Focus on Pain Management - Medical Chronicle

MEDICAL CHRONICLE’S 

<strong>Focus</strong> on Pain Management 

Recognising the huge role pain management plays in the treatment of most diseases and conditions, 

Medical Chronicle has been covering this topic quite extensively in its pain forums over the past few 

years. This booklet contains some of the most popular topics that had been covered in these forums 

providing medical practitioners easy access to information that will help them to better understand 

this vast field and better diagnose, treat and manage the different chronic and acute pain conditions. 

Featured in 

this issue 

Multidisciplinary Treatment 

Approach the Answer to 

Effective Pain Management 

Treating C difficileassociated 

Disease 

Helping Patients Cope 

with Neuropathic Pain 

Postoperative Pain Control 

a Human Right 

How Anaesthesiologists 

Can Reduce Pain 

Recommendations after 

Dextropropoxyphene 

Withdrawal 

Fibromyalgia: a 

Growing Diagnostic and 

Therapeutic Challenge 

The Choice of an 

Appropriate Analgesic 

Should no Longer be 

Painful 

Chronic Pain 

Management 

and the General 

Anaesthesiologist

Pain Management 

Multidisciplinary Treatment Approach the 

Answer to Effective Pain Management 

Prof Helgard Meyer, 

Past-President: Pain SA 

Pain has become the most common reason for 

a patient’s decision to seek medical attention, 

particularly in primary care. 

In a study of 25 primary healthcare centres 

in Finland, pain was identified as the reason 

for 40% of the visits, demonstrating that pain 

is not only a major primary healthcare problem 

but also has an enormous socio-economic impact 

on public health. Twenty per cent of these 

patients had experienced chronic pain for over 

six months. 

In a 1998 World Health Organization survey 

of approximately 26 000 primary-care patients 

on five continents, 22% reported persistent 

pain over the past year, associated with marked 

Biopsychosocial model of pain 

reductions in several different indicators of 

well-being, particularly psychological illness and 

interference with activities. No epidemiological 

data are available for SA, but it is presumed to 

follow international prevalence patterns. 

Advances in classification and management 

The explosive growth in the knowledge of pain 

in recent years has produced major advances in 

the classification and management of pain. 

The modern paradigm of pain management 

has moved from the concept of a specific pain 

pathway as the source of pain to intricate brain 

mechanisms that integrate sensory, emotional 

and cognitive systems during the processing and 

experience of pain. 

There is a heightened awareness of acute 

pain as the 5th vital sign, which may induce 

long-term sensitisation of the nervous system 

and chronic pain in some patients, if not treated 

appropriately. 

Nociceptive pain occurs when peripheral nociceptors 

are stimulated by various noxious stimuli 

(e.g. post-surgical pain), and neuro pathic pain 

follows injury to the nervous system. 

In dysfunctional pain disorders no peripheral 

abnormality is detected and the pain results from 

the abnormal sensory processing of incoming 

impulses (e.g. irritable bowel syndrome and 

fibromyalgia). 

Acute pain serves a protective purpose and 

warns of danger. 

However, chronic pain has little or no protective 

significance and may persist in the 

absence of tissue damage after normalisation of 

... to page 4 

A Medical Chronicle supplement August 2011 • 3


Multidisciplinary Treatment 

Approach the Answer to 

Effective Pain Management 

... from page 3 

injury or disease. It can therefore be regarded as 

a dysfunctional response and has been termed 

a disease in its own right by the International 

Association for the Study of Pain (IASP) and 

mostly requires long-term management. 

Chronic pain may persist long after initial 

tissue trauma has resolved and may be substantially 

influenced by emotional and psychosocial 

factors. 

Evidence-based approach 

The ‘trial-and-error’ subjective approach to 

pain management, which often prevails, has 

been replaced by evidence-based medicine with 

newer methods of assessing and controlling pain. 

This shift in the paradigm of pain management 

worldwide is based on more appropriate education 

and training, and is also driven by patients’ 

rights issues. 

In a developing healthcare system such as 

in SA, primary healthcare providers are in the 

most favourable position to be responsible for the 

initial assessment and management of patients 

in pain. Only patients with more complicated 

pain disorders would be referred to appropriate 

specialists. 

The biomedical approach to chronic pain often 

promises a cure by cutting or blocking the pain 

pathways. The biopsychosocial model views pain 

as a complex sensory/psychosocial interaction 

and more realistic management goals mostly 

include a reduction (not necessarily elimination) 

of pain, the targeting of potential pain-related 

disability (including return to work) and the 

development of self-management strategies. 

Strong efforts should be made to keep patients 

with persistent pain integrated in their lives 

to prevent subsequent mood changes, such as 

depression and anxiety. 

Best outcomes 

The best outcomes in chronic pain manage- 

ment are obtained through an interdisciplinary 

approach which often includes education, behavioural 

therapy, physiotherapy and exercise, 

and pharmacological therapy. 

Procedural interventions are indicated in a 

small subset of chronic pain patients only after 

well-managed, appropriate, conservative approaches 

have failed. 

Despite all these advances in the understanding 

and management of pain, various surveys 

repeatedly reveal that unrelieved pain remains 

a widespread problem and that pain is often 

undertreated. 

Part of the problem relates to deficiencies in 

pain knowledge among healthcare professionals, 

owing to the fact that educational programmes, 

including those for undergraduates, mostly 

include minimal or no pain content. 

References available on request. 

Components of chronic pain 

management 

• Interdisciplinary 

• Education 

• Emphasis on patient’s active role 

• Pharmacological management 

- Primary analgesics: 

s Paracetamol 

s NSAIDS/Coxibs 

s Opioids 

- Secondary analgesics: 

s Antidepressants 

s Anticonvulsants 

• Physical therapy 

• Exercise therapy (Biokineticist) 

• Behavioural therapy 

• Occupational therapy 

• Interventions 

4 • August 2011 A Medical Chronicle supplement


Helping Patients Cope with 

Neuropathic Pain 

Prof CL Odendaal 

Department of Anaesthesiology, Faculty of 

Health Sciences, Free State University 

Neuropathic pain is characterised by tingling, sharp 

paroxysmal sensations or burning dysaesthesias and 

is traditionally managed with adjuvant medica- 

tions, including antidepressant and anticonvulsant 

drugs, rather than the opioid analgesic agents used 

for visceral and somatic pains. However, lately, 

opioids are being used successfully in the treatment 

of neuropathic pain. 

Many patients suffer from neuropathic pain as 

a result of injury to the peripheral nervous system 

(e.g. limb amputation, post-herpetic neuralgia or 

diabetic neuropathy) or to the central nervous 

system (e.g. spinal cord injury or stroke). 

The most distinctive symptom of neuropathic 

pain is allodynia, whereby normally non-painful 

stimuli, such as light touch, are interpreted as pain. 

Traditionally, inflammatory and neuropathic 

pain syndromes have been considered distinct 

entities. However, recent evidence shows the contrary. 

Nerve damage can stimulate macrophage 

infiltration and increase the number of activated T 

cells. Under these conditions, neuro-inflammatory 

and immune responses contribute as much to the 

development and maintenance of chronic pain as 

the initial damage itself. Recently, studies using 

animal models have shown that up-regulation of 

chemokines is one of the mechanisms underlying 

the development and maintenance of chronic pain. 

Chronic, non-cancer-related pain (most commonly 

seen in pain clinics) involves several different 

pathophysiological problems that usually 

render the sufferer unable to enjoy life, but do not 

directly threaten life. This type of pain is most often 

described in relation to an anatomical site and typically 

engenders considerable anxiety. 

Myofascial pain (i.e. pain arising from muscle 

and connective tissue), another extremely common 

cause of patients visiting the pain clinic, accounts 

for a considerable amount of chronic, non-cancerrelated 

pain. It requires specific active therapy 

(e.g. stretching, trigger point injections, intensive 

physiotherapy) and corrective actions for pain relief. 

Neuropathic pain 

Neuropathic pain, caused by a lesion or dysfunc- 

tion of the nervous system is especially problematic 

because: 

• It is often experienced in parts of the body that 

otherwise appear normal. 

• It is generally chronic, severe and resistant to 

over-the-counter analgesics. 

• It is further aggravated by allodynia (touchevoked 

pain). 

It may result from various causes that affect the 

brain, spinal cord and peripheral nerves, including 

cervical or lumbar radiculopathy, diabetic neuropathy, 

cancer-related neuropathic pain, post-herpetic 

neuralgia, HIV-related neuropathy, spinal cord 

injury, trigeminal neuralgia and complex regional 

pain syndrome (CRPS) type II, among others. 

CRPS type I is a classic neuropathic-type pain but 

there is no definable nerve lesion. 

The epidemiology of neuropathic pain has not 

been adequately studied, partly because of the 

diversity of the associated conditions. Current 

pooled estimates suggest that neuropathic pain 

may affect as much as 3% of the population in 

the US. SA has no data regarding the incidence of 

neuropathic pain. 

The impact of neuropathic pain is most vividly 

appreciated by people who personally experience 

this devastating condition. Those affected have 

described their pain using the McGill Pain 

Questionnaire with descriptors such as ‘punishingcruel’ 

and ‘tiring-exhausting’. Ample evidence 

indicates that neuropathic pain impairs patients’ 

mood, quality of life, activities of daily living and 

performance at work. People with the condition 

have been found to generate three-fold higher 

healthcare costs compared to matched controls. 

In the US, health care, disability and related costs 

associated with chronic pain have been estimated 

at $150bn annually, of which almost $40bn is attributable 

to neuropathic pain. No such data are 

available in SA. 

Pathophysiology and molecular mechanisms 

of neuropathic pain 

Three different mechanisms play a role in the 

pathophysiology of neuropathic pain: 

1. Peripheral mechanisms 

Regeneration after nerve injury results in the 

formation of neuromas and sprouting of new 

nerve projections among uninjured neighbouring 

neurons. Collateral sprouting then leads to 

altered sensory properties that may be realised as 

expanded receptive fields. Uncontrolled neuronal 

firing after experimental nerve injury is largely 

attributed to increased expression of sodium channels. 

This mechanism is supported by several lines 

of evidence, including blockade of neuropathic pain 

with sodium-channel-blocking local anaesthetics. 

Demyelination of diseased nerves may be 

another cause of increased neuronal excitability. 

In addition to sodium channels, expression of 

voltage-gated calcium channels is also increased 

following nerve injury. Calcium entry through 

voltage-gated calcium channels is necessary for 

the release of substance P as well as glutamate from 

injured peripheral nerves. Within the dorsal root 

ganglion, increased expression of the α-2-delta subunit 

of voltage-gated calcium channels correlates 

with onset and duration of allodynia. Clinical 

support of the role of this protein in neuropathic 

pain arises from the analgesic efficacy of α-2-delta 

voltage-gated calcium-channel antagonists, gabapentin 

and pregabalin. 

... to page 6 






2. Central mechanisms 

Sustained painful stimuli result in spinal sensi- 

tisation, which is defined as heightened sensitivity 

of spinal neurons, reduced activation thresholds 

and enhanced responsiveness to synaptic inputs 

(i.e. more likely to transmit pain to the brain). 

This can manifest in expansion of the affected 

area, increased response to painful inputs and 

transmission of pain following non-painful 

stimuli. Central sensitisation is largely mediated 

by the N-methyl-D-aspartate (NMDA) receptor. 

Although experimental NMDA-receptor blockade 

clearly suppresses central sensitisation, analgesic efficacy 

of NMDA antagonists has been disappointing, 

probably because of the narrow therapeutic 

window of available agents. 

Activation of descending pathways (the periaqueductal 

grey-rostral ventromedial medulla) has 

been shown to reduce pain transmission in animals 

and humans, and is thought to contribute to the 

analgesic effect of opioids and antidepressants. 

3. Sympathetically maintained pain 

The importance of the sympathetic nervous 

system in neuropathic pain has been demonstrated 

by analgesia following sympathectomy in animals 

and humans, and by pain exacerbation through 

activation of the sympathetic nervous system. 

Sympathetically maintained pain may be explained 

by sprouting of sympathetic neurons into 

dorsal root ganglia of injured sensory neurons and 

post-injury sprouting of sympathetic fibres into 

the dermis. 

Clinical presentation and evaluation of 

patients 

The disruption of nerve conduction in neuropathic 

conditions causes nerve dysfunction, 

which can result in numbness, weakness and loss 

of deep tendon reflexes in the affected nerve area. 

Neuropathic conditions also cause aberrant symptoms 

of spontaneous and stimulus-evoked pain. 

Spontaneous pain (continuous or intermittent) is 

common, as is hyperalgesia (increased pain evoked 

by a painful stimulus). 

Allodynia can be caused by the lightest stimulation, 

such as skin contact with clothing or a light 

breeze. These sensory abnormalities may extend 

beyond nerve distributions, which may lead to the 

inappropriate diagnosis of a functional or psychosomatic 

disorder. The diagnosis of neuropathic 

pain is based primarily on history and findings on 

physical examination. 

Assessment of the patient with suspected 

neuropathic pain should focus on ruling out 

treatable conditions (e.g. spinal cord compression, 

neoplasm), confirming the diagnosis of neuropathic 

pain and identifying clinical features (e.g. 

insomnia, autonomic neuropathy) that might help 

an individual’s treatment. 

Current management 

Nonpharmacological 

Although many patients with neuropathic pain 

pursue complementary and alternative treatments, 

rigorous evidence supporting efficacy of non-drug 

therapy is limited. Some reports suggest benefits of 

conservative interventions such as exercise, transcutaneous 

electrical nerve stimulation, percutaneous 

electrical nerve stimulation, graded motor imagery 

and cognitive behavioural therapy or supportive 

psychotherapy. 

Pharmacological 

One approach to estimate treatment efficacy 

using randomised controlled trial (RCT) data is 

based on the number needed-to-treat (NNT) to 

obtain at least 50% pain relief in one patient. The 

NNT concept is hampered by methodological 

variability across different RCTs, the short-term 

nature of most RCTs and the lack of consideration 

for other important outcomes (disability, quality of 

life). Also, most RCTs have involved patients with 

diabetic peripheral neuropathy and post-herpetic 

neuralgia, and the results do not necessarily apply 

to other neuropathic pain conditions. 

Tricyclic antidepressants 

These drugs have repeatedly been shown to 

reduce neuropathic pain. Analgesic actions may 

be attributable to noradrenaline and serotonin 

reuptake blockade (presumably enhancing descending 

inhibition), NMDA-receptor antagonism 

and sodium-channel blockade. The NNT is about 

three for both balanced noradrenaline and serotonin 

reuptake inhibitors (e.g. amitriptyline) and 

predominantly noradrenaline reuptake inhibitors 

(e.g. nortriptyline). 

Selective serotonin reuptake inhibitors (NNT = 

6.7) and mixed serotonin- noradrenaline re uptake 

inhibitors (SNRIs) (venlafaxine and duloxetine, 

NNT = 4.1-5.5) do not appear to be as effective 

as tricyclic antidepressants. Duloxetine is the 

only SNRI registered in SA for the treatment of 

neuropathic pain. 

Anticonvulsants 

Based on methodologically flawed trials, carba- 

mazepine and phenytoin have NNTs of 2.1-2.3 for 

diabetic peripheral neuropathy. Both have significant 

adverse effects, making them generally poor 

candidates for first-line therapy. Carbamazepine, 

however, is still considered first-line therapy for 

trigeminal neuralgia, a unique neuropathic pain 

condition (NNT = 1.7). 

Gabapentin, an α-2-delta subunit voltage-gated 

calcium channel antagonist, has repeatedly demonstrated 

analgesic efficacy and improvements 

in mood and sleep in several RCTs (NNT = 3.8). 

Pregabalin is a gabapentin analogue with a similar 

mechanism, higher calcium-channel affinity and 

better bioavailability. Pregabalin was superior to 

placebo in several RCTs in diabetic peripheral 

neuropathy and postherpetic neuralgia (NNT = 

4.2). Pregabalin has also been registered in SA for 

the treatment of neuropathic pain. 

RCTs of other anticonvulsants, including 

valproate, lamotrigine and topiramate, have had 

equivocal results. 

Opioid analgesics 

The role of opioid analgesics in neuropathic pain 

has been controversial. However, a recent metaanalysis 

provides convincing evidence of benefit. 

Although 14 short-term RCTs (




patients (most of whom had neuropathic pain) who 

had received chronic opioid therapy for one year or 

more suggest that many patients may continue to 

enjoy persistent pain relief with opioids. 

Tramadol is a weak opioid and a mixed SNRI. 

Three RCTs of tramadol for neuropathic pain 

yielded an overall NNT of 3.9. 

Methadone is a synthetic opioid, potentially 

useful for controlling neuropathic pain because of 

its NMDA-antagonist properties. However, its long 

half-life (24-36 hours) necessitates extremely careful 

dose titration. Two small RCTs of methadone 

demonstrated benefit in managing neuropathic 

pain, and open-label experience suggests promise 

in a wide variety of neuropathic pain conditions. 

NMDA antagonists 

Because of the critical role of NMDA activity 

in central sensitisation, NMDA antagonists hold 

promise in the management of neuropathic pain. 

Unfortunately, available agents have limited efficacy 

and produce intolerable side effects. Ketamine, an 

intravenous anaesthetic with NMDA-antagonist activity, 

has been found to be effective in small RCTs. 

Approach to neuropathic pain management in 

primary care 

No single drug works for all neuropathic pain 

states, and given the diversity of pain mechanisms, 

patient responses and diseases, treatment must 

be individualised. Other than analgesia, factors 

to consider when individualising therapy include 

tolerability, other benefits (e.g. improved sleep, 

mood and quality of life), low likelihood of serious 

adverse events and cost-effectiveness to the patient 

and the healthcare system. The evidence-based approach 

presented here may require revision, as newer 

treatments and clinical evidence become available. 

Pain management requires ongoing evaluation, 

patient education and reassurance. Diagnostic evaluation 

of treatable underlying conditions (e.g. spinal 

cord compression, herniated disc, neoplasm) should 

continue concurrently with pain management. 

Patients require education regarding the natural 

history of their condition and realistic treatment 

expectations (e.g. current treatments are not curative 

and analgesia is rarely complete). Even a 30% 

pain reduction is clinically important to patients. 

Pain severity, patient complexity (e.g. coexisting 

depression or substance abuse), failure of attempted 

treatments and availability of healthcare resources 

should be considered when planning referrals to 

pain clinics and related specialists. Patient compliance 

and adequacy of analgesic drug titrations (e.g. 

dose and duration of treatment) should be continually 

evaluated and documented. 

Neuropathic pain is best managed with a multidisciplinary 

approach. Nevertheless, several different 

treatments can be initiated in the primary care 

setting. Treatments with the lowest risk of adverse 

effects should be tried first. Evidence supporting 

conservative non-pharmacological treatments (e.g. 

physiotherapy, exercise, transcutaneous electrical 

nerve stimulation) is limited. However, given their 

presumed safety, non-pharmacological treatments 

should be considered whenever appropriate. 

Simple analgesics (e.g. acetaminophen, NSAIDs) 

are usually ineffective in pure neuropathic pain but 

may help with a coexisting nociceptive condition 

(e.g. sciatica with musculoskeletal low-back pain, 

myofascial pain syndrome). Early referrals to a 

pain clinic for nerve blocks may be warranted in 

some cases to facilitate physiotherapy and pain 

rehabilitation. 

For other neuropathic pain diagnoses, oral monotherapy 

with anticonvulsants, a tricyclic antidepressant 

or a mixed SNRI is recommended. Tricyclic 

Table 1: Aetiology of neuropathic pain 

Classification Aetiology 

Hereditary Porphyria 

Metabolic Diabetes mellitus 

Nutritional deficiency 

Hypothyroid 

Amyloid 

Uraemic 

Immune mediated Multiple myeloma 

Infectious Post-herpetic 

HIV 

Toxic (including Isoniazide 

drugs) 

Nitrofuratoin 

Vincristine 

Cisplatin 

Arsenic 

Thallium 

Compression Tumour 

Radiation fibrosis 

Ischaemic Peripheral vascular 

disease 

Traumatic/ Peripheral nerve injuries 

post-surgical Stump pain and 

phantom limb pain 


antidepressants appear to be more efficacious and 

much less expensive but have a higher likelihood of 

adverse effects and are relatively contraindicated for 

use in patients with serious cardiovascular disease 

(a screening electrocardiogram is recommended before 

prescribing tricyclic antidepressants), postural 

hypotension, urinary retention and angle-closure 

glaucoma. 

Among available tricyclic antidepressants, nortriptyline 

and desipramine are more highly recommended 

because of fewer side effects. Newer mixed 

SNRIs (e.g. venlafaxine, duloxetine) may not be as 

efficacious as tricyclic antidepressants but appear 

to be better tolerated. Of these anticonvulsants, 

gabapentin and pregabalin appear to be the best 

tolerated, with very few drug interactions. 

Conclusion 

Neuropathic pain is widely recognised as one 

of the most difficult-to-treat pain syndromes. A 

common cause of poor outcome is the failure to 

properly assess and effectively treat real and significant 

psychological cofactors and emotional comorbidities 

that make coping with chronic pain so 

difficult - such as poor sleep, depression and anxiety. 

These cofactors and comorbid conditions represent a 

dynamic triad of negatively reinforcing pathologies 

that must be adequately assessed in each patient 

to optimise treatment outcome. Assessment of an 

individual patient can be carried out promptly and 

efficiently if the clinician relies mostly on patient 

self-evaluation using relatively simple screening 

questionnaires, such as the Brief Pain Inventory, 

Beck Depression Inventory and sleep diaries. These 

assessment tools can identify those patients with 

psychological distress and psychiatric comorbidities, 

who will require further evaluation to determine a 

diagnosis and begin treatment, choosing from a 

wide range of effective pharmacological therapies 

and psychotherapies. 

Effective treatment of comorbidities will enhance 

outcomes of pain treatment. Single-agent therapy is 

possible in many situations, especially when drugs 

are selected to address both the pain and the most 

significant comorbidities. Though it is relatively 

rare for a patient to obtain complete pain relief, 

improvements in functionality and quality of life 

are clearly obtainable goals in the treatment of 

neuropathic pain patients and, indeed, represent the 

most practical measures of effectiveness at this time. 




Postoperative Pain Control 

a Human Right 

Dr Milton Raff, 

President, PainSA 

The International Association for the Study of 

Pain (IASP) has declared the period from October 

2010 to September 2011 as the Year of Acute Pain 

Management. Management of acute pain is not 

a luxury - it is a human right. Postoperative pain 

management falls within this category and these 

patients should be carefully managed. 

Three broad categories of pain exist. The first 

is nociceptive pain, which is pain re sulting 

from a noxious insult to the body. This is 

often followed by the second type of pain, inflammatory 

pain, resulting from the release of inflammatory 

mediators from the various tissue types. 

The last category is neuropathic pain, which 

results from damage or disease to the nervous system. 

The picture can become complicated in that 

pain may be of a mixed variety such as that found 

in cancer and lower back pain, where there is more 

than one type of pain component involved. 

The reason for this classification is that, in 

broad terms, both nociceptive and inflammatory 

pain will respond to opioids, paracetamol, nonsteroidal 

anti-inflammatory drugs (NSAIDs) and 

cycloxygenase-2 inhibitors (Coxibs). 

Neuropathic pain is unlike the other two types, 

in that it tends to respond to other classes of drugs 

such as delta-2 calcium channel blockers, antiepileptics 

and various classes of antidepressants. For 

the purposes of our discussion, we must state that 

postoperative pain is nociceptive pain. 

There are many means and methods to achieve 

good postoperative pain control. A basic understanding 

of the mechanisms involved in pain 

perception and the management of these mechanisms 

is needed. 

The steps used to control pain are based on your 

clinical experience and the clinical state of the 

patient and their specific comorbidities. It is very 

clear that the multimodal model of pain management 

has significant benefits for the patient in 

terms of pain management and that all or some 

of the steps described below should be utilised for 

optimal management of postoperative and other 

forms of acute pain. 

The multimodal model uses the synergistic 

properties of the various agents to enhance the 

analgesia while administering lower doses of 

each agent. 

At the same time, the use of lower doses of each 

agent diminishes the frequency of the side effects 

of the various agents employed. 

The following are the physiological steps of 

pain perception. 

Step 1 

A surgical insult will result in the release of an 

‘inflammatory soup’ that contains prostaglandins. 

Managing this release is possible using NSAIDs 

or Coxibs. Evidence shows that either class of 

drug may be used, as both have equal analgesic 

properties in the acute situation. 

Step 2 

Once a nerve impulse has been generated, it 

will be transferred from the peri phery to the spinal 

cord by means of peripheral nerves. The mecha- 

nism of transfer involves sodium ions. 

Blocking of the sodium channels will, there- 

fore, inhibit transfer of the painful impulse. 

A local anaesthetic would do this. 

Several local anaesthetic solutions are available 

and the point that the block must be administered 

will be based on the individual patient. 

Table 1 outlines appropriate contexts where a 

local anaesthetic may be indicated. 

Table 1: Type and site of local anaesthetic 

Local anaesthetic Site of administration 

Lignocaine Skin infiltration 

Bupivacaine Wound infiltration 

Ropivacaine Joint infiltration 

Levobupivacaine Ring block 

Prilocaine Peripheral nerve 

block 

Amethocaine Plexus nerve block 

Epidural block 

Spinal block 

Step 3 

The impulse reaches the dorsal horn of the 

spinal cord. In order to transfer the pain sensation, 

a process involving calcium ions is involved. 

Gabapentinoids prevent influx of the calcium into 

the cells. This class of drugs blocks the alpha-2 

delta sub-unit of the calcium channel. 

Patients with 

postoperative pain 

should be carefully 

managed 

The most commonly employed agents are 

gabapentin and pregabalin. These agents may 

be used as part of a premedication and can be 

continued into the post operative phase. There is 

good evidence demonstrating the opioid-sparing 

effect of these agents. 

8 • August 2011 A Medical Chronicle supplement 

Step 4 

Further impulse conduction involves activating 

the N-methyl-D-aspartate (NMDA) receptors in 

the spinal cord. It is possible to block this receptor 

by using ketamine. This can be used in the form 

of a single bolus or a continuous infusion. 

Step 5 

Transfer of the pain message from the dorsal 

horn of the spinal cord to the cortex and limbic 

system. The cycloxygenase system plays a significant 

role in this regard and it can be inhibited 

by the use of NSAIDs and Coxibs as well as 

paracetamol. 

It is clear that the use of intravenous paracetamol 

significantly reduces opioid use and greatly increases 

postoperative pain relief. 

Step 6 

The mainstay of pain relief remains opioids. 

... to page 10


Postoperative Pain 

Control a Human Right 


However, their use is associated with a myriad of 

side effects. The aim of multimodal analgesia is 

to reduce the use of opioids in order to decrease 

their side effects. Opioids do play a significant 

role in postoperative analgesia and when other 

agents have proven ineffective, opioids must be 

administered. 

The intravenous route for administration of 

the opioids is a predictable one and acts within 

a short timeframe. It does not make sense to use 

the intramuscular, rectal or oral route in an acute 

situation, as absorption via these routes is slow and 

unpredictable, being influenced by many factors, 

including blood flow to the various body tissues. 

Step 7 

The limbic system has a mechanism of inhibit- 

ing the incoming painful impulse at the dorsal 

horn via serotonin and noradrenaline. These two 

substances affect an inhibitory response and by 

so doing, lessen the pain experience. 

We can employ this mechanism as part of a 

Table 2: Site of action, mechanism and agents 

Step Site of action Mechanism Agents 

1 Peri pheral Prosta glandins NSAIDs 

Coxibs 

2 Nerves Sodium ion Local anaesthetics 

3 Dorsal horn Calcium ion Pregabalin 

Gabapentin 

4 Dorsal horn NMDA Ketamine 

5 Spinal cord Prosta glandins Paracetamol 

NSAIDs 

Coxibs 

6 Cerebral cortex Opioid receptors Opioids 

7 Limbic system Serotonin 

Nor adrenaline 

Tramadol 

multimodal regimen, by using tramadol. This acts 

at the spinal cord level by inhibiting the reuptake 

of serotonin and noradrenaline, thus mimicking 

the natural inhibitory system. 

There are obviously many ways to administer 

these drugs. These include patient-controlled analgesic 

pumps, intrathecal drug delivery systems, 

single shot and continuous infusion techniques. 

Once again, the choice of agents, the routes of 

administration and the appropriate indications 

and contraindication for the drugs remains the 

choice of the doctor involved. 

Table 2 summarises the ‘tools’ available to 

improve the management of postoperative pain. 

This is done by understanding the mechanism of 

the physiological conduction of the pain impulse 

through the various sites of communication in 

the nervous system. 

It clearly is not appropriate to use every tool 

on every patient, but as many agents as possible 

should be used to ensure that, in applying multimodal 

analgesia and the synergism that this 

provides, patients are as pain free as possible, with 

minimal side effects. 



How Anaesthesiologists 

Can Reduce Pain 

Dr Eric Hodgson 

Secondary analgesics, such as antidepressants, 

anticonvulsants and antiarrhythmics as well 

as neuraxial techniques all have a role to play 

in terms of chronic pain management. Specific 

clinical conditions such as back pain and failedback-surgery 

syndrome will also be examined. 

Secondary analgesics are drugs that are used 

for indications other than pain relief but have 

analgesia as one of their secondary effects. 

Antidepressants 

Tricyclic antidepressants (TCAs) are still 

the mainstay of chronic pain treatment. These 

drugs have a number of beneficial effects in 

addition to their analgesic properties mediated 

by noradrenaline (NA) and 5HT3 reuptake 

inhibition. Amitriptyline and dothiepin have 

significant sedative effects that are very useful 

where chronic pain is associated with insomnia. 

Nortryptiline is a less sedating drug that is useful 

if sedation becomes problematic. Muscle spasm 

is a prominent component of many chronic pain 

conditions which, contrary to the beliefs of many 

clinicians, is better treated with a TCA than a 

benzodiazepine. Not only are the anticholinergic 

effects of the TCAs much more potent in terms 

of muscle relaxation than the effects of benzodiazepines 

on the GABA receptors, but TCAs 

are not addictive while benzodiazepines cause 

rapid dependence. 

Atypical antidepressants include duloxetine 

and venlafaxine. Despite 30 years of experience 

with amitriptyline, there are only 17 papers on 

the use of amitriptyline in the treatment of pain 

compared with 244 for duloxetine. Nonetheless, 

the approach of most pain clinicians would be to 

start with a TCA for acute treatment and only 

switch to the more expensive alternatives in cases 

of treatment failure or side effects. 

Anticonvulsants 

Carbamazepine was the first anticonvulsant 

to show benefit for the treatment of neuropathic 

pain and is still the drug of choice for trigeminal 

neuralgia. The risk of liver and bone marrow 

damage with carbamazepine and the unpredictable 

pharmacokinetics of the drug require 

regular levels. 

Clonazepam has been used, particularly for 

sciatica and phantom pain, but the dissociation 

experienced by patients on both a TCA and 

clonazepam may be felt to be more unpleasant 

than the pain itself. 

Thus, unlike the antidepressants, the newer 

anticonvulsants, gabapentin and pregabalin, 

have superior efficacy and reduced side effects 

compared with the older drugs. Pregabalin has 

predictable, linear pharmacokinetics but superior 

efficacy compared with gabapentin (clinical use 

has yet to be fully elucidated). 

Antiarrhythmics 

Some forms of neuropathic pain may prove 

refractory to TCAs, anticonvulsants and opioids. 

A small number of these patients may respond 

to lignocaine, and its oral equivalent mexelitine. 

Due to the profound gastrointestinal (GI) side 

effects of mexelitine, a diagnostic lignocaine infusion 

(5mg/kg over one hour) should be used to 

define efficacy. A good response to the diagnostic 

infusion means patients are more likely to tolerate 

the GI side effects of mexelitine to achieve 

good quality pain relief. 

Neuraxial techniques 

General anaesthetists may be requested to 

place epidural catheters for a trial of neur- 

axial drugs (local anaesthetic ±opioid ±alpha 2 

agonist /s-ketamine) in pain patients where other 

approaches have failed. The catheter should be 

placed under aseptic conditions in an operating 

theatre if possible. A wire-reinforced catheter 

should be used to avoid problems of kinking. 

Screening to confirm appropriate placement 

(using a small volume of myelogram contrast) is 

justified. Limited tunnelling of the catheter to 

6-8cm lateral to the spine, using the Tuohy needle 

as a conduit, improves patient comfort and 

reduces the risk of dislodgement. The catheter 

should be covered with a clear, semi-permeable 

dressing, which should include the connection 

between the catheter and the filter, to reduce the 

risk of disconnection. Drug delivery should be 

undertaken by a specialist pain team. 

Specific clinical conditions 

Back pain 

Non-surgical management of back pain is successful 

in more than 90% of cases. The ‘red flags’, 

indicating impending permanent neurological 

dysfunction in association with back pain may 

be remembered by the mnemonic TUNA FISH 

(J Fam Pract 2009;58(12):E1): 

Trauma - including neuraxial intervention in 

the last two weeks 

Unexplained weight loss 

Neurological signs - Motor deficits and/or loss 

of sphincter control 

Age >70 - with no previous episodes 

Fever / raised C-reactive protein (CRP) 

Intravenous drug use 

Steroid use: >20mg/day for >30 days within the 

last six months for a long time 

History of cancer 

Failed-back-surgery syndrome 

Surgery for pain relief is unsuccessful in up to 

20% of cases. Pain may persist for a number of 

reasons, the most common of which is pain coming 

from an anatomical structure other than the 

intervertebral disc. Reoperations are much less 

successful compared with primary procedures. 

Complications or failure of the first procedure 

account for 60% of reoperations, while 40% are 

required for new or uncorrected abnormalities. 

Patients presenting for spinal reoperation often 

have prolonged or severe preoperative pain with 

opioid tolerance or resistance. There is a steadily 

decreasing chance for resolution of symptoms as 

more procedures are done. 




Dextropropoxyphene Withdrawal 

Dr Milton Raff 

President PainSA and Chairperson of the WFSA 

Acute Pain Committee 

The South African analgesic market is valued at ap- 

proximately a half a billion rand. Almost one third 

of this market is attributable to products containing 

dextropropoxyphene (DPP).This often maligned 

compound has recently been withdrawn as a result 

of the findings of the Medicines Control Council. 

Many questions have subsequently arisen but two 

of the most pertinent enquiries are Why? and What 

can be used in its place? 

The ‘why’ is quite contentious but is a result of the 

fact that many reports of DPP side effects have been 

published. The adverse events described are addiction, 

arrhythmias and alcohol-related deaths. Given that 

DPP was so frequently used in SA, the validity of the 

studies should be questioned. These studies have been 

examined and found to be scientifically sound and 

valid. If this is the case, then the removal of dextropropoxyphene 

from the market is the correct decision. 

We must then ask why we have not seen similar 

problems. An explanation may be that we have not 

looked for these adverse events or have attributed any 

perceived adverse events to a different cause. The fact 

of the matter is that DPP has been withdrawn from 

the SA market with immediate effect. 

The issue of what can be used in its place must 

be discussed, as the ‘spend’ on the DPP-containing 

products was huge. Prescribing doctors will be forced 

Severe pain 

Moderate to 

severe pain 

Mild to 

moderate 

pain 

Step 3: 

Strong opioids (e.g. 

morphine), with or 

without non-opioids 

Step 2: 

Mild opioids (e.g. codeine), 

with or without non-opioids 

Step 1: 

Non-opioids - aspirin, nonsteroidal 

anti-inflammatory 

drugs (NSAIDs) or paracetamol 

Figure 1: WHO analgesic ladder 

to find an alternative and the choice should be based 

on science. 

To simplify matters, we must look at the World 

Heath Organization’s (WHO) pain ladder (see 

Figure 1). We must also look at available analgesic 

compounds and their efficacy. Surely, this ladder is 

not complete in that it makes no reference to neuropathic 

pain but it does serve as a guide to the rational 

approach to pain therapy. Analgesic efficacy needs to 

be standardised so that the efficacy of the different 

compounds can be compared. This has been made 

possible by the term ‘number needed to treat’ (NNT). 

The NNT is an epidemiological measure used 

in assessing the effectiveness of a health care intervention, 

typically a treatment with medication. 

The NNT is the number of patients who need to 

be treated in order to prevent one additional bad 

outcome (i.e. the number of patients that need to be 

treated for one to benefit compared with a control in 

a clinical trial). It is defined as the inverse of the absolute 

risk reduction. It was described in 1988 (http:// 

en.wikipedia.org/wiki/ number_needed_to_treat - 

cite_note-0). The ideal NNT is one, where everyone 

improves with treatment and no one improves with 

the control. The higher the NNT number, the less 

effective the treatment. 

We must consider whether the compound analgesics 

contain only proven analgesic molecules 

or do they also contain other substances that have 

absolutely no beneficial analgesic effects and may be 

harmful to patients. 

As mentioned, the WHO provides a guide as to 

the type of analgesics that should be used for the 

different levels of pain (see Figure 1). It is unambiguous 

in stating that for mild to moderate pain, health 

professionals should only use proven compounds such 

as paracetamol or aspirin and, should these alone 

provide insufficient pain relief, then a non-steroidal 

anti-inflammatory agent (NSAID) should be added. 

The group of agents known as the COX-2 inhibitors 

may be substituted in place of the NSAIDs. 

If the pain is more severe, then the regimen should 

be augmented by mild opioids, such as codeine 

and tramadol. The final step where pain is severe 

would require the addition of strong opioids, such 

Table 1: Oxford pain table 

Analgesic and dose (mg) NNT 

Etoricoxib 180/240 1.5 

Etoricoxib 120 1.6 

Diclofenac 100 1.8 

Celecoxib 400 2.1 

Paracetamol 1000 + Codeine 60 2.2 

Aspirin 1200 2.4 

Ibuprofen 400 2.5 


Ketorolac 10 2.6 

Naproxen 400/440 2.7 

Piroxicam 20 2.7 

Naproxen 500/550 2.7 



Tramadol 150 2.9 

Morphine 10 (intramuscular) 2.9 

Naproxen 200/220 3.4 

Ketorolac 30 (intramuscular) 3.4 

Paracetamol 500 3.5 

Celecoxib 200 3.5 


Paracetamol 1000 3.8 

Paracetamol 600/650 + Codeine 60 4.2 

Aspirin 600/650 4.4 

Paracetamol 600/650 4.6 




Aspirin 650 + Codeine 60 5.3 

Paracetamol 300 + Codeine 30 5.7 


Codeine 60 16.7 

as morphine and buprenorphine. Extreme pain may 

also be managed with transdermal fentanyl patches. 

Practitioners can be guided by the NNT as to 

which agent they should use, but their knowledge 

of their patient and the specific indications and 

contraindications will be the final determinant as 

to their choice of agent. The Oxford pain table can 

supply the necessary data to enable the choice of 

agent (see Table 1). 

The NNT of the more commonly utilised agents 

can be illustrated by Figures 2 and 3, when they are 

prescribed as single agents. 

One of the problems that we all face is compliance 

by the patients. Should doctors prescribe two, three or 

four different agents and will the patient take the correct 

agent at the correct time? The answer to this question 

is an unreserved ‘No’! This phenomenon has led 

... to page 14 




Dextropropoxyphene 

Withdrawal 


to the manufacture of combination analgesic tablets 

and capsules. SA has in excess of 90 such combination 

products, containing a variety of substances. I believe 

that it befalls us as prescribing practitioners to prescribe 

products that contain only proven analgesic agents. 

Diclofenac 100mg 1.9 

Ibuprofen 400mg 2.4 

Morphine 10mg (IM) 3.8 

Acetaminophen 1000mg 3.8 

Aspirin 650mg 4.4 

Tramadol 100mg 4.8 

Codeine 60mg 16.6 

0 1 2 3 4 5 6 7 8 

Numbers needed to treat 

Figure 2: NNT of common agents 

In this way, we can use synergism to reduce the 

dosages of the individual agents in the combination, 

thereby reducing any potential side effects while 

increasing the desired analgesic properties of the 

combination. Many such ‘pure’ combinations are 

available on the local market (see Table 2). 

Table 2: Efficacy of combination analgesics 

Analgesic (mg) NNT 

Paracetamol 1000 + codeine 60 2.2 

Paracetamol 600/650 + codeine 60 4.2 

Paracetamol 300 + codeine 30 5.7 

Paracetamol 650 + tramadol 75 2.6 

These NNTs can be further reduced by the addition 

of NSAIDs to the combination preparation. 

I have referred to non-analgesic agents used 

in combination analgesic products in SA. I have 

included a table of the agents, their drug class and 

major side effects (see Table 3). 

It should be fairly obvious that these agents have 

no role to play in analgesia. If the prescriber wishes 

to sedate his/her patient, then there are far more appropriate 

agents to use and the adverse effects of the 

agents described above offer no benefit to our patients 

and especially not in terms of analgesia. What then are 

the options available to medical practitioners who wish 

to manage pain appropriately, follow the guidelines 

of the WHO and ensure compliance by the patient? 

Mild to moderate pain 

• Paracetamol 

• NSAIDs 

• Coxibs 

• Aspirin 

Many combination preparations of these sub- 

stances are available - the most common being those 

of paracetamol and ibuprofen. 

Moderate to severe pain 

• Tramadol 

• Codeine 

Given that DPP is no longer available, the next 

most commonly prescribed combinations contain 

codeine, paracetamol and ibuprofen (or tramadol) 

and paracetamol. These combinations make perfect 

pharmacological sense in that they consist of only 

Table 3: Overview of agents 

Agent Class of drug Use Major side effects 

Meprobamate Carbamate Anxiolytic 

Convulsions 

Muscle relaxant Dependence 

Caffeine Xanthine alkaloid CNS stimulant Tachycardia 

Anxiety and headaches 

Sleep disorders 

Diphenhydramine Antihistamine Allergic reactions Anticholinergic effects 

Sedation 

Doxylamine Antihistamine Cold and allergy relief Anticholonergic effects 

Sedation 

Phenobarbitone Barbiturate Anticonvulsant Sedation 

CNS effects 

Figure 3 Etoricoxib 120 

Valdecoxib 40 

Celecoxib 400 

Paracetamol/codeine 1000/60 

Rofecoxib 50 

Ibuprofen 400 

Lumiracoxib 400 

Naproxen 500/550 

Diclofenac 50 

Morphine 10 IM 

Paracetamol 1000 

Aspirin 600/650 

Tramadol 100 

1 2 3 4 5 6 7 

95% CI of NNT for at least 50% pain relief compared with placebo 

proven analgesic substances combined in lower doses 

than as single agents alone. This ensures synergism 

resulting in better analgesia with reduced side effects 

compared to when the individual agents are used 

alone. Of course, we should expect adverse effects as 

with the use of any drug. 

Severe pain 

• Morphine 

• Buprenorphine 

• Tramadol (SR preparations) 

• Fentanyl (transdermal patches) 

Morphine remains the ‘gold standard’ for severe 

pain management. 

It may be noted that pethidine has been omitted 

from this list. This agent is certainly an extremely 

good sedative but not a good analgesic and is of great 

concern regarding its side effect profile as a result of its 

metabolite, norpethidine. It is also the leading agent 

when it comes to drug-seeking behaviour. 

There is very good evidence to suggest that this 

agent should be removed from the international 

pharmacopoeia and it is already unavailable in many 

parts of the world. 

It must be stressed that all agents must be used 

appropriately and that correct prescribing habits must 

be encouraged. Because most of the combination 

agents are composed of low-dose agents, they need to 

be taken at regular intervals rather than occasionally. 

This implies regular medication rather than the ‘pro 

renata’ (PRN). This will ensure that therapeutic levels 

of the analgesics are constant and if used as such, will 

prevent the ‘sawtooth pattern’ of intermittent pain 

relief and pain. 

If health porfessionals adhere to sound pharmacological 

principles and correct prescribing habits, then 

there is no reason for patients to suffer, following the 

withdrawal of DPP. 



Fibromyalgia: a Growing Diagnostic 

and Therapeutic Challenge 


Fibromyalgia (FM) is a chronic condition characterised 

by widespread pain and tenderness 

on examination, along with symptoms of nonrestorative 

sleep, fatigue and cognitive difficulties. 

Fibromyalgia is characterised by: 

1. Widespread pain 

• Above and below the waist 

• Right and left sides of the body 

• Axial skeleton, especially neck and lumbar spine 

2. Pain involves at least 11 out of 18 tender points. 

In addition to the primary diagnosis of fibromyalgia, 

the presence of significant comor bidities 

(see Table 1) should be identified, as therapy for the 

fibromyalgia will be ineffective if these comorbidities 

are not addressed also. 

Pharmacotherapy 

Fibromyalgia is often inappropriately managed 

with non-steroidal anti-inflammatory 

drugs (NSAIDs), particularly intramuscular 

diclofenac. 

As a non-inflammatory pain condition, fibromyalgia 

is unresponsive to NSAID therapy and 

patients are consequently exposed to the risks 

of NSAID therapy without any prospect of 

pain relief. 

Effective pain relief in fibromyalgia may be 

achieved with the following: 

Tricyclic antidepressants: Amitryptiline, at a 

starting dose of 10mg every night, escalated 

every two weeks to a maximum dose of 75mg 

every night, is the cornerstone of therapy of many 

chronic pain states, including fibromyalgia. 

Table 1. Screening questions for fibromyalgia and associated conditions 

Disorder Screening questions 

Fibromyalgia Have you had whole-body pain for a long time? 

Are various parts of your body painful to touch? 

Do you have trouble sleeping? 

Do you feel tired more days than not, without an identifiable reason? 

Anxiety Over the past two weeks, have you felt nervous, anxious, or ‘on edge’? 

Over the past two weeks, have you been unable to stop or control your worrying? 

Chronic fatigue Have you had more than six months of fatigue that is not relieved by rest and is 

syndrome severe enough to limit your daily activities? 

Have you had any of the following symptoms: fever, sore throat, enlarged or painful 

nodes, muscle weakness or pain, headaches, joint aches, trouble concentrating, or 

sleep disturbance? Did any of these symptoms occur over several hours to days? 

Depression Over the past two weeks, have you felt ‘down’, depressed, or hopeless? 

Over the past two weeks, have you had little interest or pleasure in doing things? 

Irritable bowel For three months or more in the past year: 

syndrome Have you had abdominal pain or discomfort that is not relieved with a bowel 

movement? If so, has the pain or discomfort been associated with a change in 

stool frequency or appearance? 

Do you have other symptoms such as heartburn, difficulty swallowing, nausea, 

feeling full soon after starting to eat, or bloating? 

Restless legs Do you have uncomfortable or unpleasant leg sensations when sitting or lying down? 

syndrome Do you have an urge to move when sitting or lying down? 

Are your symptoms worse when you are lying down than when moving around? 

Are your symptoms relieved by moving around or walking? 

Are your symptoms worse at night? 

Sleep apnoea Assess patient for elevated body mass index and hypertension. 

Do you snore? 

Does your snoring bother other people? 

How often have others noticed pauses in your breathing while sleeping? 

Are you tired after sleeping? 

Are you tired during the day? 

Have you ever fallen asleep while driving? 

Temporo- Do you have pain in your temples, face, temporomandibular joint, or jaws at least 

mandibular joint once a week? 

dysfunction Do you have pain at least once a week when you open your mouth wide or chew? 

Beneficial effects include: 

• Relief of insomnia by central sedative effects. 

Insomnia is a prominent and distressing 

symptom of fibromyalgia. 

• Relief of muscle spasm by acetylcholine 

receptor blockade at spinal cord level. This 

anti-spasmodic effect exceeds that of the 

benzo diazepines without the addictive potential 

of these drugs. 

• Secondary analgesic effects by increasing 

levels of noradrenalin and serotonin at spinal 

cord level through re-uptake inhibition of 

these transmitters. This helps to address the 

reduction in descending inhibitory control 

seen in patients with fibromyalgia. 

Serotonin noradrenalin reuptake inhibitors 

(SNRIs): These include drugs such as duloxetine, 

which have been shown to be effective in neuropathic 

pain states such as diabetic and postherpetic 

neuralgias. Effects in fibromyalgia are 

unclear at present, so duloxetine can currently 

only be recommended for patients who are unable 

to tolerate the tricyclic antidepressants. 

Gabapentinoids: These include gabapentin and 

pregabalin, which are both active at the alpha- 

2-delta subunit of the neuronal voltage-gated 

calcium channel. These agents have been shown 

to reduce insomnia and fatigue while improving 

quality of life. 

Opioid analgesics: These have a limited role in 

the management of fibromyalgia. Tramadol is 

a useful drug, less through its effects of opioid 

receptors than on its noradrenalin and serotonin 

reuptake blockade. Buprenorphine has also been 

shown to improve symptoms in fibro myalgia with 

limited risk of addiction. By contrast, the pure mu 

agonists - such as morphine and fentanyl - are less 

useful in the management of fibromyalgia. Mu 

agonists should never be used as first-line therapy 

in fibromyalgia, but should be reserved for patients 

who have failed to respond to appropriate trials of 

both pharmacological and non- pharmacological 

therapy. Opioid therapy for fibromyalgia should 

only be undertaken under the supervision of a 

multidisciplinary pain clinic. 




The Choice of an Appropriate Analgesic 

Should no Longer be Painful 

Dr Luc Evenepoel 

Pain relief is a human right. Trauma patients, 

and especially the severely injured, pose an extra 

challenge to the treating doctor, since there is a 

risk for significant, deleterious side effects from 

inappropriate analgesic ad ministration. 

The pain treatment of the trauma victim has 

to be individualised: excellent pain relief is, of 

course, the goal, but ‘primum non nocere’ (first do 

no harm) should never be forgotten. 

Assessment of pain 

Always ask how much pain the patient has. He/ 

she can judge this much better than the treating 

doctor. Ask awake and oriented patients to rate 

their pain from zero to 10, 0/10 signifying no 

pain and 10/10 the worst pain imaginable. Most 

patients, even children, can easily do this. Also use 

this rating to evaluate the effect of the analgesics 

administered. Most patients are relatively comfortable 

and satisfied when they come down to a 

score of 4/10 or less. For small children, a chart 

with smiley faces can be used. 

Keep in mind that the pain threshold is fairly 

similar between individuals, but that pain tolerance 

varies: the pain of an identical injury can 

be rated 8/10 by one patient, but only 4/10 by 

another. Intoxicated and confused patients, and 

those with a depressed level of consciousness, 

cannot reliably communicate their pain. Do not 

withhold analgesia, but be extra cautious, since 

opioids may further depress consciousness, with 

the added risk of respiratory depression. 

Analgesics 

The main groups are opioids, non-steroidal 

anti-inflammatory drugs (NSAIDs), paracetamol 

and local anaesthetics. To keep this text concise, 

details have been omitted, but can easily be found 

in any pharmacology manual. 

For obese patients, the doses should be calculated 

according to lean body weight (LBW), which 

is ideal body weight (IBW) + 20-30% (ideal body 

weight = 22 x (height in metres) 2 e.g. a patient 

who weighs 140kg and is 1.76m tall has an IBW 

of 22 x (1.76 x 1.76) = 68 kg. LBW is 20 or 30% 

more, about 85kg. 

Opioids 

Not only pain tolerance varies, but also the 

analgesic effect of opioids: it can differ 10-fold 

between individuals. These two factors make it 

difficult to predict a uniformly effective opioid 

dose. Opioids, like all other systemic painkillers, 

are analgesics, not anaesthetic agents; they will 

dull the pain of a fracture, but cannot take away 

the excruciating impulses from a manipulation 

or surgical procedure. Similarly, they will not 

interfere with making a diagnosis. This is, sadly, 

still one of the main reasons their use is postponed 

or withheld - such an approach is inappropriate 

and cruel. 

Excellent pain relief 

is, of course, the 

goal, but ‘primum 

non nocere’ should 

never be forgotten 

Morphine 

Morphine is still the reference opioid - very 

effective, widely available and cheap. 

The onset of analgesic effect is after 3-5 min- 

utes, peak analgesic effect after 10-20 minutes, 

duration of action 3-4 hours (six hours in the 

elderly). If respiratory depression occurs, it will 

happen approximately seven minutes after morphine 

administration. 

Morphine’s effects and side effects described 

here are also relevant to the other opioids. It is 

preferably given intravenously (IV), in principle 

never intramuscularly. Intramuscularly (IM) 

injected morphine is not reliably taken up into 

the blood stream from poorly perfused muscle, 

delaying the analgesic effect and side effects for 

many hours (not only will your patient suffer 

pain unnecessarily, but respiratory depression 

may occur insidiously, when no one is watching 

anymore). The traditional adult total dose of 0.1- 

0.3mg/kg is a rough guideline, and depends on the 

severity of injury, pain tolerance, and the patient’s 

individual opioid sensitivity. 

Give morphine in increments of 0.01-0.02 mg/ 

kg IV every 5-10 minutes. This allows titration of 

the opioid against its effect. The respiratory rate 

should stay above 14 breaths/min. Be aware that 

respiratory depression can occur before significant 

sedation. For a 60kg adult, give boluses of 0.5-1.5 

mg IV every 5-10 minutes. 

To make titration easy, prepare a dilution of 

1mg/ml: 10mg morphine (1ml) in 9ml sterile 

water (or 0.9% saline or 5% dextrose) makes 

10mg/10ml, or 1mg/ml. Don’t forget that some 

patients might require less than 10mg, others 

more or much more. Titrate to effect, aiming for 

a pain score of 4/10 or less, but stop when the 

patient becomes too sedated or suffers respiratory 

depression. With intravenous administration, the 

onset of effect and side effects are predictable: 

blood pressure drops within 2-5 minutes, maximum 

respiratory depression occurs within seven 

minutes and peak analgesic effect occurs within 

10-20 minutes. 

Start the opioid titration during or immediately 

after the initial resuscitation and ensure that the 

patient is comfortable before any painful examination, 

manipulation, or transport is attempted. Be 

aware that morphine can drop the blood pressure 

in the hypovolaemic patient, sometimes severely. 

If this occurs, resuscitate further, and change 

over to other analgesics if needed (e.g. sufentanil, 

regional analgesia). 

The analgesic effect of morphine lasts about 3-4 

hours. Prescribe regular follow-up doses every four 

hours, rather than on demand only. 

Neonates and small children are especially 

sensitive to the respiratory depressant effect 




The Choice of an 

Appropriate Analgesic 

Should no Longer be Painful 


of opioids. Recommended total doses are therefore 

smaller than for adults, i.e.: 

• Younger than three months: 0.025mg/kg 

• Three to 12 months: 0.05mg/kg 

• Older than 12 months: 0.1mg/kg. 

Note that injured children are generally anxious, 

which contributes negatively to their pain 

perception. A small amount of an anxiolytic, such 

as midazolam 0.1mg/kg orally or IV in increments 

of 0.01-0.03mg/kg, in combination with the 

opioid, can be useful. 

For children, dilute 10mg morphine (= 1ml) 

to 100ml: this makes a concentration of 0.1mg/ 

ml. Administer 0.1-0.3ml/kg IV of this mixture 

every 5-10 minutes. Neonates are very sensitive: 

use small increments, and wait for the effect, 

don’t be hasty. 

Side effects of morphine (and other opioids) 

Hypotension 

Because of histamine release, even small 

amounts of morphine may cause a drop in blood 

pressure in hypovolaemic patients. Halve the dose, 

and wait long enough in between the increments to 

ensure the blood pressure remains stable. Note that 

elderly patients are especially prone to hypotension. 

Respiratory depression 

The risk is vastly enhanced in patients who have 

ingested alcohol, benzodiazepines, barbiturates, or 

other central nervous system depressants. Titrate 

to effect and watch for side effects. The fear for 

respiratory depression is what often makes medical 

personnel underdose their patient (too little, 

too late), causing unnecessary suffering. Pain is 

an excellent antagonist for respiratory depression. 

Do not administer morphine to head-injured 

patients, where respiratory depression leads to 

hypercapnia, cerebral vasodilation, and increased 

intracranial pressure. If the patient is ventilated, 

this of course becomes irrelevant, because the 

ventilator ensures normocapnia. 

Pethidine 

Pethidine has some anticholinergic properties: 

its mild positive chronotropic effect is especially 

attractive in small children because they depend 

mainly on heart rate to maintain their cardiac output. 

Do not give to elderly patients because it can 

lead to confusion. Avoid with renal impairment 

(accumulation and toxicity, risk for convulsions). 

The duration of effect is 2-3 hours, not six hours 

as it is commonly prescribed. The recommended 

dose is 1-1.5mg/kg. 

As for morphine, intravenous titration of small 

increments is strongly preferred over intramuscular 

administration. Increments of 10-15mg are 

suitable for the average adult. In children, increments 

of 0.1-0.2mg/kg are suitable, with the same 

precautions as mentioned for morphine. 

The fear for 

respiratory 

depression is 

what often makes 

medical personnel 

underdose their 

patient (too little, 

too late), causing 

unnecessary 

suffering 

Pethidine has a dysphoric effect in some patients 

(morphine is mildly euphoric). Ask your 

patient if he/she ever had an opioid in the past, 

and about its effect and side effects. Morphine 

remains the opioid of choice. 

Tilidine 

Tilidine is effective against moderate to mod- 

erately severe pain. It is well absorbed when given 

sublingually or intranasally, but should not be 

given intravenously. The duration of action is 

4-6 hours. 

Adult dose: 50-100mg, but it should be individualised. 

It is often necessary to start with 

100mg, repeated after two hours with another 

100mg; thereafter 50-100mg every 4-6 hours. 

Paediatric drops (2.5mg per drop): generally 

1mg/kg. In children 1-9 years, give one drop per 

year of age plus two drops; or the weight in kg/2.5 

= the number of drops. In children 10 years and 

older, the weight in kg/2.5 = the number of drops. 

Do not give to children less than one year old. 

Tramadol 

Tramadol is effective against moderate to mode- 

rately severe pain, but is unsuited to treatment of 

severe pain. Its main advantage is the lack of 

respiratory depression. Tramadol is the preferred 

opioid for spontaneously breathing head-injured 

patients, as it has very little respiratory depressant 

effect. Titrate to effect, approximately 0.15mg/kg 

every 3-5 minutes, until the patient is comfortable. 

Depending on certain characteristics of 

metabolism of the patient, tramadol might not 

work well, or work stronger than expected (with, 

indeed, some respiratory depression). Again, 

titrate to effect. 

Do not use in combination with pethidine or 

HT3-antagonist anti-emetics like granisetron, 

ondansetron, dolasetron - there is the risk of 

serotoninergic syndrome. This syndrome is characterised 

by mental symptoms (disorientation, 

agitation, confusion, hallucinations), autonomic 

symptoms (hypertension, tachycardia, sweating, 

diaphoresis, hyperthermia, mydriasis) and 

musculoskeletal symptoms (tremors, shivering, 

hypertonia, stuttering). These symptoms can also 

be seen with intravenous administration that is too 

quick. The use of tramadol is not recommended 

for children less than 14 years old. 

Sufentanyl 

Sufentanyl is quicker in onset of effect and side 

effects (1-5 minutes) than morphine, and there- 

fore more efficient to titrate IV. It is much more 

cardiovascularly stable than morphine, and has a 

short duration of action (1-2 hours), so don’t forget 

to reassess the patient’s pain, and re-administer 

analgesics if needed. 

One ampoule of 2ml contains 0.01mg (10mcg) 

sufentanyl. Titrate IV with increments of 0.02- 

0.04mcg/kg every 2-5 minutes, i.e. 1.25-2.5mcg 

(0.25-0.5ml) per bolus for a 60kg adult. 

Codeine 

In spite of popular belief, codeine is a poor an- 

algesic. Codeine is popular among neuro surgeons 

to treat pain in head-injured patients, because it 

has little respiratory depressant effects. Tramadol 

remains an attractive alternative. 



Chronic Pain Management and 

the General Anaesthesiologist 


Nonsteroidal anti-inflammatory drugs (NSAIDs) 

have a unique role in pain management. Studies 

from the Brain Research Institute at the University 

of the Witwatersrand have shown that NSAIDs do 

not provide analgesia but are potent antihyperalgesics. 

To understand the difference, it is necessary 

to understand the concept of the pain threshold. 

Inflammation shifts the stimulus response 

curve for pain to the left so that stimuli that would 

not induce pain in the control situation are now 

painful - hyperalgesia. In addition, stimuli such 

as light touch, that are not painful are perceived 

as painful - allodynia. NSAIDs can return the 

stimulus response curve back towards normal but 

cannot shift the curve to the right of baseline, and 

are thus not analgesic. 

NSAIDs affect nitric oxide synthase (NOS) 

in the spinal cord via guanylate cyclase to reduce 

central sensitisation. The effect of NSAIDs on NS 

is also being implicated in the cardiovascular side 

effects of these drugs. 

Biochemically the NSAIDs may be classified 

as follows: 

1. Full inhibition of both COX-1 and COX-2 

with poor selectivity - aspirin, diclofenac, 

ibuprofen 

2. Full inhibition of COX-1 and COX-2 with 

preference toward COX-2 - celecoxib (initial), 

meloxicam 

3. Strong inhibition of COX-2 with only weak 

activity against COX-1 - celecoxib (delayed), 

etoricoxib, parecoxib 

4. Weak inhibitors of COX-1 and COX-2 - sulindac, 

paracetamol 

Clinically there are three subdivisions of the 

NSAIDs: 

1. Non-selective NSAIDs (nsNSAIDs): Block 

both COX-1 and 2 to variable extents 

a. Aspirin-like: Predominant COX-1 block 

(aspirin, ketorolac) - greatest GI side effects, 

minimal CV effects 

b. Coxib-like: Mixed COX-1 and 2 block 

(ibuprofen, diclofenac) - both GI and CV 

side effects 

2. Coxibs: Predominantly block COX-2 - fewest 

GI side effects, predominant cardio vascular 

effects 

The choice of an NSAID for clinical use in 

patients without renal dysfunction is facilitated 

by the table below: 

NSAIDs and aspirin 

Risk of CVS Events 

Low High 

Low Clinician Aspirin/ 

Risk 

of GI / 

surgical 

bleeding 

High 

choice 

Coxib 

NSAID or 

equivalent 

Avoid all 

NSAIDs and 

short-term 

coxib 

nsNSAIDs are competitive binders to COX-1 

while aspirin is a non-competitive binder. Thus, if 

aspirin is co-administered with an nsNSAID, even 

an aspirin-like NSAID, the nsNSAID will limit 

access of aspirin to the platelet COX-1. 

The plasma half-life of aspirin is only two hours, 

compared with at least four hours for commonly 

used nsNSAIDs. Inhibition of platelet COX-1 

(>95%) is required to achieve the therapeutic effect 

of aspirin for primary and secondary prevention 

of cardiovascular disease. 

Co-administration of nsNSAIDs and aspirin 

not only reduces the therapeutic effect of aspirin 

for cardiovascular disease but amplifies the GI 

side effects of both drugs. 

Coxibs do not interfere with aspirin binding to 

platelet COX-1 and do not increase the likelihood 

of GI side effects with concurrent aspirin use. In 

patients on long-term aspirin therapy, short-term 

coxib therapy may prove less harmful than shortterm 

nsNSAID therapy. However, long-term use 

is less clear. Rofecoxib increased cardiovascular 

events despite co-administration of aspirin while 

the effect of celecoxib was neutral. 

Intermediate opioids 

The majority of patients with chronic pain will 

require opioid therapy in addition to baseline antihyperalgesic 

therapy. Two drugs are extremely 

useful for long-term therapy. 

Tramadol 

Tramadol is a weak direct mu agonist with 

a potency equivalent to codeine and a ceiling 

effect with a very limited potential to cause addiction. 

The main analgesic property of tramadol 

is through re-uptake inhibition of noradrenalin 

(NA) and serotonin (5-HT) to amplify the effects 

of endogenous descending pain control in synergy 

with the tricyclic antidepressants. 

Tramadol’s side effects are due to central elevation 

of 5-HT causing dysphoria and nausea. 

Treatment of nausea with 5-HT3 antagonists, 

such as ondansetron, was thought to reduce 

the analgesic efficacy of tramadol but analgesia 

is mediated via the 5-HT1 receptor and the 

mu- and noradrenalin-mediated analgesic effects 

are unchanged. 

Buprenorphine 

Buprenorphine is a direct mu agonist with a 

ceiling effect that lies above levels achievable with 

clinically relevant doses. Like tramadol, buprenorphine 

therapy carries a low risk of addiction and 

may be used as an alternative to methadone for 

treatment of opioid addiction. 

Buprenorphine is the only opioid that has been 

shown to prolong regional blocks and is effective 

like other opioids administered neuraxially. 

Sublingual and transdermal preparations are 

available where the GI tract is non-functional or 

inaccessible. 

Potent opioids 

Morphine and fentanyl were initially used to 

treat terminal cancer patients with pain in the last 

weeks to months of life. 

The utility of these drugs has been increasingly 

recognised in patients with chronic nonmalignant 

who continue to have pain despite appropriate 

multi modal therapy as outlined above. 

Prior to initiation of long-term opioid therapy, 

both the patient and the clinician have to have a 




Chronic Pain 

Management and the 

General Anaesthesiologist 


clear idea of the goals of therapy and the obliga- 

tions that each of them has in assuring its success. 

Ideally the patient should undergo psychological 

assessment to rule out addiction/dependence issues. 

Pseudo-addiction may be seen where patients 

are receiving inadequate therapy and attempt to 

achieve pain relief by inappropriate or even illegal 

means. The major factor differentiating pseudo 

from true addiction is the purpose for which the 

opioid is used. 

Use to treat pain is pseudo addiction while use 

to achieve euphoria or dissociation is addiction. 

Patients should be randomly tested for the presence 

of opioid metabolites in the urine. Absence 

of metabolites indicates drug diversion and is an 

indication for termination of opioid therapy. Loss 

of prescriptions and/or medication on more than 

two occasions should raise suspicion of diversion. 

Morphine 

Morphine therapy, as a component of multi- 

modal pain therapy, is initiated as an immediate 

-release preparation (tablets or syrup) given in 

a dose of 10-20mg hourly as needed. For inpatients, 

a PCA device may also be used. Over a 

period of two to three days the average morphine 

requirement can be calculated. Of this total, 60- 

70% should be given as a slow-release preparation 

dosed eight hourly rather than at the 12 hourly 

intervals recommended by many manufacturers. 

The remaining 30% is taken as needed in an 

immediate -release formulation. 

Respiratory depression, coma and death are the 

most feared complications of morphine therapy 

but patients rapidly become tolerant to these effects, 

which tend to be seen most often: 

a. In the first six to eight weeks of therapy 

b. When pain is resolving without a concomitant 

reduction in morphine dose 

c. In a deliberate suicide attempt 

Fentanyl 

With significant enteral intolerance, transdermal 

fentanyl can provide effective opioid 

analgesia, albeit at higher cost. Transmucosal 

preparations are also available for rescue. Patients 

who have not achieved adequate analgesia with 

morphine may respond to fentanyl and vice versa. 

Side effects 

The common side effects of morphine therapy 

include nausea, constipation and pruritus. These 

are traditionally managed by the use of metoclopramide 

or a phenothiazine antiemetic for the 

nausea and an osmotic laxative such as lactulose 

for constipation. Phenothiazine antihistamines 

have been used for both nausea and pruritus but 

often result in additive sedation with the opioid 

used. 

New approaches to opioid side effects 

Nausea can be managed by co- administration 

of morphine and naloxone. Naloxone given 

orally does not reach the systemic circulation but 

acts directly on the stomach to reduce nausea. 

Proprietary preparations are being developed. 

Two peripheral opioid antagonists, methylnaltrexone 

and alvimopan, are being developed. 

These drugs antagonise the peripheral adverse 

effects of opioids but do not cross the blood brain 

barrier, so central analgesia is maintained. These 

drugs are currently only available in an injectable 

form that will limit their usefulness in the treatment 

of chronic pain. Transdermal formulations 

will increase the usefulness of these drugs for the 

management of chronic pain patients treated 

with morphine.

Focus on Pain Management - Medical Chronicle

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