Dr Dingle's Blog / pain
Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota has been shown to influence obesity and pain sensitivity.
Physiological pain plays a life-essential protective role, while acute or chronic pathological pain indicates a medical problem that needs treatment and imposes a medical challenge. Neurotransmitters, immune cells, and hormones have been demonstrated to contribute in pathogenesis of chronic pain.
Pain threshold is influenced by several factors, including obesity, which alters adipose tissue metabolic and endocrine functions leading to alterations in systemic physiology including an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. Studies have demonstrated that obese humans and rats are more sensitive to pain stimuli than normal weighted ones.
Previous studies have demonstrated a relationship between intestinal microbiota and diseases including pain disorders with probiotics having a positive effect.
In this study the mice taking probiotics had a significantly lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics.
Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870) on Mechanical Sensitivity in Diet-Induced Obesity Model
Sleep deprivation also contributes to the physiological state known as fatigue. A fatigued person is accident prone and judgment impaired. After approximately 20 hours of no sleep, reaction times are comparable to having a blood alcohol reading of .08. Staying awake for 24 hours leads to a reduced hand‑to‑eye coordination that is similar to having a blood alcohol content of 0.1. An example of a sleep deprivation accident occurred when a space shuttle mission was aborted 30 seconds before lift‑off because a technician who had worked several consecutive l2hr shifts accidentally released 18,000 pounds of liquid fuel just minutes before the scheduled flight. An investigation of the Challenger space shuttle disaster attributed ground crew fatigue as one of the factors contributing to the disaster. An incident such as this shows the seriousness of the situation and the potential loss of life through human related errors in technical fields. Even operating simple machinery such as forklifts can become extremely dangerous if the operators are not filly alert. Other examples of work related sleep deprivation include a flight which flew 100 miles out over the Pacific before controllers on the ground were able to wake the pilots up using chimes, piped into the cockpit audio. It is common practice for flight attendants to check in on pilots to ensure they do not fall asleep. The Exxon Valdez oil spill occurred on a ship with a crew that had had very little sleep, with the accident happening in the middle of the night.
45 to 80% of all nursing home residents suffer from chronic pain and this pain is strongly linked to insomnia (Dodla and Lyons, 2006). In Japan a survey conducted by Tanaka and Shirakawa (2004) found that one in five Japanese people suffer from insomnia, and within the elderly population one in three suffer, because of this the Japanese government increased the needs of insomnia patients at community health sites and names insomnia a refactory disease of the 21st centuary. A similar Honk Kong based study found 11.9% of Chinese people living in Honk Kong suffer from insomnia approximately three times a week and the females were 1.6 times more likely to show symptoms of insomnia than males (Li et a!. 2002).
Accidents, errors and Risk taking
Studies using card games have found that with little sleep, players get stuck in a strategic rut. Sleepy people keep taking risks, even though it’s obviously not working for them.
A study of musicians who practised a new song had improved in speed and accuracy compared with before a night’s sleep. a good night’s sleep can also improve motor performance.
In a study of 1891 male employees compared with those working 6-8 h day(-1) with good sleep characteristics, positive interactive effects for workplace injury were found between long work hours (>8-10 h day(-1) or >10 h day(-1) ) and short sleep duration (<6 h). This study suggests that long work hours coupled with poor sleep characteristics are synergistically associated with increased risk of workplace injury. Greater attention should be paid to manage/treat poor sleep and reduce excessive work hours to improve safety at the workplace (Nakata 2011).
A study looking at the effect of working “standard shifts” (that is, the traditionally accepted long, sleepless shifts) for hospital interns showed that the interns made 36 percent more serious medical errors during a standard work schedule compared to during an intervention schedule that eliminated extended work shifts. The errors included significantly more serious medication errors and 5.6 times as many serious diagnostic errors. As a consequence, the overall rates of serious medical errors were significantly higher during the standard schedule than during the intervention schedule (Landrigan, 2004). Fortunately, most serious medical errors were either intercepted by people who were awake and concentrating or did not result in clinically detectable harm to the patient. How does this affect you? It might be all right if you could always go into hospital at the beginning of the shift or be operated on only by doctors who had just started a shift.
One study found that interns who worked 24-hour shifts made 36 percent more medical errors than those working 16-hour shifts and five times the number of diagnostic errors, and were 61 percent more likely to accidentally cut themselves during procedures.
The study found that the rates of serious medical errors in two intensive care units “were lowered by eliminating extended work shifts and reducing the number of hours interns worked each week.” By asking interns to work less, the hospitals improved their performance.
A number of studies have highlighted the increased number of motor vehicle accidents associated with young adults driving fatigued. It’s conservatively estimated that at least 112 lives could be saved in Australia if fatigue and falling asleep at the wheel were eliminated.
Several studies have highlighted the increased number of motor vehicle accidents associated with young adults driving while fatigued. Fatigue is estimated to be responsible for 35 percent of road accidents. It’s conservatively estimated that at least 112 lives could be saved in Australia every year if fatigue and falling asleep at the wheel were eliminated. In the United States, the National Highway Traffic Safety Administration (NHTSA) reports that fatigue and sleep deprivation contribute to about 100,000 highway crashes each year, causing more than 1,500 deaths annually (Sullivan, 2003). At a grander level the 1989 Exxon Valdez oil spill off Alaska, the Challenger space shuttle disaster and the Chernobyl nuclear accident have each been attributed to human errors in which sleep deprivation played a role (Grunstein, 2000).
Obvious symptoms of sleep deprivation constant yawning and the tendency to doze off when not active for a while; for example, when watching television, Grogginess when waking in the morning Sleepy grogginess experienced all day long (sleep inertia) Poor concentration and mood changes (more irritable).
Some of the physical effects found from long term fatigue are heart disease, diabetes, high blood pressure, gastrointestinal disorders and depression (Workplace health and safety QLD, 2008). A study conducted by Andersen involving rats also showed sleep deprivation affects the expression of genes related to metabolic processes, response to stimulus and signalling pathways (Andersen et al, 2009).
Numerous studies have shown that even a little bit of sleep deprivation decreases efficiency and increases risk of disease, including cardiovascular disease, cancer and diabetes. Sleep deprivation has been shown to negatively affect endocrine (hormones) and metabolic functioning as well as nervous system balance (Nilsson, et al., 2004). Sleep deprivation is associated with an increased concentration of cortisol plus other indicators of increased stress such as elevations in pulse rate, body temperature and adrenaline secretion (Vgontzas, et al.,1999). Sleep deprivation also appears to increase blood concentrations of certain chemicals called cytokines and C-reactive proteins (Irwine, 2001 and Vgontzas, et al., 1998), indicating an inflammatory reaction. The effect of unremitting low-grade inflammation may be to damage the inner walls of the arteries, which sometimes leads to vessel narrowing, high blood pressure, stroke, and heart disease (Irwine, 2001). During truncated sleep, your heart might have to work harder, constricting blood vessels and increasing blood pressure even more, which could conceivably result in a heart attack or stroke (Martins, 2003).
Sleep is as important to the human body as food and water, but most of us don’t get enough sleep. Insufficient sleep or disruptions to the sleep contribute to adverse health effects. Numerous studies have also shown that even a little bit of sleep deprivation decreases efficiency and increases risk of disease, including cardiovascular disease.
Initial changes to cardiovascular system from insomnia include hypertension, which is a potent co‑morbidity for other cardiovascular diseases. Hypertension has been linked to reduced sleep duration, with the highest correlation shown under 6 hours sleep per night (Gottlieb et al. 2006). However, associations have also been made between sleep of over 9 hours per night and hypertension and obesity. Furthermore this has not been supported at all in some studies and PPI in one older North American population actually showed a reduced risk of hypertension (Phillips, BOková and Enrigh, 2009.).
A study of 71,617 female health professionals found that sleeping fewer than five hours per night was associated with a 39 percent increase in the risk of coronary heart disease; even six hours per night showed an increase of 18 percent compared to sleeping eight hours per night (Najib, et al., 2003). In an analysis of data on more than one million people, the levels of nearly all forms of death were two-and-a-half times higher for people who slept four hours or less compared to those who slept between seven and eight hours on average
A study of 71,617 female health professionals found that sleeping fewer than five hours per night was associated with a 39 percent increase in the risk of coronary heart disease; even six hours per night showed an increase of 18 percent compared to sleeping eight hours per night. In an analysis of data on more than one million people, the levels of nearly all forms of death were two-and-a-half times higher for people who slept four hours or less compared to those who slept between seven and eight hours on average
Experimentally, sleep deprivation has been shown to negatively affect glucose metabolism and to enhance factors associated with Type 2 diabetes (Nilsson, et al., 2004). Research has also shown that people who experience sleep disorders were as much as three times as likely to develop Type 2 diabetes (Kawakami, 2004). Subjects in one study demonstrated impaired glucose tolerance for ten days after four hours of sleep deprivation (Spiegel, et al.,1999). It is also found that sleep deprivation can play a role in obesity. Sleep deficits bring about physiologic changes in the hormonal signals that promote hunger and, perhaps thereby, obesity (Spiegel, et al., 2004). One study found that after two days of sleep curtailment the subjects had reduced levels of the fat-derived hormone leptin and increased levels of the stomach-derived hormone ghrelin. These hormones are responsible for regulating hunger and appetite (Spiegel, et al., 2004). These hormonal differences are likely to increase appetite, which could help explain the relative high BMI in short sleepers.
Part 5 and more coming
Inflammation is literally the body "on fire" and is a primary immune mechanism response of the body to a range of noxious stimuli. This can include infectious agents, such as bacteria or virus, oxidation or acidosis, damaged or diseased tissues; however, the inflammatory response can also occur in response to other external or internal cues 1. Inflammation is essentially the body’s first line of defence in common acute conditions 2.
The main function of inﬂammation is a short term response to resolve infection and to repair the damage in order to achieve homeostasis equilibrium balance back to the body. The ideal inﬂammatory response is therefore rapid and destructive, yet speciﬁc and very limited. The release of inflammatory mediators, predominantly from activated leukocytes that migrate into the target area and proteins called cytokines attack the threatening germ and repair damaged tissues. This is the reddening and swelling you see around any infected or injured area. most of us are familiar with: redness, heat, swelling, and pain associated with inflammation. These symptoms are created by the activity of immune cells working to break down injured and dying tissues so that new, healthy ones can replace them.
Unfortunately, we have created a situation in our lives where we now suffer from chronic low level inflammation over decades of our lives as a result of our unhealthy and unbalanced lifestyles and diet. Chronic inflammation is being shown to be involved in the onset and the development of most if not all chronic illness that are now at epidemic proportions in our society. These include atherosclerosis (damaged and blocked arteries), heart disease, stroke, obesity, neurodegenerative diseases, depression, Alzheimer’s, Parkinsons Disease, thyroid disorders, diabetes, asthma, autism, arthritis, celiac disease, eczema, psoriasis, Multiple Sclerosis, lupus, migraines, periodontal disease, sleep apnoea, chronic kidney failure and cancer. It is a long list but it is only the main ones I have mentioned.
Even though chronic inflammation in the body is hard to detect there are some common symptoms to look out for. These include the following:
Chronic pain in the joints and/ or muscles
Allergies or asthma
Elevated blood pressure
Fluctuations in blood sugar levels
Gut issues (constipation or diarrhoea)
To judge the level of inflammation in individuals, a number of markers have been identified that are directly associated with inflammatory processes 3.4.5. C‑reactive protein (CRP), interleukin‑6 (IL‑6), fibrinogen, and tumor necrosis factor‑alpha (TNF‑a) are the most common markers that the medical system uses, with CRP leading in terms of assessing risk. Each marker has a different role in the inflammatory process and the development of chronic illness and are also often linked to each other. For example, IL6 plays a central part in the inflammatory process and is known to be linked to the production of C-reactive protein (CRP) in the liver. CRP is commonly used to monitor inflammatory states as it is secreted by the liver in response to a variety of inflammation, trauma and infection and decreases rapidly with the resolution of the condition. If the person has high C reactive protein and does not have an infection of some sort, then they probably have chronic inflammation. It is like the body is trying to fight off an illness all the time rather than just short term acute situations. It becomes exhausting for the body and is also likely to result in some long term damage.
The inflammatory process is driven by the immune system in your body. Therefore, in order to reduce the incidence of disease you must reduce inflammation, and to reduce inflammation you must identify and eliminate the immune system trigger(s). The typical approach of allopathic medicine is to treat the symptoms of the disease itself or the immune system (immune-suppressive drugs) or inflammation (anti-inflammatory drugs) directly without addressing the underlying cause of the disease. But not dealing with the underlying causes. Sustainable health looks at identifying and eliminating the sources of the inflammation to address the situation at its cause. While I will leave much more of the detail to the next months edition some good examples of anti inflammatory nutrients include turmeric, probiotics, vitamin C and D and Magnesium. While physical activity, meditation and strategies to de-stress are all anti inflammatory. Get the idea.
Inflammation and Cardio Vascular Disease (CVD)
CVD is no longer considered a disorder of lipid (fat) accumulation or elevated cholesterol, but rather a disease process characterized by low-grade inflammation of the vascular (artery) lining and an inappropriate wound healing of the blood vessels 5. It is similar to a low-grade wound on your skin that does not heal, but it is on the inside. There is now extensive and rapidly growing evidence that inflammation, which is what you get with every wound, plays a critical role in all stages of CVD 6,7,8,9. That is why if you treat the cholesterol you are treating the symptoms, yet if you treat the inflammation you are treating the underlying cause of the disease. To highlight the direct link in one study weekly injections of the cytokine (inflammation protein) given to mice caused a 2.5 fold increase in atherosclerotic lesions, that is 250% 10.
Since half of all myocardial infarctions (heart attacks) occur in individuals that display normal plasma lipid (cholesterol) levels, using markers of inflammation is much more effective to detect those at risk of CVD before its onset 4,5,11. Atherosclerosis (arterial plaque build up also known as artheriosclerotic vascular disease or ASYD) is a chronic inflammatory disease occurring in the innermost layer of the artery, the intima, where it thickens resulting from a build up of plaque. An injury or oxidation (free radicals) activity damages the blood vessel lining and induces an inflammatory response resulting in the adhesion of platelets and build up of macrophages (a type of white blood cell that swallows and destroys damaged tissue and infectious agents) and white blood cells at the site of injury. The inflammatory response, is mediated by activated T cells, macrophages and mast cells and produces cytokines (chemical messengers). Modified (through oxidation or enzymes) low‑density lipoproteins in the arterial intima initiate an inflammatory response in the arterial wall that leads to a cascade of inflammatory responses. As arteries lose flexibility and lesions occur, IL‑6 increases leading to further inflammation.
Inflammation and cancer
The link between chronic inflammation and cancer has long been recognized since the 19th century German pathologist Rudolph Virchow first hypothesized that the origin of cancer was at sites of chronic inflammation. Now it seems that modern science has caught up with the observations of the 19th Century. Considerable advances in cancer research relates to the role of inflammation in the development of cancer. Research in 2003 demonstrated that there is a link between inflammation and tumour growth 12. In 2010 several piece of the puzzle came together when researchers reported they could definitively show that inflammation in the breast is key to the development and progression of breast cancer 13. In an earlier study, women with high levels of two markers of inflammation―C-reactive protein and serum amyloid A―were two to three times more likely to die early or have their cancer return than women with lower level 14.
Now there is a large body of evidence that chronic inflammation is involved in all stages of cancer development. Generally inflammatory white blood cells (leukocytes such as neutrophils; monocytes, macrophages and eosinophils) mediate the growth of inflammation associated cancer, although other cells including cancer cells are also involved 15,16. Animal testings provide strong evidence that chronic inflammation contributes to the promotion of cancer 15 and through suppression of the immune system it allows the outgrowth and proliferation of malignant cells 17. Inflammation affects the micro environment of the cancer; it increases malignant growth 17; may alter blood flow processes; and the cancers response to remedial substances and hormones 18.
There is now convincing evidence that carcinogenesis often evolves as a progressive series of highly specific cellular and molecular changes in response to induction of constitutive over-expression of COX-2, an enzyme responsive for inflammation, and the prostaglandin cascade in the ‘inflammation of cancer’. Molecular studies reveal that over expression of COX-2 is a prominent feature of virtually every form of cancer while the expression intensifies with stage at detection, cancer progression and metastasis. It appears that COX-2 expression is not only an early event in the genesis of cancer, but is required throughout the entire evolutionary process of cancer development
In support of this back in 2005 Prof. Houghton 19 and her colleagues found that an infection with Helicobacter felis (a bacterium related to infectious Helicobacter pylori in humans) which causes a large amount of inflammation leads to an influx of bone marrow-derived stem cells (BMDCs), as the body tries to repair the injury caused by the infection. They were able to show that this transformation of BMDCs is the event that actually sparks malignant tumors of the stomach. They showed that bone marrow-derived stem cells attempt to participate in repair but, under conditions of inflammation and oxidation, are unable to behave normally and instead progress towards cancer. BMDCs have other cancer-like properties, including: the capacity for unlimited growth and the ability to avoid apoptosis (programmed cell death) signals. These properties give them a significant growth advantage making them difficult to control once they have mutated. the BMDCs, depending on environmental cues for development and differentiation, encounter an abnormal environment of conflicting growth signals. There follows a downward spiral of metaplasia (the conversion of normal to abnormal tissue); dysplasia (emergence of a precancerous growth); and finally carcinoma (frankly malignant cancer, capable of metastasizing). It appears that cancers are just the body trying to adapt to a toxic internal environment of inflammation and oxidation.
Inflammation depression and mental health
Depression itself is not a disease, but a symptom of an underlying problem. A new theory called the “Immune Cytokine Model of Depression” holds that depression is not a disease itself, but instead a “multifaceted sign of chronic immune system activation”, inflammation. Instead depression may be a symptom of chronic inflammation. And a large body of research now suggests that depression is associated with a low-grade, chronic inflammatory response and is accompanied by increased oxidative stress. Not a serotonin imbalance.
Researchers discovered in the early 1980s that inflammatory cytokines produce a wide variety of psychiatric and neurological symptoms which perfectly mirror the defining characteristics of depression 20. Cytokines have been shown to access the brain and interact with virtually every mechanism known to be involved in depression 21 including neurotransmitter metabolism, neuroendocrine function, and neural plasticity.
This is now supported by increasing lines of scientific evidence 22 including:
- Depression is often present in acute, inflammatory illnesses.
- Higher levels of inflammation increase the risk of developing depression.
- Administering endotoxins that provoke inflammation to healthy people triggers classic depressive symptoms.
- One-quarter of patients who take interferon, a medication used to treat hepatitis C that causes significant inflammation, develop major depression.
- Up to 50% of patients who received the cytokine IFN-alpha therapy to help treat cancer or infectious diseases developed “clinically significant depression” 21.
- An experiment involving the administration of a Salmonella typhi vaccine to healthy individuals produced symptoms of fatigue, mental confusion, psychomotor slowing and a depressed mood 23. These symptoms correlated with the increase in cytokine concentrations.
- Remission of clinical depression is often associated with a normalization of inflammatory markers.
- There is now a large body of literature in laboratory animals demonstrating that cytokines … can lead to a host of behavioural changes overlapping with those found in depression. These behavioural changes include decreased activity, cognitive dysfunction and altered sleep 24.
- All the activities associated with reducing the prevalence of depression and depression symptoms are anti inflammatory. These include increased sunlight and time spent outside, exercise and physical activity, relaxation and meditation techniques, healthy eating as well as administering anti inflammatory nutritionals.
There is further support from large epidemiological studies. A number of longitudinal studies have now shown that inflammation in early adulthood predicts depression at a later stage in life. In a large longitudinal study the risk for depression and psychotic experiences in adolescence was almost 2-fold higher in individuals with the highest vs the lowest levels of of inflammation as indicated by interleukin-6 (IL-6) levels in childhood. Children who were in the top third of IL-6 levels at the age of 9 years were 55% more likely to be diagnosed with depression at the age of 18 than those with the lowest childhood levels of IL-6. Children in the highest tertile of IL-6 levels at the age of 9 were also 81% more likely to report psychotic experiences at the age of 18 25.
Perhaps this is a message that we need to start acting now and early with children to avoid the epidemic of inflammation and chronic illness including depression everyone is predicting for the future.
- Shelton and Miller: 2010
- Schwarzenberg and Sinaiko: 2006
- Taubes 2002
- Ridker et al. 1997
- Ridker et al. 2000
- Dixon et al. 2009
- Loppnow et al. 2008
- Packard and Libby 2008
- Sukhanov et al. 2007
- Tracy 2003
- Guigliano et al 2006
- Vakkila and Lotze
- Liu, et al. 2010
- Pierce, et al. 2009
- Schacter, 2002,
- Lin and Karin, 2007
- Bunt et at, 2006
- Chekhun, 2009
- 2004 Prof. Houghton et al
- Smith R Cytokines and Depression
- Miller et al, 2009,
- Berk et al 4
- Brydon et al, 2008
- Dantzer et al, 2008, p.48
- Khandaker et al, 2014