The management of neuropathic pain in cancer

Invited review

The management of neuropathic pain in cancer Robert D Searle1 and Michael Bennett2 1

Academic Unit of Anaesthesia, Leeds General Infirmary, Leeds, UK International Observatory on End of Life Care, Institute for Health Research, Lancaster University, UK

2

Neuropathic pain is a common problem amongst cancer patients, yet it can be challenging to diagnose and treat successfully. The diagnosis of neuropathic pain has been helped by the identification of common descriptors and symptoms often used by patients and several screening tools now exist to identify neuropathic features. The management of neuropathic pain in cancer is a balance of pharmacological, physical and psychological interventions used skilfully in patients that are often frail and with cognitive, hepatic or renal impairment. Commonly used drugs for the treatment of neuropathic pain include opioids, antidepressants and anti-epileptics, although the evidence for their use in the cancer population is often poor. Other drugs that have shown to be of benefit include NMDA receptor antagonists and local anaesthetic agents, although side effects often limit their use. Physical interventions include intrathecal drug delivery, neurolytic sympathetic plexus blockade and spinal cord stimulation. These therapies should be considered in patients who have refractory pain or intolerable side effects to systemically administered analgesics. New intrathecal drugs, such as the N-type calcium channel blocker ziconotide have shown promise in managing neuropathic pain. Keywords: Neuropathic pain, cancer, management, review

Introduction Neuropathic pain is defined by the International Association for the Study of Pain (IASP) as pain initiated or caused by a primary lesion or dysfunction within the nervous system.1 Historically, the term neuropathic pain was used to describe conditions affecting peripheral nerves. One of the earliest descriptions of peripheral neuropathic pain

Correspondence to: Robert D. Searle, Specialist Registrar in Anaesthesia, Academic Unit of Anaesthesia, Leeds General Infirmary, Great George St, Leeds LS1 3EX, UK E-mail: [email protected]

Michael Bennett, Professor of Palliative Medicine, International Observatory on End of Life Care, Institute for Health Research, Bowland Tower East, Lancaster University, Lancaster LA1 4YT, UK. E-mail: [email protected]

© 2008 W.S. Maney & Son Ltd DOI 10.1179/096992608X291207

depicts symptoms similar to tic douloureux in the distribution of the radial nerve, caused by a musket ball injury during the Spanish Peninsula War.2 By the 20th century, pain caused by lesions or damage to the central nervous system was well described. Behan,3 in 1914, coined the phrase ‘central pain’ and the definition was refined in 1938 by Riddoch4 who described it as ‘a pain worse than pain’. The most recent definition of neuropathic pain encompasses both peripheral and central nervous system causes. In addition, the inclusion of ‘dysfunction’ in the definition allows complex regional pain syndrome type 1 (reflex sympathetic dystrophy), which does not have identifiable primary pathology within the nervous system, to be classified as neuropathic pain also. Neuropathic pain amongst cancer patients is common. The prevalence of cancer pain inferred to have neuropathic mechanisms was 39.7% in an

Progress in Palliative Care

2008

Vol 16

No 1

7

Searle & Bennett

The management of neuropathic pain in cancer

international survey conducted on behalf of the IASP.5 Neuropathic pain is clearly comprised of a number of heterogeneous aetiologies. Among cancer patients, neuropathic pain may be caused directly by tumour infiltration or compression, or indirectly by chemotherapy, radiotherapy or surgery. Similarly, individuals suffering neuropathic pain can have varying symptoms even if they have the same underlying pathology. This makes the identification and treatment of neuropathic pain a challenging prospect. With an ageing population, and improved cancer treatments leading to better survival rates, neuropathic pain is likely to become an increasing problem in the cancer population.

The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) was developed as a simple bed-side test to aid the diagnosis of neuropathic pain.6 During its development, it demonstrated sensitivity and specificity of 85% and 80%, respectively, compared to clinical diagnosis. It has also been validated in a cancer neuropathic pain population with similar classification rates.7 The S-LANSS has been developed as a self-report version of the LANSS scale, enabling completion by patients or in non-clinical settings. Although the LANSS was not designed as a measurement tool, it has also shown sensitivity to treatment effects.8

Management of neuropathic pain Identification of neuropathic pain The IASP has defined a number of symptoms associated with neuropathic pain.1 Broadly, these can be divided into positive and negative phenomena. Positive phenomena can be spontaneous (arising without stimulus) or evoked (stimulus-dependent). Examples of positive phenomena include allodynia, hyperalgesia, hyperpathia and dysaesthesia. Negative phenomena include hypoaesthesia and hypo-algesia. When patients describe neuropathic pain, they often use adjectives such as ‘burning’, ‘lancinating’ or ‘electric-shock like’. These contrast with the often ‘dull’, ‘aching’, ‘sharp’ or ‘tender’ descriptors used to describe nociceptive pain. Signs of neuropathic pain are often missed on superficial examination. It is important to corroborate a diagnosis of neuropathic pain with demonstrable sensory changes in the painful area (‘pain in an area of altered sensation’ is a clinically useful definition). Common changes include the presence of allodynia; pain evoked by a non-painful stimulus such as stroking the skin with cotton wool. Altered pin-prick threshold is another feature; this can be raised such that normally painful stimuli are not felt, or it can be lowered so that these stimuli are perceived as very painful when compared to an adjacent or contralateral non-painful site. Patients may also exhibit the effects of autonomic dysfunction. These include trophic changes (such as hair loss), sudomotor changes (such as hyperor hypohidrosis), vasomotor changes (oedema, erythema) or musculoskeletal changes (muscle wasting, osteopenia). Although no single symptom or sign is pathognomic of neuropathic pain, the identification of common descriptors and signs has led to the development of screening tools designed to distinguish neuropathic from nociceptive pain.

8


2008

Vol 16

No 1

The management of neuropathic pain comprises pharmacological, physical and psychological therapies. This article will focus on pharmacological and physical interventions. Pharmacological management

Drugs provide an easily accessible and convenient therapy for the treatment of neuropathic pain. However, there remain issues surrounding the response to drugs (such as the predictability and magnitude of response) and their tolerability. Cancer patients tend to be older, have a poor performance status and are more susceptible to drug side effects. Consequently, the NNH (number needed to harm) for a given drug maybe lower in this population and influence prescribing as much as the NNT (number needed to treat). Additionally, most of the evidence for the effectiveness of drug therapies in neuropathic pain comes from a non-cancer setting. Prescriptions should, therefore, reflect a balance between efficacy and side effects. Commonly, three group of drugs are prescribed for neuropathic pain – opioids, antidepressants and anti-epileptics. Opioids

Strong opioids have traditionally been avoided in neuropathic pain due to a perceived lack of efficacy. However, recent research has shown that, while neuropathic pain may be less responsive than nociceptive pain, it is not resistant to opioids. This has led to the introduction of strong opioids as third-line treatment in patients with chronic neuropathic pain. However, the cancer population represents a different subgroup. Many cancer patients are already treated with opioids, and this class of drugs is often more acceptable as a form of analgesia than in non-cancer patients. In practice, opioids are often used as first-line therapy in this setting.

Searle & Bennett

Morphine has been shown to be equally as effective as tricyclic antidepressants (TCAs) and anti-epileptics (e.g. gabapentin) in the treatment of post herpetic neuralgia and diabetic neuropathy.9–12 The frequency of adverse effects was similar in each group and in one study patients preferred morphine to TCAs.11 There is the possibility that morphine has synergistic effects when combined with gabapentin. In a recent trial, the combination of morphine and gabapentin achieved significantly better results at lower doses of both drugs than when used alone.12 A systematic review by Finnerup et al.13 has estimated morphine to have an NNT of 2.5 (that is, 4 in every 10 treated patients will experience a 50% reduction in their pain). Fentanyl is commonly used in patch form and as a transmucosal lozenge for break-through pain in cancer. Although a double-blind, crossover study of 53 patients with a variety of neuropathic pains showed intravenous fentanyl improved pain compared to placebo or diazepam, a follow-up study converting the patients to transdermal patches was disappointing.14,15 Two-thirds of these patients experienced no pain improvement or withdrew because of side effects. Oxycodone has been shown to be effective in neuropathic pain. Randomised control trials in patients with post herpetic neuralgia and diabetic neuropathy have shown significant improvement when compared to placebo.16,17 A recent trial over 6 weeks showed oxycodone to be effective in treating moderate-to-severe neuropathic pain.18 Finnerup et al.13 estimated oxycodone to have an NNT of 2.6. Other opioids have also shown benefit. A Cochrane Review of tramadol concluded it was effective in treating neuropathic pain, with an NNT of 3.5.19 Buprenorphine has demonstrated efficacy treating post thoracotomy neuropathic pain and animal and volunteer studies suggest it has a high anti-hyperalgesic effect.20 Antidepressants

Probably the most commonly prescribed group of drugs for the treatment of neuropathic pain is the tricyclic antidepressants (TCAs). Oddly, they are not commonly given to cancer patients with neuropathic pain which probably represents undertreatment.21 TCAs work by inhibiting serotonin and noradrenaline re-uptake in the CNS, enhancing inhibitory descending pain pathways. They also bind to sodium channels and may block voltage-gated calcium channels and NMDA receptors (directly or indirectly). Systematic reviews have demonstrated tertiary TCAs (such as amitriptyline and imipramine) to have an NNT of 2.1 in patients with painful peripheral neuropathy.22 Similarly, in post herpetic neuralgia the


NNT was 2.5. In cancer neuropathic pain, a randomised, placebo-controlled, double-blind trial in 16 patients already receiving morphine showed an improvement in ‘worse pain’ but no improvement in global pain intensity or reduction in opioid doses.23 SSRI antidepressants have been investigated in painful peripheral neuropathy although not in cancer patients. In general, they are less effective than TCAs with a calculated NNT of 6.7. SNRI antidepressants (such as venlafaxine and duloxetine) have shown superiority to placebo when treating diabetic neuropathy in randomised control trials (RCTs); their calculated NNT is 4. The evidence for use in cancer patients with neuropathic pain is limited to those with treatment related peripheral neuropathy such as post mastectomy pain syndrome.24 Evidence in non-cancer conditions suggests TCAs are likely to be the first-line choice of antidepressant in cancer patients. However, although SNRIs have a higher NNT, they may be better tolerated in the long term, although evidence for this is lacking. Anti-epileptics

Anti-epileptics are well established in the treatment of neuropathic pain. Their mode of action varies according to the class of anti-epileptic used. The older drugs (such as carbamazepine and phenytoin) block sodium channels in peripheral nerves. These drugs have a limited license for use in neuropathic pain (trigeminal neuralgia only). Newer drugs (such as gabapentin and pregabalin) achieve analgesia by blocking the α2δ-subunit of voltage-dependent calcium channels. These drugs are thought to inhibit the release of excitatory neurotransmitters in the dorsal horn of the spinal cord reducing glutamate availability at NMDA and non-NMDA receptors. To a greater or lesser extent, all anti-epileptics suffer from dose-limiting side effects. One advantage of gabapentin and pregabalin is that they do not inhibit or induce hepatic cytochrome enzymes (unlike classical antiseizure medications such as carbamazepine) reducing significant interactions with other drugs. This is an important consideration in patients such as those with cancer who may be taking a large number of other medications. Like TCAs, anti-epileptics are not commonly used in the treatment of cancer neuropathic pain. Berger et al.21 found that only 17% of patients in the US with a diagnosis of cancer and painful neuropathy were prescribed an anti-epileptic. The evidence for their use in cancer patients is poor, especially for the newer antiepileptics. Gabapentin, probably the most widely used anti-epileptic, has shown good results in RCTs


2008

Vol 16

No 1

9

Searle & Bennett


investigating the treatment of post herpetic neuralgia and diabetic neuropathy.25–27 Systematic reviews have calculated an NNT of between 3.2 and 3.8 for these conditions.28 In cancer patients, gabapentin has been added to opioids for the management of neuropathic pain in a double-blind RCT.29 Average daily pain scores were significantly better for the treatment group but further analysis showed this was achieved in the first 5 days of treatment. Thereafter, pain scores were no different between the groups.30 In other, noncontrolled studies in cancer neuropathic pain, 45% of patients experienced a 30% reduction in pain score after 15 days of treatment with gabapentin.31 These two studies highlight the need for placebo-controlled trials in palliative care populations in order to quantify treatment and placebo responses. Of the older anti-epileptics, phenytoin has been studied in combination with buprenorphine in difficult to control cancer pain (although not exclusively neuropathic pain).32 The study, comparing buprenorphine with phenytoin and a combination of both drugs, found combined therapy provided the best analgesia. A case report has also described the successful use of intravenous phenytoin for rapidly progressive cancer neuropathic pain.33 A Cochrane Review of carbamazepine calculated an NNT of 2.5 in trigeminal neuralgia and 2.3 in diabetic neuropathy.28 Sodium valproate has been widely prescribed in the past for neuropathic pain despite this being an unlicensed indication and relatively poor evidence supporting its use. In cancer neuropathic pain, an observational study over a 2-week period showed around 30% of patients had a 50% reduction in absolute pain when given valproate.34 Case reports exist describing the successful use of lamotrigine and levitiracetum in neuropathic cancer pain.35,36 The importance of glutamate in modulating neuropathic pain suggests drugs like lamotrigine may have an important role in the future, although currently gabapentin and pregabalin remain the first choice of anti-epileptic treatment for most patients with neuropathic pain. NMDA-receptor antagonists

Ketamine is a phencyclidine derivative with complex pharmacological actions; it interacts with sodium and calcium channels, it inhibits noradrenaline and serotonin re-uptake and affects cholinergic transmission. However, its principal action is antagonism of NMDA receptors and this has led to studies of its use in neuropathic pain. Current opinion suggests the NMDA receptor plays an important role in neuropathic pain. Repeated stimulation of NMDA

10


2008

Vol 16

No 1

receptors may be responsible for the phenomenon of ‘wind up’ resulting in amplified and prolonged responses to stimuli, both noxious and non-noxious. Evidence suggests ketamine has a role in the management of refractory cancer pain, although there is little research into its use in exclusively neuropathic pain.37 In one, small, randomised study in patients with cancer pain unrelieved by morphine alone, all 10 patients benefited from an intravenous bolus of ketamine but six had unpleasant side effects.38 Magnesium is also known to block NMDA receptors and may reduce ‘wind up’. In a small observational study of 12 cancer patients with neuropathic pain, each received either 500 mg or 1 g of intravenous magnesium. Four patients reported complete relief, six partial relief and two patients had no relief.39 Local anaesthetics

Local anaesthetics have been administered both enterally (mexilitine) and parenterally (lidocaine) to treat neuropathic pain by blocking voltage-gated sodium channels. Intravenous lignocaine relieves noncancer neuropathic pain (in doses of 5 mg/kg over 30–60 min), although the effects are short lived. Two small RCTs in cancer neuropathic pain failed to show any benefit over placebo (although the trials may have been underpowered to show a treatment effect).40,41 A recent systematic review of oral mexilitine suggested it had a similar efficacy and side-effect profile to opioids, amitriptyline and gabapentin.42 It has a narrow therapeutic index and can be complicated by side effects, nausea in particular, and these features undoubtedly contribute to its lack of use by most palliative care clinicians. In contrast, topical lidocaine patches can be useful when treating localised allodynia, for example, in post-herpetic neuralgia or over a healed post-thoracotomy wound or chest drain site. Lidocaine patches have few systemic effects. Physical management

Physical interventions for the treatment of neuropathic pain can be simple (TENS, acupuncture) or complex (intrathecal drug delivery systems, neurolytic blocks, spinal cord stimulators). In refractory neuropathic cancer pain, intrathecal drug delivery systems and neurolytic sympathetic plexus blockade can provide analgesia where standard drug therapy has failed. TENS and acupuncture

Acupuncture is generally considered less effective at treating neuropathic pain than pain of nociceptive origin. A recent systematic review of acupuncture in

Searle & Bennett

all types of cancer pain concluded that insufficient evidence exists to support its use.43 There remains a lack of high-quality trials investigating acupuncture and TENS in neuropathic cancer pain. Despite this, TENS and acupuncture are relatively cheap, free from side effects and do not interact with drug therapy; therefore, it may be worth considering their use until quality evidence suggests otherwise. Intrathecal drug delivery

Intrathecal drug delivery systems were pioneered for use in cancer pain. Intraspinal opioids have successfully been used to treat nociceptive pain states such as those arising from wide-spread bony metastasis, diffuse cancer pain, and pelvic pain. However, many cancer patients have mixed nociceptive and neuropathic pain elements and it is recognised that intrathecal drugs may play a role in the management of this type of cancer pain.44 Patient selection is important when considering intraspinal therapy and conservative measures should be exhausted before considering this course. The main indication for intraspinal opioids in cancer pain is when systemic opioids are effective but produce doselimiting or intolerable side effects.45 Patients should undergo evaluation by a multidisciplinary team (including psychosocial assessment) and show a good response to a test dose before proceeding to implantable devices.45 Cancer patients who have an expected survival of less than 3 months should receive external devices rather than implanted pumps.46 A variety of drugs have been used to provide analgesia via the spinal route. These include opioids, midazolam, neostigmine, ketamine, baclofen, clonidine and ziconotide. The Polyanalgesic Consensus Panel issued guidelines in 2003 suggesting that, for pain with a predominantly neuropathic element, starting therapy should be an opioid plus adjuvant (bupivicaine or clonidine); however, there is no specific data to support this approach.47 The panel is due to update its guidelines with the inclusion of ziconotide as an alternative or adjunct to the opioids morphine and hydromorphone. Ziconotide is a synthetic N-type calcium channel blocker based on a peptide found in neurotoxic marine snails. It has been shown to produce antinociception and reduction in allodynia when given intrathecally and a double-blind, placebocontrolled RCT demonstrated efficacy in cancer and AIDS patients.48 Neurolytic sympathetic plexus blockade

Sympathetic plexus blockade is no longer commonly performed but may have a role to play in the treatment


of refractory neuropathic cancer pain. The concept that some neuropathic pains were maintained by the sympathetic nervous system led to the use of chemical and surgical sympathectomy as a treatment option. However, a Cochrane systematic review in 2003 concluded that evidence for the use of sympathectomy was weak and that the procedures often had significant side effects (including de-afferentation pain).49 The World Health Organization (WHO) currently recommends the use of neurolytic nerve blocks as a last resort. However, in the management of cancer neuropathic pain, the celiac plexus block has shown efficacy in managing upper abdominal symptoms. Conditions like pancreatic cancer can provoke neuropathic abdominal pain through a number of possible mechanisms. The tumour may compress or stretch the nerves of the pancreas, and can secrete neurolytic enzymes permitting cancer spread via nerve sheaths. A meta-analysis of neurolytic celiac plexus block for cancer pain demonstrated long-lasting benefit for 70–90% of patients with pancreatic and other abdominal cancers.50 A recent double-blind, randomised, sham-controlled trial compared neurolytic celiac plexus block with systemic analgesia alone.51 The study was confined to patients with unresectable pancreatic adenocarcinoma and investigated pain relief, quality of life and cancer survival. After 1 week, pain was significantly improved with a larger decrease in pain in the celiac plexus block group and pain remained significantly lower in this group over time. However, there was no difference in opioid consumption and quality of life between the two groups. The results of this study suggest celiac plexus blockade improves pain relief in pancreatic cancer patients when compared with systemic analgesia alone. Spinal cord stimulation

Spinal cord stimulation (SCS) is an invasive technique involving placement of electrodes in the epidural space and implanting an electrical pulse generator. It began after Melzack and Wall proposed the gate theory of pain in 1965 and its mechanism of action was thought to be closure of the ‘gate’ to the transmission of pain. The mechanisms of action are still not fully understood but SCS probably has a number of effects which play a greater or lesser role in the provision of analgesia depending on the pain mechanism being treated. For example, in neuropathic pain states, SCS is thought to modulate the neurochemistry in the dorsal horn of the spinal cord; in ischaemic pain, it may provide sympathetically mediated improvement in tissue oxygen supply and demand.


2008

Vol 16

No 1

11

Searle & Bennett


Figure 1 Suggested oral analgesic ladder for neuropathic cancer pain. First-line adjuvants – TCA, gabapentin, pregabalin; second-line adjuvants – other antidepressant, local anaesthetic

The indications for SCS are essentially neuropathic pain and ischaemic pain due to peripheral vascular disease or angina. SCS is not effective in treating pain of nociceptive origin. There is little evidence to support its wide-spread use in cancer pain; however, case reports suggest it is effective in the treatment of chemotherapy induced painful peripheral 52 neuropathy. It is important to note that spinal cord stimulators are not magnetic resonance imaging (MRI) compatible, an important consideration if patients are receiving MRI surveillance.

following the WHO guidelines, neuropathic pain in cancer patients can be successfully managed using a step-wise approach incorporating standard non-opioid, ‘weak’ opioid, and ‘strong’ opioid analgesia. Based on their NNH and NNT, first-line and then second-line adjuvants can be added in to take advantage of the effects of combination therapy. Other guidelines exist for the management of neuropathic pain but are not specific to the cancer population.55

References Cervical cordotomy

Percutaneous cervical cordotomy has been used for pain relief refractory to other measures, and may still have a role in the treatment of terminal cancer patients with unilateral incident or neuropathic pain.53

Conclusions Pharmacological therapy remains the mainstay of treatment for cancer patients with neuropathic pain. Given the large number of processes that are involved in the development and maintenance of neuropathic pain, it is logical that targeting several separate mechanisms with concurrently administered drugs should improve symptoms. Clinical studies suggest such a drug synergy exists between opioids and gabapentin.12 A suggested treatment algorithm for the pharmacological management of neuropathic pain in cancer is shown in Figure 1. Grond et al.54 showed that, by

12


2008

Vol 16

No 1

1. Merskey H, Bogduk N. Classification of chronic pain. Seattle, WA: IASP, 1994. 2. Denmark A. An example of symptoms resembling tic douloureux produced by a wound in the radial nerve. Med Chir Trans London 1813; 3: 48–52. 3. Behan RJ. Pain: its origin, conduction, perception and diagnostic significance. New York: V Appleton, 1914; 198–203. 4. Riddoch G. The clinical features of central pain. Lancet 1938; 234: 1093–1098, 1150–1156, 1205–1209. 5. Caraceni A, Portenoy RK. An international survey of cancer pain characteristics and syndromes. Pain 1999; 82: 263–274. 6. Bennett M. The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain 2001; 92: 147–157. 7. Potter J, Higginson IJ, Scadding JW, Quigley CW. Identifying neuropathic pain in patients with head and neck cancer: use of the Leeds Assessment of Neuropathic Symptoms and Signs Scale. J R Soc Med 2003; 96: 379–383. 8. Khedr EM, Kotb H, Kamel NF, Ahmed MA, Sadek R, Rothwell JC. Long lasting analgesic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J Neurol Neurosurg Psychiatry 2005; 76: 833–838. 9. Rowbotham MC, Reisner-Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology 1991; 41: 1024–1028. 10. Jadad AR, Carroll D, Glynn CJ et al. Morphine responsiveness of chronic pain: double-blind randomized crossover study with patientcontrolled analgesia. Lancet 1992; 339: 1367–1371. 11. Raja SN, Haythornthwaite JA, Pappagallo M et al. Opioids versus

Searle & Bennett

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22. 23.

24.

25.

26.

27.

28.

29.

30.

31.

32. 33.

antidepressants in postherpetic neuralgia. A randomized, placebocontrolled trial. Neurology 2002; 59: 1015–1021. Gilron I, Bailey JM, Dongsheng TU et al. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 2005; 352: 1324–1334. Finnerup NB, Otto M, McQauy HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain 2005; 118: 289–305. Dellemijn P, Vanneste JA. Randomized double-blind active-placebocontrolled crossover trial of intravenous fentanyl in neuropathic pain. Lancet 1997; 349: 753–758. Dellemijn PL, van Duijn H, Vanneste JA. Prolonged treatment with transdermal fentanyl in neuropathic pain. J Pain Symptom Manage 1998; 16: 220–229. Watson CPN, Babul N. Efficacy of oxycodone in neuropathic pain a randomized trial in post herpetic neuralgia. Neurology 1998; 50: 1837–1841. Watson CPN, Moulin D, Watt-Watson J et al. Controlled-release oxycodone relieves neuropathic pain; a randomized controlled trial in painful diabetic neuropathy. Pain 2003; 105: 71–78. Gimbel JS, Richards P, Portenoy RK. Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial. Neurology 2003; 60: 927–934. Duhmke RM, Cornblath DD, Hollingshead JR. Tramadol for neuropathic pain. Cochrane Database Syst Rev 2004; (2): CD 003726. Benedetti F, Vighetti S, Amanzio M et al. Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain. Pain 1998; 74: 205–211. Berger A, Mercadante S, Oster G. Use of antiepileptics and tricyclic antidepressants in cancer patients with neuropathic pain. Eur J Cancer Care 2005; 15: 138–145. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev 2005; (3): CD005454. Mercadante S, Arcuri E, Tirelli W, Villari P, Casuccio A. Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled, double-blind crossover study. Tumori 2002; 88: 239–242. Reuben SS, Makari-Judson G, Lurie SD. Evaluation of efficacy of the perioperative administration of venlafaxine XR in the prevention of postmastectomy pain syndrome. J Pain Symptom Manage 2004; 27: 133–139. Rice AS, Maton S, Post-therapeutic Neuralgia Study Group. Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study. Pain 2001; 94: 215–224. Backonja A, Beydoun A, Edwards KR et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus. JAMA 1998; 280: 1831–1836. Serpell M, Neuropathic Pain Study Group. Gabapentin in neuropathic pain syndromes: a randomised, double blind, placebo controlled trial. Pain 2002; 99: 557–566. Wiffen P, Collins S, McQuay H, Carroll D, Jadad A, Moore A. Anticonvulsant drugs for acute and chronic pain. Cochrane Database Syst Rev 2005; 3: CD001133. Caraceni A, Zecca E Bonezzi C et al. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the gabapentin cancer pain study group. J Clin Oncol 2004; 14: 2909–2917. Bennett MI. Gabapentin significantly improves analgesia in people receiving opioids for neuropathic cancer pain. Cancer Treatment Rev 2005; 31: 58–62. Ross JR, Goller K, Hardy J et al. Gabapentin is effective in the treatment of cancer-related neuropathic pain: a prospective, openlabel study. J Palliat Med 2005; 8: 1118–1126. Yajnik S, Singh GP, Singh G, Kumar M. Phenytoin as a co-analgesic in cancer pain. J Pain Symptom Manage 1992; 7: 209–213. Chang VT. Intravenous phenytoin in the management of crescendo pelvic cancer-related pain. J Pain Symptom Manage 1997; 13: 238–240.


34. Hardy JR, Rees EA, Gwilliam B, Ling J, Broadley K, A’Hern R. A phase II study to establish the efficacy and toxicity of sodium valproate in patients with cancer-related neuropathic pain. J Pain Symptom Manage 2001; 21: 204–209. 35. Devulder JE. Lamotrigine in refractory cancer pain. A case report. J Clin Anesth 2000; 12: 574–575. 36. Dunteman ED. Levetiracetam as an adjunctive analgesic in neoplastic plexopathies: case series and commentary. J Pain Palliat Care Pharmacother 2005; 19: 35–43. 37. Jackson K, Ashby M, Martin P et al. ‘Burst’ ketamine for refractory cancer pain: an open-label audit of 39 patients. J Pain Symptom Manage 2001; 22: 834–842. 38. Mercadante S, Arcuri E, Tirelli W, Casuccio A. Analgesic effects of intravenous ketamine in cancer patients on morphine therapy: a randomised double blind, crossover, double-dose study. J Pain Symptom Manage 2000; 20: 246–252. 39. Crosby V, Wilcock A, Corcoran R. The safety and efficacy of a single dose (500 mg or 1 g) of intravenous magnesium sulphate in neuropathic pain poorly responsive to strong opioid analgesics in patients with cancer. J Pain Symptom Manage 2000; 19: 35–39. 40. Ellemann K, Sjogren P, Banning AM, Jensen TS, Smith T, Geertson P. Trial of intravenous lidocaine on painful neuropathy in cancer patients. Clin J Pain 1989; 5: 291–294. 41. Bruera E, Ripamonti C, Brenneis C, Macmillan K, Hanson J. A randomized double-blind crossover trial of intravenous lidocaine in the treatment of neuropathic cancer pain. J Pain Symptom Manage 1992; 7: 138–140. 42. Challapalli V, Tremont-Lukats IW, McNicol ED, Lau J, Carr DB. Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev 2005; (4): CD003345. 43. Lee H, Schmidt K, Ernst E. Acupuncture for the relief of cancer related pain: a systematic review. Eur J Pain 2005; 9: 437–444. 44. Krames E. Implantable devices for pain control: spinal cord stimulation and intrathecal therapies. Best Prac Res Clin Anaesthesiol 2002; 16: 619–649. 45. Prager J, Jacobs M. Evaluation of patients for implantable pain modalities: medical and behavioural assessment. Clin J Pain 2001; 17: 206–214. 46. Krames ES. Practical issues when using neuraxial infusion. Oncology 1999; 13 (Suppl 2): 37–44. 47. Hassenbusch SJ, Portenoy RK, Cousins M et al. Polyanalgesic Consensus Conference 2003: an update on the management of pain by intraspinal drug delivery – report of an expert panel. J Pain Symptom Manage 2004; 27: 540–563. 48. Staats PS, Yearwood T, Charapata SG et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS. JAMA 2004; 291: 63–70. 49. Mailis A, Furlan A. Sympathectomy for neuropathic pain. Cochrane Database Syst Rev 2003; Issue 2. 50. Eisenberg E, Carr DB, Chalmers TC. Neurolytic celiac plexus block for treatment of cancer pain: a meta-analysis. Anesth Analg 1995; 80: 290–295. 51. Wong GY, Schroeder DR, Carns PE et al. Effect of neurolytic celiac plexus block on pain relief, quality of life and survival in patients with unresectable pancreatic cancer. JAMA 2004; 291; 1092–1099. 52. Cata J, Cordiella J, Burton AW, Dougherty P, Hassenbusch SJ. Spinal cord stimulation effectively treats chemotherapy induced peripheral neuropathy. J Pain Symptom Manage 2004; 27: 72–78. 53. Crul BJ, Blok LM, van Egmond J, van Dongen RT. The present role of percutaneous cervical cordotomy for the treatment of cancer pain. J Headache Pain 2005; 6: 24–29. 54. Grond S, Radbruch L, Meuser T et al. Assessment and treatment of neuropathic cancer patients following WHO guidelines. Pain 1999; 79: 15–20. 55. Attal N, Cruccu G, Haanpaa M et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol 2006; 13: 1153–1169.


2008

Vol 16

No 1

13

Physical Therapy Reviews An essential tool for physical therapy professionals

Physical Therapy Reviews publishes contemporary reviews, discussion papers and editorials within physical therapy. This international journal is aimed at all those involved in research, teaching, and practice within the area of physical therapy. The wide diversity of peerreviewed papers cover both basic and clinical sciences which form the basis of physical therapy.

EDITOR-IN-CHIEF Professor David Baxter University of Otago, New Zealand. Email: [email protected]

ASSISTANT EDITOR Professor Susan McDonough University of Ulster, UK. Email: [email protected]

Reduced subscription rate for members of the Polish Physiotherapy Society and the Polish Rehabilitation Society! For more information visit www.maney.co.uk/journals/ptr Email: s u b s c r i p t i o n s @ m a n e y . c o . u k

WWW.MANEY.CO.UK