In this communication, we argue about the need for an extensive investigation of the relationship between body fatness and fat distribution and experimental pain to explore the factors that might contribute to the increased prevalence of pain conditions in obese individuals

Charles A

Duncan Sharp

Haslam D

Hitt HC

Kim SW

Mark I. Johnson

McVinnie DS

Osama A. Tashani

Rehab A. Astita

PubMed

Astita, R

Tashani, OA

Sharp, D

Johnson, MI

Leeds Beckett Repository

LETTER TO THE EDITORArgument for the need of investigation of the relationshipbetween body fatness and experimental pain sensitivityRehab A. Astita*, Osama A. Tashani, Duncan Sharp and Mark I. JohnsonCentre for Pain Research, Faculty of Health and Social Sciences, Leeds Beckett University, Leeds, UKIn this communication, we argue about the need for an extensive investigation of the relationship betweenbody fatness and fat distribution and experimental pain to explore the factors that might contribute to theincreased prevalence of pain conditions in obese individuals.Keywords: obesity; chronic pain; experimental pain; body fat; cytokines*Correspondence to: Rehab A. Astita, Centre for Pain Research, Faculty of Health and Social Sciences, LeedsBeckett University, City Campus, LS1 3HE, Leeds, UK, Email: R.Astita@leedsbeckett.ac.ukReceived: 21 April 2015; Accepted in revised form: 6 June 2015; Published: 16 June 2015Obesityand pain are significant public health pro-blems and contribute to significant disability world-wide (1). There appears to be tentative evidencethat individuals with a high body mass index (BMI), whichis often used as a proxy measure of obesity, report higherpain intensity compared with individuals with normalBMI (2). However, the relationship between obesityand pain has received little attention and the potentialmechanisms underlying a putative relationship is not wellunderstood (3, 4).Obesity is defined as an increase in body weight asa result of an excessive accumulation of body fat andis associated with increased morbidity and mortality(5). Obesity is commonly measured using the BMI, withobesity characterised as a BMI greater than 30 kg/m2,overweight between 25 and 29.9 kg/m2, and normalweight from 18 to 24.9 kg/m2 (6, 7). The World HealthOrganization (2013) reports that more than 1.5 billionadults worldwide are overweight and approximately500 million adults meet the criteria for obesity. In theUnited States, approximately 78 million adults and 12.5million children and adolescents are obese (8).Obesity and chronic painObesity is usually associated with comorbidities (9, 10)such as diabetes. There is very strong evidence that obesityis a high-risk factor for elevated cholesterol, heart disease,type 2 diabetes, cancer, and stroke (10). Obesity may beinfluenced by genetic and physiological factors, such as athyroid disorder, growth hormone and leptin deficiency,and lifestyle factors including overeating, especially excessconsumption of sugary and processed foods, and lack ofexercise associated with a sedentary way of life (11).Obesity is also associated with painful conditions,including low back pain, fibromyalgia headache, andosteoarthritis (12). It has been estimated that approxi-mately 50% of people who are obese regularly experiencepain (13). The International Association of the Study ofPain (IASP) defines pain as ‘an unpleasant sensory andemotional experience associated with actual or potentialtissue damage, or described in terms of such damage’(14). It is unclear whether obesity causes chronic pain orchronic pain could cause increased weight, or some otherfactor(s) cause both conditions concurrently (2, 15). Ithas been assumed that pain in obese people could be theresult of the excessive weight, causing mechanical stress toweight-bearing structures, particularly joints of the backand lower limbs (16). More recently, attention has been onthe possibility that obesity produces a pro-inflammatorystate and that inflammatory substrates may contributeto the development of pain (2).Body fatness and experimental painLaboratory investigations into the pain sensitivity re-sponse of healthy individuals has been used extensivelyin pain science to investigate relationships between painsensitivity and sex, gender, ethnicity, and other factors thatmay influence pain experience. To date, the mechanismsunderlying the supposed relationship between obesityand an individual’s pain sensitivity response has receivedlittle attention (3, 4, 16, 17). Pain sensitivity is the level atwhich an individual reacts to a noxious stimulus and ismeasured using controlled experimental stimuli (18).Libyan Journal of MedicineLibyan Journal of Medicine 2015.# 2015 Rehab A. Astita et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), permitting all non-commercial use, distribution, and reproduction in anymedium, provided the original work is properly cited.1Citation: Libyan J Med 2015, 10: 28457 - http://dx.doi.org/10.3402/ljm.v10.28457(page number not for citation purpose)Laboratory investigations into the pain sensitivityresponse of obese pain-free individuals would be usefulto determine whether obesity contributes to pain experience,in addition to other factors already known to influencepain sensitivity response, including age, sex, gender,ethnicity, and psychological factors such as anxiety andcatastrophising. These factors should be accounted forin any study of pain sensitivity (19).The role of pro-inflammatory cytokinesSusceptibility to pain in obese individuals may be affectedby increases in the concentrations of pro-inflammatorycytokines in the blood (2, 17). Cytokines are proteinssecreted by cells to regulate the immune response toinfection and trauma (17, 20, 21). Some cytokinespromote the healing of wounds; pro-inflammatory cyto-kines increase inflammation and cause diseases to pro-gress; anti-inflammatory cytokines suppress the activity ofpro-inflammatory cytokines (20). Inflammatory responsesin the peripheral and central nervous systems play keyroles in the development and persistence of the hallmarksof pain: redness, swelling, temperature rise, and pain (22).Cytokines are regulators of adipose tissue metabolism andare secreted by many cells in the body. Pro-inflammatorycytokines are predominantly produced by activated macro-phages and are involved in the up-regulation of inflam-matory reactions. There is abundant evidence that certainpro-inflammatory cytokines such as IL-1b, interleukin-6(IL-6), and tumour necrosis factor-a (TNF-a) are involvedin the process of pathological pain (23). The significanceof cytokines in the development of pain and hyperalgesiaas well as their mechanisms of action on nociceptors hasbeen realised only during the last decade (24, 25). Adiposetissue releases inflammatory mediators, including prosta-glandin, histamine, and interleukin (25). Visceral adiposetissue in particular is a rich source of pro-inflammatorycytokines, which appear to be major regulators of adiposetissue metabolism. There is evidence that obese individualshave elevated circulation levels of pro-inflammatory cyto-kines, such as TNF-a, IL-6, and C-reactive protein (CRP).IL-6 is a circulating cytokine secreted from different typesof cells, including activated macrophages and lympho-cytes. The biological activity of IL-6 is elevated in thepresence of systemic infection or inflammation (26), and itis known that IL-6 and TNF-a play key roles in chronicpain conditions (27).Obese individuals may be in a pro-inflammatory state(17). It is unclear whether an increased prevalence ofpain conditions and pain sensitivity in obese individualsis the result of the inflammatory mediators associatedwith adipose tissue or else some other factors, such asbody size and accumulation and distribution of fat, arealso linked to pain sensitivity responses (28).ConclusionOne way of investigating whether inflammatory mediatorsin obese people are associated with pain sensitivity isto correlate the concentrations of biomarkers of systemicinflammation in pain-free individuals using experimentalpain induction techniques. However, before undertakingexperimental studies, it is necessary to review the currentstatus of research literature to contextualise the preva-lence of chronic pain among obese individuals and thecurrent understanding of the mechanism by which fatcontent of the body affects pain. It is also necessary toconduct a systematic review of research on experimentalpain sensitivity response and body fatness to determinethe status of current research on the topic and to informthe design of the experimental studies. Therefore, there isa need to investigate the relationship between pain sensiti-vity, body fat distribution, and levels of pro-inflammatorycytokines. Such a study should be based on an experi-mental investigation of the relationship between painsensitivity, body fat distribution (measured by a state-of-the-art device), and blood levels of IL-6, CPR, TNF-a, andleptin.Conflict of interest and fundingThe first author was supported by The Medical TechnologyHigher Institute, Al-Bayda, Libya.References1. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK,Paciorek CJ, et al. National, regional, and global trendsin body-mass index since 1980: systematic analysis of healthexamination surveys and epidemiological studies with 960country-years and 91 million participants. Lancet. 2011; 377:55767.2. Ray L, Lipton RB, Zimmerman ME, Katz MJ, Derby CA.Mechanisms of association between obesity and chronic pain inthe elderly. Pain. 2011; 152: 539.3. Hitt HC, McMillen RC, Thornton-Neaves T, Koch K, AG C.Comorbidity of obesity and pain in a general population: resultsfrom the southern pain prevalence study. J Pain. 2007; 430: 6.4. McVinnie DS. Obesity and pain. Br J Pain. 2013; 7: 16370.5. Haslam D. Obesity: a medical history. Obesity Rev. 2007; 8:316.6. Wright LJ, Schur E, Noonan C, Ahumada S, Buchwald D,Afari N. Chronic pain, overweight, and obesity: findings from acommunity-based twin registry. J Pain. 2010; 11: 62835.7. WHO. 2010. Available from: http://www.ic.nhs.uk/statistics-and-data-collections/health-and-lifestyles-related-surveys [cited25 August 2014].8. Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM.Prevalence of high body mass index in US children andadolescents, 20072008. JAMA. 2010; 303: 2429.9. Brown CD, Higgins M, Donato KA, Rohde FC, Garrison R,Obarzanek E, et al. Body mass index and the prevalence ofhypertension and dyslipidemia. Obes Res. 2000; 8: 60519.10. Pischon T, No¨thlings U, Boeing H. Obesity and cancer. ProcNutr Soc. 2008; 67: 12845.Rehab A. Astita et al.2(page number not for citation purpose)Citation: Libyan Journal of Medicine 2015, 10: 28457 - http://dx.doi.org/10.3402/ljm.v10.2845711. Wijga AH, Scholtens S, Bemelmans WJ, de Jongste JC,Kerkhof M, Schipper M, et al. Comorbidities of obesity inschool children: a cross-sectional study in the PIAMA birthcohort. BMC Public Health. 2010; 10: 184.12. Kim SW, Mintz GS, Escolar E, Ohlmann P, Pregowski J,Tyczynski P, et al. The impact of cardiovascular risk factors onsubclinical left main coronary artery disease: an intravascularultrasound study. Am Heart J. 2006; 152: 712.13. Kerns RD, Otis J, Rosenberg R, Reid MC. Veterans’ reportsof pain and associations with ratings of health, health-riskbehaviors, affective distress, and use of the healthcare system.J Rehabil Res Dev. 2003; 40: 37180.14. Mersky H, Bogduk N. (Eds.) Classification of chronic pain:descriptions of chronic pain syndromes and definitions of painterms. Seattle, WA: IASP Press; 1994, p. xi. Available from: http://www.iasppain.org/files/Content/ContentFolders/Publications2/FreeBooks/Classification-of-Chronic-Pain.pdf [cited 9 September2014].15. Shiri R, Karppinen J, Leino-Arjas P, Solovieva S, Viikari-Juntura E. The association between obesity and low back pain:a meta-analysis. Am J Epidemiol. 2010; 171: 13554.16. Ray L, Lipton RB, Zimmerman ME, Katz MJ, Derby CA.Mechanisms of association between obesity and chronic pain inthe elderly. Pain. 2011; 152: 539.17. Stolzman S. The influence of cytokines on obesity-associatedpain. 2013. Available from: http://epublications.marquette.edu/cgi/viewcontent.cgi?article=1010&context=dittman [cited 9 Sep-tember 2014].18. Nielsen CS, Stubhaug A, Price DD, Vassend O, Czajkowski N,Harris JR. Individual differences in pain sensitivity: genetic andenvironmental contributions. Pain. 2008; 136: 219.19. Caldwell J, Hart-Johnson T, Green CR. Body mass index andquality of life: examining blacks and whites with chronic pain.J Pain. 2009; 10: 607.20. Charles A, Dinarello MD. Proinflammatory cytokines. Chest.2000; 118: 5038.21. Coppack SW. Pro-inflammatory cytokines and adipose tissue.Proc Nutr Soc. 2001; 60: 34956.22. Watkins LR, Milligan ED, Glial MS. Proinflammatory cyto-kines mediate exaggerated pain states: implications for clinicalpain. Adv Exp Med Biol. 2003; 521: 121.23. Zhang J-M, An J. Cytokines, inflammation and pain. IntAnesthesiol Clin. 2007; 45: 27.24. Koltzenburg M, Kress M, Reeh P. The nociceptor sensitiza-tion by bradykinin does not depend on sympathetic neurons.Neuroscience. 1992; 46: 46573.25. Fain JN. Release of interleukins and other inflammatorycytokines by human adipose tissue is enhanced in obesityand primarily due to the nonfat cells. Vitam Horm. 2006; 74:44377.26. Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V.Inflammation, obesity, stress and coronary heart disease: isinterleukin-6 the link? Atherosclerosis. 2000; 148: 20914.27. Puglisi MJ, Fernandez ML. Modulation of C-reactive protein,tumor necrosis factor-a, and adiponectin by diet, exercise, andweight loss. J Nutr. 2008; 138: 22936.28. Tashani OA, Alabas OA, Johnson MI. Cold pressor painresponses in healthy Libyans: effect of sex/gender, anxiety, andbody size. Gend Med. 2010; 7: 30919.Obesity and Experimental PainCitation: Libyan Journal of Medicine 2015, 10: 28457 - http://dx.doi.org/10.3402/ljm.v10.28457 3(page number not for citation purpose)

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