Professor Ramani Vijayan Department of Anaesthesiology, University of Malaya, Kuala Lumpur

Understanding the pathophysiology of pain is the key to treating it effectively. As Prof Vijayan put it, "Only when we have tools to identify the mechanisms responsible for pain in a particular individual can we have the capacity to reverse it."

Pain may be classified pathophysiologically as either nociceptive or neuropathic. Nociceptive pain is normal physiological pain when the signal transmitting system is functioning normally. This type of pain is relatively easy to manage, being responsive to opioids, the traditional non-steroidal anti-inflammatory drugs (NSAIDs) and some nerve block techniques.

Neuropathic pain may be defined as 'pain caused by a lesion of the peripheral or central nervous system (or both) manifesting with sensory symptoms or signs'.' The nerve damage involved makes it much more difficult to manage than nociceptive pain.

The prevalence of neuropathic pain is thought to be around 1 % to 1.5% in both the US and the UK, and about one third of US patients with cancer pain have a neuropathic component to their pain.2 There are currently no prevalence figures for Malaysia but, according to Prof Vijayan, "From my experience, the figures here are probably similar."

The pathophysiological mechanisms of neuropathic pain can be divided into peripheral and central. Examples of central mechanisms include central sensitisation and loss of inhibitory controls. Peripheral mechanisms include membrane hyperexcitability and peripheral sensitisation.

Associate Professor Goh Khean Jin Division of Neurology Department of Medicine, University of Malaya, Kuala Lumpur

There are many conditions associated with neuropathic pain (Table 1). Furthermore, the sensory symptoms associated can vary greatly. For example, they may be stimulusevoked (hyperalgesia or allodynia [see 'Important definitions']) or stimulus-independent (eg, intermittent lancinating pain or persistent burning sensation). Many patients also experience negative symptoms, such as numbness or impaired sensory quality, in addition to the positive symptoms.
 

Accurate evaluation of the patient is crucial. There are four components to this:

1. Take a full medical history
   It is particularly important to ascertain' from the patient the characteristics of his/her pain, including its severity, quality, location, duration and any aggravating/relieving factors. The two scales that are most commonly used to assess pain severity are the Numerical Rating Scale and the Visual Analogue Scale, both of which essentially ask the patient to rate their pain on a scale of 0-10 or 0-100. These scales are particularly useful for evaluating the value of any subsequent treatment given.
   
    

   Table 1. Causes of neuropathic pain
   Cause	Example neuropathic pain conditions
   Trauma	Brachial plexus avulsion Phantom limb pain Post-surgical pain syndromes Spinal cord injury
   Nerve compression	Carpal tunnel syndrome
   Infection	Postherpetic neuralgia HIV myelopalhy
   Metabolic	Peripheral neuropathy caused by diabetes
   Inflammation	Rheumatoid arthritis' Multiple sclerosis-related pain
   Neoplasms	Direct infiltration into nerves, spinal cord, etc
   Toxins and drugs	Peripheral neuropathy caused by alcohol, arsenic, taxol, etc
   Vascular	Central post-stroke pain syndrome
   Genetic	Amyloidosis
   Idiopathic	Trigeminal neuralgia

   'Also classified as vascular

    

2. Conduct a comprehensive physical examination, particularly a neurological assessment
   This can be divided into three parts:
   
   " Motor system evaluation, to localise the lesion to either the peripheral or central nervous system;
   
   " Somatosensory assessment, to assess the extent of the lesion;
   
   " Autonomic nervous system evaluation.
    
3. Use ancillary diagnostic tests, where appropriate
   Ancillary diagnostic tests, such as electromyography and imaging techniques, may be useful in defining the pain syndrome in specific patients.
    
4. Assess the impact of the patient's pain on functionality and quality of life
   This may be achieved by asking the patient questions such as:
   
   " What can you not do because of the pain?
   
   " How long can you sit/stand/walk before pain begins?
   
   " Does the pain affect your ability to sleep?

Dr Mary Suma Cardosa Department of Anaesthesiology, Hospital Selayang, Selangor

A multidisciplinary approach to neuropathic pain is likely to produce the best outcome. This may include psychological therapy, physical/occupational therapy and even complementary/alternative treatments, in addition to the pharmacotherapy or interventional treatment that a doctor might initiate.

However, pharmacotherapy remains the most common first-line treatment choice. Only a small number of drugs (eg, gabapentin) are specifically indicated for the treatment of neuropathic pain in their product labelling. However, four drug classes are widely used, based on their consistent efficacy in randomised, controlled clinical trials, and these are considered to be the first-line treatment options:

• Anticonvulsants (eg, gabapentin);
• Tricyclic antidepressants (eg, amitriptyline);
• Opioids (eg, tramadol); and
• Topical agents (eg, lignocaine 5% patch, which is currently not available in Malaysia).

Anticonvulsants

A systematic review of the use of anticonvulsants to treat diabetic neuropathy (ON) and postherpetic neuralgia (PHN) was conducted in 2000.' The results from four different trials were included. Overall, 54% of patients treated with anticonvulsants had >50% pain relief, compared with only 20% of those on placebo. Discontinuations due to side effects were similar between the anticonvulsant and placebo groups.

Another systematic review, this time of literature specifically regarding the anticonvulsant, gabapentin, reached similar conclusions:⁴

• Two high-quality randomised controlled trials showed a positive effect of gabapentin in ON (Figure 1) and PHN;
• Several uncontrolled studies demonstrated benefits with gabapentin in a variety of neuropathic syndromes.

Tricyclic antidepressants and opioids

A review of data pertaining to antidepressants showed that 64% of patients experienced >50% relief, compared with 30% of patients on placebo.' The opioid tramadol has also been shown to be more effective than placebo in reducing pain intensity scores in patients with DN.⁶


Other options
Other pharmacotherapeutic options for the treatment of neuropathic pain include the second-line anticonvulsants and NMOA-receptor antagonists. Surgical procedures may be considered in some cases. Physical (eg, exercises for strengthening and flexibility, postural correction), occupational (eg, ergonomics) and psychological (eg, patient education, relaxation) therapies should also be applied in conjunction with pharmacotherapy.
 

• The prevalence of neuropathic pain in Malaysia is probably around 1 % to 1.5%.
   
• Accurate patient evaluation and diagnosis is crucial.
   
• Pharmacotherapy (particularly anticonvulsants, antidepressants, opioids and topical agents) is usually the best first-line treatment option.
   
• A multidisciplinary approach, which includes patient education, physical, occupational and psychological therapies in addition to pharmacotherapy, should be considered in many cases.

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