The International Association for the Study of Pain defines neuropathic pain as that initiated or caused by a primary lesion or dysfunction of the nervous system.1 There is often initial difficulty in diagnosing this condition in the primary care setting followed by unfamiliarity in managing it by the treating physicians.
A recent survey by Smith et al.2 showed that around 8% of the general population have chronic pain with a predominant neuropathic component. This statistic is increased when associated with other conditions such as post-amputation,3 and multiple sclerosis.4 The survey also showed that people with neuropathic pain had poor health and greater disability than those with chronic pain without neuropathic features.
Integrated care pathwaysAn effective integrated care pathway (ICP) allows the progress of each patient to be monitored against the expected course for a specific healthcare journey. Following the patient through an ICP can, therefore, help to deliver clinical governance. Integrated care pathways set standards for effective interventions that are evidence-based, and prompt clinicians to involve patients in their care by providing them with information and seeking feedback. Unlike guidelines, an ICP will allow for individual clinical discretion to be exercised, but with the safeguard that any variance from the expected clinical management path can be tracked.
Developing the ICP for neuropathic pain
An ICP for neuropathic pain with a detailed evidence base to support key decisions was developed by a working group of healthcare professionals from diverse backgrounds and perspectives, and comprised GPs, pain management specialists, palliative care specialists, and a pharmacist.1,5
This ICP consists of an easy-to-use evidence-based booklet, a process map (Figure 1) illustrating the patient journey, and a series of related forms that can be modified by each practice according to their circumstances.
The ICP was developed to:
- raise awareness of neuropathic pain and to optimise patient outcomes
- give the user confidence in identifying and prescribing the currently available pharmacotherapy at initial presentation
- support healthcare professionals in assessing, diagnosing, and managing neuropathic pain
- address the issue of waiting time to see a chronic pain specialist, which in some parts of the country is too long
- facilitate the process of patient management from diagnosis through to treatment.
The ICP is a useful assessment tool for all specialities involved in managing neuropathic pain and encourages the treatment of more patients in a primary care setting, which is high on the new Department of Health agenda.
It is not intended to be a definitive 'must-do' system, but rather to provide structure and guidance in patient management and choice of management strategy.
When should the ICP be initiated?
The diagnosis of neuropathic pain relies on taking an accurate history and examination. It is commonly described as 'burning', 'electric', 'tingling', and 'shooting' in nature.1 If the patient complains of an abnormal sensation/pain, then neuropathic pain should be considered. Box 1 lists the hallmarks of neuropathic pain, and Box 2 highlights the common causes that should be considered when determining a patient's history.
Box 1: Hall marks of neuropathic pain are chronic and include:1,5
|The hallmarks of neuropathic pain are chronic and include:1,5
Examination should concentrate on the location, quality, intensity, and duration of neuropathic characteristics (Box 1).
In most cases of neuropathic pain, the abnormal sensory findings will be neuro-anatomically logical and compatible with a definite lesion type;1 for example, neuropathic pain secondary to a lesion at the L5 nerve root produces symptoms and signs in the distribution of the L5 root in the foot. The impact of management can be monitored at each visit using the Visual Analogue Scale (VAS) for pain intensity.6
Initial consultation During the initial consultation, a Leeds Assessment of Neuropathic Symptoms and Signs7 (LANSS) and neuropathic pain questionnaire8 can be used to identify pain with neuropathic characteristics.
Common neuropathic conditions that a GP may come across include:1
- diabetic neuropathy
- central post-stroke pain
- spinal cord injury pain
- multiple sclerosis
- post-herpetic neuralgia
- phantom limb pain
- post-incision chronic pain
- brachial plexus avulsion
- trigeminal neuralgia
- HIV neuropathy
- neuropathy secondary to vascular insufficiency
- complex regional pain syndrome.
Urgent referralPatients with complex regional pain syndrome should be referred urgently, as early intervention can help recovery of mobility and improve dysfunction.1 It is also important to consider cancer-related pain and refer urgently as necessary.
Non-urgent referralNon-urgent referral is recommended for patients who do not respond adequately to the two categories of drug—anticonvulsants or antidepressants—after using them at a suitable dose for a reasonable time. This can also be done in cases where there is a need for an intervention procedure such as epidural injection to relieve nerve root pain.
Pharmacotherapy choices based on evidence1,9The ICP also has an easy to use table of commonly prescribed drugs showing the dosage and side-effects (Table 1).1
Tricyclic antidepressants (TCAs) are commonly used to treat neuropathic pain. They produce blockade of serotonin and norepinephrine re-uptake in the central nervous system, thereby increasing the activity of the descending inhibitory pathway.1
Tricyclic antidepressants can be beneficial in central post-stroke pain, diabetic and non-diabetic polyneuropathy, post-herpetic neuralgia, and post-mastectomy pain syndrome.1 However, they might not be as effective in spinal cord injury pain, phantom limb pain, and pain in HIV neuropathy, even though the reduced efficacy can be attributed to low dosing and very low inclusion criteria.9
First generation anti-epileptic drugs, such as carbamazepine, sodium valproate, and phenytoin, are commonly used in the treatment of neuropathic pain. Anti-epileptics achieve analgesia through the blockade of voltage-dependent sodium channels in the peripheral neurons (e.g. phenytoin, carbamazepine, valproic acid), or by acting on glutamate secretion(e.g. lamotrigine), or calcium channels (e.g. gabapentin, pregabalin). Differences in their mechanism of action suggest a rationale for using polypharmacy.1 Carbamazepine and phenytoin work by slowing the recovery rate of voltage-gated sodium channels from depolarisation. Whereas valproic acid blocks voltage-gated sodium channels and increases levels of gamma aminobutyric acid by decreasing degradation.
The long-term use of oral opioids in peripheral neuropathic pain conditions has only been tested in placebo-controlled studies.1 Although opioids can effectively manage neuropathic pain, their use in non-malignant pain is controversial. The concerns are in relation to possible addiction and associated consequences. Further information regarding opioid use can be found in the British Pain Society's guideline 'Recommendations for the appropriate use of opioids for persistent non-cancer pain'.10
Other therapiesTopical therapies such as lidocaine and capsaicin are also useful for localised treatment. Paracetamol and non-steroidal anti-inflammatory drugs can be good adjuvants to the overall management of neuropathic pain.
Which therapy should be used firstThe choice of pharmacological agent depends on either pain relief or pain relief with a better quality of life, which means improving the patient's ability to enjoy normal life activities (Figure 2).1 Unfortunately, there is no evidence on quality of life for the older TCAs.1
Figure 2: Choice of pharmacological agent depending on the main outcome criteria
Table 1: Treatment plans for each drug intervention and side-effect profile
|Amitriptyline||10 to 25 mg||150 mg||Increase by 10 to 25 mg weekly||Dry mouth, sedation, cardiotoxicity, postural hypotension, bladder problems, constipation.|
|Nortriptyline||10 to 25 mg||75 mg||Increase by 10 to 25 mg weekly||Similar to amitriptyline but less sedating.|
|Venlafaxine||37.5 to 75 mg||225 mg||Increase by 37.5 mg weekly||Dizziness, sweating, and constipation. Re-evaluate patients on long-term use; withdraw gradually over at least one week.|
|Duloxetine||60 mg||120 mg||Dizziness, somnolence and fatigue.|
|Carbamazepine||200 mg||800 mg||Increase slowly to 200 mg 2–4 times daily||Dizziness, ataxia. Avoid sudden withdrawal.|
|Gabapentin||300 mg||1800 mg||Increase by 300 mg every day to a max of 1.8 g||Dry mouth, dizziness, and cognitive impairment. May be tolerated by patients who react to pregabalin.|
|Pregabalin||50 mg||600 mg||Increase, if necessary, by 25–50 mg every day over 3–7 days||Dry mouth, dizziness, and cognitive impairment. Helpful in patients not able to tolerate gabapentin.|
|Tramadol||50–100 mg||400 mg||50–100 mg to 3–4 times daily||Nausea and vomiting. Less respiratory depression and constipation.|
|Morphine||20–120 mg||200 mg||Increase weekly at the discretion of the GP||Cognitive effects, emesis, sedation, constipation.|
|Oxycodone||20–80 mg||200 mg||Increase daily by 25–50% of the dose, depending on the patient's need||Cognitive effects, emesis, sedation, constipation.|
|Capsaicin||0.075%||4 times daily||Burning, care with application — warn patients as appropriate.|
|Lidocaine||5%||Patch should be worn for 12 h, then removed for 12 h, in rotation||Patch may cause skin irritation. Due to the very low dose, no systemic side-effects.|
|SNRI=serotonin and noradrenaline re-uptake inhibitors. Reproduced with kind permission of the Neuropathic Pain Advisory Group|
Challenges facing GPsIt will be challenging for the GP to identify and to initiate management after examination because of the time limitations of GP appointments. Once the patient is diagnosed, this ICP will make the management of neuropathic pain much quicker, simpler, and more effective.
Piloting the ICPThe ICP is currently being piloted in primary care clinics. If your clinic would like to take part in this pilot scheme, please contact us at the following address or via the email below:
Dr G. Baranidharan
The ICP to manage neuropathic pain has been driven by the advisory group's desire to promote awareness of neuropathic pain and to optimise patient outcomes. A brief summary of the evidence base has been given in this article. The ICP will be a useful tool in the primary care setting to manage this difficult condition.
- Neuropathic Pain Advisory Group. Neuropathic Pain: Integrated Care Pathway Evidence Base. 2006.
- Smith B, Torrance N, Bennett M et al. Health and quality of life associated with chronic pain of predominantly neuropathic origin in the community. Clin J Pain 2007; 23 (2): 143–149
- Jensen M, Chodroff M, Dworkin R. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology 2007; 68 (15): 1178–1182.
- Kalman S, Osterberg A, Sorensen J et al. Morphine responsiveness in a group of well-defined multiple sclerosis patients: a study with i.v. morphine. Eur J Pain 2002; 6 (1): 69–80.
- Bennett M, Archard G, Baranidharan G et al. Neuropathic pain integrated care pathway. In Foord-Kelcey G, editor. Guidelines—summarising clinical guidelines for primary care. 31st ed. Berkhamsted: MGP Ltd. February 2007pp. 435–437.
- Cruccu G, Anand P, Attal N et al. EFNS guidelines on neuropathic pain assessment. Eur J Neurol 2004; 11 (3): 153–162.
- Bennett M. The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain 2001; 92 (1–2): 147–157.
- Bouhassira D, Attal N, Alchaar H et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a ne
- w neuropathic pain diagnostic questionnaire (DN4). Pain 2005; 114 (1–2): 29–36.
- Finnerup N, Otto M, McQuay H et al. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain 2005; 118 (3): 289–305.
- A consensus statement prepared on behalf of The Pain Society, the Royal College of General Practitioners, and the Royal College of Psychiatrists. Recommendations for the appropriate use of opioids for persistent non-cancer pain. The Pain Society, 2004. www.britishpainsociety.org/opioids_doc_2004.pdfG