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Handbook of Neuropathic Pain Management Guidelines 2nd Edition

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2nd Edition

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A Summary of Recommendations Issued by the Multidisciplinary Panel on Neuropathic Pain (MPNP)

Table of Contents
Introduction to neuropathic pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . ......................................... 2 Introduction to the Multidisciplinary Panel on Neuropathic Pain (MPNP) ............. 4 MPNP members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ......................................... 5 Overview of contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ......................................... 6 Diagnosis and assessment of pain severity . . . . . . . . . . . . . . . ......................................... 7 Drugs used in the treatment of neuropathic pain . . . . . . ......................................... 9 Drug options and dosages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....................................... 10 Side effect profiles and management tips . . . . . . . . . . ....................................... 12 Recommendations for postherpetic neuralgia . . . . . . . . . . . . ....................................... 14 Recommendations for idiopathic trigeminal neuralgia ..................................... 16 Recommendations for painful diabetic peripheral neuropathy ........................ 18 Recommendations for neuropathic pain associated with peripheral nerve entrapment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....................................... 20 Recommendations for central post-stroke pain . . . . . . . . . . ....................................... 22 Recommendations for neuropathic cancer pain . . . . . . . . ....................................... 24 Recommendations for neuropathic pain due to spinal cord pathologies ................. 26 Recommendations for complex regional pain syndrome .................................. 28 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....................................... 30

Handbook of Neuropathic Pain Management Guidelines – 2nd Edition


Introduction to neuropathic pain
Neuropathic pain
europathic pain covers a diverse group of pain conditions characterized by a primary lesion or dysfunction of the sensory nervous system. It is particularly challenging for clinicians to manage because of its chronicity and severity, poor responsiveness to traditional pain therapies, and wide individual variations in pain responsiveness.1,2 Unfortunately, neuropathic pain conditions are likely to increase as populations age and age-related disorders, such as herpes zoster, diabetes mellitus, cerebrovascular accidents, Parkinson’s disease and cancer, rise in prevalence.3 Medical treatment of neuropathic pain remains unsatisfactory for a substantial proportion of patients, and with the rising rates of disorders known to incite neuropathic pain syndromes, it is vital to improve patient outcomes with existing treatment options and continue to pursue new therapeutic strategies.


What is the difference between neuropathic pain and nociceptive pain?
There are two types of pain: nociceptive pain and neuropathic pain. Nociceptive pain serves as a warning of ongoing tissue damage due to injury or disease (eg, a wound, thermal insult or inflammation).3 It comprises somatic pain (in skin, muscles, joints, bone) and visceral pain (in an organ or its covering), and is an acute, self-limiting symptom. In contrast, neuropathic pain is initiated by injury or dysfunction of the peripheral or central nervous system, resulting in a delayed chronic response to damage that is no longer acute, but which continues to evoke pain.3

What causes neuropathic pain?
This disorder can be caused by injury to neuronal cell bodies in the peripheral or central nervous system via compression, transection, infiltration, ischaemia or metabolic injury, or any combination of these effects. Examples of peripheral neuropathic pain conditions include diabetic peripheral neuropathy, postherpetic neuralgia, tumour infiltration neuropathy, phantom limb pain, complex regional pain syndrome and trigeminal neuralgia. Central neuropathic pain conditions include multiple sclerosis, spinal cord injury, central post-stroke pain and Parkinson’s disease. Although the underlying neuronal mechanisms of neuropathic pain are not completely understood, various distinct pathophysiological mechanisms appear to be involved, resulting in both peripheral and central sensitization.4 Nerve lesions can trigger molecular changes in nociceptive neurons, making them abnormally sensitive and evoking pathological spontaneous activity. Inflammation in the damaged nerve trunk can induce ectopic nociceptor activity, causing spontaneous pain. This hyperactivity in nociceptors can induce


Handbook of Neuropathic Pain Management Guidelines – 2nd Edition

cold. temporal variations in pain intensity and functional impact. light touch) when applied to the affected area. Other common symptoms include3: • Allodynia – Pain due to nonnoxious stimuli (clothing. A physical examination of gross motor function. pressure. searing or scalding. dynamic or thermal • Anaesthesia – Loss of normal sensation to the affected region • Dysaesthesia – Spontaneous or evoked unpleasant abnormal sensations • Hyperalgesia – Exaggerated response to a mildly noxious stimulus applied to the affected region • Hyperpathia – Delayed and explosive response to a noxious stimulus applied to the affected region • Hypoaesthesia – Reduction of normal sensation to the affected region • Paraesthesias – Nonpainful spontaneous abnormal sensations • Phantom pain – Pain from a specific site that no longer exists (eg. May be mechanical. The pain may be continuous or paroxysmal in presentation. neuroplastic changes in the central pain modulatory systems can lead to further hyperexcitability. Clinical evaluation should include a history to assess pain intensity. vibration and temporal summation in the area of maximal pain. pinprick. deep tendon reflexes. crushing. electric shock-like. shooting. so that input from mechanoreceptive A fibres is perceived as pain.4 . and the somatosensory system should be performed. heat. sensory descriptions of the pain quality. tingling. The sensory examination should include assessment of responses to touch. cold. tingling and shooting in nature. numbness.What are the symptoms of neuropathic pain? Neuropathic pain is commonly described as burning. electric. Examples of screening tools include ID Pain and painDETECT. or vise-like. In addition. Handbook of Neuropathic Pain Management Guidelines – 2nd Edition 3 Neuropathic pain secondary changes in processing neurons in the spinal cord and brain. amputated limb) or where there is no current injury • Referred pain – Occurs in a region remote from the source How to assess a patient for neuropathic pain Neuropathic pain should be suspected in patients who present with pain that they describe in any of the following terms: burning.2 Patient-completed neuropathic pain screening tools can assist primary care physicians in differentiating between nociceptive and neuropathic pain. stabbing.

4 Handbook of Neuropathic Pain Management Guidelines – 2nd Edition . neurosurgery. Hong Kong physicians lacked local guidelines for managing neuropathic pain. the MPNP has endeavoured to improve the understanding and general awareness of neuropathic pain syndromes. and were potentially unaware of the most appropriate referral pathways and treatments. It aims to act as an information source for medical professionals on the treatment and management of neuropathic pain and provide evidence-based resources on neuropathic pain. The panel includes specialists from a range of disciplines involved in treating neuropathic pain: neurology. For some time. geriatric medicine. anaesthesiology and orthopaedics. and to contribute to better diagnosis.Introduction to the Multidisciplinary Panel on Neuropathic Pain (MPNP) T The MPNP he Multidisciplinary Panel on Neuropathic Pain (MPNP) comprises local thought leaders dedicated to improving the awareness and understanding of neuropathic pain in Hong Kong. management and treatment of these conditions in Hong Kong. Therefore.

DipPainMgt(HKCA). FHKAM(Ana). FRCS(Edin). FFPMANZCA. DipHandSurg (FESSH) Dr Tak hong TsoI MBBS. Prince of Wales Hospital. and Adjunct Associate Professor. Department of Orthopaedic Surgery. Josephine WY iP and Phoon Ping CHen . Department of Medicine and Therapeutics. FANZCA. FHKCP Honorary Consultant and Honorary Clinical Associate Professor. Division of Neurosurgery.MPNP members Current members Dr Phoon Ping Chen MBBS. DipPainMgt(HKCA) Past members Dr Tsun Woon Lee MBBS. DipPainMgt Consultant Anaesthesiologist and Head of Pain Management Team. FFPMANZCA. The Chinese University of Hong Kong. Hong Kong SAR Associate Professor and Honorary Associate Consultant. FRCP(Lond). MRCP. Department of Surgery. Division of Neurology. MRCP. Pamela Youde Nethersole Eastern Hospital. FHKAM (Ana). FHKAM(Surg) Dr Chun Por Wong MBBS. FRCS(Edin). Hong Kong SAR Dr Josephine WY IP MBBS. Ruttonjee and Tang Shiu Kin Hospitals. Hong Kong SAR Chief of Service. Joseph MK LaM. Department of Anaesthesiology and Operating Services. FHKAM(Ortho). MS. The Chinese University of Hong Kong. FRCP(Glas). Department of Medicine. FHKAM(Med). Hong Kong SAR Professor and Head. Pok Oi Hospital. Queen Mary Hospital. FANZCA. Department of Anaesthesiology and Operating Theatre Services. Hong Kong SAR Dr Joseph MK LaM MBChB. Tak Hong TSoi and Vincent MoK. Hong Kong SAR Dr steven ho shan Wong MBBS. FHKAM(Ana). The Chinese University of Hong Kong. The Chinese University of Hong Kong. Division of Hand and Foot Surgery. FHKCP. FHKAM (Med). Integrated Medical Services. Prince of Wales Hospital. Hong Kong SAR Professor Lawrence Ks Wong MBBS. Prince of Wales Hospital. FRCP Hospital Chief Executive. Alice Ho Miu Ling Nethersole Hospital and North District Hospital. Department of Medicine and Therapeutics. FRCP(Lond). Hong Kong SAR 5 Handbook of Neuropathic Pain Management Guidelines – 2nd Edition The MPNP L-R (standing): Steven Ho Shan Wong. Hong Kong SAR Neurologist and Consultant Physician. FRCP(Edin). MD(CUHK) Consultant and Chief of Service. FRCP(Edin). Division of Neurology. FCSHK. FRCP(Glas). FHKAM(Med). FANZCA. FHKAM(Med) Associate Professor and Chief. Consultant and Head. The University of Hong Kong. L-R (seated): Chun Por Wong. Department of Geriatrics. MHA Dr Vincent MoK MBBS. FRCP(Edin). Queen Elizabeth Hospital. FHKCA. MD.

and notes on the most common side effects associated with neuropathic pain medications. Full prescribing information should always be consulted before initiating therapy. It is hoped that this concise guide will assist Hong Kong physicians in their daily management of patients suffering from neuropathic pain conditions. physicians are encouraged to consult the original versions of the MPNP recommendations. For full details. which are endorsed by the Hong Kong Pain Society and are updated The booklet is provided as a convenient summary of the medical management options in neuropathic pain conditions. The contents include simple tools to assist in the diagnosis and evaluation of neuropathic pain. which are available on the MPNP Web site (www.Overview of contents ince its inception in 2001. the diagnosis and management of neuropathic pain will undoubtedly change. It is important to note that not all drugs mentioned are licensed for use in neuropathic pain conditions. and is not meant as a comprehensive guide to the complete multidisciplinary management of patients with these conditions. S Overview Disclaimer Every effort has been made to ensure that the information contained in this handbook is accurate at the time of publication. Particular emphasis is paid to details of appropriate treatment options. thus ultimately helping to improve the quality of life of patients with these disabling conditions. The MPNP cannot be held liable for any consequence arising from inappropriate application of the information provided in this handbook.neuropainhk. summary tables of dosage and administration details of many of the drugs used for neuropathic pain. 6 Handbook of Neuropathic Pain Management Guidelines – 2nd Edition . This booklet summarizes these recommendations. As new research and clinical experience broadens medical knowledge. the MPNP has published recommendations on a variety of neuropathic pain conditions. The largest section of the handbook is devoted to reproducing the treatment algorithms recommended by the MPNP for the management of neuropathic pain conditions.

called ID Pain. can assist primary care physicians in differentiating nociceptive from neuropathic pain.Diagnosis and assessment of pain severity T he following patient-completed screening questionnaire. The Chinese version has recently been validated. The two other items can help patients describe the extent and severity of pain. and can be used to monitor the effectiveness of therapy. Screening Questionnaire5. and facilitate earlier and more appropriate treatment.6 Handbook of Neuropathic Pain Management Guidelines – 2nd Edition 7 Assessment of neuropathic pain .

Assessment of neuropathic pain 8 Handbook of Neuropathic Pain Management Guidelines – 2nd Edition .

EMLA) may be useful for patients who have small areas of hyperaesthesia. The local anaesthetic mexiletine is structurally similar to lignocaine.Anticonvulsants Anticonvulsants act as membrane-stabilizing agents by altering abnormal sodium channel function and calcium channel activity. The alpha-2-delta (A2D) ligands gabapentin and pregabalin may have a number of actions. Opioids relieve neuropathic pain in some patients. The molecular mechanisms of opioid action in neuropathic pain are not yet fully understood. Local anaesthetics The local anaesthetic lignocaine is used systemically and topically in neuropathic pain. Opioids Despite the initial belief that neuropathic pain was opioid-resistant. thus reducing the potential for transmission of abnormal pain signals. which has a membrane-stabilizing effect and disrupts transmission of pain signals. Other possible mechanisms of action include α–adrenergic blockade. The assumed analgesic mechanism of action of these drugs is acute inhibition of sodium channels. a 5-HT and NA reuptake inhibitor (SNRI). on average. pain relief appears to be only moderate and treatment-limiting side effects are common. it appears that reduced sensitivity to systemic opioids is present. but binding to the α2-d subunit of the voltage-gated calcium channel appears to play a significant role in their antineuropathic activity. is thought to relieve neuropathic pain by increasing NA and 5-HT activity in the central nervous system. The topical application of local anaesthetics (eg. however. necessitating the use of higher doses. 5% lignocaine patch. Duloxetine. sodium channel effects and N-methyl D-aspartate (NMDA) receptor antagonism. Antidepressants Tricyclic antidepressants (TCAs) enhance the descending pain inhibitory system by preventing cellular reuptake of noradrenaline (NA) and serotonin (5-HT). orally active and has antiarrythmic activity. Handbook of Neuropathic Pain Management Guidelines – 2nd Edition 9 Drugs for neuropathic pain Drugs used in the treatment of neuropathic pain .

300 mg bid on Day 2. oxycodone. slurring of speech. then by 150 mg/d every 3–7 days as tolerated Increase by 300 mg tid every 1–7 days as tolerated 100 mg every 3–7 days Increase to 50 mg/day for 2 wks. perioral numbness.and second-line drugs mentioned in the treatment algorithms included in this booklet. then increase by 50–100 mg every wk Increase by 10 to 25 mg weekly Recommended for starting dosage Dose titration (if necessary) Gabapentin* 300 mg at bedtime on Day 1. convert total daily dosage to long-acting opioid analgesic and continue short-acting medication as needed Increase by 50–100 mg daily in divided doses every 3–7 days as tolerated 60 mg/day 10–15 mg morphine q4h or as needed (equianalgesic dosages should be used for other opioid analgesics) 50 mg daily or bid DPN (2nd line) 5 mg/kg over 30–60 min Titrated based on symptoms of cyclic antidepressant toxicity. desipramine Duloxetine opioids Morphine. eg. 300 mg tid on Day 3 100 mg bid 25 mg/day for 2 weeks Carbamazepine† Lamotrigine antidepressants Amitriptyline PHN (1st line) DPN (1st line) TN (2nd line) PHN (1st line) DPN (1st line) TN (2nd line) DPN (1st line) PHN (2nd line) 10–25 mg daily at bedtime Nortriptyline. methadone. convulsions Increase by 50 mg every 2 to 3 days prn None needed – Mexiletine 5% lignocaine patch EMLA® PHN (1st line) PHN (1st line) 150 mg daily to 200 mg bid Apply patch for a maximum of 12 h tid. diplopia. levorphanol Tramadol Local anaesthetics IV lignocaine 10–25 mg at bedtime Increase by 25 mg daily every 3–7 days as tolerated – After 1–2 wks.Drug options and dosages Drugs for neuropathic pain This table covers most of the first. tinnitus. but does not represent an exhaustive list of treatment options. Drug anticonvulsants Pregabalin* PHN (1st line) DPN (1st line) TN (2nd line) PHN (1st line) DPN (1st line) TN (2nd line) TN (1st line) PHN (2nd line) TN (2nd line) 150 mg/day as 75 mg bid Increase to 300 mg daily after 3–7 days. dizziness. Full prescribing information should be consulted before initiating therapy. under occlusive dressing if possible 10 Handbook of Neuropathic Pain Management Guidelines – 2nd Edition .

There is no evidence that paracetamol and NSAIDs are effective for the treatment of neuropathic pain. * Pregabalin and gabapentin are licensed in Hong Kong for the treatment of neuropathic Guidelines/pdfdocs/NeuropathicPainGuideline200711. IV. CMaJ 2006.lmsg. Moulin DE.200 mg tid) 3–8 wks for titration plus 2 wks at maximum tolerated dosage 8-12 wks 12 wks (including titration period) 3 months at maximum tolerated dosage 6–8 wks with at least 2 wks at maximum tolerated dosage – 4–6 wks 1.html#CACIDGIH. trigeminal neuralgia N.600 mg/day 200–400 mg/day Up to 75 mg daily 150 mg daily 60 mg/day No maximum dosage with careful titration 400 mg daily (100 mg qid). 2008. Pain. 3.175:265-275. intravenous. Watson CPN.200 mg/day 3 patches daily for no more than 12 h in 24 h – – 2–4 wks – Handbook of Neuropathic Pain Management Guidelines – 2nd Edition 11 Drugs for neuropathic pain . The Merck Manual for Healthcare Professionals. ch209/ch209a. 2008. Sources: American Medical Association. Available at: http://www. 300 mg daily in patients >75 years 4 wks – 1. September 2007. information unavailable/incomplete.pdf. –. DPN. May 2007. diabetic polyneuropathy. Module 9. Assessing and Treating Neuropathic Pain.nhs. 2008. Available at: http://www. amacmeonline. Available at: http://www. eutectic mixture of local anesthetics.pdf. PHN. Accessed April 18.merck. Accessed April 18. Guideline for treating patients with neuropathic pain. Cahill CM. Neuropathic pain: a practical guide for the clinician.Maximum dosage Duration of adequate trial 600 mg daily (200 mg tid or 300 mg bid) 4 wks wks. postherpetic neuralgia. Gilron I.B.600 mg daily (1. TN. Neurological Disorders. Leicestershire Medicines Strategy Group. Accessed April 18. † Carbamazepine is licensed in Hong Kong for the treatment of trigeminal neuralgia and diabetic polyneuropathy.

postural hypotension. weight gain. slurred speech. constipation. The list is not exhaustive and full prescribing information should be consulted before initiating any therapy. sweating. dizziness. constipation. ataxia. insomnia. dizziness. agitation. nystagmus. memory impairment. euphoric mood. disturbed vision. nystagmus. blurred vision. dizziness.Side effect profiles and management tips Drugs for neuropathic pain This table summarizes some of the more commonly encountered adverse effects associated with neuropathic pain treatments. somnolence. vomiting. palpitations. increased appetite. unsteady gait. urinary retention. dizziness. GI distress. disturbed attention. nausea. tremor. hallucinations. serious AEs: hyponatraemia. dry mouth. blurred vision. a change in personality. insomnia. Stevens-Johnson syndrome* Potential adverse effects Lamotrigine Skin rash (potentially severe). emotional lability Lightheadedness. impaired haemodynamics Constipation. irritability. peripheral oedema. depression. change in sensorium. lightheadedness. nausea. dry mouth. gait abnormalities. headache. sedation. inco-ordination. GI distress. nausea. tiredness. dizziness. somnolence. back pain antidepressants Amitriptyline Dry mouth. redness or swelling at the application site. decreased appetite. diarrhoea. ataxia. burning. sedation. tremor. dry mouth. blurred vision. increased sweating. cardiotoxicity. nausea/vomiting. levorphanol Tramadol Local anaesthetics IV lignocaine Tremor. drowsiness Nortriptyline. oxycodone. desipramine Duloxetine Nausea. constipation. methadone. ataxia. risk of serotonergic syndrome if combined with SSRIs Mexiletine 5% lignocaine patch EMLA ® Mild localized skin reactions around application site Pale skin. constipation. risk of seizures/ epilepsy. Drug anticonvulsants Pregabalin Gabapentin Carbamazepine Dizziness. insomnia or drowsiness. respiratory depression Dizziness. somnolence. vomiting. aplastic anaemia. painful menses. diplopia. arthralgia. agranulocytosis. balance disorder Sedation. constipation. nausea & vomiting. fatigue opioids Morphine. trembling. change in hot or cold sensation 12 Handbook of Neuropathic Pain Management Guidelines – 2nd Edition . proarrhythmia. nervousness. nausea/vomiting. drowsiness.

Backonja M. most cases of rash occur within first 8 weeks CI. EMLA. IV. selective serotonin reuptake inhibitor. May 2007. monitor blood pain_mgmt/printversion/ama_painmgmt_m9. Assessing and Treating Neuropathic Pain. Guideline for treating patients with neuropathic pain.lmsg. Pharmacologic management of neuropathic pain. monitor and adjust dose to prevent QTc prolongation. Cahill CM. complete blood count. Evidence-based recommendations. Leicestershire Medicines Strategy Group. administer with food or prescribe antacids to reduce GI AEs. Give dose at bedtime to minimize effect of sedation. Accessed April 18. rash or mouth ulcers. The Merck Manual for Healthcare Professionals. AV block or with concomitant MAO inhibitors. GI. SSRI. patients should seek immediate medical assistance if fever.html#CACIDGIH. sore throat. titrate dose slowly. Pain 2007. 2008. apply to affected area – Handbook of Neuropathic Pain Management Guidelines – 2nd Edition 13 Drugs for neuropathic pain . AV. adverse effects.merck. Watson CPN. 2008. MAO. Available at: http://www. Dworkin RH. Module 9. CI in patients with glaucoma and those taking MAO inhibitors Nortriptyline causes less sedation and anticholinergic effects than amitriptyline. et al. monoamine oxidase. Accessed April 18. Gilron I. CI in patients with glaucoma and those taking MAO inhibitors – Coadminister pre-emptive stool softeners and antiemetics Initiate therapy at low dose and titrate as tolerated. eutectic mixture of local anesthetics. liver enzymes and sodium levels for 1 year. 2008. Neurological Disorders.nhs.amacmeonline. Sources: American Medical Association. intravenous. Available at: http://www. has a narrow therapeutic index Only apply to healed intact skin.175:265-275. Accessed April 18. may be poorly tolerated by the elderly. Moulin DE. contraindicated in porphyria. AEs. use with caution in epileptic patients Decrease the infusion rate or discontinue treatment if signs of toxicity Consider cardiac evaluation before initiating therapy in patients with a significant heart sec16/ch209/ch209a. –. contraindicated. CMaJ 2006. information unavailable/incomplete * Genetic susceptibility for Stevens-Johnson syndrome (HLA-B1502) should be assessed in Asian patients before commencing treatment with carbamazepine.Comments Dose adjustment needed in renal dysfunction Dose adjustment needed in renal dysfunction Monitor CBC. Neuropathic pain: a practical guide for the clinician. bruising/bleeding develop Very slow dose titration minimizes risk of rash. Available at: http://www. CBC.132:237-251.pdf. O’Connor AB. September 2007. Pain. pdf. atrioventricular.

TENS. EMLA. N-methyl D-aspartate The A2D ligands are pregabalin and gabapentin * Genetic susceptibility for Stevens-Johnson syndrome (HLA-B1502) should be assessed in Asian patients before commencing treatment with carbamazepine. Postherpetic neuralgia is a neuropathic pain syndrome that occurs following acute herpes zoster infection or shingles. NMDA.Recommendations for postherpetic neuralgia7 Postherpetic neuralgia TCA. transcutaneous electrical nerve stimulation. 14 Postherpetic neuralgia . eutectic mixture of local anaesthetics. A2D. alpha-2-delta. tricyclic antidepressant.

• Carbamazepine is commonly used.17. • If adequate pain control is not achieved after 8 weeks.21 intrathecal steroids. • Consider tramadol19 or opioids20 if antidepressants and anticonvulsants are ineffective or are contraindicated.24 or combination therapy.8-13 In some practices.18 This can be first-line treatment if antidepressants and anticonvulsants are contraindicated. such as NMDA receptor antagonists.26 A multidisciplinary approach to managing these difficult-to-treat patients may be necessary. the A2D ligands pregabalin or gabapentin may be used. but there is little evidence to support its use.23. • Consider transcutaneous electrical nerve stimulation (TENS) as adjunctive therapy. Postherpetic neuralgia 15 Postherpetic neuralgia . • Add a topical local anaesthetic.• Start low-dose amitriptyline or nortriptyline therapy (10 to 25 mg at night) and titrate weekly up to the maximum tolerated dose or a maximum of 150 mg. consider referring the patient to a pain medicine specialist for alternative therapies. or in cases where TCAs are not tolerated or are contraindicated. such as a lignocaine patch14-16 or EMLA cream. • For patients older than 60 years. pregabalin and gabapentin are considered first-line therapy.22 intravenous adenosine 5’-triphosphate (ATP).25.

BCR. balloon compression rhizotomy.Recommendations for idiopathic trigeminal neuralgia27 Diabetic neuropathy A2D. alpha-2-delta. percutaneous radiofrequency rhizotomy. PRGR. percutaneous retro-Gasserian glycerol rhizotomy The A2D ligands are pregabalin and gabapentin * Genetic susceptibility for Stevens-Johnson syndrome (HLA-B1502) should be assessed in Asian patients before commencing treatment with carbamazepine. The second or third division of the trigeminal nerve is affected in most trigeminal neuralgia patients. 16 Painful diabetic peripheral neuropathy . PRFR.

43 – Gamma knife radiosurgery (GKR) should be reserved for patients who have failed both surgical and percutaneous procedures.35 baclofen.45 Painful diabetic peripheral neuropathy 17 Diabetic neuropathy .42 – In cases involving the ophthalmic division or all three divisions. • Selecting a procedure is both difficult and controversial. intractable pain.33 clonazepam.34. a patient should be referred to a multidisciplinary pain management centre. an operation or interventional treatment should be considered.36 lamotrigine33 and antidepressant agents.29-31 gabapentin. for patients younger than 70 years who have a low surgical risk and prefer to preserve trigeminal nerve function. and may be used while pharmacotherapy is being optimized. Patients should be allowed to consider all of the available options. The second-line drugs include pregabalin.33 sodium valproate. • Peripheral trigeminal nerve block is a useful adjunctive therapy. balloon compression rhizotomy (BCR) should be considered over PRFR.44.41 – Percutaneous radiofrequency rhizotomy (PRFR) can be considered for patients who have failed medical treatment and suffer from intractable TN.11-13. one or two second-line drugs may be tried.32 phenytoin. microvascular decompression should be recommended.• The primary care physician should try carbamazepine first.28 • If the response is not satisfactory or the patient cannot tolerate treatment.38-40 • If treatment is not successful following a trial of two or three medications for an adequate period (3 to 6 months). – In general.37 • For chronic.

serotonin–norepinephrine reuptake inhibitor The A2D ligands are pregabalin and gabapentin Trigeminal neuralgia Approximately 20 to 40% of diabetic patients develop some sort of neuropathy. tricyclic antidepressant. TENS. A2D. 18 Idiopathic trigeminal neuralgia . PENS. SNRI. transcutaneous electrical nerve stimulation.Recommendations for painful diabetic peripheral neuropathy46 TCA. Diabetic neuropathy may lead to foot ulceration and even the need for amputation. N-methyl-D-aspartate. NMDA. percutaneous electrical nerve stimulation. alpha-2-delta.

but these can be minimized by starting with a low dose at night and increasing gradually. may be considered as a last option. Also.51 • Patients remaining refractory to a reasonable trial of pharmacotherapy (eg. as these may aggravate the skin and lead to infection. 2 to 3 months with two to three different agents) should be referred to a multidisciplinary pain clinic for further therapeutic initiatives. ineffective and/or not well tolerated. the side effects can be further minimized by slow dosage titration. • For acute pain. SNRIs should also be considered as an alternate first-line choice. TCAs (eg. Nortriptyline. • Physical stimulation. Regular walking.28-31. such as spinal cord stimulation. such as TENS52 and acupuncture. Some patients cannot tolerate the side effects of TCAs.47 In addition. TCAs are contraindicated in patients with cardiac and hepatic disease.• A2D ligands (eg. or as an add-on therapy to A2D ligands. However. Idiopathic trigeminal neuralgia 19 Trigeminal neuralgia . acupuncture and topical treatments should be used with caution in the lower leg in patients with diabetes. A2D ligands are generally associated with fewer side effects compared with TCAs.53 • Pain management programmes and behavioural therapy can also be used with pharmacological approaches to teach patients how to live with pain. warm baths or elastic stockings may also help to relieve leg pain. pregabalin and gabapentin) should be considered as first-line treatment options due to their efficacy and safety. desipramine) should be considered first-line therapies. • If TCAs are contraindicated . imipramine and desipramine are less sedating than amitriptyline. amitriptyline.48-50 • Tramadol may be an effective alternative for some patients. nortriptyline. if necessary. start with simple analgesics and progress to TCAs or other adjuvant analgesics. • For chronic pain. carbamazepine or phenytoin. More invasive stimulatory interventions. may counteract painful sensations.28 Pain relief may not be apparent for up to 3 weeks.

nonsteroidal anti-inflammatory drugs. PENS. TENS. transcutaneous electrical nerve stimulation Carpal tunnel syndrome results from compression of the median nerve at the carpal tunnel. percutaneous electrical nerve stimulation.Peripheral nerve entrapment Recommendations for neuropathic pain associated with peripheral nerve entrapment54 Cervical radiculopathy Conservative treatment • Cervical collar • Oral NSAIDs • Physiotherapy/neck care exercises • Anticonvulsants or antidepressants • Epidural corticosteroid injection • Anterior discectomy with spinal fusion • Microforaminotomy • Cervical arthroplasty Lumbar radiculopathy • • • • • Lumbar corset Oral NSAIDs Physiotherapy PENS/TENS Anticonvulsants or antidepressants • Epidural corticosteroid injection • Chemonucleolysis • Discectomy • Microdiscectomy • Percutaneous discectomy • Lumbar foraminotomy • Lumbar spinal fusion Carpal tunnel syndrome • Physiotherapy • Wrist splinting • Oral steroids and local steroid injections • Diuretics Cubital tunnel syndrome • Educate patient on how to avoid provoking symptoms • Conservative treatment does not have a great role in management surgical interventions • Carpal tunnel release (open or endoscopic) • Simple neurolysis • Anterior transposition of ulnar nerve • Medial epicondylectomy of distal humerus • Cubital tunnel release (open or endoscopic) NSAIDS. 20 Neuropathic pain associated with peripheral nerve entrapment .

neck-care exercises. or may benefit from short-term use of a cervical collar. nonsteroidal anti-inflammatory drugs (NSAIDs). Cubital tunnel syndrome • Frequently requires a release operation.55 . anterior transposition of the ulnar nerve or medial epicondylectomy of the distal humerus.58-60 • Gabapentin was effective in patients with chronic radiculopathy (L4-5 and/or L5-S1 bulging and/or protrusion). Epidural corticosteroids and percutaneous or transcutaneous electrical nerve stimulation may give short-term relief. Pregabalin has demonstrated some benefit in cervical radiculopathy. Acupuncture and ultrasound may also reduce pain. and intermittent cervical traction.63. rest at intervals and minimizing hand or wrist movements. Lumbar radiculopathy • Bed rest is not recommended. such as simple neurolysis.61 Pregabalin as monotherapy or add-on therapy improved patientreported clinical outcomes in painful lumbar or cervical radiculopathy. postural training and activity modification.56 • Oral NSAIDs57 and physiotherapy may be beneficial. splinting of the wrist in a neutral position. diuretics and oral corticosteroids are options for mild-to-moderate carpal tunnel syndrome.55 Carpal tunnel syndrome • Conservative strategies that may be of benefit include good ergonomics. decompression via an anterior cervical approach with spinal fusion or a posterior approach with laminectomy) is indicated for more severe cases or when other treatments have failed. or motor involvement or severe numbness is present. mobility must be maintained.Cervical radiculopathy • Surgery (eg. Neuropathic pain associated with peripheral nerve entrapment 21 Peripheral nerve entrapment • Mild cases may improve without treatment.62 • NSAIDs.64 • Carpal tunnel release surgery (open or endoscopic) is indicated when conservative therapy has failed. Local steroid injection may be superior to oral corticosteroids.

tricyclic antidepressant.Recommendations for central post-stroke pain65 Central post-stroke pain A2D. Central post-stroke pain . TCA. CPSP. alpha-2-delta. central post-stroke pain The A2D ligands are pregabalin and gabapentin CPSP is characterized by constant or intermittent pain following a stroke. Around 8% of stroke patients will develop CPSP.

• The A2D ligand pregabalin is a first-line treatment option as it has been shown to significantly reduce pain and improve health status in patients with central pain.76 Central post-stroke pain 23 Central post-stroke pain • Gabapentin.71 • Mexiletine may be used as an adjunct to TCAs when patients do not respond to TCAs alone.66 • Lamotrigine may be used as a second-line agent or an alternative first-line treatment to TCAs.68 . is approved for the treatment of neuropathic pain and may be effective in treating CPSP.74 but should only be considered after the failure of other pharmacologic therapies. but not totally unresponsive. • Intrathecal baclofen may be effective in some patients with CPSP. commence at a low dose and titrate to a higher maintenance dose.67 • Central pain appears to be poorly responsive. To minimize side effects.72 • Patients remaining refractory to a reasonable trial of pharmacotherapy should be referred to a multidisciplinary pain clinic for further therapeutic initiatives.69 • Intravenous lignocaine may provide pain relief in some patients with CPSP.73. spinal cord stimulation and stereotactic mesencephalic tractotomy may be beneficial. • Surgical interventions can be considered for patients unresponsive to pharmacological therapy. another A2D ligand. to opioids. Motor cortex stimulation. but may be associated with morbidity and mortality.75.• TCAs such as amitriptyline or nortriptyline should be considered as first-line therapy for central post-stroke pain (CPSP).70. including CPSP.

central post-stroke pain The A2D ligands are pregabalin and gabapentin 24 Neuropathic cancer pain . alpha-2-delta. tricyclic antidepressant.Recommendations for neuropathic cancer pain77 Neuropathic cancer pain A2D. CPSP. TCA.

89 Neuropathic cancer pain 25 Neuropathic cancer pain • Systemic ketamine may be effective. radiation therapy or chemotherapy.87 .• For neuropathic pain caused by direct tumour involvement.82 • Interventional therapy may also be effective for neuropathic cancer pain. but because of its adverse effects should be limited to experienced teams.78 For example. spinal cord compression) should be managed appropriately.83. • Anticonvulsants should be considered if neuropathic pain is unresponsive to conventional analgesics.81 Anticonvulsants should be initiated at a low dose and slowly titrated until the patient achieves adequate pain relief or side effects develop. radiotherapy can relieve neuropathic pain due to tumour-induced neural compression or irritation. are poorly tolerated or inappropriate.87 • Patients with postsurgical neuropathic pain may also benefit from topical capsaicin cream when appropriate.84 Antidepressants may be given together with anticonvulsants when there is unsatisfactory response to either medication. Neuropathic pain specifically due to cancer treatment may be treated with gabapentin.79 • Correctable causes of neuropathic pain (eg.88 However.86.85 • Other adjunctive therapies include systemic lignocaine. certain interventional techniques for neuropathic pain should only be considered when pharmacologic interventions have failed.82 • Antidepressants such as TCAs or selective serotonin reuptake inhibitors are alternative options for management of neuropathic pain. first-line management is oncologic treatment and may include surgery.80 Pregabalin after epidural anaesthesia significantly improved visual analogue scale (VAS) and quality-of-life scores in chronic cancer patients.

and about one third will report severe pain. 26 Neuropathic pain due to spinal cord pathologies .Recommendations for neuropathic pain due to spinal cord pathologies90 A2D. alpha-2-delta. TCA. tricyclic antidepressant The A2D ligands are pregabalin and gabapentin Spinal cord pathology Pain develops in around 60 to 70% of patients with spinal cord injury.

transdermal or intravenous analgesics may be considered for invasive procedures. pregabalin. such as intrathecal drug administration. maintain treatment for 48 hours if initiated between 3 and 8 hours after injury. TCAs may also be considered as a first-line management option despite limited evidence.28 Patients may also be given other anticonvulsants or opioids to improve pain control.93.91 Many patients achieve significant pain relief from physical therapy. If neuropathic pain is due to direct compression by tumour.91 Methylprednisolone may be given as a 30 mg/kg-bolus dose. If initiated within 3 hours.95. incontinence). but requires meticulous monitoring for side effects. spinal cord stimulation.104-114 • A multidisciplinary approach should be taken to rehabilitation. surgery for certain structural abnormalities) and other neurological sequelae (eg.100.94 Neuropathic pain due to spinal cord pathologies 27 Spinal cord pathology .96 Alternatively. electroacupuncture) and dorsal root entry zone lesioning (DREZotomy).93.92 • There is very little evidence that NSAIDs have benefit for pain due to spinal cord lesions.103 • Patients who respond poorly to oral.102. neurostimulation (eg. motor deficits.• Treatment of neuropathic pain due to spinal cord lesions includes primary treatment of the underlying cause (eg. then maintained at a dose of 5. treatment should be maintained for 24 hours. gabapentin) may be used in conjunction with physical and psychological therapy as first-line treatments for neuropathic pain due to spinal cord lesions.96-100 • Intravenous ketamine may be used as third-line therapy. if possible. • Spinal cord injury (SCI) causing compression should be treated within 8 hours of compression.4 mg/kg/h. antineoplastic treatment may reduce tumour size and provide pain relief.94 • A2D ligands (eg.

nonsteroidal anti-inflammatory drug. transcutaneous electrical nerve stimulation Adapted from treatment algorithm proposed by the International Coalition on Neuropathic Pain. The efficacy of sympathetic blocks in the treatment of CRPS is still poorly defined. CRPS. TENS. tricyclic antidepressant.116 28 Complex regional pain syndrome .Complex regional pain syndrome Recommendations for complex regional pain syndrome115 *Primarily diagnostic and/or to facilitate physical rehabilitation. NSAID. complex regional pain syndrome. TCA.

Destructive or ablative surgery is not recommended127 and only has a limited role in providing relief for patients with a short life expectancy. • Whenever appropriate. Complex regional pain syndrome 29 Complex regional pain syndrome • Patient outcomes are improved if treatment is started at an early stage: patients should be referred as soon as possible to pain specialists or physicians with experience in managing complex regional pain syndrome (CRPS). is essential to treat the secondary complications of CRPS. pain relief may not be apparent for 3 weeks at the maximum tolerated dosage. sympathetic blocks provide effective pain relief to facilitate physical rehabilitation. especially for at-risk patients. pregabalin).119 • Primary pain management should include tricyclic antidepressants ([TCAs] eg. This will improve pain control and mobility. gabapentin.118. amitriptyline)120.117 • Psychological support and cognitive behavioural management programmes can help patients manage their pain. anti-inflammatory medications are useful in the acute phase following injury to minimize pain and swelling.123 Slow dosage titration (up to 8 weeks) is necessary to minimize side effects of both TCAs and anticonvulsants.122.• An early programme of physical and occupational therapy.124 • For patients remaining refractory to trials of pharmacotherapy and physiotherapy.125. a trial of combined TCA and anticonvulsant may be effective. and reduce depression and dependence on health care. but this should only be used for shortterm treatment. • For patients with sympathetic maintained pain (SMP). invasive procedures can be considered.66. • When the response to TCAs and anticonvulsants is unsatisfactory.121 or anticonvulsants (eg. such as decreased joint and tendon movement.116 • Rescue therapy with opioids may be necessary. Neurostimulation of the spinal cord or peripheral nerves may be effective.126 but may not improve long-term prognosis.117 .

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