How Can We Improve Chronic Back Pain Treatment?

Most people I see in my clinic in Truro have chronic low back pain, and often they don't know the cause.

This is an area I am passionate about – as a physiotherapist with a specialist interest in treating people with chronic low back pain in my physiotherapy clinic in Truro, I am always reading the research to see what the future might hold for people who suffer from pain.

Chronic pain is no exception – here are my brief (but positive) thoughts on what I think the future might hold for chronic back pain treatments.

Current best evidence for chronic back pain treatment

Cognitive functional therapy is the brainchild of Peter O’Sullivan – the framework has shaped my approach to helping people in pain (even athletes) and to-date remains the only approach that has resulted in meaningful changes in chronic low back pain and disability 1-year following the intervention above and beyond standard care (Kent et al., 2023).

Current research suggests that roughly 50% of mediating factors for improvements in back pain following CFT relate to reducing fear avoidance around movement and pain, tackling and reducing catastrophising and improving pain self-efficacy (Schütze et al., 2025).

This approach has shaped my practise and is how I currently help people with low back or knee pain or hip pain in my Physiotherapy clinic in Truro, Cornwall.

If you suffer with chronic pain of any joint and you want to see a physio who looks at the person - not just the joint, then head over to our home page to see how we can help you.

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And it works! There is now emerging evidence it is effective for most other painful joints as well!

But I am not entirely sold that pain doesn’t get stuck simply because we get scared of moving or because we don’t think we can get better and remember, it only accounts for ~ 50%! So where is the other 50% coming from?

Beliefs and fear influence biology and vice versa - there is something more fundamental at play that I feel is being missed.

Let me explain.

What is fundamental to life

I apply a first-principles approach to as many things as possible in life and when you apply it to chronic back pain treatment you arrive at an interesting intersection.

Inflammation and immune responsiveness shapes low back pain recovery trajectories.

So much so that it can accurately predict the transition to chronic low back pain based on expression of CD11c on monocytes, higher innate immune system sensitivity and B-cell maturation at first onset of initial acute low back pain episode (Brown et al., 2026).

But what’s the catch?

Immune profiles and inflammation represent middle management activity – someone is still telling these guys what to do (in my opinion) and how to do it. The CEO?

The mitochondria.

Systemic inflammation is a downstream consequence of mitochondrial dysfunction – it does not just pop up out of nowhere. There is a signal, and a source.

There is now strong evidence across multiple lines of research that imbalance of fission and fusion dynamics in mitochondria lead to damage-activated membrane proteins (DAMP) and higher levels of reactive oxygen species (ROS) which consequently initiate the first steps in systemic inflammation and immune dysregulation (Geto et al., 2020).

I believe that the mitochondria and their symbiotic relationship with the eukaryotic cell (our cells) represent the CEO of chronic pain, and by extension low back pain!

What are the mitochondria?

The mitochondria (or singular, mitochondrion) are organelles (think of them as workers) that live in the cell. They have a double membrane and have two purposes: the generation of heat and the generation of energy to re-couple adenosine diphosphate with a phosphate molecule to make adenosine triphosphate (aka ATP, the energy currency of the cell).

The mitochondria take the energy from our food (in the form of electrons and protons) and move them along their membrane via carriers and in doing so generate membrane potential which spins a tiny, quantum motor in the mitochondrion membrane. This energy is then used to reform adenosine triphosphate from the phosphate and adenosine diphosphate molecules.

Mitochondrial dysfunction and disease

Doug Wallace published a seminal paper in 2004 elucidating that mitochondria are the root cause of health and disease and responsible for the plague of chronic health diseases that now affect the globe (Wallace et al., 2004). The important takeaway, as emphasised by Doug in the paper is that the mitochondrial and nuclear genome has not changed in the last 150 years at all, despite the explosion in disease and ill health.

It is the environment that has changed. Drastically.

It is the shifting environment that has placed great stress on the mitochondria, consequently changing their function. The downstream consequences of this are mitochondria that are stressed out and thus initiate the immune and inflammatory pathways that constitute systemic low-grade inflammation.

Evidence for mitochondrial dysfunction in chronic musculoskeletal pain

In people born with mitochondrial diseases due to mutations in their mitochondrial DNA, 91% of them have chronic pain and the remaining people that do not have pain, all have neuropathy-related diseases (Löffler et al., 2020).

The pain apparatus (the nervous system) is almost completely susceptible to mitochondrial changes from DNA mutations thus paving the way for possible mitochondrial-related problems arising from a mismatch between modern day environmental conditions and the evolutionary environment that the mitochondrion is built to thrive in. 

I would say this is fairly strong evidence that the mitochondria play a central role in pain.

Let’s explore this further.

Following an acute nociceptive stimulus by inflammatory injury to the peripheral primary afferent neurons (these are the nerve ends and nerves that go from the tissues to the spinal cord), disturbances in redox balance and oxidative stress persist in the mitochondria of dorsal root ganglion neurons after resolution of inflammatory pain and these changes DRG drive the transition from acute to chronic pain (Willemen et al., 2023).

All known pain conditions including peripheral neuropathic pain, cancer-induced neuropathic pain, spinal cord injury, inflammatory pain, nociplastic pain, fibromyalgia, nociceptive pain share a common theme of bioenergetic crisis of the cell, driven by dysfunction of the mitochondria (Macchi et al., 2024) and is characterised as follows:

• Reduced oxidative phosphorylation which leads to a severe ATP supply deficit, impairing neuron capacity because of a bioenergetic crisis

• This ATP loss impairs membrane pumps leading elevated intracellular Na+ and Ca+ which in turn increase neuron excitability and spontaneous firing, responsible for symptoms like sudden, random onset of pain and reduces the pain pressure threshold

• Production of excessive mitochondrial reactive oxygen species (mtROS) and oxidative stress secondary to a reduced efficiency of the electron transport chain. The mtROS are signalling molecules for pro-nociceptive pathways and initiate the pro-inflammatory cascade that leads to chronic widespread inflammation in the

• The Mitochondria are calcium (Ca+) buffers. The increased Ca+ because of reduced pump efficiency overloads the mitochondria leading to higher levels of mtROS production. Consequently, inhibiting ETC function and tiggering the mitochondria to burst and spew pro-apoptotic factors into the cell leading to death of the cell.

On a fundamental level, persistent pain is a problem of bioenergetic failure.

The mitochondrial dysfunction leads to an energy crisis whereby it struggles to meet the demands of the cell of that tissue e.g. neuron, lumbar disc, muscle… and consequently (as per evolutions safety switch), puts the cell into a state of stress-management, which leads to inflammatory cascades but preserves function.

In severe cases where it is unable to meet demands at all, simply dies via apoptosis (which is programmed and initiated by the mitochondria!).

Interestingly, there is solid evidence that lumbar disc degeneration is a consequence of unchecked apoptosis secondary to the initiation of widespread cell death from mitochondrial dysfunction (Han et al., 2019; Chen et al., 2014).

This reshapes our view of chronic pain.

When treating the person with persistent pain we must look at their environment and understand it from a perspective of allostatic load – that is the total cumulative stressors that effect the mitochondria.

In my opinion, it answers a few questions that are thrown around in physiotherapy – why imaging is generally poor for determining pain intensity and trajectory, and why the growing evidence-base portrays lifestyle and environmental health as having a greater cumulative effect on shifting the trajectory of pain than exercise.

Future therapies (perhaps in the next decade) will no doubt focus on the mitochondria and their relationship with the cell… and death. However, in the spirit of Doug Wallace, I am sceptical it will deliver the panacea it promises us.

Not because it doesn’t work.

Because you can’t heal in the same environment that made you sick.

This is where I believe physiotherapy needs to go – take our same detective skills for pathoanatomic analysis and exercise prescription and apply it to the environment of the person. This is where my clinical practise is going and it is ever evolving as we learn more how mitochondria are governed by four fundamental forces.

Light, Magnetism, Food and Circadian rhythm.

These are our first principles for life itself, and the challenge of the 21^st century is applying these to people in pain – and educating the public on the why and what of the mitochondria and their importance to health and recovery from pain.

Part of my three pillars approach – the whole-body health – has been shaped largely by the growing body of research around mitochondrial health, inflammation and immune dysregulation and is underpinned by the making sense of pain pillar so that the patient actually understands the link between the two.

If you suffer with persistent pain or nagging injuries and wondering how you can supercharge your recovery, then head over to our home page and see how our physiotherapy services can help you!

References

Willemen, H. L. D. M., Santos Ribeiro, P. S., Broeks, M., Meijer, N., Versteeg, S., & Tiggeler, A. (2023). Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain. Cell Rep Med. 2023; 4 (11): 101265.

Brown, M. C., Kosinski, A. S., Fillipo, R., Howell, G., Giang, M. H., Hurewitz, M., ... & Goode, A. P. (2025). Patterns and trajectories of peripheral inflammatory cytokines, immune tolerance, and lymphocyte differentiation predict transition from acute to chronic low back pain in a sex and age specific manner. Pain, 167(2), 477.

Löffler, M., Gamroth, C., Becker, S., & Flor, H. (2020). Chronic pain as a neglected core symptom in mitochondrial diseases. Neurology, 94(8), 357-359.

Fan, Y. L., Dai, F. Y., Wang, J. Y., Dai, X. Y., Song, W. L., Wu, H., ... & Mei, W. (2026). Mitochondrial dysfunction as a driver of chronic pain: New insights and therapeutic prospects. Pharmacological Research, 108170.

Macchi, C., Giachi, A., Fichtner, I., Pedretti, S., Sarzi-Puttini, P., Mitro, N., ... & Gualtierotti, R. (2024). Mitochondrial function in patients affected with fibromyalgia syndrome is impaired and correlates with disease severity. Scientific Reports, 14(1), 30247.

Wallace, D. C. (2005). A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu. Rev. Genet., 39(1), 359-407.

Kent, P., Haines, T., O'Sullivan, P., Smith, A., Campbell, A., Schutze, R., ... & RESTORE Trial Team. (2023). Cognitive functional therapy with or without movement sensor biofeedback versus usual care for chronic, disabling low back pain (RESTORE): a randomised, controlled, three-arm, parallel group, phase 3, clinical trial. The Lancet, 401(10391), 1866-1877.

Geto, Z., Molla, M. D., Challa, F., Belay, Y., & Getahun, T. (2020). Mitochondrial dynamic dysfunction as a main triggering factor for inflammation associated chronic non-communicable diseases. Journal of inflammation research, 97-107.

Han, Y., Li, X., Yan, M., Yang, M., Wang, S., Pan, J., ... & Tan, J. (2019). Oxidative damage induces apoptosis and promotes calcification in disc cartilage endplate cell through ROS/MAPK/NF-κB pathway: Implications for disc degeneration. Biochemical and biophysical research communications, 516(3), 1026-1032.

Chen, J. W., Ni, B. B., Li, B., Yang, Y. H., Jiang, S. D., & Jiang, L. S. (2014). The responses of autophagy and apoptosis to oxidative stress in nucleus pulposus cells: implications for disc degeneration. Cellular Physiology and Biochemistry, 34(4), 1175-1189.

Schütze, R., Liew, B., Caneiro, J. P., O'Sullivan, P., Kent, P., Hancock, M., ... & Smith, A. (2025). Mechanisms of change in cognitive functional therapy: A longitudinal mediation analysis of the RESTORE clinical trial for disabling chronic low back pain. Behaviour Research and Therapy, 193, 104853.