Cancer Pain

Cancer Pain
Photo by National Cancer Institute / Unsplash

Take home messages

  • Cancer pain is complex and personal, and requires an individualised approach
  • You can get most patients tolerably comfortable using the WHO ladder properly
  • Interventional techniques can be considered at any time

This topic was examined in the CRQ exam in:

  • March 2018

Common things are common

Cancer is common, and increasingly so as we live longer and get better at spotting it and surviving other previously-fatal things.

10-year cancer survival has doubled in 40 years, so we're getting better at surviving that too.

There are probably a whole host of lifestyle and environmental factors that are contributing to a rise in cancer diagnoses, but for now that remains beyond the scope of this post.

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The lifetime cancer risk in the UK is now over 45%

What are the most common cancers in the UK?

  • Breast
  • Lung
  • Prostate
  • Bowel

Oral cancer and melanoma are also increasing in incidence.

Now think about the fact that half of these people are going to experience some form of pain related to their cancer, and a third will still have chronic cancer-related pain even after treatment and remission.


Tell me about the pain

The definition of pain is:

An unpleasant sensory and emotional experience associated with actual or potential tissue damage.

By definition, therefore, it is subjective in its nature, and every patient will feel their pain in a unique way, and for a variety of reasons.

  • Mrs Jones has a pathological fracture from her bony metastasis
  • Mr Simmonds has spasmodic intermittent bowel obstruction pain
  • Miss Reynolds is struggling with letrozole-induced arthralgia

The list of possibilities is enormous.

What are the types of cancer pain?

Start with the categories of pain:

  • Nociceptive - pain nerves stimulated by something bad
  • Neuropathic - pain nerves firing off signals by themselves
  • Mixed

These can be intermittent (e.g. bowel spasm) or constant (e.g. liver capsule stretch).

Then add in how cancer causes these types of pain:

  • Local mass effect - inflammation, compression, ischaemia, oedema
  • Direct nerve damage - leads to peripheral and central sensitisation
  • Paraneoplastic pain - neuronal antibody production (anti-Hu and Yo)
  • Indirectly related - infection, hypercalcaemia, herpes reactivation, pathological fractures from bony metastases

Then for bonus marks, throw in the fact that the treatments can also cause pain:

  • Chemotherapy induced neuropathy
  • Radiation induced neuritis
  • Chronic post surgical pain

Up to 25% of the time, the pain is mainly as a result of the treatment.

If you think about cancer as rapid and uncontrolled proliferation of badly organised tissue in a location that it's not supposed to be, it makes sense that these cells then fall apart and necrose relatively easily, releasing their caustic and inflammatory content all over the surrounding nerve fibres.

Don't forget many of our patients also already have a pre-existing chronic pain condition that they're having to deal with, which is only going to get worse when you add in a heap of cancer pain on top.


What about pain from the treatment?

Just in case our poor patients weren't having a tough enough time already, it's very common for the treatments with inflict upon them to cause pain by themselves as well.

  • 25% of cancer pain is attributable to the treatment
  • Some drugs have direct effects such as aromatase-inhibitor induced arthralgia or immune checkpoint inhibitor induced myositis
  • Immunotherapy can cause abdominal pain, arthralgia, myalgia, arthritis, colitis, pancreatitis, neuropathic pain
  • Radiotherapy can cause painful neuritis
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Be sure to mention chemotherapy-induced peripheral neuropathy (CIPN) in the exam.

Tell me about CIPN

A common side effect of a range of chemotherapy agents, this condition leads to pain as well as sensory, motor and autonomic dysfunction as a result of chemical damage to peripheral nerves.

Some drugs are directly neurotoxic

  • Platinum compounds
  • Vinca alkaloids
  • Taxanes

However they're still widely used because their toxicity is precisely what makes them good cancer drugs.

The precise pathology of how the drug induces neuropathy depends on the mechanism of the drug itself, and largely falls into:

  • Microtubule disruption
  • Axonal injury
  • Dorsal root ganglion toxicity
  • Demyelination
  • Glial injury

Clearly the severity and likelihood of developing CIPN is going to depend on the:

  • Dose
  • Duration
  • Number of cycles
  • Combinations of agents
  • Speed of infusion
  • Pre-existing neuropathy

For example: Cisplatin combined with paclitaxel sees up to 70% suffering from neuropathy.

How is CIPN diagnosed?

  • History - burning pain, hyperalgesia, sensory and motor loss, autonomic dysfunction
  • Quantitative Sensory Testing
  • Electrophysiological studies - more useful for large fibre neuropathy

Sometimes it's temporary, but we're still talking months for any sort of improvement to be noticed by the poor patient, and that's if they're lucky.

It's very tricky to prevent, affects men and women fairly equally, and management is almost entirely symptomatic, with CIPN patients frequently referred to pain clinics for ongoing management.

What topical agents can be used for neuropathic pain?

  • Menthol cream
  • Lidocaine patches
  • Capsaicin
  • Topical doxepin

What neuromodulation techniques are there?

  • TENS - transcutaneous electrical nerve stimulation
  • Spinal cord stimulators
  • Acupuncture

It's all in your head

This isn't a flippant comment - pain is literally in your head.

Everything is in your head.

You're hallucinating the entirety of your reality with its vibrant cacophony of touches, smells, sights and sensations from inside a silent pitch-dark bone box atop your shoulders, based solely on its ability to interpret the relentless stream of electrical signals flung in its direction.

In reality the world is a colourless, odourless and silent soup of tiny particles and packets of energy fizzing around in varying degrees of chaos, upon which you have imposed the perception of colour, smell and sound in order to survive.

I'll put the existentialism cannon away for today.

The point is you've only evolved to perceive the sense modalities that have made you more likely to live long enough to procreate, and one of these modalities is pain.

  • It's useful to know about actual tissue damage so you can avoid damaging it further
  • Pain stops you walking on a broken foot, and at least gives it some chance to heal

But this also means that pain isn't just a matter of controlling or preventing the electrical signals from reaching the brain, it's just as much about managing the interpretation of those signals.

  • If the central interpretation of the inbound signals malfunctions, then the hallucinated sensation will be inappropriate

This is how our pain patients end up with things like hyperalgesia and allodynia.

Which fibres do what and how?

This is exam fodder at Primary and Final level, so get good now.

The fibres

There are two main types of nociceptor afferents to be aware of:

  • Aฮด fibres transmit sharp, well defined localised pain
  • C fibres are responsible for diffuse, dull pain

The triggers

Both can detect and depolarise in response to chemical, mechanical and thermal stimuli, which establish an afferent action potential.

The pathway

They then synapse in the dorsal horn in the Rexed laminae:

  • C fibres terminate in I and II
  • Aฮด in I, II and V

Second and third order neurons then transmit up the spinothalamic and spinoparachracial tracts to sensory-discriminative and affective-emotional areas of the brain respectively.

Here, depending on how the sensory cortex, amygdala and limbic system have acclimatised or sensitised to both the physical and emotional components of pain over time, the sensation of pain is brought screeching into life.

See - in your head.

This doesn't mean you shouldn't try and sort the causative or peripheral problems out, it just highlights how important a patient's mindset is in managing chronic pain, and how psychological and cognitive therapies can be.

๐Ÿ’ก
Depression and anxiety, unsurprisingly, significantly worsen cancer pain, as do smoking and insomnia.

What can we do?

What are the options for treating cancer pain?

Classic exam question - start by categorising, and let the examiner tell you where to go next.

"Effective treatment of cancer pain requires a multidisciplinary, holistic and personalised approach to the individual, with collaboration between primary care, surgeons, oncologists, pain specialists, allied health professionals and palliative care teams."

Options include:

  • Pharmacological
  • Psychological
  • Surgical
  • Interventional
  • Oncological
  • Physical therapy
  • Complementary therapy

Climb the ladder

That WHO analgesic ladder that we all love to reel off down the phone at the poor surgical SHO at 3am on the weekend was actually specifically developed to address the fact that cancer pain has historically been under-treated.

  • The main emphasis is on regular oral analgesia that maintains therapeutic plasma levels

When done properly, over 80% of patients will see their pain controlled to within tolerable limits, so it's not to be sniffed at.

Tell me about the WHO analgesic ladder

Grandmother, eggs, I get it.

  • Step 1 - Regular paracetamol +/- NSAID +/- adjunct*
  • Step 2 - Weak opioid
  • Step 3 - Swap weak opioid for strong and wind up the dose as required

*Gabapentinoid, steroid, TCA, bisphosphonate

Most patients on strong opioids end up requiring some combination of long acting opioid plus immediate release for breakthrough pain (usually 1/6th of the daily dose).

Interventional procedures (see below) can be considered at any stage, if the risk/benefit ratio is in the patient's favour.

The issue with opioids

While very effective for acute pain, opioids tend to cause more trouble when used chronically, as the patient develops tolerance to their dose and side effects start to set in.

The dose should be titrated up to manage their pain, however more than 120mg of morphine per day seems to add more side effects but no additional analgesic benefit.

  • These patients might benefit from switching to a fentanyl patch

There's also a cruel condition called 'opioid hyperalgesia' where increasing the dose actually starts to make things worse.

How to manage opioid hyperalgesia

  • Reduce the dose
  • Switch to something else (e.g. oxycodone)
  • Employ other adjuncts if not already
  • Make sure you're managing other side effects like constipation

What interventions can we do?

It's nice to actually do a thing to take away pain, rather than prescribing endless rounds of constipating hallucinogens in the hope it wanders off by itself.

If you can't stop the painful stimulus, and you can't stop the brain from feeling them, you can try cutting the cable instead.

Interventional techniques are generally employed when cancer pain is unresponsive to opioids or they're inducing intolerable side effects, but they can be considered at any stage.

These generally fall into one of two categories:

  • Destructive
  • Non-destructive

As one might have guessed, destructive techniques cause irreversible disruption of nerve conduction in the target areas, while non-destructive techniques offer temporary relief.

There are three options

  • Central - cordotomy, intrathecal neurolysis, neuraxial anaesthesia
  • Autonomic - sympathetic blocks
  • Somatic - chemical or radiofrequency ablation of peripheral nerves

The two most commonly used chemical agents are alcohol and phenol. Glycerol is another option for the trigeminal ganglion but used less frequently these days.

Tell me briefly about cordotomy

  • Radiofrequency neurodestruction of the lateral spinothalamic tract at C1/2 contralateral to the side affected by pain
  • Usually done under fluoroscopy
  • Used for severe unilateral cancer pain below C4, such as Pancoast tumours and mesothelioma
  • Doesn't work for anything higher than C4
  • Risk of deafferentation pain (compensatory neuropathic pain that develops from having the pain signals turned off completely)

Tell me briefly about radiofrequency ablation

  • Conventional radiofrequency current ablation heats the target pain nerve up using a needle tip to around 80 to 90ยฐC for 60 to 90 seconds
  • Pulsed techniques use a 2Hz pulse at <43ยฐC for around five minutes

Tell me briefly about surgical options

Some examples of surgical interventions to manage cancer pain include:

  • Operating on the underlying cancer itself
  • Fixing pathalogical fractures
  • Treating side effects like bowel obstruction
  • Spinal cord stimulators (require surgical implantation)

Surgically neurodestructive things like myelotomies and dorsal root entry zone lesioning aren't used as often any more as a result of their risk and side effect profiles.

What are the oncological options?

These target the pain by attempting to destroy the thing causing it.

  • Chemotherapy
  • Radiotherapy - local or wide field
  • Hormonal
  • Immunotherapy
  • Radio-isotope therapy for multiple bony mets

Being sympathetic

This applies to both bedside manner and interventional procedures, as visceral pain is transmitted largely via the autonomic nervous system.

  • Parasympathetic outflow is cranial and sacral, making blocking it more tricky
  • Sympathetic ganglia (T1 - L2) are far more accessible as they tend to gather in plexi that we can target

What blocks can we offer for cancer pain?

  • Thoracic splanchnic
  • Coeliac plexus
  • Lumbar sympathetic
  • Hypogastric plexus
  • Ganglion impar

We can also do stellate ganglion blocks to treat sympathetically mediated pain and hot flushes in breast cancer.

Around 8% of cancer patients will need some form of nerve block.

Some sympathetic nerves and their plexi

  • Greater splanchnic - (T5 - 9)
  • Lesser splanchnic - (T10 - 11)
  • Least splanchnic - (T12)

One wonders whether there is a 'most' splanchnic, and what it did to deserve such a title.

The splanchnics ender the abdomen posterior to diaphragm and join the phrenic and vagus nerves, along with the sympathetic chains in the coeliac plexus around the aorta at L1.

This plexus then continues southwards to the superior and inferior mesenteric and aortic plexi.

  • The superior hypogastric plexus is anterior to L5/S1 between the common iliac arteries
  • The ganglion impar is the only unpaired ganglion and sits in front of the sacrococcygeal joint, forming the end of the sympathetic chain

Coeliac plexus block

This gets examined in its own right, so it's worth some detail here.

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Coeliac plexus block works in over 80% of pancreatic cancer patients.

What are the indications for coeliac plexus block?

To treat intractable pain from malignancy of:

  • Pancreas
  • Stomach
  • Liver
  • Gallbladder
  • Transverse colon
  • Spleen
  • Kidneys
  • Proximal ureters

What are the contraindications for a coeliac plexus block?

Nothing complex here:

  • Patient refusal
  • Sepsis
  • Severe coagulopathy

What are the complications of coeliac plexus block?

Star with the same answer as literally any local anaesthetic block:

  • Failure
  • Trauma to surrounding structures
  • Bleeding and haematoma
  • Infection
  • Intravascular injection
  • Local anaesthetic toxicity

Then add in the complications specific to coeliac plexus block:

  • Diarrhoea
  • Hypotension
  • Visceral trauma
  • Nerve root damage
  • Sexual dysfunction
  • Paraplegia

If you're answering a CRQ that asks for complications 'specific' to the coeliac plexus block, you will get zero marks for any of the first six listed - only give them what they're asking for.

We'd be amazed if you need to know more than this to ace all of the FRCA exams, however please do get in touch if you feel something is missing!


Useful Tweets and Resources

In case this wasn't a cool enough topic for you guys, these heroes managed a refractory VF ARREST with a stellate ganglion block.


References and Further Reading


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