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Multiple Choice Questions
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7.1. A 54-year-old woman presents to the emergency department
with fevers and a sore throat. She has recently been diagnosed
with left-sided breast cancer and associated axillary lymph
node disease. Twelve days ago she received her rst cycle of
neoadjuvant cytotoxic chemotherapy (5-uorouracil, epirubicin
and cyclophosphamide). On clinical examination her temperature
is 38.3°C, she appears dehydrated and there is evidence of
oral candidiasis. An intravenous catheter is placed and bloods,
including blood cultures, taken. What is the most appropriate next
step in this patient’s care?
A. Start oral uconazole
B. Await blood test results to inform further management
C. Start intravenous uids
D. Perform a chest X-ray, collect a urine sample and throat
swab to complete the infection screen
E. Start high-dose broad-spectrum intravenous antibiotic
therapy immediately
Answer: E.
The clinical features here are of fever in a patient at high risk of neutropenia. This is an oncological emergency. Patients are at risk of neutropenia at any point during their systemic anti-cancer therapy treatment
cycle, with the highest risk typically 10–14 days after a treatment. In
patients with potential neutropenic sepsis high-dose broad spectrum
intravenous antibiotics should be commenced, ideally within 1 hour of
admission, without awaiting test results. In this patient uconazole (A)
for oral candidiasis, intravenous uids (C) and further tests (D) are also
appropriate, but should not delay the rst dose of antibiotic therapy.
Test results may later inform changes to antimicrobial therapy and its
duration.
7.3. A 59-year-old woman is seen in the emergency department with
a 2-day history of severe diarrhoea. She has had 10 loose stools
today, the most recent of which have been bloody and associated
with crampy abdominal pain. Her past medical history includes
metastatic melanoma and she had her fourth cycle of ipilimumab
and nivolumab therapy 20 days ago. At the time of her treatment she
was constipated and the outpatient systemic anti-cancer therapy unit
doctor prescribed her a macrogol laxative. She notes that the evening
prior to the diarrhoea starting she had reheated some leftover rice for
her supper. What is the most important likely diagnosis?
A. Bacillus cereus -associated food poisoning
B. Overow diarrhoea
C. Laxative overuse
D. Immunotherapy-related colitis
E. Clostridioides difcile infection
Answer: D.
Immune-related adverse events should be considered in all patients
who present acutely unwell following immunotherapy treatments for
cancer. Although the other options are on the differential diagnosis list,
severe IRAEs are oncological emergencies and prompt recognition and
management are vital. This is a grade 3 colitis and should be treated
with IV methylprednisolone in the rst instance. Investigations such as
bloods, stool sample, radiological imaging and exible sigmoidoscopy or
colonoscopy are also appropriate.
7.4. A 58-year-old man is seen in clinic with a diagnosis of metastatic
lung cancer. He is coping well at home, where he lives alone.
However, he has taken early retirement as a brick-layer as he feels
unable to work due to increasing fatigue. He awakes early each
morning and goes to the shops to collect his newspaper, but has
taken to napping for an hour in the afternoon. What is this man’s
ECOG performance status?
7.2. A 61-year-old man recently diagnosed with colon cancer and
associated liver and lung metastases is seen in the oncology
clinic. He is keen to talk about treatment for his cancer. His ECOG
performance status is 1 and he has no signicant comorbidities.
He has some mild symptoms of abdominal discomfort and has
lost 5 kg in weight. His routine bloods demonstrate anaemia
(Hb105 g/L) and mild elevations in his liver enzymes. A biopsy of
his tumour has shown a moderately differentiated adenocarcinoma
which is KRAS/NRAS wildtype and BRAF mutant. What is the
most appropriate treatment option for this patient?
A. Cytotoxic chemotherapy (5-uorouracil, folinic acid and
oxaliplatin) alone
B. Surgery to all cancer sites
C. Cytotoxic chemotherapy (5-uorouracil, folinic acid and
oxaliplatin) with an EGFR inhibitor (cetuximab)
D. Cytotoxic chemotherapy (5-uorouracil, folinic acid and
oxaliplatin) with a BRAF inhibitor (dabrafenib)
E. Refer to palliative care
Answer: A.
This man wishes to pursue anti-cancer therapy and, from the information provided, appears t to do so. In patients with metastatic disease
systemic anti-cancer therapies are most often used, unless there is a
need to palliate a specic symptom. Cytotoxic chemotherapy would be
an appropriate option here. As the tumour is BRAF mutant he is unlikely to
respond to an EGFR inhibitor such as cetuximab. BRAF inhibitors such
as dabrafenib are not used in colon cancer regardless of the mutational
status.
A. 0
B. 1
C. 2
D. 3
E. 4
Answer: B.
This man is ambulatory and capable of self-care, but unable to undertake strenuous activity. He is up for more than 50% of waking hours.
Performance status is a key assessment tool in patients with cancer.
7.5. You have been asked to see a 70-year-old man on a medical
ward. He was admitted 2 weeks ago following a fall. On admission
he had abnormal liver function tests and an elevated CRP. He
has been treated for a urinary tract infection. A CT scan has
demonstrated multiple liver, lung and bone metastases, but no
obvious primary cancer. The ward nurses tell you he remains
mildly confused at times, sleeps for most of the day and does not
wish to engage with physiotherapy. What is the most appropriate
management for this man?
A. Refer to the Hepatobiliary Pancreatic Cancer
Multidisciplinary Team
B. Ultrasound-guided liver biopsy
C. Colonoscopy
D. Palliative care
E. Cytotoxic chemotherapy
Answer: D.
This man has a new diagnosis of metastatic cancer of undened pri-
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mary origin (MUO). His ECOG performance status (3), requirement for
hospital admission, multi-organ metastatic disease, end-organ dysfunction and raised inammatory markers are poor prognostic features.
Further investigations may not be warranted and honest conversations
about the likely diagnosis, palliative care and end-of-life care, taking into
account the patient’s wishes are often preferable.
C. RCTs are considered to be the ‘gold standard’ for determin-
ing efcacy and safety in clinical research
D. RCTs always have a control arm that uses placebo
E. RCTs always equally divide patients between each
treatment arm
Answer: C.
7.6. A 56-year-old woman is seen in oncology clinic following surgery
to remove a localised clear cell renal cell carcinoma. She is eligible
for a phase III clinical trial comparing adjuvant immunotherapy
to the current clinical standard of observation. Patients will be
randomised to receive either the immunotherapy treatment or
a placebo every 4 weeks for 1 year. Neither the patient nor the
investigator will know what treatment she is receiving. Which of the
following statements regarding randomised controlled trials (RCTs)
is true?
A. Patients may choose which treatment they receive
B. RCTs are always ‘double blinded’
Phase III RCTs are often used to determine whether a treatment
should be licensed for clinical use. Patients are randomised to each arm,
sometimes with stratication to ensure equal allocation of patient subgroups. RCTs may be double-blinded, as is the case here, single-blinded
or ‘open-label’. The control arm should be the current clinical standard
treatment. In this example a placebo is used in the place of observation
only to ensure blinding and avoid potential bias of results. Patients may
be divided in alternative ratios. This is sometimes the case when earlier
studies suggest large differences between the investigational and current
treatment.
LA Colvin
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M Fallon
8
Pain and palliative care
Clinical examination in pain and palliative care 154
Clinical evaluation and management in a patient with chronic pain or in the
palliative care setting 155
Pain 156
Functional anatomy and physiology 156
Investigations 158
Principles of management 160
Interventions 162
Chronic pain syndromes 165
Palliative care 167
Presenting problems in palliative care 167
Death and dying 172
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Clinical examination in pain and palliative care
Mouth
5
Increased secretions due to
dysphagia
4
Venous system
SVC obstruction due to lung
carcinoma
5
4
6
7
Drowsiness due to hypercalcaemia
or brain metastases
Lungs
7
Dyspnoea due to pleural effusion
Nervous system
6
Spine
3
Back pain due to bone metastases
Hand
2
Muscle wasting and pain due
to nerve compression
1
Extremities
Neuropathic pain due to CRPS type I
3
8
8
Abdomen
Abdominal swelling secondary to
malignant ascites
2
9
9
Lower limb
Phantom limb pain (CRPS type II)
following amputation
1
Insets (SVC obstruction, wasting in the hand, pleural effusion, ascites, amputation) From Forbes CD, Jackson WF. Color atlas and text of clinical
medicine, 3rd edn. Edinburgh: Mosby; 2002. (CRPS = chronic regional pain syndrome; SVC = superior vena cava)
Clinic al ev aluat ion a nd ma nagemen t in a pat ient with chro nic p ain o r in the p allia ti ve ca re sett ing 155
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Clinical evaluation and management in a patient with chronic pain or in the palliative care setting
VAS
score
Record severity of painTake careful history, recording
character and radiation of pain
Conduct biopsychosocial
assessment
Assess mood and screen
for depression
8
Conduct general examination
Educate patient on nature of pain
and promote self-management
Check gait and whether
using a walking aid
Formulate management plan
with patient and set goals
Assess pinprick, fine touch
and heat/cold sensation
Optimise medication
Conduct neurological
examination
Consider psychological
therapies and mindfulness
Increase physical activity
(TENS = transcutaneous electrical nerve stimulation)
Consider yoga, pilates or tai chi
Consider TENS and
acupuncture
Consider nerve block
or ablation
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Pain
Pain is dened as ‘an unpleasant sensory and emotional experience
associated with actual or potential tissue damage or described in terms
of such damage’. It is one of the most common symptoms for which
people seek health-care advice. Our understanding of the mechanisms
of pain has evolved considerably from Hippocrates’ suggestion in 450
BC that pain arose as a result of an imbalance in vital uids. We now
know that pain is a complex symptom that is inuenced and modied
by many social, cultural and emotional factors, as illustrated in Figure 8.1.
The sensation of acute pain that occurs in response to inammation or
tissue damage plays an important role in protection from further injury.
Chronic pain serves no useful function but results in signicant distress
and suffering for the patient affected, as well as having a wider societal
impact.
Functional anatomy and physiology
The functional anatomy of the somatosensory system is shown in Figures
28.3 and 28.6. Here, discussion will focus on the mechanisms and medi-
ators that are involved in pain processing.
Peripheral nerves
Peripheral nerves contain several types of neuron. These can be classied into two groups, depending on whether or not they are surrounded
by a myelin sheath. Myelinated neurons have a fast conduction velocity
and are responsible for transmission of various sensory signals, such as
proprioception, light touch, heat and cold, and the detection of localised
pains, such as pin-prick. Unmyelinated bres have a much slower conduction velocity and are responsible for transmitting diffuse and poorly
localised pain, as well as other sensations (Box 8.1).
Sensory neurons (also known as primary afferent neurons) connect
the spinal cord to the periphery and supply a dened territory or a dermatome, which can be used to identify the position of a nerve lesion
Social
and cultural
(socioeconomics,
religion, family)
Illness and
pain behaviour
(underlying disease, impact
on quality of life, fear avoidance)
Affect and
emotional state
(mood, self-efficacy)
Cognition
(catastrophising,
acceptance)
8.1 Types of nerve bre
Fibre
type
Large myelinated
Aα
Diameter
(µm)
Conduction
velocity (ms
Function
1
)
12–20 70–120 Proprioception
Motor to muscle bres
Aβ
A
Small myelinated
5–12 30–70 Light touch, pressure
3–6 15–30 Motor to muscle spindles
A 2–5 12–30 Well-localised pain
Thermal sensation
B
Unmyelinated
<3
3–15 Pre-ganglionic autonomic
C 0.4–1.3 0.5–3 Diffuse pain
Poorly localised thermal
sensation
Post-ganglionic autonomic
(see Fig. 28.10). In healthy individuals, dermatomes have distinct bor-
ders, but in pathological pain syndromes these may become blurred as
the result of neuronal plasticity, which means that pain may be felt in an
area adjacent to that supplied by a specic nerve root. Autonomic neurons also contain pain bres and are responsible for transmitting visceral
sensations, such as colic. In general, visceral pain is diffuse and less well
localised than pain transmitted by sensory neurons.
Anatomical features of the afferent pain pathway are illustrated in
Figure 8.2. Pain signals are transmitted from the periphery to the spinal
cord by sensory neurons. These have the following components:
A cell body, containing the nucleus, which is situated in the dorsal
root ganglion close to the spinal cord. The cell body is essential for
survival of the neuron, production of neurotransmitters and neuronal
function.
The nerve bre (axon) and peripheral nerve endings, which are
located in the periphery and contain a range of receptors in the
neuronal membrane.
Specialised receptors in the periphery, consisting of bare nerve end-
ings known as nociceptors or pain receptors, which are activated by
various mediators. They are situated mainly in the epidermis.
The central termination, which travels to the dorsal horn of the spinal
cord to form the rst central synapse with neurons that transmit pain
sensation to the brain.
When a noxious stimulus is encountered, activation of nociceptors
leads to generation of an action potential, which travels upwards to the
dorsal root ganglion and also stimulates the release of neurotransmitters
that have secondary effects on surrounding neurons.
(genetic, anatomical,
Fig. 8.1 The biopsychosocial model of pain. The perception of pain as a
symptom is dependent not only on sensory inputs but also on the individual’s
cognitive reaction to the pain, their emotional state, their underlying disease and their
social and cultural background.
Sensory
biomedical)
Spinal cord
Sensory neurons, through their central termination, synapse with second-order neurons in the dorsal horn of the spinal cord. There is considerable modulation of pain messages at this site, both from local neurons
within the spinal cord and from neurons that descend from the brain,
as depicted in Figure 28.11. Several neurotransmitters are involved in
pain processing at this level and these are summarised in Box 8.2. They
include amino acids, such as glycine and γ-aminobutyric acid (GABA),
which are inhibitory, and glutamate, which is excitatory; neuropeptides,
such as substance P and calcitonin gene-related peptide (CGRP); and
endorphins. Whether or not they increase or decrease pain perception
depends on the connectivity of the neurons on which they act.
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Emotional
Cognitive Sensory Sensory
Thalamus
Synapse
Emotional
Amygdala
Hypothalamus
PAG
Mid-brain
Medulla
RVM
Dorsal root
ganglion
Cerebral cortex
8
Second-order
neuron
Spinal cord
Primary afferent
neuron
Peripheral
C fibre
input
Cell
body
First central
synapse
Nociceptors: chemicals,
changes in pH, cytokines
Spinothalamic
tract
Fig. 8.2 Ascending and descending pain pathways. Ascending pathways are shown in blue and descending in red. Pain signals are detected in the periphery by
nociceptors, which are activated by chemicals, changes in pH and cytokines. The signal is transmitted by the primary afferent neuron to the spinal cord, where there is a
synapse with a second-order neuron, which transmits the signal onwards to the thalamus. Thereafter, the pain signal is transmitted to the cerebral cortex. The intensity of pain
signals is subject to extensive modulation at several levels within the nervous system. Cognitive inuences derived from the frontal lobe, coupled with sensory inuences from
cortex and emotional inuences from the amygdyla, affect pain perception in the mid-brain around the periaqueductal grey matter (PAG) and the rostroventrolateral medulla
(RVM) in the medulla. These structures form part of the descending modulatory systems, which, under normal circumstances, inhibit pain perception. In some chronic pain
states, however, dysfunction of the descending pathways can occur, increasing pain.
Central processing of pain
The signals transmitted by second-order neurons in the spinal cord are
relayed to the sensory cortex by third-order neurons, which synapse with
second-order neurons in the thalamus. At this site, perception of pain
is inuenced by interactions between a range of structures in the brain,
where sensory, cognitive and emotional aspects are integrated. This is
termed the pain neuromatrix (see Fig. 8.2). Signals within the neuromatrix
are multidirectional in nature, involving modulation of incoming messages
by the cerebral cortex (top-down regulation), as well as a complex network of connections between other subcortical structures. Under normal
conditions, there is a degree of descending inhibition from the brainstem
that reduces input from peripheral stimuli.
It is thought that chronic widespread pain (CWP) and opioid-induced
hyperalgesia may result, at least in part, from abnormalities in central processing of pain signals. It has also been suggested that variations in the
levels of descending inhibition between individuals may make some people more vulnerable than others to developing chronic pain. Over recent
years, there has been increasing interest in the role that glial cells (see Fig.
28.1) play in pain processing. Both astrocytes and microglial cells can
become activated in chronic pain states and release pro-inammatory
cytokines, as well as altering re-uptake of excitatory neurotransmitters
such as glutamate, which can inuence pain perception considerably.
As our understanding of these processes improves, there is increasing
potential to develop novel therapies targeted at these mediators, with
some early clinical studies in neuropathic pain (pain related to nerve injury
or disease, with characteristic neurobiological changes).
Sensitisation
Sensitisation is one of the key features of pain processing. It refers to the
fact that both peripheral and central nervous systems adapt rapidly to the
presence of pain, especially in response to tissue damage. This adaptive
process is called neuronal plasticity. In some situations, neuronal plasticity can lead to prolonged changes in the pathways that are involved
in detecting and processing nociceptive stimuli, resulting in chronic pain
syndromes. The specic changes in key neurotransmitters and receptors differ between chronic pain states, with implications for the efcacy
of treatments. For example, mu opioid receptors are down-regulated in
neuropathic pain, potentially leading to limited opioid responsiveness.
Peripheral sensitisation
Peripheral sensitisation can occur in association with a variety of clinical conditions, including sepsis, cancer, inammatory disease, injury,
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8.2 Neurotransmitters and receptors involved in pain processing in the spinal cord
Neurotransmitter Receptor(s) Receptor type Comments*
Amino acids
Glutamate AMPA Ion channel
NMDA Ion channel
Kainate Ion channel Post synaptic – excitatory
Gp I GPCR
Excitatory; permeable to cations: can be Ca
subunit structure
Excitatory; blocked by Mg
2+
in the resting state; block can be altered if
membrane potential changes; permeable to Ca
Pre-synaptic – inhibitory through GABA release; permeable to Na
2+
+
+
or K
2+
, Na
, depending on
+
+
and K
+
and K
, Na
Gp II GPCR Activates a range of signalling pathways; long-term effects on synaptic
excitability
Gp III GPCR Probably inhibitory; can decrease cAMP production; pre-synaptic; decreases
glutamate release
Glycine GlyR Ion channel
GABA GABA
A
Ion channel
Mainly inhibitory; permeable to Cl ; blocked by caffeine
Mainly inhibitory in spinal cord; permeable to Cl ; indirectly modulated by
benzodiazepines (increased ion channel opening); not specically involved in
nociception, generally depressant effect on spinal cord activity
GABA
B
GPCR Predominantly inhibitory; activated by baclofen
Neuropeptides
Substance P Neurokinin receptors GPCR Mainly excitatory; increased in inammation, decreased in neuropathic pain
Cholecystokinin CCKRs1–8 GPCR Excitatory; clinical trials of antagonists in progress
Calcitonin gene-related
CALCRL GPCR Excitatory; slows degradation of substance P; implicated in migraine
peptide
Opioids
Dynorphin DOP GPCR Excitatory?; may be pro-nociceptive
β-endorphin
MOP GPCR Inhibitory
Nociceptin NOP GPCR Inhibitory; also expressed by immune cells
(AMPA = α-amino 3-hydroxy, 5-methyl, 4-isoxazole propionic acid; CALCRL = calcitonin receptor-like receptor; cAMP = cyclic adenosine monophosphate; CCKR = cholecystokinin receptor;
DOP = delta opioid receptor; GABA = γ-aminobutyric acid; Gp = group; GPCR=G-protein-coupled receptor; MOP = mu opioid receptor; NMDA = N-methyl-D-aspartate;
NOP = nociceptin/orphan receptor)
*Excitatory = increased pain; inhibitory = reduced pain.
+
surgery and obesity. The nal common pathway by which sensitisation
takes place in all of these conditions is inammation. Inammation is
accompanied by increased capillary permeability and tissue oedema
with the release of a diverse range of mediators, including bradykinin,
hydrogen ions, prostaglandins and adenosine, which bind to receptors
and ion channels on nociceptors of primary afferent neurons ( Fig. 8.3).
The signalling pathways activated by these mediators generate action
potentials, which are transmitted by sensory neurons to the spinal cord.
If these pain-provoking stimuli persist, the activation threshold of sensory
neurons is reduced, resulting in an increased transmission of pain signals
to the spinal cord.
Central sensitisation
Sensitisation may also take place at the level of the spinal cord in
response to a sustained painful stimulus. It can occur acutely and rapidly,
such as immediately after surgery, or may progress to chronic changes,
such as chronic infection, cancer, repeated surgery or multiple traumatic episodes. Glutamate, acting via the N-methyl-D-aspartate (NMDA)
receptor complex, plays a key role in central sensitisation (Fig. 8.4). In
response to a sustained peripheral painful stimulus, increased amounts
of glutamate are released in the spinal cord, overcoming the inhibitory
action of magnesium ions and resulting in activation of the NMDA receptor. This initiates a cascade of intracellular signalling events that lead to
prolonged modications of somatosensory processing, with amplication of pain responses within the spinal cord and continued neuronal
ring, even after the noxious stimulus has stopped. This phenomenon is
termed ‘after-discharge’. In neuropathic pain, prolonged activation of the
NMDA pathway results in a decrease in the number of inhibitory interneurons, which further potentiates pain.
Genetic determinants of pain perception
There are marked ethnic and individual variations in how people respond
to painful stimuli and studies in twins have estimated that the heritability
of CWP ranges between 30% and 50%. In the general population, the
individual variants in response to pain and perception of pain are most
likely due to a complex interaction between genetic and environmental
inuences. Few variants have been identied with robust evidence of
association with CWP. Several rare syndromes have been described,
however, in which insensitivity to pain or heightened pain responses
occur as the result of a single gene disorder, as summarised in Box 8.3.
Most are due to mutations affecting ion channels that play a key role in
neurotransmission (see Fig. 8.3), but other causes include mutations in
the NTKR1 gene, which encodes the receptor for nerve growth factor,
and mutations in the PDRM12 transcription factor, which is involved in
neuron development.
Investigations
Pain can be a presenting feature of a wide range of disorders and the
rst step in evaluation of a patient with pain should be to perform whatever investigations are required to dene the underlying cause of the
pain, unless this is already known. However, with most chronic pain
syndromes, such as bromyalgia, complex regional pain syndrome and
CWP, investigations are negative and the diagnosis is made on the basis
of clinical history and exclusion of other causes. Specic investigations
that are useful in the assessment of selected patients with chronic pain
are discussed below.
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A
B
Stimulus
ATP
Temperature or low pH
Osmosis
Cold or limitants
Cool
Low pH
Mechanical
Bradykinin
Prostanoids
ATP
NGF
Transducer
P2X
TRPV1/2
TRPV4
TRPA1
TRPM8
ASIC
Unknown
BK1/2
EP
P2Y
NTRK1
Na
K
1.7
v
Na
1.8
Na
v
v
HCN2
v
1.9
C
Agonists
+
[H
]
Receptors
Sensitisation
Response
Stimulus
Fig. 8.3
channels that act as mediators of pain. They include sodium channels implicated in congenital pain syndromes; the purinergic 2X (P2X) and purinergic 2Y (P2Y) receptor for
adenosine triphosphate (ATP); members of the transient receptor potential (TRP) superfamily of ion channel receptors, which detect changes in osmolality and temperature;
acid-sensing ion channel (ASIC) receptors, which detect hydrogen ions; G-protein-coupled receptors, which detect bradykinin (BK), prostaglandins and ATP; sodium-potassium
hyperpolarization-activated cyclic nucleotide-gated channels (HCN2), and voltage gated potassium channels (Kv) and the neurotrophic tyrosine kinase 1 (NTRK1) receptor, which
+
] and high temperature (> 42°C) amplies action potentials, which increase pain
signals and cause peripheral sensitisation. (EP = E-prostanoid receptor) Adapted from Bennett DL, Woods CG. Painful and painless channelopathies. The Lancet Neurol 2014;
13:587–599; reproduced with permission from Elsevier.
NMDA receptor
NR1 NR2
Glycine
Mg
Glutamate
2+
Amplified
signal
Amino acids
(and other
neurotransmitters)
Dorsal root
ganglia
8
Fig. 8.4 Mechanisms of central sensitisation. Post-synaptic activation of the N-methyl-D-aspartate (NMDA) receptor requires the amino acids glycine and glutamate, which
bind to the NR1 and NR2 subunits, respectively; these amplify pain signals at the level of the spinal cord. In contrast, magnesium ions block receptor activation.
Magnetic resonance imaging
Magnetic resonance imaging (MRI) can be helpful in the assessment of
an underlying cause in patients with focal pain that follows a nerve root
or peripheral nerve distribution. Imaging is seldom helpful in individuals
with CWP.
Regulation of
pain response
Kinase
Pain
signal
Neurotransmitter
changes
Blood tests
Blood tests are not generally helpful in the diagnosis of chronic pain,
except in patients with peripheral neuropathy; in this case, a number of
blood tests may be required to investigate the underlying causes of the
neuropathy. Full details are provided in Box 28.85. Genetic testing may
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8.3 Genetic regulators of pain perception
Gene (protein) Mutation (inheritance) Protein function Phenotypes
SCN9A (Na,1.7) LoF (AR) Ion channel Absent pain, hypohydrosis, anosmia
SCN9A (Na,1.7) GoF (AD) Ion channel Erythromelalgia, paroxysmal pain, burning pain,
autonomic dysfunction
SCN11A (Na,1.9) GoF (AD) Ion channel Absent pain, hyperhydrosis, muscular weakness,
gut dysmotility
SCN10A (Na,1.8) GoF (AD) Ion channel Burning pain, autonomic dysfunction
TRPA1 (TRPA1) GoF (AD) Ion channel Absent pain
PDRM12 (PDRM12) LoF (AR) Transcription factor; neuron development Absent pain
NTRK1 (high-afnity
NGF receptor)
(AD = autosomal dominant; AR = autosomal recessive; GoF = gain of function; LoF = loss of function; NGF = nerve growth factor)
LoF (AR) Tyrosine kinase; promotes neuron
development
Absent pain; anhydrosis, mental retardation,
increased cancer risk
be of value in patients with clinical features that point to an inherited
disorder of pain processing (see Box 8.3).
Quantitative sensory testing
Quantitative sensory testing can be helpful in the detailed assessment
of patients with chronic pain. A simple set of tools can be used in the
clinical setting (Fig. 8.5). Lightly touching the skin with a brush, swab or
cotton-wool ball can be used to test for abnormalities of ne touch. This
may include allodynia, where a normally non-painful stimulus is perceived
as painful. Assessing the patient’s response to a pin-prick can be used
to test for abnormalities in mechanical hyperalgesia. Finally, touching the
patient’s skin with warm and cool thermal rollers can be used to test for
abnormalities of thermal sensation. An unaffected area of skin should
be tested rst, to establish normal sensation, before testing the affected
area.
Nerve conduction studies
Nerve conduction studies can be helpful in demonstrating and quantifying a denitive nerve lesion, either peripherally or centrally. They can
be used to help differentiate between central and peripheral neuropathic
pain. They do not, however, effectively examine small nerve bre function.
Nerve blocks
Performing a nerve block with inltration of a local anaesthetic such as
1% lidocaine can be used diagnostically, in assessing whether a pain
syndrome is due to involvement of a specic nerve or nerve root. Where
inammation and or swelling may be contributing to the underlying pain –
for example, if there is compression of a nerve root – then a mixture of
local anaesthetic and depot glucocorticoid may be helpful in alleviating
pain. Nerve blockade can also be used to determine whether more radical therapies, such as nerve ablation, might be helpful in controlling pain,
particularly that related to cancer.
Pain scoring systems
Various questionnaires and other instruments have been devised to
localise pain, rate its severity and assess its impact on quality of life.
Some of the most widely used are listed in Box 8.4. The distribution of
pain can be documented on a diagram of the body, on which the patient
can mark the sites that are painful. Similarly, other methods have been
developed with which to assess the severity of pain using verbal, numerical and behavioural rating scales. Visual scoring systems employing different facial expressions may be of value in paediatric patients and those
Cotton wool Neurology pin
Allodynia
Warm and cool thermal rollers
Increased or decreased thermal sensation
Hyperalgesia
Fig. 8.5 Equipment for bedside sensory testing.
with cognitive impairment. Documenting changes in pain scores using
questionnaires can be helpful in indicating to what extent drug treatments have been successful and can reduce the time taken to achieve
pain control.
Principles of management
Effective management of chronic pain depends in part on the underlying
cause but some general principles can be applied. In general terms, the
treatment goals are to:
educate the patient
promote self-management
optimise function
enhance quality of life
control pain.
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