VOL: 99, ISSUE: 37, PAGE NO: 28
Carolyn Middleton, BSc, RGN, is clinical nurse specialist, Pain Service, Nevill Hall Hospital, Gwent Healthcare NHS Trust
A noxious stimulus or pain is a stressor that can threaten homeostasis (a steady physiological state). The adaptive response to such a stress involves physiological changes that, in the initial stages, are useful and are also potentially life-saving.
Peripheral adaptation involves moving energy substrates from storage sites to the bloodstream to overcome the stressor. It also includes an analgesic response, a reflex escape response and a variety of other physiological changes mediated by the sympathetic nervous system (Johnson et al, 1992). However, if the stress response is allowed to continue, a variety of harmful effects may ensue that involve multiple systems of the body and are potentially life-threatening.
Transmission of pain
The initial physiological changes that take place within the body after a painful episode are concerned with the transmission of pain. The four basic principles that are involved are:
- Transduction: this process involves changing a noxious stimulus in the sensory nerve endings into a nerve impulse. Nociceptors (primary afferent neurones) are nerve endings with the capacity to distinguish between noxious and innocuous stimuli. When they are exposed to noxious stimuli, a number of substances, including prostaglandins, bradykinin, serotonin, substance P and histamine, are released that facilitate the movement of the pain impulse from the periphery to the spinal cord;
- Transmission: the movement of impulses from the site of transduction to the brain. Transmission occurs in three stages: from the nociceptor fibres to the spinal cord, from the spinal cord to the brain stem and thalamus, and finally from the thalamus to the cortex. For the pain stimulus to be changed to an impulse and move from the periphery to the spinal cord, an action potential must be created; that is, the movement of sodium and potassium ions from the extracellular fluid to the intracellular fluid, and vice versa. Transmission occurs in C fibres and A delta fibres and neurotransmitters are needed at each synapse to continue the pain impulse across the synaptic cleft;
- Perception: the process involved in recognising, defining and responding to pain. It is a result of neural activity and is where pain becomes a conscious experience. Perception takes place predominantly in the cortex, but the limbic system and reticular systems are also involved;
- Modulation: this involves the activation of descending pathways that exert inhibitory effects on pain transmission. Descending fibres release substances such as endogenous opioids, serotonin, noradrenaline, gamma-aminobutyric acid, and neurotensin that have the capacity to inhibit the transmission of noxious stimuli and produce analgesia (McCaffery and Pasero, 1999).
The stress response includes the production of naturally occurring endogenous opioids, which are also known as encephalins and endorphins. They are found throughout the central nervous system and bind to opioid receptor sites. These substances prevent the release of neurotransmitters such as substance P and, therefore, inhibit the transmission of pain impulses, bringing about an analgesic effect. Unfortunately endogenous opioids degrade too quickly to be considered as useful analgesics (McCaffery and Pasero, 1999).
Reflex escape response
Activation of the sympathetic nervous system during an episode of acute pain is known as the ‘fight or flight’ response. The physiological responses that take place via the sympathetic nervous system and the neuro-endocrine system are numerous and intrinsically linked.
Sympathetic nervous system
The sympathetic nervous system consists of a double chain of ganglia in front of the vertebral column in the cervical, thoracic and lumbar regions, giving rise to nerves supplying the internal organs. This system is involved in the immediate bodily response to emergencies, such as severe, acute pain.
Although the initial effects of the sympathetic nervous system allow survival of an individual, prolonged activation can be detrimental (Marieb, 2000).
The sympathetic nervous system is particularly concerned with the regulation of vascular tone, blood flow and blood pressure because sympathetic nerves have a stimulating effect on the heart to improve circulation. It also has a stimulating effect on the respiratory system by causing dilation of the bronchioles to increase oxygen intake (Ganong, 1995).
The sympathetic nervous system has an inhibiting effect on digestion by reducing or preventing the secretion of digestive enzymes throughout the alimentary canal and inhibiting peristaltic action in the gut wall. It achieves all of these physiological responses via the endocrine system and an increase in hormone production (Ganong, 1995).
The endocrine system comprises the pancreas; thalamus; hypothalamus; kidneys; pituitary, thyroid, parathyroid, pineal and adrenal glands; and the ovaries and testes. Its principal function is to maintain internal homeostasis despite changes in the environment.
The endocrine and nervous systems work in conjunction with each other to achieve this metabolic regulation (Vander et al, 1994). Multiple hormones cooperate to bring about appropriate biochemical and physiological responses to noxious stimuli such as pain.
These stimuli activate a coordinated neuroendocrine stress response by increasing levels of certain hormones, including adrenocorticotrophic hormone (ACTH), catcholamines, antidiuretic hormone (ADH), angiotensin and glucagon. The hormones are secreted directly from the endocrine organs into the bloodstream (Fig 1).
Corticotrophin-releasing hormone (CRH) is released, as a result of stimulation by noradrenaline, and transported to the anterior pituitary gland where it activates the sympathetic nervous system and stimulates ACTH biosynthesis. CRH increases blood pressure and heart rate and also produces behavioural responses to stress. Cardiovascular responses are also controlled by CRH signals (Marieb, 2000).
The release of CRH from the hypothalamus into the systemic circulatory system stimulates the secretion of ACTH in the anterior pituitary gland. Increased levels of ACTH activate the sympathetic nervous system. However, the main function of CRH is to regulate the endocrine activity of the cortex portion of the adrenal gland so as to stimulate cortisol production and increase the levels of circulating glucocorticoids (Johnson et al, 1992).
Cortisol is the principal glucocorticoid that promotes normal cell metabolism. It is produced and released by the adrenal cortex in response to rising blood levels of ACTH. An increased plasma concentration of adrenal corticosteroids is the major regulator of an adaptive response to stress that, in the short term, is beneficial.
However, in the long term it is disruptive and harmful. It has a widespread effect on most organs and is particularly involved in the coordination of the actions of catecholamines.
Cortisol also has the function of maintaining blood glucose levels and energy metabolism during periods of stress. It suppresses the inflammatory response by inhibiting prostaglandin activity and has an adverse effect on the immune system. Glucocorticoids are also thought to prevent other stress-induced changes from becoming excessive (Marieb, 2000).
Adrenaline and noradrenaline
These are both catecholamines released from the adrenal medulla when it is stimulated by the sympathetic nervous system during the stress response. The adrenal medulla is not essential for life but contributes to the stress situation by secreting catecholamines, which act directly on blood vessels, causing vasoconstriction. Blood pressure then rises to allow better perfusion of vital organs, and cardiac output also increases. In addition, adrenaline and noradrenaline dilate the small passageways of the lungs to increase oxygenation (Vander et al, 1994).
Adrenaline has an effect on metabolism and has a role in the inhibition of insulin release. It also causes an increased glycogenolysis in the liver (Thomas, 1998). Finally, heightened emotional awareness occurs with increased adrenaline levels.
Glucagon is a polypeptide produced by the pancreatic islets in the upper gastrointestinal tract. The stress response causes glucagon levels to increase, so elevating the metabolic rate and lowering insulin levels. The result is hyperglycaemia and impaired glucose tolerance, together with carbohydrate, protein and fat destruction (Park et al, 2002). An increase in glucagon and catecholamines stimulates glycogenolysis and the release of glucose from the liver into the circulation for immediate use by critical organs, such as the brain.
Vasopressin or ADH
This hormone is released from the posterior pituitary gland. Its function is to excrete water via the kidneys. During the stress response it causes sodium and water to be retained by the renal tubules and stored in the extracellular fluid (Thomas, 1998). It also has a role in controlling blood pressure.
Renin and angiotensin II
Renin is an acid protease enzyme secreted by the kidneys into the bloodstream. Its major function is the stimulation and release of aldosterone from the adrenal gland, promoting sodium re-absorption by the kidney. Renin secretion is increased by sympathetic activity and is mediated by increased circulating catecholamines (Fig 2). Renin is also involved in the conversion of enzymes to form angiotensin II, which causes generalised arteriole constriction resulting in hypertension.
Growth hormone is secreted by the anterior pituitary gland and has a direct action on cellular activity and the metabolism of protein, carbohydrate and fat. Increased protein breakdown leads to a negative nitrogen balance, resulting in reduced wound healing (Marieb, 2000).
Following tissue damage, interleukin 1 (IL-1) is released from the hypothalamus and its effects are widespread, including activation of the inflammatory effects of the immune system. IL-1 interacts with the hypothalamic pituitary adrenal axis at two levels. First, it acts in the hypothalamus to induce the production of corticotrophin-releasing factor, which mediates ACTH release. Second, IL-1 acts directly with the adrenal cortex. Both of these events lead to the release of anti-inflammatory glucocorticoids such as cortisol (Vander et al, 1994).
Effects of physiological changes
The physiological changes described above have an impact on the cardiovascular, gastrointestinal, respiratory, genitourinary, musculoskeletal and immune systems. Increased heart and breathing rates facilitate the increasing demands of oxygen and other nutrients to vital organs (O’Hara, 1996). The physiological changes that take place can also induce vomiting and potentially can pre-empt chronic pain conditions. Psychological and cognitive adverse effects are also relatively common.
The cardiovascular system responds to the stress of unrelieved pain by increasing sympathetic nervous system activity which, in turn, increases heart rate, blood pressure and peripheral vascular resistance. As the workload and stress of the heart increase, owing to hypertension and tachycardia, the oxygen consumption of the myocardium also increases. When oxygen consumption is greater than oxygen supply, myocardial ischaemia and, potentially, myocardial infarction, occur. The myocardial oxygen supply may be further compromised by the presence of any pre-existing cardiac or respiratory disease or by hypoxaemia due to impaired respiratory function (Macintyre and Ready, 2001).
Hypercoagulation occurs when there is a reduction in fibrinolysis together with an increased cardiac rate, workload and blood pressure. This activity increases the risk of deep vein thrombosis (DVT) and pulmonary embolism (Wood, 2003).
Increased sympathetic nervous system activity can lead to temporarily impaired gastrointestinal function. This can include delays in gastric emptying and reduced bowel motility with the potential for the development of paralytic ileus (Macintyre and Ready, 2001).
Unrelieved pain can result in a patient limiting the movement of the thoracic and abdominal muscles in a bid to reduce pain. This may cause some degree of respiratory dysfunction with secretions and sputum being retained because of a reluctance to cough. Atelectasis and pneumonia may follow (Macintyre and Ready, 2001). This pulmonary dysfunction, caused by painful excursion of the diaphragmatic muscles of the chest wall, is also associated with a reduction in vital lung capacity, increased inspiratory and expiratory pressures and reduced alveolar ventilation. The resulting hypoxia can cause cardiac complications, disorientation and confusion and delayed wound healing (Wood, 2003).
Unrelieved pain can increase the release of hormones and enzymes, such as catecholamines, aldosterone, ADH, cortisol, angiotensin II and prostaglandins, which help to regulate urinary output, fluid and electrolyte balance as well as blood volume and pressure (McCaffery and Pasero, 1999). This causes retention of sodium and water, resulting in urinary retention. Increased excretion of potassium causes hypokalaemia (Park et al, 2002). A decrease in extracellular fluid occurs as fluid moves to intracellular compartments, causing fluid overload, increased cardiac workload and hypertension (McCaffery and Pasero, 1999).
Involuntary responses to noxious stimuli can cause reflex muscle spasm at the site of tissue damage (McCaffery and Pasero, 1999). Impaired muscle function and muscle fatigue can also lead to immobility, causing venous stasis, increased blood coagulability and, therefore, an increased risk of developing DVT (Park et al, 2002).
Pain can limit thoracic and abdominal muscle movement in an attempt to reduce muscle pain, a phenomenon known as ‘splinting’. The lack of respiratory muscle excursion can potentially lead to reduced respiratory function (McCaffery and Pasero, 1999).
Depression of the immune system can be caused by unrelieved pain. This may predispose the patient to wound infection, chest infection, pneumonia and, ultimately, sepsis (Wood, 2003).
Psychological and cognitive effects
Anxiety and pain are positively correlated (Johnson et al, 1992). Individuals who express unusually high levels of anxiety also tend to have a higher than expected incidence of early noxious stress. The acute stress-induced hormonal changes that have been described in this article closely resemble the symptom complex of anxiety and depression and, finally, hypercortisolism, which is a consistent feature of anxiety physiology (Johnson et al, 1992). Therefore, the stressor effects of unrelieved pain have the potential to increase anxiety levels further and interfere with activities of daily living, such as diet, exercise, work or leisure activities and to interrupt normal sleep patterns causing varying degrees of insomnia (Macintyre and Ready, 2001).
Unrelieved pain can also result in an individual experiencing distressing cognitive impairment, such as disorientation, mental confusion and a reduced ability to concentrate (Wood, 2003).
Nausea and vomiting
When pain receptors in the central nervous system are stimulated, the true vomit centre in the brain is activated, causing vomiting to occur. Disturbance of the gastrointestinal tract can activate the release of the neurotransmitter 5-hydroxytryptamine (5-HT3), which can also initiate vomiting. Initially, 5HT3 travels via the circulatory system to the chemoreceptor trigger zone in the brainstem and on to the true vomit centre, again initiating vomiting (Jolley, 2001).
Poorly controlled acute pain can lead to debilitating chronic pain syndromes. Appropriate aggressive acute pain management is essential to prevent this from occurring (McCaffery and Pasero, 1999).
Unrelieved pain has serious side-effects, therefore the containment of such a stressor is vital. The chronic activation of the catabolic process of the stress response can ultimately cause multiple system dysfunction (Johnson et al, 1992).
Good acute pain management, including an expert knowledge of analgesic drugs and an understanding of the physiological effects of pain, is an essential element of holistic nursing care.