SUBJECTS

This interventional pilot study was conducted on patients with chronic pain referred to the Department of Anesthesiology, Resuscitation and Intensive Care of the University Hospital Osijek, Croatia. This is the first programme of this kind in Croatia, active since 2003. Nutrition education has been integral part of the multidisciplinary programme since 2016. The team comprise anaesthesiologist, nurse, physiotherapist, endocrinologist, nutritionist, occupational therapist, psychologist, and psychiatrist. They are conducting a series of educations focused on self-management of the pain, both pharmacological and non-pharmacological. Despite being recognized as important, nutrition is rarely integrated into programs for the management of chronic pain, even on an international scale (¹⁷,¹⁸).

Patients were referred to the Department by primary care physicians, and then enrolled into groups by anaesthesiologists. In groups of 10, patients during 4 weeks go through a series of group and individual educations and therapies.This population is a heterogeneous group of chronic pain patients with different localisations of pain, such as low back pain, neck pain, shoulder pain, fibromyalgia, different forms of headache, and neuropathic pain syndrome. Only patients with a long history (at least 5 years) of chronic pain unresponsive to various treatments are eligible for the programme.

PAIN QUESTIONNAIRE

At the initial assessment, patients were given pain DETECT questionnaire (PD-Q) as an easy-to-use and reliable screening tool that can determine the prevalence of neuropathic pain components. PD-Q is used worldwide, to establish neuropathic pain component on patients with lower back pain, rheumatoid arthritis and osteoarthritis, thoracotomy, tumour diseases, fibromyalgia, diverse musculoskeletal conditions and other conditions (¹⁹,²⁰).

QUESTIONNAIRE ON BASIC, SOCIOECONOMIC AND DIAGNOSIS-RELATED CHARACTERISTICS AND DIET

Basic information, nutrition and lifestyle habits, along with self-perception of the quality of life were assessed with a study-specific questionnaire. The first part of the questionnaire included questions about general and demographic characteristics, e.g. age, gender, body mass, body weight, education, monthly income per person, etc. On the basis of self-reported body mass and height patients’ BMI was calculated and they were categorized according to their state of nourishment (²¹).

The second part of the questionnaire included questions about the diagnosis, course of the disease and the treatment (e.g. use of medications). Additional two questions in a form of a visual-analogue scale (VAS method) were used to assess patients’ subjective opinion on how much does the pain they are experiencing influences their 1) psychophysical condition and 2) the quality of life. Patients were asked to place a vertical line on the scale (100 mm long). Marked place on the scale was measured with a ruler, counted and transformed to a score. The score range was 0 to 100 for each item. Higher score reflects better condition. VAS is a widely used instrument for the assessment of complex measures, including pain (²²).

The third part included questions about lifestyle and dietary habits, i.e. number of meals per day, breakfast consumption, physical activity, frequency of alcohol, coffee and tobacco consumption. The last part of the questionnaire assessed consumption frequency of 27 foods/food groups on a weekly basis. The list of foods was prepared based on the literature search, so that foods or food groups with documented positive or negative effect on chronic pain were included in the list (¹²-¹⁶,²³,²⁴). Each consumption corresponds to a certain number of points and higher number of points corresponds to higher consumption of particular food/food group. Offered categories and corresponding points were: 2 or more times per day (2 points), once per day (1 point), up to 5 times per week (0.71 point), 1 to 2 times per week (0.21) and rarely/never (0 points). The list of foods was divided into foods with positive (e.g. olive oil, cruciferous vegetables) and negative (e.g. foods with high content of added sugars, food sources of saturated fats) effect on chronic pain (¹²-¹⁶,²³,²⁴). Based on the change in scores pre- and post-intervention patient’s diet was rated as improved (higher score for positive, lower score for negative characteristics) or unchanged/worse (all other score combinations).

NUTRITION EDUCATION INTERVENTION

We designed specific nutrition education for the management of chronic pain. Principles of the Medditeranean are the basis of the education, with special emphasis on regular consumption of meals to avoid hypoglycaemia. Besides explain the role of meal skipping, overeating, and obesity as pain amplifiers, patients are counselled on specific techniques on how to introduce foods with proven anti-inflammatory properties (olive oil, nuts, fish, green leafy vegetables, etc.) in their daily diet. Food cravings (for foods rich in saturated fats and simple carbohydrates) are explained from the aspect of pain management, and patients are introduced to potential substitutes.

During the 4-week programme every patient went through one individual and two group sessions with the nutritionist. Individual counselling was partially adapted to individual needs of the patient, based on their BMI, food preferences and lifestyle (e.g. impaired mobility).

At the end of the 4-week programme, at the final, wrap-up session, patients were given the same questionnaires to assess the effectiveness of the programme.

The study was approved by the Ethical Committee of the University Hospital Osijek and served as the pilot for the registered randomized clinical trial (NCT03837080). The analysis was performed on four groups of patients who received nutrition education (from February until June 2017), 40 patients altogether. Signed informed consent was obtained from all patients.

STATISTICAL ANALYSIS

Normality of data distribution was tested by the non-parametric Kolmogorov-Smirnov test for the comparison of medians and arithmetic mean, and histograms plotting. For the comparison of categorical data within and between groups Fishers exact test was used, and Pearson’s test of correlations was used to calculate correlations between numerical data. T-test for independent samples was used to test differences between groups according to change in pain scores.

By an inferential statistics the association of a number of independent variables with change in pain scores as a binary dependent variable was tested with a univariate logistic regression. Independent variables tested were: age, BMI, number of diagnosis, number of meals per day, consumption of breakfast, meal skipping, and the change in consumption of foods with positive and negative effect on chronic pain. Independent factors that were found significant in a univariate logistic regression were included in the multiple logistic regression model. If the probability of alpha error was less than 0.05 we considered the relationship significant. Software tool Statistica 13.3 (StatSoft Tulsa, Oklahoma, USA) was used for the statistical analysis.

THE CONNECTION BETWEEN BMI AND CHRONIC PAIN

Substantial amount of evidence points to a coexistence between obesity and chronic pain, and therefore requires utmost attention. Patients with higher BMIs often report increased pain, decreased quality of life and difficulties performing every-day activities (²³,²⁵). The prevalence of obesity is higher in those with chronic pain and the prevalence of chronic pain is higher in those who are obese (¹⁶,²³,²⁵-²⁷). Compared to normal weight people, overweight people reported 20 % higher rates of recurring pain, class I obesity people 68 %, people with class II obesity reported 136 % higher rates, while morbidly obese reported 254 % higher rates of recurring pain (²⁷). The inter-relationship between obesity and chronic pain is not yet completely elucidated, but potential mechanisms have been hypothesised to include structural, mechanical, metabolic and behavioural changes (²³). The pressure on joints and spine increases due to weight (²⁷). Obese patients commonly have altered body mechanics, postures and gait patterns, which may be involved in the link between obesity and pain (¹⁶). Alternately, chronic pain may result in weight gain and obesity through reduced physical activity (¹⁶,²⁶).

Furthermore, adipose tissue is not a passive storage space, but metabolically active tissue, which conducts endocrine function, producing and releasing cytokines, such as interleukins (IL), tumor necrosis factor alpha (TNF-α), and adipokines such as adiponectin, leptin, and adipsin (²⁸). Leptin and adipsin have been proposed as a possible causative link between obesity and osteoarthritis while TNF-α and ILs-6 and −8 have been associated with structural joint abnormalities, nociceptive pathways, and in the development and progression of chronic pain. Higher adipsin levels were further related to back pain in overweight or obese, otherwise healthy adults, independently of adiposity, as well as in knee osteoarthritis (²⁹). Elevated levels in inflammatory markers in the serum (such as [IL-6], and C-reactive protein [CRP]) have been observed in obese patients; therefore obesity may be characterized as chronic inflammatory state (²⁷,²⁹).

A randomized 18-month clinical trial (³⁰) showed that intensive diet and exercise reduce plasma levels of IL-6 in patients with osteoarthritis. Participants in the group with combined diet-exercise and diet group had higher weight loss and greater reductions in IL-6 levels than those in the exercise group only (³⁰).

High prevalence of depression and chronic pain has been documented both in patients with chronic pain and obesity. Chronic pain is related to high levels of anxiety, depression, social and occupational dysfunction, where pain related fear and catastrophizing play a prominent role. The combination of decreased life reinforcement in depression and chronic pain seems to promote emotional eating and craving for comfort, high-caloric foods (²³,²⁶). These patients often report so-called binge episodes, which are connected with short reduction in pain and instant mood elevation (²³). Many patients describe eating as the only activity that continues to bring them regular and reliable pleasure, especially if they feel physically limited due to constant pain. Those episodes include eating more frequently, in large amounts, and choosing foods high in sugar, sodium, fat and calories in response to pain or a combination of pain and mood (²³,²⁶,³¹,³²). Foods mentioned above turn on the inflammatory response in the body, which makes pain worse (²⁴). One must also remember that chronic inflammatory states have also been linked to major depression (⁷). Geha et al. (²⁶) gave neuroscientific explanation for disrupted food hedonics describing them as hedonic blunting (a reduced ability to experience pleasure) which is plausible mechanistic link between pain and obesity.

Behavioural factors associated with chronic pain and obesity are physical deactivation and deconditioning, also known risk factors for developing both conditions, and represent major barrier for successful rehabilitation (²³,²⁷). Since obese patients find it more difficult to participate in active therapy, this comorbidity often leads to a vicious cycle of pain-inactivity-obesity-depression-food cravings (²³,³¹). Sedentary lifestyle further intensifys isolation which may worsen both depression and trigger emotional eating (⁸).

Regardless of the causal underpinnings, chronic pain and obesity have additive effects, resulting in decreased quality of life and increased disability. Encouragingly, weight loss seems to reduces and even prevents pain (⁸,³⁰,³³). Larsson (³⁴) showed musculoskeletal pain in obese women significantly improved after losing 14 % of weight. Another observational study of approximately 800 women estimated that by losing only 5 kg, risk of developing knee osteoarthritis can be reduced by 50 % (³⁵).

THE CONNECTION BETWEEN FOOD AND PAIN

Diet based on the Mediterranean principles (rich in unrefined carbohydrates, nuts, fish and olive oil) has been shown to pose strong anti-inflammatory properties (decrease in IL-6 and subsequently CRP) and has an overall positive impact on health (¹¹,¹⁵,²⁴,³⁶-³⁸).

Food cravings, especially for simple carbohydrates are compensatory mechanisms. Sugars stimulate endorphine secretion which, as endogenous opioid, modulate physical and emotional pain. Endogenous opioids potentiate reward processes and motivate appetite, concurrently diminishing emotional responsiveness to noxious stimuli and thus giving the analgesic effect (³⁸). Hunger has the opposite effect. Pain threshold and tolerance are reduced in hypoglycaemia, therefore it is very important for patients not to skip meals (³⁹,⁴⁰). Fasting periods, through activity of hormone ghrelin, can influence brain mechanisms, which make high caloric foods subjectively attractive, and increases the overeating occurrence (²⁷,⁴⁰,⁴¹).

The very same aspects were achieved with the nutrition education we developed, proving the education to be suitable and effective. Even modest, positive effect of fewer meal skipping and lower consumption of foods with negative effect on chronic pain were found to independently contribute to decreased pain.

The most desired benefits in patients’ diet achieved after the education were higher consumption of high-fiber and nutrient dense foods such as fruits (e.g. raisins, prunes, peaches, and apples), vegetables (e.g. squash, broccoli, carrots, and celery), and whole grains. These changes have well documented contributing effect not only to prolonged satiety but also weight loss and contain precursors of endogenous opioids (³⁹-⁴¹). Fish should be consumed at least two times per week due to anti-inflammatory properties of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (¹²,⁴²), but the consumption remained low post-intervention. Intake of EPA and DHA is related to decrease concentration of CRP, proinflammatory eicosanoids, cytokines, chemokines and other inflammation biomarkers (¹⁴,²⁴,⁴²). Polyunsaturated fatty acids (PUFA) and phenolic fractions in extra-virgin olive oil also have strong anti-inflammatory properties (¹¹) highlighting why it is the preferred source of dietary fats (²⁴,³¹,³⁷). However, consumption of olive oil also remained unchanged post-intervention. These aspects (fish and olive oil consumption) need to be addressed more thoroughly through adaptation of the education. Sinergistic effects of all previously mentioned foods pose the strongest anti-inflammatory effect and more attention is needed on the ways how patients can introduce these foods into their daily diet to achieve the strongest analgesic effect.