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Introduction
Pain is a multidimensional, complex phenomenon requiring effective assessment and interventions. Because pain is
complex and multidimensional, it is difficult to define. The effective management of patients’ pain requires the
involvement and interaction of the interdisciplinary team. The nurse is a key player who has frequent contact with
patients and as such is in a unique position to identify, assess, initiate actions to alleviate pain, and evaluate the
effectiveness of the actions taken to relieve pain.
Learning Objectives
1. Define pain.
2. Discuss the neurophysiology of pain modulation.
3. Describe acute pain.
4. Differentiate between the three types of acute pain.
5. Identify the adverse effects of pain.
6. Discuss the principles of pain management.
7. Differentiate the various modalities of pain management.
8. To analyze the effects of pain in special populations.
Definition
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The precise mechanisms of pain perception and transmission in the central nervous system have not been
determined. However, serotonin and norepinephrine , monoamine neurotransmitters, are cited as being involved in
the modulation of pain (Marks et al., 2009). As serotonin is also a chemical modulator of depression, it is common
to find depression and pain as comorbid conditions and antidepressants may be used for the management of pain.
Pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or
described as in terms of such damage” (IASP) or as McCaffery (1979) describes it as “whatever the experiencing
patient says it is and existing whenever the person says it is” (p. 11) .
Pain is a symptom not a condition (Lemone, Burke, & Bauldoff, 2011). There is no predictable relationship between
the identifiable tissue injury and the sensation of pain. Often the patient’s description of pain may be
disproportionate to the evidence of tissue damage. Pain is a highly personal and subjective experience and self-
report of pain is the single most reliable indicator of pain. Pain not only is sensory but may also be associated with
affective and cognitive changes.
Four distinct processes, all of which operate simultaneously and are required for pain to occur, are widely believed
to determine the perception of and response to pain (McCaffery & Pasero, 1999).
1. The first process, transduction, happens when a noxious, painful or tissue-damaging stimulus affects a
peripheral sensory nerve ending, depolarizing it and generating the initial electrical impulse (McCaffery & Pasero).
This starts in the periphery (skin, subcutaneous tissue, somatic structures) where primary afferent neurons
(nociceptors) are scattered. A nociceptor is a free nerve ending preferentially sensitive to a noxious or potentially
noxious chemical, mechanical, or thermal stimulus. A mechanical, thermal, or chemical noxious stimuli, tissue
damage or potential damage occurs that causes the release of numerous chemicals (prostaglandins, bradykinin,
serotonin, substance P, histamine, leukotrienes).
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An action potential must be must be created for pain stimulus to become an impulse. The intracellular surface of the
neuron carries a negative charge compared to the positive charge of the extracellular surface (called resting
membrane potential). With pain transmission, enough noxious stimuli cause the receptor membrane to become
permeable to Na+ ions and cause ions to rush into cell, creating a temporary positive charge relative to outside
(called depolarization). Potassium leaves the cell causing repolarization. “If enough depolarization and repolarization
occurs the action potential is created and the stimulus is converted to an impulse” (McCaffery & Pasero, p. 18).
Transduction takes milliseconds to occur with the impulse ready to be transmitted along nociceptor fibres that
extend along nociceptor cell body.
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2. The next process, transmission, involves the subsequent impulses that extend throughout the sensory nervous
system to the brain. The spinothalamic tract is the most important pathway for transmission. Nociceptors terminate
in the dorsal horn of the spinal cord. This is where neurotransmitters glutamate and substance P continue the pain
impulse across the synaptic cleft between nociceptors and dorsal horn neurons. From the dorsal horn, numerous
different ascending fibre tracts within the larger spinothalamic tract transmit pain. These originate in the spinal cord
and terminate in brain stem and thalamic regions.
Nociceptor fibres responsible for transmission of pain from the site of transduction to the spinal cord are: (a) C fibres
(sensitive to mechanical, thermal, and chemical stimuli) unmyelinated, small-diameter, slow-conducting fibres
transmitting poorly localized, dull and aching pain and (b) A-delta fibres (sensitive to mechanical and thermal
stimuli), sparsely myelinated, large-diameter, fast-conducting, transmitting well-localized, sharp, cutting, or stabbing
pain. A-delta fibres also result in activation of the sympathetic nervous system (fight or flight response) allowing the
individual to react; however, this response is time-limited (Keck & Baker, 2001).
3. Perception, the third process, is less an actual physiological event than a subjective phenonemon of pain (how it
feels) that encompasses complex behavioural, psychological and emotional factors. Pain always carries
unpleasantness and desire to escape. Exact location pain is perceived is unclear as are individual differences in
subjective experience of pain. It is thought that the reticular system is responsible for autonomic response to pain
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and for warning individual to attend to it. The somatosensory cortex localizes and characterizes pain. The limbic
system is responsible for emotional and behavioural response (McCaffery & Pasero). It is thought that pain
perception occurs in cortical structures. This is why cognitive-behavioural strategies can be applied to reduce the
sensory and affective components of pain.
4. Modulation, the fourth process, is a neural activity that controls pain transmission to neurons in both the
peripheral and central nervous systems. The pathways involved are referred to as the descending pain system
because of the neurons that originate in the brain stem and descend to distal horn of spinal cord. These descending
fibres release substances (endogenous opiods, serotonin (5HT), norephinephrine (NE), g-aminobutyric acid
(GABA), neurotensin) that have the ability to inhibit the transmission of noxious stimuli and produce analgesia
(McCaffery & Pasero). Endogenous pain modulation helps to explain the wide variations in perception of pain seen
from one person to another. Endogenous opioids (enkephalins and endorphins) are found throughout the CNS and
play an important role in basic survival mechanisms. Much like exogenous opioids, endogenous opioids bind to
opioid receptor sites and prevent the release of neurotransmitters (like substance P) and inhibit the transmission of
pain impulses. However, they usually break down too quickly to be useful as analgesics (McCaffery & Pasero).
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Diagrams originally printed in McCaffery, M. & Pasero, C. (1999): Pain: Clinical manual (p. 21). Toronto, ON: Mosby.
Reproduced with permission.
It is the somatosensory system that transmits signals about touch, temperature, pressure, pain, movement,
vibration, and body position (Gleveckas-Martens, 2011). This system is organized segmentally into dermatomes.
Each segment is supplied by a single dorsal root ganglion that contains the neuronal cell bodies for the sensory
units of the segment. Remember that the nerve fibres overlap between the dermatomes, boundaries of pain may not
always be as well-defined as the dermatome diagrams indicate. For more specific details on the somatosensory
system: http://emedicine.meds cape.com/article/1948621
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http://images.devilfinder.com/go.php?q=dermatomes
Acute pain is of sudden onset, often sharp in quality, is self-limited and localized. The cause can be identified. Acute
pain persists for less than 6 months, and disappears when the underlying cause of pain has been treated or has
healed. Unrelieved acute pain can result in persistent pain.
Acute pain is a response by the sympathetic nervous system to actual or potential injury. The flight-or-flight
response (catecholamine release) to a stressor results in tachycardia, rapid, shallow respirations, elevated blood
pressure, dilated pupils, sweating, and pallor. Acute pain may be accompanied by nausea and vomiting. Anxiety and
fear may also occur and potentiate the physical response to pain.
Activity
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Source: B. Swart
Pain Management
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Source: B. Swart
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World Health Organization Analgesic Ladder for Acute Pain Management (adapted from WHO)
Source: B. Swart
Nonopioid Analgesics
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The most common nonopioids are aspirin, other nonsteroidal antiinflammatories (NSAIDs), and acetaminophen.
Source: B. Swart
Opioid Analgesics
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Prescription opioid analgesics with morphine-like actions are generally considered the treatment of choice in
moderate to severe pain. It is well established that opioids administered routinely for the temporary relief of severe
pain are more effective when administered before pain starts (preemptive analgesia) or before it becomes severe. In
general, this management results in less drug dosages and individuals can resume activity sooner (Litwack, 2010).
Opioids interact with three types of opioid receptors: mu (µ for morphine), delta (б), and kappa (Κ). Mu receptors
modulate the therapeutic effect of analgesia, as well as the adverse effects of respiratory depression, miosis,
reduced gastrointestinal motility resulting in constipation, feelings of euphoria, and physical dependence.
Opioid Receptors
Source: Wyeth
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The mu receptors are found at pre- and postsynaptic sites in the dorsal horn, in the “ascending pathways of the
brain stem, thalamus, and cortex, and the descending inhibitory system that modulates pain at the spinal cord”
(Litwack, 2010, p. 1197). Opioids injected directly into the epidural space cause segmental or selective spinally
mediated analgesia by binding to opioid receptors in the dorsal horn of the spinal cord. Regional anesthesia such as
this reduces respiratory depression, nausea and vomiting, and sedation that occurs with systemically administered
drugs. The lipophilic (lipid soluble) property of an opioid determines its effectiveness when introduced into the
epidural space. Opioids with low lipid solubility (e.g., hydrophilic opioids) such as hydrocondone and oxycodone,
have a slow onset of action and a long duration of action. Opioids with high lipid solubility (e.g., lipophilic opioids)
such as fentanyl citrate, have a quick onset of action but a short duration of action (Bennett, 2012). Common opioids
include codeine, hydromorphone, morphine, fentanyl, oxycodone. Note: Fentanyl patches are not used for acute
pain. Patients who use fentanyl patches need to be opioid tolerant (e.g., taking opioids regularly for 2 weeks prior to
initiating the patch). As well, it can take up to 48 hours for an effective analgesic blood level to be established
(D’Arcy, 2010). Also, oxycodone controlled release (long acting) tablet was withdrawn from the Canadian market in
2012. A new formulation called OxyNeo is supposed more tamper-resistant as the tablet is more difficult to crush
and if it is crushed and added to water, a gel-like substance is the result (Minnistry of Health and Long Term Care,
2012).
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PCA Pump Configured for Administration of Fentanyl Citrate and Bupivacaine Hydrochloride
Source: Wikipedia Commons
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Adjuvant Analgesics
Adjuvant analgesics that intervene at different receptor sites include steroids, anxiolytics, antidepressants
(impiramine, amitriptyline, apo-doxepin), hypnotics, anticonvulsants (carbamazepine), antiepileptic-like
gabapentinoids (gabapentin and pregabalin), membrane stabilizers (e.g., valproate), sodium channel blockers (e.g.,
lidocaine), and N-methyl-D-aspartate receptor antagonists (e.g., ketamine for management of neuropathic pain).
Newer management strategies such as cannabinoids may be used in the future for acute pain management
although currently are used for chronic pain (Vargas-Schaffer, 2010).
Please note that some of the adjuvants are suitable only for persistent pain but they are mentioned here because of
their increasingly popularity in the management of pain.
Balanced analgesia or multimodal analgesia is the concept of multiple receptor occupancy leading to synergism,
which lowers the amount of each medication and, therefore, the overall adverse effect profile. The goal is to arrest
or retard formation of neuropathic circuits, to affect multiple components of the pain signalling, to reduce
inflammation, to decrease nociceptor input, and hopefully, to retard the formation of neuropathic signalling (Bennett,
2012).
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The Pain Pathway and Interventions That Can Modulate Activity At Each Point
Source: Kehlet, H. & Dahl, J. B. (1993). Anesthetic Analgesia. 77,1048-1056.
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Epidural pain management is recommended for patients with large surgeries such as thoracotomy, large abdominal
surgeries, multiple rib fractures, and labour and delivery. As interventional techniques have grown, the use of
epidural catheters has diminished. To use epidural analgesia, the catheter is placed into the epidural space at the
level of the surgery.
A needle is inserted into the epidural space, a potential space, filled with blood vessels, fat, and a network of nerve
extensions. Anything put in the epidural space basically goes up and down and around the site. Approximately 90%
is absorbed by the vasculature within the epidural space. Often a combination of an opioid and a local anesthetic
(e.g., hydromorphone (Dilaudid) 0.015mg/mL and bupivacaine 0.1% (Marcaine) on continuous dose may be used.
The catheter is placed as close as possible to the dermatones that when blocked produce the most effective spread
of analgesia for the site of nociceptive input.
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Spinal nerves are named for the vertebral interspace at their point of exit, usually referred to by letters and numbers
(e.g., L23 for the space between the second and third lumber vertebra). Each dermatome represents a specific
region of spinal nerve reception of sensory impulses. The dermatomes for each nerve root have been mapped out
for the human body. Because the dermatomes have been mapped out, a particular area of the body can be
anaesthetized depending on where the spinal nerves are blocked.
Intraoperative Blocks
Intraoperative blocks are used over the perioperative period. They can be used for shoulder surgery, joint
replacements, circumcision pain, and many different procedures. A local anesthetic is placed in the surgical or
procedural area and blocks the involved nerves. One disadvantage is that the effect of most blocks last for six to
eight hours postoperatively and patients expeience more pain once the effect of the block wears off (D’Arcy, 2012).
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Children
The nociceptor system is functional in a fetus at twenty to twenty-four weeks gestation despite minimal cortical
experience ((Lemone, Burke, & Bauldoff, 2011). “Pain pathways, cortical and subcortical centres, and
neurochemical responses associated with pain transmission are developed and functional by the last trimester of
pregnancy (Litwak, 2010). Also because infants and young children have a healthy inflammatory response, they
have an accentuated neural response (elevated pain sensation and pain-related anxiety and stress as well as a
decreased pain tolerance for months following the pain-producing event) than adults do (American Medical
Association, 2010).
Generally pain in infants and children can be managed by many of the same drugs as adults. Pain management,
however, should be reflective of age-related differences in physiological functioning. The majority of the major organ
systems are well developed at birth but the ability to function adequately is often delayed until approximately 3
months of age.
Remember that many topical anesthetics (e.g., the mixture of lidocaine/prilocaine (EMLA) for use on intact skin) are
available for pain relief before needle-stick procedures.
Think
What newborn physiology will have an effect on the pharmacology of opioids and
local anesthetics in infants and children?
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The areas of the nervous system are indicated where developmental changes and plasticity impact pain detection
and treatment in this group. (1) Peripheral innervation is vulnerable and sensitive to tissue injury. (2) Dorsal horn
sensory pathways undergo considerable postnatal reorganization. (3) Nociceptive reflex pathways are diffuse and
poorly tuned. (4) Primary hyperalgesia develops before secondary hyperalgesia. (5) Endogenous descending
controls via the brainstem are unbalanced. (6) Extensive cortical development begins postnatally, but little is known
of the development of intracortical network connections in infancy. (7) The somatosensory cortex is activated by
noxious stimulation from an early age, but little is known of activation in other cortical regions.
Source: Fitzgerald, M. & Walker, S. M. (2009). Infant pain management: A developmental
neurobiological approach. Nature Clinical Practice Neurology,5, 35-50.
doi:10.1038/ncpneuro0984
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Older Adults
As everyone knows, the percentage of older adults over the age of 65 is increasing. As many as 75% of
hospitalized adults (aged eighteen to sixty-four) experience moderate to severe pain at some point in their
hospitalization while 19% of older individuals admitted to the hospital have moderately or extremely severe pain
(International Association for the Study of Pain, 2006). Thus, accurate, comprehensive information on pain and its
management in adults of advanced age is essential. Older adults tend to have a higher pain threshold (reduced
sensitivity to mild pain); however, pain tolerance decreases with age because of degenerative changes in serotonin
and norepinephrine levels that may contribute to impaired descending inhibition and reduced pain tolerance. There
is also reduced efficacy of endogenous opioid analgesic systems. Age-related changes in the function of
nociceptive pathways that includes alterations in afferent transmission and descending modulation also exist.
Interesting, women experience more pain than men (Ruau, Liu, Clark, Angst, & Butte, 2012).
The body of knowledge on age differences in the phenomenology of the pain experience, age-appropriate pain
assessment tools, and controlled outcome studies of various pain management options in older adults has grown.
However, evidence-informed research is required to better inform about pain needs of the older adults.
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Those who are being treated for pain in the hospital, and are actively misusing substances, or those with a
substance misuse history need more analgesics than the average patient. They will also have more difficulty
achieving pain control.
It is useful to determine how much intravenous pain medication is needed via a PCA. This can facilitate medication
use over a 24-hour period, which can then be converted to oral medications. Those patients with an addiction are
tolerant to opioids and require high doses of medication frequently to manage pain (D’Arcy, 2012).
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Summary
Pain is a protective and complex phenomenon. Appropriate assessment using a variety of evidence-informed tools
is essential to adequate control of acute pain. An interdisciplinary approach to acute pain involving the use of
nonopioid analgesics, opioid analgesics, adjuvant medications as well as interventional techniques are essential.
References
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