years clinical experience working with people in pain. After spending some time as a Nuffield Medical Research Fellow at Oxford University he returned to Australia in 2009 to take up an NHMRC Senior Research Fellowship at Neuroscience Research Australia (NeuRA). In 2011, he was appointed Professor of Clinical Neurosciences & the Inaugural Chair in Physiotherapy at the University of South Australia, Adelaide. He runs the Body in Mind research groups. He is the only Clinical Scientist to have knocked over a water tank tower in Outback Australia.

Link to Lorimer’s published research hereDownloadable PDFs here.

Reference

Latremoliere A, & Woolf CJ (2009). Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain, 10 (9), 895-926 PMID: 19712899

Comments

  1. I’d like to share a couple of interesting cases from this week.

    1– 16 yo basketballer with 3 month history of patella tendon pain. Intensity of pain is 4/10 with hopping and 6/10 with resisted knee extension. 5 minutes of guided visualization and both pains disappeared completely on aggravating tests. He couldn’t reproduce it at all.

    2– Middle aged man with foot/lower leg numbness and weakness, 12 months history, seen many different practitioners for no effect. Objective testing showed no numbness or weakness in supine, but the numbness would appear with any pressure (eg. weight-bearing or palpatory pressure). Lx was normal to palpation, gd 1 lysthesis at L5. With guided visualization I removed 60% of the numbness in 15 minutes and a lot of repetitions. Then I suggested that he would allow the numbness to disappear completely for 1 minute. He got up to test it and it had disappeared 100%…. he kept walking and after a minute it reverted to the 60% improvement mark. Will review.

    3– Middle aged woman with mild frozen shoulder. Approx. 80% ROM elevation, restricted by pain and stiffness. All symptoms removed 100% [with over-pressure] in 20 minutes. No physical techniques used. Will review to check sustainability.

  2. Thanks EG – I appreciate your insight. I get trapped in language with listening.
    I listen to words however my observation skills wander. I look for stickiness.
    Facilitation is a word I use – as nerve network or circuit (or ?neurotag) is fired over and over, multiple changes act together to make process more efficient.

    Thoughts or patterns? I still see separation between affective processes and cognition – I see layers to consciousness – is it important in the meeting with the person in pain? Maybe not – an intellectual pursuit that I am slow to learn.

    Presence is something more – not there yet – some moments yes / some no.
    Marshall Rosenberg helpful to me on this (again he drew from others). Thanks.

    EG Reply:

    Hi Stu,

    Presence is extremely hard for me too – seems it is for everyone. But you can still be effective without it. I consider it to be the most pure form of healing, and hardest to master.

    — “I still see separation between affective processes and cognition”.

    Yes, the conscious mind often has no idea what the subconscious is doing, and yet the subconscious is creating all these painful symptoms. The story of pain consciously relayed to the therapist often bears no resemblance to deeper truths.

    It’s possible to observe body language and other cues very carefully to find out how the subconscious is using certain beliefs to create pain, and then craft a ‘mismatch’ experience or verbal statement. I do that occasionally, but prefer to be more direct and open with treatments nowadays.

    — “I see layers to consciousness”.

    Yes. And since the mind causes pain, symptoms can also be layered. Sometimes an unbearable emotional pain will be exposed when the presenting physical pain is removed. Is that good or bad? Depends if you have the Presence to deal adequately with the underlying emotional symptoms. It’s not easy work we’re doing.

  3. Hi all,

    I’d like to remind everyone that the notion of threat can only occur to a self-image (aka. self, individual, ego). Therefore, suffering can only occur if the self-image is operational. If/when the self-image is in abeyance, suffering also vanishes (though pain may still be present). This fact about suffering was famously realized and documented by Buddha (alongside many others, before and since). It is possible to switch off the circuits dedicated to self-imaging and end the potential for suffering (NB. suffering, not pain). Pain without suffering is just another interesting sensation, ie. it is no longer a problem to be solved.

    Therefore, the most powerfully healing thing any human can do for another is to provide Presence. I spell it with a capital P to denote something much, much more than just “showing up and nodding and smiling”. Presence = immediate-moment, laser-focussed attention to the suffering of the patient, without judgment. Sounds easy, but I’ve never met anyone who can do it consistently. And this is why we have a society which is beset by chronic pain – therapists don’t know what they’re supposed to be doing in order to provide relief. LEARN IT!

    There are two standard defenses to the suffering of others. We practitioners engage them all the time:

    1- we subtly distance ourselves and block the patient’s experience from entering our psyche
    2- we judge the pain and suffering as bad; as something which needs ‘fixing’.

    Both of these reactions are unhelpful. Presence is a skill that needs constant practice. One need learn nothing else, because this trumps everything. Pain education can be helpful when the hurt=harm meme has taken over, but doesn’t appear to heal most people. If it did we could just tell GPs to get patients to watch a Youtube educational video.

    Other skills, like mental manipulation, are fun and interesting. Last year I found out that it’s possible to switch off many acute and chronic pains like a light switch – *click*. I was shocked so many times to see pain just vanish in minutes when certain techniques are applied. However, the vanishing of pain is not the same as healing, even when the effect is permanent. In certain situations, deep and rapid pain relief is preferable, but most people are in need of healing. By ‘healing’ I mean the release of stuck negative thoughts related to the self-image. And just to re-state it, healing is achieved through Presence.

  4. Lorimer, thanks for reposting this – always amazed by the changes happening at the cellular level and at the dorsal horn. Glutamate and AMPA and NMDA receptors, magnesium plugs, NK1 and substance P, switch from NS to WDR neurones, AB fibre mediated pain (I struggle following this and understand how AB fibres infiltrate more superficial areas of dorsal horn and then mediate pain – seems too linear).

    I can get lost in the acronyms and the complexity – hard to turn it into a story that I can understand or with colleagues or people in pain. Hard to know sometimes what to pay attention to (competitive bias). I think that the discovery of C tactile fibres has helped in my understanding (a bit). Magnesium deficient rats don’t do as well with nociceptive or neuropathic drivers. Omega 3s, Vitamin D, Mg – what to take, what to take? Relevant?

    Where does expectation, anxiety and meaning fit into the discussion? Where does the work by Gallace, Ianetti and yourself (and others) on defensive peripersonal space come into the picture. The amazing work on GMI that has been done. The ultimate modulator happens centrally. The output / input discussion still prevails however I think that it is easier to have the discussion if the brain is not seen in isolation – levels until a message is generated (output) that is perceived internally – implicit perception of threat. The concept of a facilitated neurotag may be easy to say but hard to follow.
    I have had colleagues say to me ‘I know that pain is an output because that is what is written in the readings that I do but I still feel it is an input’ Cognition and emotion seem separate sometimes, do they not? Integrated and dys-integrated – just like movement patterns that I see post stroke – gradual reintegration with neuroplasticity.
    The patients I see with aphasia – easier to think of Broca’s area and Wernicke’s area as key nodes in a network of an external output of communication for social interaction.
    Pain Asymbolia – easier to think of key nodes in salience network for an internal message of danger / threat – no longer drives behaviour – just noise – still aware of it.
    Attention has both bottom up and top down processes – awareness is the model (Graziano’s work makes sense).
    From my understanding, people in vegetative state typically only have brainstem, thalamus and sensory areas activated with noxious stimulus. Orientation is old – where am I or where is it in relation to something? Thalamus and brainstem – lots of interaction.
    However, is the output contained in the neurotag? Hard to get my head around it.
    I realize there are multiple distinct and interacting networks in the brain – amazing.
    So many different ways to get to the output of pain however are there not key nodes?
    Any help with understanding? I appreciate all your amazing work. Thanks.