neurobiology

Widespread pain, aka fibromyalgia – does it really belong in rheumatology?


ResearchBlogging.org
I’ve asked it before, and I’ll probably ask it again, but does widespread pain really belong with the rheumatologists? I think the answer is rapidly becoming “No”.
The “so what” question begs: does it really matter who looks after people with widespread pain? I think the answer is “yes”, only because it’s becoming clear that helping unravel the problem of fibromyalgia (widespread pain) is going to take a different tack from looking at peripheral mechanisms alone. In fact, it could be that peripheral mechanisms are by and large irrelevant to this enigmatic disorder.

What is fibromyalgia?

Good question: there are clear diagnostic criteria for the disorder, but developed mainly for research purposes. In clinical terms, fibromyalgia is a little more tricky. Essentially, if a person says “I hurt all over”, and they also report unrefreshing sleep, foggy thinking, fatigue and sensitivity to multiple sensory modalities, chances are the person has fibromyalgia, especially if the usual diagnostic tests fail to show anything else out of order. The American College of Rheumatology released revised criteria in 2010 (Wolfe, Clauw, Fitzcharles, et al., 2010) and now doesn’t require the presence of tender points.

And this is why I don’t think it’s necessary for people to be diagnosed by a rheumatologist: there are too many people who experience this range of symptoms for diagnosis to remain the province of a single specialty. At the same time, it seems quite evident that hunting for mysterious explanations for the problem by undertaking multiple investigations is also not the answer – instead, a GP using good clinical techniques can make a diagnosis and then focus on helping the person to manage his or her symptoms quickly and without fuss.

A recent paper by Fitzcharles, Ste-Marie & Pereira (2013) argues this point, saying that “the diagnosis is made on the basis of a composite of symptoms, centred on chronic widespread pain and absence of physical findings that would indicate another condition”, and “a physical examination is required for all patients, and findings may be completely within normal limits”, and “only limited laboratory testing should be conducted for most patients” (p. E646).

What about the neurobiology?

Here’s where the situation gets a little murky, and it’s going to take a while before we really begin to understand the problem.

Neurophysiologic studies show abnormal pain processing at various levels of the nervous system, and no single unique change associated with fibromyalgia. I use the term “pain” advisedly here, because while nociception may be involved, it is not obligatory, so what we are left with is the experience of pain and some really weird abnormalities that are associated with the experience. Remember, people have pain, it’s an experience, it’s formed by the interaction of biological, psychological and social elements, and we only know about it because people do something about it – look for help.

Studies show peripheral sensitisation of the primary somatosensory neuron, central sensitisation at the dorsal horn, changes at the thalamus and gray matter of the brain, impairment or reduced functioning of the descending noxious inhibitory control mechanisms, not to mention alteration of endogenous opioid uptake. Treatments are, therefore, focused primarily on reducing the ascending information and increasing the descending inhibitory mechanisms, or working to alter the way this information is managed or prioritised by the cortex.

This means that for most people with this kind of pain, some sort of neuromodulatory drug is part of the mix – something to reduce the “reactivity” of the neural circuitry involved in processing this kind of information.  Anticonvulsants such as gabapentin or pregabalin seem to do something useful, while tricyclic antidepressants or SNRI’s are also helpful, together or separately from the anticonvulsants. BUT medications really don’t alter the pain terribly much for many people with FM. I’m one of those who fail to respond to medications. What I, and many others with fibromyalgia are left with, is learning to use the most powerful of mechanisms in the world – our fabulous cortex.

A teeny bit more neurobiology

In a paper that is in preprint right now, a group of Spanish researchers have been l0oking not just at one part of the brain, but more at the connectivity and subtle interplay between various parts of the brain while a person with fibromyalgia experiences pain. The usual culprits involved in processing nociception such as the periaqueductal gray, anterior insula, pariental operculum/secondary somatosensory cortex (SII), and the primary somatosensory cortext.

Normally, there is activity between the perietal operculum/SII and the various sensory cortices such as the auditory, visual, primary somatosensory cortex and posteria insula. This is called the “default mode” and seems to provide support for Melzack’s “neuromatrix” theory where this network is assumed to monitor and maintain “normal representation” of the body. In people with fibromyalgia, there is reduced functional connectivity between these regions.  Interestingly, there were increased functional connections between the parietal operculum/SII and the posterior cingulate cortext, precuneus, ventral putamen and ventral insula. Subjective pain ratings were positively correlated with measures of functional connectivity between the parietal operculum and PCC, ACC, left angular gyrus (also parts of the default mode network), and the left prefrontal cortex.

The authors conclude that “Overall the data suggest a strong association of clinical pain with a general weakening of sensory integration in fibromyalgia.” They point out that the amgydala and the insula are two major parts of the descending limbic input to the PAG – suggesting down-regulation of the cerebral influence on the PAG. Normally the PAG provides a “brake” on ascending sensory information – if, in people with FM, this is not working properly, it provides some explanation for the poor sensory filtering in people with fibromyalgia.

What the authors argue is that because non-nociceptive information is downregulated, it provides an opportunity for more nociceptive information to reach various parts of the brain – and this occurs not just in pain, but also in other sensory modalities such as scent, sound and vision. A bit like migraineurs perhaps? Anyway, these researchers argue that “spontaneous pain may be a consequence of partial damage in the nociceptive system with a subsequent nociceptive system hyperexcitability and a secondary inhibition of the transmission of tactile signals.”

What does this mean for treatment?

Some treatments are based on providing competing information between nociceptive and non-nociceptive input – things like peripheral nerve stimulation, whole-body vibration therapy, heated water body stimulation – and probably far closer to my heart, whole body movement, body awareness and cognitive behavioural therapy. These provide opportunities for people with FM to develop (refine, enhance) discrimination between various body states and sensory inputs. By learning to be more aware of what is really happening in the body, paying mindful attention to what is, rather than what has happened or might happen, and by carefully structuring these experiences to grade the complexity and psychosocial variables associated with them including the emotions associated with them, people with FM may begin to “retune” the out of sync central mechanisms involved in sensory processing.

To me this means we need to go beyond a biomedical approach to managing fibromyalgia, or widespread pain. We need to incorporate occupational therapists, who have specific training in analysing occupations (activities) and can grade the complexity of these occupations to titrate the level of input to where the individual needs it. We need physiotherapists to guide movements and grade complexity of movement patterns. We need to work as a team to help people understand and reconceptualise their role in managing fibromyalgia – and overall, we need to help people with FM learn to live well despite their pain. My question is: should this be the province of a single speciality in medicine? I don’t think so, I think it belongs to us all, and especially to people living with the problem.

Fitzcharles, Mary-Ann, Ste-Marie, Peter A., Pereira, John X., & Iglar, Karl. (2013). Fibromyalgia: evolving concepts over the past 2 decades. Canadian Medical Association Journal. doi: 10.1503/cmaj.121414

Pujol, J., Macià, D., Garcia-Fontanals, A., Blanco-Hinojo, L., López-Solà, M., Garcia-Blanco, S., Poca-Dias, V., Harrison, B., Contreras-Rodríguez, O., Monfort, J., Garcia-Fructuoso, F., & Deus, J. (2014). The contribution of sensory system functional connectivity reduction to clinical pain in fibromyalgia PAIN® DOI: 10.1016/j.pain.2014.04.028

Wolfe, F., Clauw, DJ., Fitzcharles, M-A., et al. (2010). The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity. Arthritis Care Research (Hoboken), 62, 600-610.

The pain system is so complicated!


ResearchBlogging.orgThere are a couple of ways to approach the problem of pain – the one I grew up with is the medical one: diagnose the problem, fix the problem, life returns to normal.  The person’s role in this is to be open about what is wrong, let the treatment provider know the information (and only the information) relevant to the problem, follow the medical instructions, and all will be well.

Of course the majority of readers of this blog can see some short-comings in this model.  It forgets that people choose when to seek treatment and that they make decisions about this based on ‘common knowledge’ (or what the community around them says they should do), family history, current stressors and activities, degree of distress, and how much the symptoms get in the way of living life (or represent a potential something that might get in the way of life).

Not only this – people process what happens to them.  They relate what is happening now against what has happened in the past, and how much this experience has affected them.  They have thoughts, emotions, they take actions on the basis of these thoughts and emotions.  And some of these thoughts are not exactly accurate – but none-the-less they affect the person living his or her life.

For some people who use a medical model (and even some who say they use another model), the whole area of thoughts, emotions, attention, perception – it’s just so complicated.  And so their focus is entirely on the bits of the nervous system they can understand.  Bits below that amorphous ‘brain’.  So if we take a look at many diagrams and descriptions of the nervous system, we start at the outside, and work our way in towards the central nervous system, maybe show some connections at the spinal level, perhaps go even as far as the thalamus – but the rest is some sort of blank.  Take a look at this excerpt, written for postgraduate students, written by a medical practitioner lecturing on the neurobiology of pain:

As the second order neurons are activated, transmission continues from the dorsal horn to higher centres. The axons of second order neurons cross the midline in the anterior white commissure and ascend in the anterolateral funiculus (spinothalamic tracts) via the medulla and the midbrain to the thalamus. Transmission from the thalamus to the cerebral cortex occurs via third order neurons.
PERCEPTION
Perception is the final phase of nociception and it occurs in the cerebral cortex. It involves interpretation and evaluation of the transmitted neural signal to form the subjective experience of pain

Thus nociception pathways extend from the periphery, where transduction occurs, and transmit nociceptive stimuli through the peripheral nervous system and the central nervous system to the cerebral cortex, where perception occurs.

While this isn’t incorrect, it falls far short of our knowledge about how our brain detects and brings to consciousness threats to our body.

If you’re looking to do better than this. If you’re serious about learning about how our nervous system works to protect us – and learn about potential areas of the nervous system that could be dysfunctional and contribute to things like chronic pain – then three papers I’ve recently been reading are well worth a look.

They’re all from the journal Brain Research Reviews, and were published in 2009 – but don’t let that stop you from reading them!

The first is Descending control of nociception: Specificity, recruitment and plasticity by M.M. Heinricher, I. Tavares, J.L. Leith, B.M. Lumb, Brain Research Reviews, 60, 214-225. doi:10.1016/j.brainresrev.2008.12.009
The next, Forebrain pain mechanisms by Volker Neugebauer, Vasco Galhardo, Sabatino Maione, Sean C. Mackey. Brain Research Reviews, 60, 226-242.doi:10.1016/j.brainresrev.2008.12.014
And the final one, The cerebellum and pain: Passive integrator or active participator? by Eric A. Moulton, Jeremy D. Schmahmann, Lino Becerra, David Borsook. Brain Research Reviews, 60, 14-27. doi:10.1016/j.brainresrev.2010.05.005

Before readers start yelling things like ‘You geeky grrl, you she-nerd’ – I didn’t enjoy neuroanatomy all those years ago when I first started working in pain management.  Now, however, I watch the information unfolding about the role of these areas of the brain and nervous system, and I see how important they are in our understanding of our experience of pain.  It is not enough to look at the lower levels and the periphery to ‘know about’ pain.  While it’s true to a certain extent that (quoting from my learned medical friend again):

…the experience of pain is fundamentally related to tissue damage; it is the means by which an individual becomes aware that injury has occurred, is continuing to occur or is likely to occur. Thus the biological processes that enable perception of pain are vital to the body’s defence against tissue damage; they are normal, physiological processes essential for survival. They are the fundamental key to understanding pain for without them there would be no pain.

Where I disagree with him is that I assign a rather more significant role to the central processes that occur.

As I mentioned, most descriptions of pain systems begin at the periphery and work in – why not turn that upside down? Let’s start with the role that various parts of the brain play in first seeking information relevant to the primary goal of the person.  Is it to stay alive by swimming very fast to shore after being bitten by a shark? Is it to detect further harm after being sunburned? Is it to notice a discrepancy in inward-flowing information that doesn’t match what the brain’s neuromatrix expects?

For each of these situation, the brain is working hard to actively seek information from the tissues – so maybe we should start with the status of the brain and look at why it might selectively attend to and modulate ‘issues in the tissues’.  And maybe we might then start to consider that events occur to a person-in-context, not a tissue in isolation.

And yes, I know I haven’t even started to consider the family, community, social aspects of pain yet!

Neugebauer, V., Galhardo, V., Maione, S., & Mackey, S. (2009). Forebrain pain mechanisms Brain Research Reviews, 60 (1), 226-242 DOI: 10.1016/j.brainresrev.2008.12.014

An interview with F Sommer Anderson – & central sensitisation syndromes


ResearchBlogging.org
How many of you have headed off to ‘Therapy Worksheets’ blog? Yes, that’s the one I’ve linked to in my roundup of the best CBT resources on the internet.  Will Baum, the editor of that blog is also the author of where the client is, a blog about professional private practice in mental health care.  Will contacted me the other day and sent me a link to a really interesting interview with Frances Sommer Anderson, a clinical psychologist who works with people experiencing chronic pain.  Her take on chronic pain management is influenced by John Sarno, who has a hypothesis that much chronic pain is influenced by psychological factors (often emotional issues) from childhood.  One of the premises of his approach is that people need to heal their ‘repressed’ emotions and in doing so, their chronic pain will vanish.

Now unfortunately there is not a lot of good evidence for Dr Sarno’s hypothesis, particularly the second part (that people need to ‘heal’ their repressed emotions).  Having said that, some of the mindfulness and acceptance material I’ve been reading suggests that, instead of repressing, controlling or focusing on negative emotions, we may find it more helpful and less distressing to experience these ‘lightly’ or nonjudgementally, and in doing so, release ourselves from their influence and choose to act according to our values.

In this interview of Dr Sommers Anderson, we are introduced to her approach of helping people identify when they first started to experience their pain, often finding that at that time there were intense and emotionally-laden events.  Often memories and emotions from these events have been avoided, and the hypothesis is that by processing this in a supportive environment, the symptoms of pain reduce.

IMHO?  I’d prefer to use a neurobiological model for this, because it has fewer assumptions, draws on a large body of empirical evidence, and explains more.  I often refer to the work of Muhammed Yunus, who describes the connection between a range of chronic pain disorders such as fibromyalgia, dysmenorrhea, tempero-mandibular disorder,  PTSD and others as being of ‘neuroendocrine’ immune dysfunction.

We already know that people in an increased state of physiological arousal appear to trigger a series of events that can lead to central sensitisation.  We could call this ‘being under stress’ and there are lots of things that seem to place our nervous system in a state of heightened sensitivity – things like having an accident, having a virus, or being vulnerable due to genetics or events during development.    The hypothesis as described by Yunus is that dysfunction in the neuroendocrine immune system initiates ‘hyperexcitement’ of central neurones (in other words, they respond more quickly and to less input than normal), and this leads to general central sensitisation – and the symptoms of ‘central sensitivity syndrome’ are experienced.

These symptoms include increased detection of tactile input (such as pressure), fatigue, poor sleep, and other ‘psychological’ or emotional aspects such as low mood, anxiety and so on.  CS is manifested by an abnormal and intense enhancement of pain by central nervous system (CNS) mechanisms.  Pain signaling involves activation of a variety of simple nerve endings in skin, muscle and internal organs.  The peripheral impulses travel through A-delta and C fibers to both nociceptive and wide dynamic range (WDR) neurons in the dorsal horn of the spinal cord.  In a person with a sensitive nervous system, the WDR neurones integrate input from these neurones (both noxious and nonnoxious) so that nearby neurones now transmit information that is normally ‘light touch’ or ‘gentle pressure’ as if it were noxious.  As a result, this is felt as painful.

This set of nerve fibres transmit information up the spinal cord to the thalamus, hypothalamus, the limbic system, and finally, the somatosensory cortex; each of which has a job to process the information so that it can be experienced and acted upon.

At the same time as all this information is travelling up the spinal cord, a number of neurochemicals are also released.  These chemicals increase the excitability of the neurones in the spinal cord.  One of the main chemicals is cutely named ‘substance P’.  It spreads the area of excitement by ‘unmasking’ the silent receptors in the synapses and it can diffuse some distance to excite other neurons nearby.    There are numerous other substances that also contribute to increased excitability of neurones, so that less and less input is needed to produce a painful experience.

Thankfully, just when you thought all was lost, there are also pathways downward from the brain that work to dampen down this sensitivity.  Several descending pathways from the
cortico-reticular system, locus ceruleus, hypothalamus, brain stem, and local spinal cord interneurons use neurotransmitters such as serotonin, and norepinephrine, among others.  These work to reduce the reactivity of various neurones and in so doing, reduce the amount of information reaching the areas of the brain that work to detect and interpret information from the body.

The ascending system and the descending system are not directly linked – it’s quite possible to have increased sensitivity in the ascending fibres but a normal descending pathway.  I guess one of the problems with our nervous system, or maybe a really valuable aspect, is that there are multiple systems that all interact with each other, with various in-built redundancies, all designed to help us stay alive!  BUT all those systems that can also fail to work properly.  Just as we can have dysfunctions of every other body system, it’s not surprising we can also have dysfunctions of the system designed to alert us to potential damage.  Some people seem to forget this – and keep on looking for the tissue damage that simply ‘must’ be there.

Back to Frances Sommer Anderson and her approach to managing pain.  She (and others like her) work to help people get in touch with, or process negative emotional experiences, and help them become more comfortable with experiencing and regulating their emotions.  This is also part of CBT and ACT, but may also feed back into some of the information I’ve been blogging about – emotional regulation and self regulatory systems.  The line between ‘psychological’ and ‘biological’ is becoming ever more difficult to define.   I encourage you to read this interview, and then go back to the posts that I’ve put up, and others like Body in Mind, that start to ponder the way in which our neurobiology underpins what used to be only ‘psychological’.

YUNUS, M. (2007). Fibromyalgia and Overlapping Disorders: The Unifying Concept of Central Sensitivity Syndromes Seminars in Arthritis and Rheumatism, 36 (6), 339-356 DOI: 10.1016/j.semarthrit.2006.12.009