Neck pain: can we learn anything from histochemistry?

Image from: Jensen, L, LL Andersen, HD Schrøder, U Frandsen, and G Sjøgaard. 2015. "Neuronal nitric oxide synthase is dislocated in type I fibers of myalgic muscle but can recover with physical exercise training." BioMed research international 2015. https://www.hindawi.com/journals/bmri/2015/265278/

Let’s attempt a brief thought experiment: I want you to imagine that you’ve been born into a world devoid of all things ‘psychosocial’. This is a world where the influence of the mind and society on the body has not yet been recognised.  In this version of events, Sigmund Freud stuck with electrotherapy, Robert Melzack deemed the neuromatrix too far fetched to warrant further work and George Engel remained sceptical of psychosomatic medicine and failed to develop his vision of ‘biopsychosocial‘  medicine.

Feeling a sense of relief? I certainly do…

In this imaginary world of course we don’t need to bother with whether we should spell catastrophisation with an ‘S’ or ‘Z’ because frankly it’s not relevant to our work. All we are concerned with is the biological aspect. It is all we have. The physical. That’s it.

And so it is in this wonderful fugue-like state that we now turn our attention to the muscles of the neck and some fascinating research that concerns itself with microscopic change in muscle fibre size, appearance, microcirculation and chemistry. In this post we will be concerning ourselves solely with sedentary work-related neck pain e.g. computer work (as opposed to whiplash). And there shall be no mention of the psyche (promise). So, let’s get physical…

Introducing Trapezius Myalgia

Pain, tightness and tenderness of the upper trapezius muscle that is associated with static, sedentary and repetitive working postures has been termed ‘trapezius myalgia’.

An early Google machine

Lars Andersen – a leading researcher in this field – has referred to trapezius myalgia as ‘the most common type of chronic neck/shoulder pain’ (Andersen et al. 2014).

Whilst ‘trapezius myalgia’ is a diagnosis that few clinicians might currently consider in the clinical setting, it does appear to be a useful working definition from a research perspective – judging from the findings of a number of publications that have used the concept – and thus perhaps, is more deserving of attention from clinicians. Also note that weakness also accompanies ‘trapezius myalgia’ – but muscle strength will not be our focus here. For example women with trapezius myalgia have decreased maximal voluntary shoulder elevation force compared to healthy controls (Andersen et al. 2014).

The Cinderella Hypothesis

So what effect do static working postures involving very low loads have upon the neck muscles?

It has been noted (Hägg 2000) that working at submaximal levels – e.g. sitting at a desk typing – engages only a fraction of the motor units available in a muscle. As a result these ‘stereotyped recruitment patterns’ – arising from the repetitive nature of the work – can cause overload of a few specific motor units; this has been termed the ‘Cinderella hypothesis’: the hypothesis that low threshold motor units become overloaded during long term occupational static work (‘Cinderella’ referring of course to the harsh treatment of Cinderella by the ugly sisters, when they forced her to carry out boring and repetitive chores). Indeed in sedentary occupations when muscles work continuously at intensities below 5% of maximal capacity, only very few of the many type I postural muscle fibres are activated (Blangsted et al. 2004).

Megafibres

What effect does this overload have on the few type I postural muscle fibres that are activated?

Hagg (Hägg 2000) reviewed 10 biopsy studies looking at structural and histochemical muscle fibre abnormalities related to muscular pain, eight of which were related to the upper trapezius muscle. The studies clearly demonstrated increased fibre cross-sectional area in those individuals engaged in static sedentary work. Andersen (Andersen et al. 2008) also found an increased proportion of type I megafibres in female office workers with trapezius myalgia (50%), compared to healthy matched controls (11%). Interestingly the percentage of megafibres was positively related to age and weekly working hours, indicating an effect of long term exposure. To put this in perspective, type I megafibres were on average larger than 10,000 µm2, whilst the trapezius type I fibre sizes of healthy and highly resistance-trained athletes are on average less than 6000 µm2 (Kadi et al. 1999) –  that’s nearly twice the size in a sample of sedentary female workers. See Figure 1.

As has been noted (Andersen et al. 2008), whether these changes represent a pathological condition or a functional adaptation, is yet to be determined.

Figure 1 Trapezius muscle biopsy from a female with trapezius myalgia, notice the large type I megafibre in the middle of the picture  (Andersen et al. 2008).

Muscle fibre appearance

Trapezius myalgia has also been associated with pathophysiological changes i.e. an increased occurrence of both moth eaten and ragged red fibres  (Larsson et al. 2000) (Andersen et al. 2014). ‘Moth eaten’ and ‘ragged red’ fibres refer to the appearance of the muscle fibres when stained and imaged through a microscope. See Figure 2.  

Figure 2 Numerous type 1 fibres with moth-eaten appearance (asterisk) and one ragged red fibre (arrow) can be seen. NADH-TR staining. Bar = 100 pm (Larsson, Libelius, and Ohlsson 1992)

 

These changes have been referred to as a hallmark of mitochondrial dysfunction / myopathy and are usually found in muscle biopsies from patients with diverse neuromuscular disorders (Larsson, Libelius, and Ohlsson 1992). Hägg (2000) noted a graded occurrence of ragged red fibres in trapezius myalgia according to what the author termed ‘the seriousness of the disorder’ and hypothesised that the presence of moth eaten fibres (considered to be pre-cursors of ragged red fibres) in the trapezius muscle of pain-free subjects indicated that early signs of abnormalities are frequent in this muscle in the general population.

Microcirculation

Impaired regulation of the microcirculation in the painful trapezius muscle (Andersen et al. 2014) and reduced capillarisation per normal fibre cross-sectional area (Hägg 2000) have also been identified in trapezius myalgia.

Both decreased levels and adaptability of the microcirculation may have knock-on effects: Rosendal et al. (2004) have demonstrated during repetitive low intensity work tasks, increased levels of lactate, leading to speculation that prolonged acidosis may cause or maintain the pain condition. (It is worthy of mention that Larsson et al (1994) investigated the regulation of the microcirculation in painful trapezius muscles following whiplash injury. Their study showed decreased ability to increase blood flow above a certain level during increasing static muscle contractions. In healthy persons an increased microcirculation in the trapezius muscle is a normal response to increased contraction levels. Thus they demonstrated disturbed regulation of the local microcirculation following neck trauma and further suggested that if this is a prominent feature of persisting chronic neck pain it may well explain the self-generating character of the condition.)

Nitric Oxide

It’s time to get really geeky. There are clinicians who love this stuff and clinicians who don’t. I fall firmly into the latter camp but for the sake of completeness I shall mention this: more recent work on trapezius myalgia has investigated the role of nitric oxide (NO). Yes. Nitric oxide. Here’s a picture:

Nitric Oxide

Any wiser? No, neither am I. We’re talking molecules here. Next stop, the atom. Helmets on? Let’s proceed…

In healthy muscle under normal physiological conditions, production of NO plays a role in inhibiting vasoconstriction i.e. maintaining microcirculation during muscle contractions. It performs this function through a complex pathway involving neuronal nitric oxide synthase (nNOS).  In this way microvascular tone is regulated and muscle homeostasis maintained. There is also evidence that nNOS/NO mediates muscle atrophy. Jensen et al. (2015) found that nNOS expression was disrupted in moth-eaten type I fibres and further that nNOS was missing in the enlarged type I muscle fibres in the trapezius muscle of women with repetitive work tasks. See Figure 3. It is hypothesised that these changes increase cellular susceptibility to metabolic stress, leading to lower force production and increased fatigability in the painful trapezius muscle.

Figure 3 Trapezius myalgia (MYA) shows sarcoplasm-localised nNOS. Data from the case-control study (CON) showed an increased proportion of muscle fibres with nNOS protein localised in the sarcoplasm in trapezius myalgia (MYA) patients compared to healthy controls (CON) detected by immunohistochemistry. 18.8 ± 12 versus 12.8 ±8%, 𝑃 = 0.049 (Jensen et al. 2015).

Can exercise change the composition of muscle?

Andersen et al (Andersen et al. 2014) have demonstrated significant muscle fibre hypertrophy and increased capillarisation per muscle fibre in response to 10 weeks of specific strength training – that did not occur with leg cycling. The specific strength training consisted of five dumbbell exercises specifically for the shoulder and neck muscles (shoulder abduction, shoulder elevation, 1-arm row, reverse flys, and upright row) for 20min three times a week. Three of the five exercises were performed during each session for three sets of each exercise using relative loadings of 8–12 repetitions maximum (RM). In a randomised controlled trial study by Jensen et al. (2015) specific strength training also induced an increased capillarisation and altered the nNOS expression to more normal levels.

Conclusion

This body of work is a subtle reminder that histochemical changes can underlie manifestations of pain but more importantly these studies demonstrate that histochemical changes can be reversed through specific exercise.

The process whereby the body converts mechanical loading into cellular responses has been termed mechanotransduction (see here for a beautifully illustrated introduction by Khan & Scott). Usually the preserve of tendon aficionados, it is to heartening to see a body of work referring to mechanotransduction and mechanotherapy in neck pain.

Whilst clearly the contemporary literature on pain stresses the importance of psychosocial factors – and correctly so in my opinion – it remains all too easy for clinicians to fall into a binary way of thinking i.e. seeing only physical or psychological drivers of symptoms. In this way we denigrate the role of purely physical processes in individuals with pain.

Surely, it is only in an open minded and skilful synthesis of the physical, the psychological and the social that we begin to realise the true power of our work?

Let’s not forget the ‘bio’ in the biopsychosocial.

Take home massages:

  1. Individuals who suffer from painful trapezius (so called ‘trapezius myalgia’) exhibit increases in fibre size and changes in both cellular composition and microcirculation.

  2. These changes occur as a result of chronic overload of a few specific motor units due to low load tasks eg typing – the so called ‘Cinderella effect’.

  3. Pain free individuals who perform static and repetitive work also demonstrate changes in fibre type size, cellular composition and microcirculation of the trapezius muscle but these changes appear to occur to a greater extent in individuals with painful trapezius.

  4. These changes in the composition of the muscle can be reversed through a specific neck and shoulder strengthening program in as little as 10 weeks, and they parallel improvements in pain and disability.

  5. The exercise must be specific to the neck and shoulder. General exercises (e.g. cycling) do not appear to change the composition of the neck muscles.

References

Andersen, Lars L, Christoffer H Andersen, Jørgen H Skotte, Charlotte Suetta, Karen Søgaard, Bengt Saltin, and Gisela Sjøgaard. 2014. “High-intensity strength training improves function of chronically painful muscles: case-control and RCT studies.”  BioMed research international 2014.

Andersen, Lars L, Charlotte Suetta, Jesper L Andersen, Michael Kjær, and Gisela Sjøgaard. 2008. “Increased proportion of megafibers in chronically painful muscles.”  Pain 139 (3):588-593.

Blangsted, Anne Katrine, Karen Søgaard, Hanne Christensen, and Gisela Sjøgaard. 2004. “The effect of physical and psychosocial loads on the trapezius muscle activity during computer keying tasks and rest periods.”  European journal of applied physiology 91 (2-3):253-258.

Hägg, Göran M. 2000. “Human muscle fibre abnormalities related to occupational load.”  European Journal of Applied Physiology 83 (2):159-165. doi: 10.1007/s004210000274.

Jensen, L, LL Andersen, HD Schrøder, U Frandsen, and G Sjøgaard. 2015. “Neuronal nitric oxide synthase is dislocated in type I fibers of myalgic muscle but can recover with physical exercise training.”  BioMed research international 2015.

Kadi, Fawzi, Anders Eriksson, Staffan Holmner, Gillian S Butler-Browne, and L-E Thornell. 1999. “Cellular adaptation of the trapezius muscle in strength-trained athletes.”  Histochemistry and cell biology 111 (3):189-195.

Larsson, Barbro, Jonas Björk, K-G Henriksson, Björn Gerdle, and R Lindman. 2000. “The prevalences of cytochrome c oxidase negative and superpositive fibres and ragged-red fibres in the trapezius muscle of female cleaners with and without myalgia and of female healthy controls.”  Pain 84 (2):379-387.

Larsson, Britt, Rolf Libelius, and Kerstina Ohlsson. 1992. “Trapezius muscle changes unrelated to static work load: chemical and morphologic controlled studies of 22 women with and without neck pain.”  Acta orthopaedica Scandinavica 63 (2):203-206.

Larsson, Sven-Erik, Martin Ålund, Hongming Cai, and P Åkc Öherg. 1994. “Chronic pain after soft-tissue injury of the cervical spine: trapezius muscle blood flow and electromyography at static loads and fatigue.”  Pain 57 (2):173-180.

Lindman, Rolf, Mats Hagberg, Karl-Axel Ängqvist, Karin Söderlund, Eric Hultman, and Lars-Eric Thornell. 1991. “Changes in muscle morphology in chronic trapezius myalgia.”  Scandinavian journal of work, environment & health:347-355.

Nielsen, Pernille Kofoed, Lars L Andersen, Henrik B Olsen, Lars Rosendal, Gisela Sjøgaard, and Karen Søgaard. 2010. “Effect of physical training on pain sensitivity and trapezius muscle morphology.”  Muscle & nerve 41 (6):836-844.

Rosendal, Lars, Britt Larsson, Jesper Kristiansen, Michael Peolsson, Karen Søgaard, Michael Kjær, Jan Sørensen, and Björn Gerdle. 2004. “Increase in muscle nociceptive substances and anaerobic metabolism in patients with trapezius myalgia: microdialysis in rest and during exercise.”  Pain 112 (3):324-334.