(Obesity and Chronic Pain: Similar physiology. Same aetiology?)

1. Chronic Pain & Lifestyle (Obesity and Chronic Pain: Similar physiology. Same aetiology?) Prof Garry Egger MPH PhD Southern Cross University

3. …and if you get caught out - act sorry!

4. Main Points • Obesity and chronic pain are linked biologically through a form of low-grade, systemic inflammation (‘metaflammation’), with glia playing a major role. • ‘Metaflammation’ is caused by lifestyles – the key driver being the modern western environment. • Hence (much) chronic neuropathic (‘gliapathic’?) pain is lifestyle-related – leading to the conclusion that: • Lifestyle change needs to be incorporated into any new ‘wholistic’ paradigm for chronic pain management.

7. Lucky Boyd

8. Obesity and Chronic Pain Obesity Chronic Pain • ~30 % of popn • ~20% of popn • Increasing (~2%pa) • Predicted increase (~4%pa)* • Lifestyle related • Lifestyle related (?) • Inflammatory link • Inflammatory base Both a bigger problem in developed countries Both higher in lower SE groups Both have environmental aetiologies *Hohenberg KW, Lyons J, Daley TL. Chronic Pain. Decision Resources Report. March 2008.

9. (UK) Prevalence of Overweight and Obesity Risk Factors: • low income • age • frequency of snacks • amount of exercise of owners 50% 38.9% 35.3% 25% Prevalence 20.4% 5.3% o% Underweight Normal weight Overweight Obese Ref: Courcier EA, Mellor DJ, Yam PS. J. Small Animal Practice 2010; 3rd Feb

10. Environment Biology Behaviour Equilibrium fat stores Physiological adjustments = Energy in-Energy out X Moderators Ways of thinking about Obesity X The ‘linear’ approach: Weight = Energy in - Energy out A ‘systems’ approach: Influences Ref: Egger G, Swinburn B. Brit Med J. 1996; 20:227-231

11. Obesity: Always offender or often just accomplice?

12. The Fat ‘Spill-Over’ Hypothesis Inflammatory signaling Maximal adipocyte expandability (genetically determined) Inflammation Adipocyte (fat cell) Pre-adipocyte Macrophage accumulation Lipid pool Expanded Lipid pool Insulin sensitive Insulin resistant Lipid ‘spill-over’ Adipocyte expanded to maximal capacity Blood Liver Muscle

13. Our inflammatory internal environment – ‘metaflammation’

14. Forms of Inflammation Basal Homeostasis Resolution Microbial Pathogen/ ‘Antigen’ Lifestyle/ Environmental ‘Inducer’ Immune Reaction Chronic Allostasis ‘Agent’ (LDL) Oxidative stress Disease ‘Dys- Metab Olism’ Immune Defense ‘Meta- flammation’ Insulin Resistance Inflammation Classical, Acute, Infectious Response Modern, Chronic. Non-infectious Response Ref: Egger G, Dixon J. Obes Rev 2009 (in press)

15. Inflammation (“metaflammation”) in chronic disease Ref: Lamon BD, Hajar DP. Am J Pathol 2008;173(5):1253-1264

16. Metaflammation ‘Inducers’ of Metaflammation E N V I R O N M E N T Lifestyle Smoking Over- Nutrition Inactivity Drug use Starvation Pollution Over- exercise Excess Alcohol Inadequate Sleep Diet Stress/ Depression Obesity + Other Mechanisms(eg. oxidative stress, insulin resistance etc) Chronic (Non-Communicable) Disease Ref: Egger G, Dixon J. Ob Rev 2009;10:237-249.

17. ADAPTED – PRE-INDUSTRIAL REVOLUTION UNADAPTED – POST-INDUSTRIAL REVOLUTION Egger G, Dixon J. Ob Rev (in press) -100,000 ~1800 today

19. Range of ‘Metaflammatory’ Effects Affected Organs • Endothelium (atherosclerosis) •Lung (COPD) • Brain (Alzheimer’s/ Dementia) • Joints (arthritis) • Bowel (IBD) • Neuron/Glia (neuropathic/ ‘gliapathic’? pain) Ref: Libby P. Nature, 2010

20. Modulation of the Neurovascular Unit by Pain Ref: Willis CL, Davis TP. Current Pharmaceutical Design, 2008, 14, 1625-1643

21. Glia – More Than Just Brain Glue Figure 1 | Glia–neuron interactions. Different types of glia interact with neurons and the surrounding blood vessels. Oligodendrocytes wrap myelin around axons to speed up neuronal transmission. Astrocytes extend processes that ensheath blood vessels and synapses. Microglia keep the brain under surveillance for damage or infection. Ref: Allen NJ, Barres BA, Nature, 2009

22. The Potential Impact of Glia on Central Pain Signaling Glia Glia Glia Glia Neuron Neuron Neuron Glia Ref: Fields D. ‘The Other Brain’, 2009

23. The links between Chronic Pain and Lifestyle

24. Lifestyle Factors and Chronic Pain – SE Factors Ref: Saastamoinen P et al., Pain, 2008

25. Number of Pain Sites by Lifestyle Behaviours – Norway N=2926 Ref: Kalameri et al., Eur J Pain, 2008

26. Lifestyle, ‘Metaflammation’ and Chronic Pain Metaflam- Endothelial Chronic Chronic Prevalence mation Dysfunction Disease Pain Lifestyle processes Inactivity + + + ? 50% Smoking + + + + 20% Passive smoking + + + ? - Poor sleep + + + + 33% Overweight/Obesity + + + + 60% Stress + ? ? + ~20% Nutrition Sat/trans fat intake + + + + - High GI load + + + ? - + = positive effect ? = not sufficient evidence Ref: Shiri R et al. Eur Spine J, 2007;16:2043-2054

27. Why nutrition & chronic pain? Nutrition obesity CVD M E T A F L A M M A T I O N!!! cancer diabetes aging C H R O N I C P A I N??? insulin resistance arthritis immune function gut health ”We literally eat ourselves into an inflamed and painful state and then seek out passive care from doctors to intervene on our behalf.” Seaman DR. “The diet induced pro-inflammatory state: A cause of chronic pain and other degenerative diseases”. J Manip &Physio Ther 2002;25(3):168-179

28. Why exercise & chronic pain? Exercise obesity CVD M E T A F L A M M A T I O N!!! cancer diabetes aging C H R O N I C P A I N??? insulin resistance arthritis immune function gut health ”Recent evidence suggests that the protective effect of exercise may to some extent be ascribed to an anti-inflammatory effect of regular exercise.” Inflammation PL et al.. “Persistent low grade inflammation and regular exercise.” Front Biosc 2010 Jan

30. Can we unknowingly contribute to the persistence of pain ? Inflammatory actions Inflammatory attitudes • over doing • under doing • poor sleep • stress • anger • bitterness Tissue inflammation Neural sensitisation Inflammatory eating Inflammatory environment • excess starchy carbohydrate • toxins • smoking • medication Inflammatory relationships

31. Models in Pain Management Traditional (dualistic) Model Emerging (Holistic) Model • Medical or psychological focus • + Social and environmental focus • More clinician centred • More patient centred • Limited benefits for limited time • Significant, long term benefits • Individual treatment approach • individual + group treatment • Patient as recipient of treatment • Patient as partner in treatment • Potential dependency/ complications • Limited dependency/complications • Distracts recipient from active • Involves recipient in active self- management management • “Siloed” health system approach • Integrated health system approach • Neural plasticity disregarded • Neural plasticity vital for treatment • Ongoing/discontinued biomedical • ‘Tapered’ biomedical treatment treatment • Individual health perspective only • Population health perspective • Little or no attention to lifestyle • Significant attention given to lifestyle change

32. The Australian Lifestyle Medicine Association (ALMA) www.ALMA.net.au

33. Thank you

35. Chronic Pain and Lifestyle Medicine Garry Egger Southern Cross University, Lismore and Centre for Health Promotion and Research, Sydney Chronic pain is an increasingly common phenomenon in modern societies. It’s not coincidental that this corresponds to an increase in several other lifestyle-related chronic diseases or risk factors (type 2 diabetes, depression, cancers etc), which have recently been shown to have a common physiological aetiology in low grade, systemic, inflammation (‘metaflammation’). Coupled with findings of increased plasticity in the brain, it is not outrageous to speculate that metaflammation may extend to both central and peripheral glial connections associated with pain perception, thus linking lifestyle-related ‘inducers’ to non-specific and unresolvable chronic pain. Even without such a biological basis, there is evidence to suggest that lifestyle change may have a positive effect as part of a systems-theory approach to chronic pain management. The potential benefits of a ‘Lifestyle Medicine’ approach to chronic pain management are considered in this regard.