pain in palliative care

Pain :


Pain is more or less present on a permanent basis at a certain point in cancer progression, particularly during palliative care phases (in at least 70% of patients). The aim of this chapter is not to teach everything about pain but rather to define practical attitudes and reasoning. At least 90% of pain can be relieved.

Pain can be defined as an unpleasant personal sensorial and emotional experience associated with real, potential or feared tissue damage.

It is clear from this large definition that all pain, even if perfectly isolated and described, very rapidly involves affective, emotional, cognitive or behavioural components. Physical pain is most often completed by 'moral' pain or total pain.
 
contents:

Neural pathways in pain
Assessment of a painful patient
Cancer pain
Treatment principles
Therapeutic scales
Opioid rotation
Neuropathic pain

Neural pathways in pain :

Pain origin

Following tissue aggression, independently of its type, nociceptive messages are transmitted from various nociceptors towards spinal cord roots through small sensitive calibrated nervous fibres. Many algogen products are implicated in pain genesis: bradykinin, H⁺ or K⁺ ions, histamine, serotonin, various derivatives of arachidonic acid (prostaglandins, prostacyclins, leucotriens).

Prostaglandins sensitise receptors to many algogen compounds. Therefore, the use of anti-inflammatory drugs, aspirin or glucocorticosteroids has a positive effect.

Transmission within the spinal cord

The dorsal horn of the spinal cord is the first step for the transmission and modulation of pain. Nociceptive afferent neuronal fibres transmit information to converging neurons, then to the ascending spinothalamic tract.

There, many peptides are involved in pain transmission: substance P, vasoactive intestinal peptide (VIP), ocytocin, galanine, angiotensin 2, dynorphine, enkephalin.

The classical theory considers that all of these chemical molecules are a gate filtrating pain transmission towards the superior centres. Pain is transmitted:

    either if it provokes stimulation that is too important to be inhibited at medullar level,or if the medullar filter is altered.

Thus two different types of pain are considered: nociception pain (too much stimuli) or deafferentation pain (no inhibition), with different therapeutic attitudes.

The presence of such a medullar filter allows local medullary treatment (peridural injection, intrathecal injection), particularly by morphine or its derivatives, in order to reduce the general dosing and diminish side effects.

Transmission towards the brain

Pain is then transmitted through spinothalamic tracts (anterolateral medullar chord) towards brainstem reticular formations and ventral thalamic nuclei.

The lateral thalamus discriminates sensitive information to precisely locate its origin.

The central thalamus has less systematised information responsible for motor reactions and the emotional components of pain.

From the thalamus, the pain information is transmitted to the ascending parietal area (precisely discriminating pain location) as well as towards the limbic system provoking emotional and behavioural reactions and towards the hypothalamus inducing neurovegetative and endocrine manifestations.

Assessment of a painful patien:

Treating pain requires precise knowledge on analgesic medications but, first and foremost, it requires listening to and examining the patient in order to precisely diagnose the origin of pain.

Assessment of patient pain

The first principle is to always believe the patient (and his/her family) when complaining about pain. Pain is a purely subjective phenomenon, the quality and the intensity of pain and the way it is described will vary from one patient to another. The physician should therefore precisely analyse the symptoms described by the patient.
 
Pain evaluation should be the basis of treatment: it must be performed by both th physician and the patient. This evaluation should be performed:

at regular intervals,
for each new painful episode,
after any analgesic action (half an hour after any IV analgesic treatment, one to two hours after oral treatment).

During cancer, some causes are most frequent:

chronic osseous pains from metastases,
osseous pain with mechanical outbursts: for which fracture or vertebral crushing should be feared,
pain through organ compression or nerve infiltration (sciatica, plexalgia),

headache from brain metastases,
digestive pain in relation to transit disturbance,
mucuous pain (mucitis, esophagitis, cystitis, rectitis).

During the palliative phase, cancer pain generally is chronic, persisting, progressively aggravating, disturbing the patient's liberty and sleep. Nocturnal pain is very typical of cancer.
When questioning the patient, the physician should consider:

the words the patient uses to describe pain ('it pinches', 'it burns', 'it twists', and so on)factors influencing its arrival, its aggravation, its duration, its variation throughout the day, 

precise pain location, asking the patient to trace pain on the body or a body diagram, 

pain intensity (as evaluated by the patient but also in relation to induced perturbation of normal life),
 sometimes, trying to guess when the patient can no longer easily express himself/herself.

The clinical examination should be careful and cautious since the patient is in pain:

mucuous examination,
mild limb mobilisation,
soft pressure on painful zones (provoking pain!)
pelvic examination in case of sciatica.

Diagnosing pain type

Classically, two types of pain are observed:

pain due to excessive stimulation, generally related to extension of the tumour towards nearby structures with, most often, a precise, permanent topography with pain exacerbation attacks.

pain due to deafferentation, located on neural routes, by the deterioration of peripheral neurones, with fulgurating pains similar to electric shock, but also hypoesthesia or localised hyperesthesia, burning or stinging sensations (for instance post zoster pain, phantom limb pain), 

psychogenic pain, with no systematisation but occurring in a major anxiety context,

Pain scales

Many 'scales' have been developed in order to objectify pain intensity. Among them:

simple verbal pain scale: no pain, mild pain, moderate pain, intense pain, intolerable pain, 

analogic visual pain scale (marked from 1 - no pain to 10 intolerable pain) which necessitates patient cooperation, 

pain questionnaires (Mc Gill Pain Questionnaire, QDSA: Questionnaire de Saint-Antoine) which also needs good patient cooperation and allows multifactorial analysis, 

behavioural scales: observing the patient permits an evaluation of pain, in particular child pain (DEGR scale: douleur enfant de l'Institut Gustave Roussy) or in elderly patients (Doloplus scale),

precise study of analgesic consumption.

 Cancer pain:

Pain during cancer may have three different causes:

Pain in relation with tumour progression

In approximately 70% of cases, pain is related to tumour progression:

bone pain (most frequent): 

- in relation to metastatic bone tumours, 

-unique or multiple locations,

without or with fracture (specific problem of prefracture syndrome),

potentially concerning all bones (skull, spine, limb bones, ribs, pelvis).

compression or infiltration of neural structures:

peripheral or central nerves,
with or without associated motor deficiency,
with or without associated sensitive deficiency,
potentially concerning various nerves (vertebral nerves, brachial plexus, cervical plexus, lumbosacral plexus, medullary compression, cranial nerves).

visceral or muscular infiltration

intestinal occlusion through infiltration,
inflammation and serous effusion,
compressive muscle pain.

mucinous lesions

mouth, oesophagus, vagina, rectum, bladder, and so on

Iatrogenic pain

Treating cancer is difficult and treatment generally agresses the patient. Approximately 20% of pain are due to treatment.

in relation to surgical or diagnostic procedures:

abnormal wound healing,
neuropathy in relation to neural section, phantom limb syndromes,
stomy complications.

in relation to chemotherapy:

mucitis,
sensitive neuropathies,
muscle pain (taxane, interferon),
osseous pain (growth factors),
drug extravasation (cf. chemotherapy chapter).

in relation to radiotherapy

mucitis, cystitis, rectitis, ..
radionecrosis,
radiotherapy induced plexalgias,
visceral post radiotherapy alterations.

Pain from other origins

In about 10% of cases, pain is not related to cancer or its treatment and the patient may have previously taken analgesics for its treatment.

Treatment principles :

False dilemma

Faced with a cancer patient, the clinician has two objectives:

To treat the patient's pain as soon as possible, to make it disappear, if possible totally and indefinitely,
To treat (if feasible) the cause of pain in order to adjust the drug prescription.

There is no contradiction between these two aims: what is the use in asking for analgesic radiotherapy if the patient cannot lie five minutes on the table without suffering major pain? On the contrary, what is the use in prescribing high doses of morphine to a patient suffering from a mobile fracture? In the former situation, the administration of a strong initial analgesic allows efficient radiotherapy; in the latter, rapid immobilisation (involving surgery if necessary) offers quick relief to the patient.

The clinician should propose realistic and demonstrable aims:

The patient should:

not suffer at night thus allowing sleep repair,
not suffer during meals,
not suffer during movement,
be able to eat, urinate without pain,
whilst remaining as clear-headed as possible.

Principle: pain should not appear

Pain is not a fatality for patients with cancer. Cancer does not have be be a 'prolonged and painful disease'. Good palliative management should transform the last months of our patients' lives.

Pain should be anticipated and should not be left to overwhelm the patient. Pain provokes patient anxiety. The patient, as his/her family, believes that disease progression is quicker when pain is present. Such anxiety increases the pain sensation. Even benign procedures should not provoke pain: for instance, more or less powerful analgesics could be prescribed before body care in order to restore the pleasure of feeling clean and fresh.

Treatment is preferably prescribed by oral or transdermal routes rather than via intramuscular or intravenous injections. The two former routes give more regular pain relief and promote patient autonomy.

The patient (and his/her family) should be taught the benefits of regular intake. Patients may try to be less of an 'addict' and may try to space out analgesic intake until pain resumes. In such situations, analgesic dosage should be increased to be efficient: however, this also provokes unnecessary side-effects. Regular analgesic intake may lead to complete and permanent pain control without side-effects or drug dependency.

Medication associations

Following the precise analysis of pain, performed together by both the patient and his/her physician, the treatment of pain will then associate several therapeutic resources:

pure analgesic drugs,

 other adjuvant drugs depending on the type of cancer and the cause of pain, 

non medicinal therapies (such as surgery, radiotherapy, dressing) depending on pain 

psychotropic medications, when a major psychological component increases the pain sensation.

Without going into detail, we will describe analgesic treatment principles (only for cancer pain).

Pain therapeutic scale  :


The World Health Organisation (WHO) published, some time ago, pain scales in order to improve pain management with increasingly potent analgesics. Below, we have reproduced this scale with a few modifications made:

• after the emergence of new opioid non morphine analgesics (Scale II B)
• considering poorly relieved morphine treated pain necessitating specific administration techniques.

The WHO scale mainly concerns nociception pain.

WHO Level I

Pain is generally moderate (1 to 4 on the visual analogic pain scale).
The main analgesic drugs are:

Acetaminophen
Nonsteroidal anti-inflammatory drugs
Aspirin
Noramidopyrin

WHO level II (A)

Pain is more intense (between 4 to 8 on the visual analogic pain scale).
Two drugs are used:

Codeine and dihydrocodeine
Dextropropoxyphen

WHO level II (B)

Same pain intensity, but inefficiency of previous drugs.
Three drugs are used:

Tramadol
Nalbuphine
Buprenorphine

WHO level III

Intense sustained pain resistant to previous medications

Injectable morphine
Oral morphine
Fentanyl
Hydromorphone chlorhydrate
Oxycodone chlorhydrate.

In level II or III, other adjuvant drugs can be administered, such as anti-inflammatory drugs.

WHO level III B

This pain requires specific pain consultation for various techniques:

specific morphine administration,
stimulation,
pain surgery.

Neuropathic pain :


Neuropathic pain is pain related to the abnormal function of the peripheral or central nervous system which does not correctly control pain influx. Such pain can be very difficult to treat even with opioids.
We can distinguish:

Neuropathic peripheral pain

Pain is related to the destruction mechanism of peripheral nerves: this pain can therefore concern one or several nerves.

It is characterised by acute transfixing attacks complicating a permanent dull pain. Furthermore local paresthesia can be observed.

Two examples:

neurapathy by inflammatory or toxic lesion of the small nerves of major neurological trunks (nervi nervorum),
or by the formation of a neuroma after axon section.

These neuroma are particularly sensitive to touch or chemical stimuli (such as norepinephrin).

Central neuropathic pain

Two different types of central neuropathic pain are observed:

Deafferentation pain

Many syndromes illustrate this deafferentation: pain from phantom limb pain, post-zoster burning sensations, painful anaesthesia, central pain.

Dystrophic pain

This sympathetic or dystrophic pain (also called causalgia or burning pain) is accompanied by:

autonomic dysregulation (cold or hot sensations, limb moistness, swelling, redness,..),

motor symptoms (stiffness, muscle weakness, abnormal movement),

trophic symptoms in bone (bone algodystrophy) or skin (reduced dermal thickness, dermoskeleton modification).

Dystrophic pain is most frequent after plexus radiation fibrosis (head and neck cancer with painful stiff shoulder) and constitutes a major therapeutic challenge.

Therapy of neuropathic pain

This type of pain requires the competence of a specialised multidisciplinary medical team.
Opioid treatment

Opioid treatment should always be attempted: dosages are slowly and progressively increased up to major (if not complete) clinical pain remission or to major morphine intolerance symptoms.
In fact, most often, neuropathic pain requires a very high dosage but is not truly insensitive to morphine drugs.

Adjuvant medications

Many adjuvant drugs have been tried in order to prevent hyperalgic crises: their number and the diversity of their therapeutic classes demonstrate the difficulty in treating such acute pain phenomena:

• tricyclic antidepressive drugs: amitriptyline, imipramine, desipramine
• other antidepressive drugs: paroxetine, maprotiline, gabapentin,
• local anesthetic drugs: mexiletine , flecainide,
• anticonvulsivant : carbamazepine, phenytoin, valproate,
• alpha-2 adrenergic antagonist: clonidine,
• anesthetic drug: ketamine,
• other sympathic drugs: prazosin , propranolol , nifedipine.

Anesthetic approach

This approach concerns the testing of typathetic blockade, for instance for brachial plexus pain or peripheral nerve blockade or opioid intrathecal injections.

 These techniques should be performed by a specialised anaethesiologist.

Neurostimulatory approach

Transcutaneous electrical nerve stimulation may be of benefit among patients with untreatable and intolerable pain. Since many adaptations are necessary in order to maintain, for as long as possible, the obtained benefit, a perfect technique is mandatory to ensure success.

Surgical approach

The surgical approach concerns the resection of neuroma, or the denervation of a painful zone (cordotomy). Since this surgery leads to permanent lesions, a multidisciplinary discussion should be organised in order to specify appropriate indications.