Severe Pain And Stroke: Is There A Link?

Chronic pain and heart disease are two health conditions that often occur as a result of the other. Research has shown that people with chronic pain may be more likely to have a heart attack or stroke than those without.

Chronic pain can put a strain on the heart and circulatory system, leading to severe cardiac episodes, stroke, or even death. It can also cause stress and anxiety, which can elevate blood pressure and pulse rate. On the other hand, heart disease can lead to chronic pain conditions, with inflammation, ischemia, and neuropathy causing pain symptoms.

Chronic low back pain, in particular, has been linked to an increased risk of stroke, with one study finding that patients with this condition were 20-30% more likely to experience a stroke. The increased risk was highest in patients under 50.

Chronic pain and stress

Stress can be defined as any type of change that causes physical, emotional, or psychological strain. The stress response is the physiological and biological response of the body to any situation causing such strains. The two main neural circuits through which our body adapts to stress are the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. These systems usually work in synchrony and influence each other through mutual, positive feedback loops.

The ANS converts physical and psychological stressors in the appropriate and situational stress response. It is activated by brainstem catecholaminergic neurons and efferent spinal cord neurons of the dorsal intermediolateral column, which converge in pre-ganglionic sympathetic neurons. These neurons synapse directly to chromaffin cells in the adrenal medulla, which secretes adrenaline and noradrenaline in the circulation. In addition, other pre-ganglionic neurons project to several post-ganglionic sympathetic neurons in paravertebral ganglia, using acetylcholine (ACh) as neurotransmitter. Consequent activation of nicotinic receptors on these post-ganglionic neurons results in noradrenaline secretion at the target tissue. Adrenaline and noradrenaline have diverse physiological functions, depending on the adrenergic receptor (AR) they bind to. The overall effect of α1- and α2-ARs activation is increased heart rate (HR) and blood pressure (BP), and decreased heart rate variability (HRV). Blood flow is increased to the skeletal muscles and decreased towards the abdominal organs, metabolic activity such as glycogenolysis in skeletal muscle and lipolysis in adipocytes are promoted to increase energy availability. On the contrary, β1- and β2-ARs stimulation foster vasodilation, decrease blood pressure and increase HRV, though can either increase or decrease HR.

The HPA axis provides a protracted response, yet its activation is delayed compared to the SNS. This response originates when the hypothalamus, the paraventricular nucleus (PVN) in particular, is triggered by stressors. The PVN releases several neurochemicals, such as oxytocin, vasopressin, and corticotrophin-releasing hormone (CRH). CRH reaches the anterior pituitary (adenohypophysis) and stimulates it to synthesise and secrete adrenocorticotrophic hormone (ACTH). ACTH, on its part, stimulates the cortex of the adrenal gland to produce and release glucocorticoids, mostly cortisol. Cortisol in turn also exerts an effect on the PVN and anterior pituitary, by limiting synaptic plasticity and suppressing neural excitability, thus creating a long and short negative feedback loop. Glucocorticoid secretion in humans follows a general ultradian and circadian rhythm with basal peak cortisol levels around weaking-up time. Cortisol exerts its functions through binding mineralocorticoid receptors (MR) or glucocorticoid receptors (GR), both ligand-activated transcription factors. These receptors are widely expressed throughout the body. Not surprisingly, cortisol affects several organs and systems. The HPA axis regulates blood pressure and vascular tone homeostasis, as well as raises blood glucose levels through gluconeogenesis in the liver during the stress response. Moreover, it is widely known that cortisol signalling in most immune cells generally leads to an immunosuppressive phenotype.

Both systems convert physical and psychological stressors in the appropriate and situational stress response and are vital for several, if not most, processes in body homeostasis. Dysregulations in these systems may lead to severe disorders, such as a dysfunctional stress response, i.e., stress intolerance. Both the SNS and the HPA axis have been found to be disturbed in several disorders, including chronic pain syndrome.

Chronic pain and insomnia

The mechanisms underpinning the pain-sleep relationship are not yet fully understood. However, it is thought that the disruption of sleep continuity, rather than sleep deprivation, impairs pain tolerance and increases pain perception. Depression and cognitive-behavioural factors may also mediate the association between sleep and pain.

The treatment of insomnia in people with chronic pain is often complicated by the fact that pain medications can themselves disrupt sleep. Opioids, for example, can prevent patients from entering deep sleep and cause sleep-related breathing disturbances.

Cognitive behavioural therapy for insomnia (CBT-I) is often used as a treatment for insomnia in people with chronic pain. CBT-I is a multi-component approach that targets various psychological mechanisms contributing to the persistence of insomnia. Treatment components may include stimulus control therapy, sleep restriction, relaxation training, paradoxical intention, biofeedback, cognitive therapy, sleep hygiene education and imagery training.

Chronic pain and depression

Chronic pain is defined as pain that lasts much longer than would be expected from the original problem or injury. It can lead to increased levels of stress hormones and a decrease in mental and physical performance. It can also disrupt sleep, causing fatigue and irritability during the day. The ongoing pain can make it difficult to interact with others and carry out daily tasks, leading to feelings of depression and, in some cases, even suicide.

According to the American Pain Foundation, about 32 million people in the US have experienced pain lasting longer than a year. Furthermore, between one-quarter and half of those who complain of pain to their doctors are depressed, and on average, 65% of depressed people complain of pain. People whose pain limits their independence are more likely to become depressed.

In addition to medication, physical activity can help to manage chronic pain and depression. Exercise releases brain chemicals that can improve mood and reduce pain. Cognitive therapy is also beneficial for both conditions, as it helps individuals to identify and change negative thought patterns associated with chronic pain and depression.

Chronic pain and obesity

Obesity involves various endocrine changes. Obesity can be considered to reflect systemic inflammation, which may contribute to pain. Enhanced reactivity of proinflammatory cytokines has been noted in obese people following surgery. In fibromyalgia women, CRP level was significantly correlated with BMI. A recent population-based study suggests that a high level of CRP adds a risk of having low back pain in obese people.

Obesity is usually defined by using weight and height to calculate “body mass index” (BMI). Normal weight status ranges from 18.5 kg/m2 to 24.9 kg/m2, and overweight status ranges from 25 kg/m2 to 29.9 kg/m2 of BMI. A BMI that is greater than 30 kg/m2 is considered to reflect obesity. The obese category is further subdivided into class I (30–34.9 kg/m2), class II (35–39.9 kg/m2), and class III (≥40 kg/m2). A BMI that is greater than 40 kg/m2 is considered as “morbid” obesity.

Obesity may also be a leading factor for needing surgical intervention for osteoarthritis patients. The relative risk of having total hip or knee replacement increases as BMI increases. Research suggests that obesity is not only a risk factor for osteoarthritis but also may complicate recovery from joint replacement surgery.

Obesity in chronic joint pain may also be related to greater consumption of analgesics. Obese patients were more likely to be taking strong opioids than normal-weight patients. Morbidly obese patients required 18% longer time for their total knee arthroplasty. Similarly, morbid obesity appears to be related to longer hospital stay and greater postsurgical complications.

Longitudinal studies also suggest that obesity may be a risk factor for developing chronic pain. A population-based study with over 30,000 people over 10+ years in Norway suggests that obese individuals, particularly those who are inactive, have a greater risk of developing chronic arm pain. A large population-based survey of over 25,450 people showed that a greater number of obese people at the baseline developed low back pain 11 years later compared to those who were not obese.

Obesity may also contribute to the chronicity of back injury. Evaluation of people with acute work-related back injury revealed that obesity was one of the factors associated with persistent pain 3 months later.

Conversely, weight gain may occur as a result of chronic pain. Chronic pain is one of the major reasons that obese patients list for their weight gain. Frustration associated with functional limitation may lead to overeating. Other common adverse effects of chronic pain, such as sedentary lifestyle, poor sleep, and side effects of medications, may also contribute to weight gain in chronic pain patients.

Obesity is known to have various adverse impacts on people’s functional capacity and quality of life in general. When obesity co-occurs with chronic pain, obesity may have further health consequences for chronic pain patients. Several studies have shown reduced life expectancy for individuals with chronic pain, mostly due to cardiovascular disease. Although the exact mechanism underlying the increased mortality in chronic pain patients is not known, it has been suggested that metabolic syndrome is common in chronic pain patients, and that it may lead to compromised cardiac health. Overall, research suggests that obesity makes chronic pain more problematic in general. Obesity is related to greater physical disability and psychological distress in chronic pain patients.

Obese patients exhibit higher heart rate while exercising under a comparable workload relative to non-obese patients. Obesity is considered a major barrier to successful physical rehabilitation. This suggests that obese patients may find an activating therapy more exerting and difficult, and consequently, this may impact their willingness to comply with an activation therapy. Conversely, weight management for pain patients may be complicated by the presence of chronic pain and fatigue. Comorbidity of pain and obesity often leads to a vicious cycle of pain–inactivity–obesity.

The literature suggests that the two conditions are significant comorbidities, adversely impacting each other. The nature of the relationship, however, is not likely to be direct, but many interacting factors appear to contribute. Weight loss for obese pain patients appears to be an important aspect of overall pain rehabilitation, although more efforts are needed to determine strategies to maintain long-term benefit.

Chronic pain and medication

Chronic pain is a type of pain that lasts for three months or more. It can be caused by spinal disorders, arthritis, headaches, and other conditions. Treatment of chronic pain usually involves a combination of medication and therapy.

Medications used for chronic pain include pain relievers, antidepressants, and anticonvulsants. Different types of medicines are used depending on the type of pain. For instance, short-acting medicines are used for pain that comes and goes, while long-acting medicines are used for constant pain.

• Acetaminophen (e.g. Tylenol): Helps with many kinds of chronic pain. Can be found in prescription and over-the-counter pain medicines. May cause liver damage if taken in excess, especially with alcohol.
• Non-steroidal Anti-Inflammatory Drugs (NSAIDs): Examples include ibuprofen (Advil), diclofenac (Cataflam), naproxen (Aleve), and celecoxib (Celebrex). Can be taken occasionally or regularly. May cause stomach issues, kidney damage, and interfere with blood pressure medicines.
• Antidepressants (e.g. amitriptyline, nortriptyline, duloxetine): Can improve function and provide pain relief for nerve damage, arthritis, fibromyalgia, headaches, and back pain. Can also improve sleep and induce relaxation. Need to be taken daily, even on pain-free days. May cause insomnia.
• Gabapentinoids (e.g. gabapentin, pregabalin): Effective for nerve pain caused by various conditions. Work by reducing nerve activity in irritated or damaged nerves. Need to be taken consistently every day.
• Opioids (e.g. codeine, tramadol, hydrocodone, morphine, oxycodone, fentanyl): Reserved for moderate-to-severe acute pain or chronic pain due to cancer. May cause constipation, nausea, dizziness, and sleepiness. Long-term use can lead to dependency and addiction.

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