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Evidence-based Recommendations for the Pharmacological Management of
Neuropathic Pain
Position Statement, June 2008
Australian Pain Society
• Internationally recognized guidelines
Background to this Position Statement

There are now several internationally-published evidence-based Guidelines which are worthy of
recognition within the Australian context.
This Position Statement is based on the studies that have specifically addressed the management
of neuropathic pain as an entity. However the Australian Pain Society recognises that any pain
condition whether with or without neuropathic pain components mandates a broad approach
recognizing the multidimensional physical, emotional, cognitive, social and vocational impacts of
persistent pain. To this end, it is appropriate that common and easily-available non-pharmacological
strategies be considered in any management plan.
However, in recognizing the overall context for assessing and treating pain, the Australian Pain
Society provides this Position Statement to support and guide specific treatment, in particular
pharmacologic treatment, for neuropathic pain based on best-available evidence and consensus
internationally.
An important framework with a strong evidence and experiential basis for achieving the best
therapeutic outcome in the management of neuropathic pain is Australia’s national strategy for
achieving quality use of medicines (QUM) that is found within the National Medicines policy (see
Appendix for more detailed definition).
The Statement confines itself to treatment recommendations, without more broadly addressing
clinical features and diagnosis of neuropathic pain for which assessment by an experienced
clinician will be important.
Definition

Neuropathic pain has been defined by the International Association for the Study of Pain (IASP) as
“pain initiated or caused by a primary lesion or dysfunction of the nervous system” (Merskey and
Bogduk 1994). This is in contrast to the other broad type of pain, nociceptive pain, in which the pain
system conveys or processes information from a pain source such as diseased tissue.
Common descriptors that may suggest the presence of neuropathic pain include sharpness,
burning, ache, stabbing, spasms, and paroxysms, often in or around an area of perceived
numbness, Such symptoms would occur where there is reasonable likelihood of nerve injury and is
often in a scenario of inadequate response to use of opioids. Neuropathic pain can occur, however
without these descriptors.
Epidemiology

Neuropathic pain is estimated to affect up to 7% of people (Gilron et al 2006, Bouhassira D et al
2007). This is approximately 15-20% of Australians who suffer from chronic pain, (17% males, to
20% females) (Blyth et al 2001). Pain (including that of neuropathic basis) is one of the commonest
symptoms that people present with to their family practitioners. It is recognised that in 20 – 50% of
visits to primary care practitioners, pain is part of their presenting complaint (Mantyselka et al 2001,
Dobecki et al 2006). Neuropathic pain also occurs in the acute pain setting (Hayes 2001). There is
evidence more than 50% of chronic pain sufferers have pain predominantly neuropathic in nature
((Kaki et al 2005)
Evidence-based Recommendations for the Pharmacological Management of
Neuropathic Pain
Position Statement, June 2008
Australian Pain Society
People with chronic pain are five times more likely to use health care services than those without
chronic pain (Becker et al 1997).
Neuropathic pain can be classified as central, peripheral and mixed aetiologies. Examples of central
neuropathic pain include post stroke pain, affecting up to 8% of patients post stroke, and
neuropathic pain associated with multiple sclerosis, with pain reported in more than 50% (Finnerup
et al 2007) and spinal cord injury 40% (Werhagen et al 2007). Peripheral neuropathic pain states
include painful peripheral neuropathies, including painful diabetic neuropathy affecting
approximately 25% of people with diabetes, sciatica, post-surgical and post-traumatic neuralgias.
Post herpetic neuralgia is an example of a mixed neuropathic pain, with both peripheral and central
mechanisms, affecting a significant proportion of patients following shingles.
Cancer-related pain very frequently has a significant neuropathic component as part of a mixed
nociceptive and neuropathic pain presentation. The approach to individuals in a palliative care
setting with a relatively short prognosis by its nature requires a more aggressive and intensive
multimodal approach but is outside of the scope of these guidelines. There is however a significant
proportion of cancer survivors with chemotherapy- and radiation-related neuropathic pain requiring
ongoing management.
In the past 2 decades neuropathic pain has received increasing attention in both the clinical and
research spheres. At the same time new therapies have offered promise of more effective treatment
with less side-effect.
The gathering pace of such research and product development over the last two decades has
resulted in the publication in recent years of several evidence-based treatment algorithms for
chronic neuropathic pain.
Internationally Recognised Guidelines of Pharmacological Treatment of
Neuropathic Pain.

There are several guidelines that been developed by the worlds’ leading researchers in the field of
neuropathic pain (Finnerup et al 2005, Attal et al 2006, Finnerup et al 2007, Dworkin et al 2007,
Moulin et al 2007). Their uniform salient findings are presented in table 1 as follows:
Table 1. Evidence-based pharmacologic treatment options for neuropathic pain.

nortriptyline, desipramine, amitriptyline, venlafaxine, duloxetine  It is acknowledged that for the specific diagnosis of trigeminal neuralgia carbamazepine is the drug of choice. However carbamazepine is of lesser effectiveness in general neuropathic pain and central pain conditions and hence does not appear in the above table. Medications in the above table all provide a highly-effective and efficient treatment likelihood of obtaining 50% pain reduction as measured by Number Needed to Treat (NNT) of the order of 3-6. The Canadian Pain Society went further to recommend the following order of preferences based on quality of evidence of analgesic efficacy, side-effect profiles, ease of use and cost. Moreover ‘medications were considered first- or second-line if there was high-quality evidence of efficacy and if they were considered straightforward to prescribe and monitor’. Third-line may require more specialised follow-up and monitoring to assess and address issues related to opioids such as tolerance and dependency, and fourth-line medications had at least one positive RCT to support it. Evidence-based Recommendations for the Pharmacological Management of
Neuropathic Pain
Position Statement, June 2008
Australian Pain Society
Table 2. Canadian Pain Society pharmacologic treatment priorities for neuropathic pain.

Tricyclic anti-depressants (eg amitriptyline) , gabapentin, pregabalin Serotonin noradrenergic reuptake inhibitors (venlafaxine), topical lignocaine cannabinoids, methadone, anticonvulsants with lesser efficacy (lamotrigine, topiramate, valproic acid) It is recognised that cannabinoids are not readily available for prescription, but this does not
preclude its addition to this list as there is a substantial research base that supports some efficacy
in some varieties of neuropathic pain such as multiple sclerosis.
There are many other medications in common use for historical, cost and perceived benefit
reasons, but have either been shown not to, or for some have not yet been shown (due to a lack of
studies) to have the same order of effectiveness as those indicated in the above table. These
include:
Antiepileptic medications: carbamazepine (except for trigeminal neuralgia), valproic acid,
lamotrigine, topiramate, oxcarbazepine, clonazepam;
Antidepressant medications : citalopram, paroxetine, bupropion;
Others: mexiletine, NMDA receptor antagonists (including ketamine), topical capsaicin,
cannabinoids.
The APS recognizes that the existing pharmacological treatments as exemplified in the above table
used for neuropathic pain provide a limited albeit proven benefit However successful treatment
obtaining approximately 50% relief of pain or greater occurs in no more than 40-60% of such
patients with mono-therapy. It is therefore likely that a multiple drug regime may increase the
successful outcome rate, the drugs may require rotation, and the continued effectiveness and side-
effects for the patient under consideration must be continually monitored (Dworkin et al 2007).
For clinically relevant and practical guidelines in the Australian context, the Western Australian
Therapeutic Advisory Group (WATAG, 2007) has formulated a condition-specific hierarchy of
medications for a range of Neuropathic conditions, generally utilizing the established evidence as
described in the above tables and including dosage regimens.
It is also recognized that among the many non-pharmacological treatment strategies, there is
evidence which supports good outcomes for chronic pain in general being cognitive-behaviourally
based Pain Management Programs (Norrbrink et al 2006). For chronic neuropathic pain where all
other pain management strategies have failed to sufficiently alleviate the pain intensity
neuromodulation by spinal (Sundaraj SR et al 2005) and peripheral stimulation (Mobbs et al 2007)
has established itself as an effective and efficient contributor to the management of neuropathic
pain in selected candidates.


Evidence-based Recommendations for the Pharmacological Management of
Neuropathic Pain
Position Statement, June 2008
Australian Pain Society
AUSTRALIAN PAIN SOCIETY POSITION STATEMENT ON
PHARMACOLOGIC MANAGEMENT OF NEUROPATHIC PAIN.

It is thus incumbent upon the Australian Pain Society to acknowledge the growing recognition of the
benefits, and limitations, of the current range of pharmacological treatments for chronic neuropathic
pain by developing and promulgating its own treatment recommendations.

To this end the Australian Pain Society recognises that the following medications as listed in Table
3 are preferred treatments available within Australia in a range of neuropathic pain conditions.
These are presented by non-prioritised classes, within each of which there are options that can be
considered.
Australian Pain Society evidence-based recommendations for the
pharmacologic management of neuropathic pain.

nortriptyline, amitriptyline, venlafaxine, duloxetine Conversely it is recognized that other medications of probable overall lesser effectiveness may
warrant consideration particularly in the scenario where first–line medications have proven to be
insufficiently effective, poorly tolerated, or are contraindicated. It is recognised that carbemazepine
is a first-line treatment for trigeminal neuralgia, one particular form of neuropathic pain, but it has
not shown effectiveness for the wider range of neuropathic pain conditions.
It is recognised that there is a paucity of studies comparing medications within and across these
classes.
Neuropathic pain related to cancer and its sequelae presents its own urgency and priorities
whereby it is acknowledged that the above Guidelines may assist in pharmacological management
but that many other options may be required to assist in pain control. The guidelines are not
designed to be prescriptive or restrictive.
The Australian Pain Society commends these guidelines as one more step along the way of
assisting the people of Australia and their treating clinicians obtain efficacious pain control as
efficiently and effectively as possible.
As a final comment, it is difficult to surpass the concluding comments in ‘An Evidence-based
Algorithm for the Treatment of Neuropathic Pain’ (Finnerup et al 2007):
“Clearly, improvements can be made to this treatment algorithm, and as more evidence is
generated from high-quality, randomized, controlled, head-to-head comparative clinical trials, this
treatment algorithm can be refined to ultimately benefit the patient with neuropathic pain
”.
(APS emphasis).


Evidence-based Recommendations for the Pharmacological Management of
Neuropathic Pain
Position Statement, June 2008
Australian Pain Society

APPENDIX

Definition of Quality Use of Medicines, within the National Medicines Policy, Commonwealth
Department of Health.

Quality use of medicine means:
• Selecting management options wisely by:
o Considering the place of medicines in treating illness and maintaining health, and o Recognizing that there may be better ways than medicine to manage many disorders • Choosing suitable medicines if a medicine is considered necessary so that the best available o The individual o The clinical condition o Risks and benefits o Dosage and length of treatment o Any co-existing conditions o Other therapies o Monitoring considerations o Costs for the individual, the community, and the health system as a whole, • Using medicines safely and effectively to get the best possible results by: Minimizing misuse, over-use, and under –use; and Improving people’s ability to solve problems related to medication, such as negative effects or managing multiple medications. REFERENCES
1. Attal N et al. EFNS Guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol.
2006; 13:1153-1169.
2. Becker N et al. Pain epidemiology and health-related quality of life in chronic non-malignant pain
patients referred to a Danish multidisciplinary pain centre. Pain. 1997; 73:393-400.
3. Blyth FM, et al. Chronic Pain in Australia: a prevalence study. Pain. 2001; 89(2-3):127-134.
4. Bouhassira D , et al. Prevalence of chronic pain with Neuropathic characteristics in the general
population. Pain. 2007;
5. Commonwealth Department of Healthand Ageing. The National Strategy for Quality Use of
Medicines. Canberra: 2002.
6. Dobecki DA et al. Update on pharmacotherapy guidelines for the treatment of neuropathic pain.
Curr Pain Headache Rep. 2006; 10:185-190.
7. Dworkin RH et al. Pharmacologic management of neuropathic pain: Evidence-based
recommendations. Pain. 2007; 132:237-251.
8. Finnerup NB et al. Algorithm for the treatment of neuropathic pain: an evidence-based proposal.
Pain. 2005; 118:289-305.
9. Finnerup NB et al. An evidence-based algorithm for the treatment of neuropathic pain. Med Gen
Med. 2007; 9(2):36
Evidence-based Recommendations for the Pharmacological Management of
Neuropathic Pain
Position Statement, June 2008
Australian Pain Society
10. Gilron I et al. Neuropathic Pain: a practical guide for the clinician. CMAJ. 2006; 175:265-275. 11. Hayes C, Browne S, Lantry G, Burstal R. Acute Pain 2002;4:45-48 Neuropathic pain in the acute pain service: a prospective survey. 12. Kaki AM et al. Identifying Neuropathic pain among patients with chronic low-back pain: use of the Leeds Assessment of Neuropathic Sumptoms and Signs Pain Scale. Reg Anaesth Pain Med. 2005; 30:422-8. 13. Mantyselka P et al. Pain as a reason to visit the doctor: a study in Finnish primary care. Pain. 2001; 89: 175-180. 14. Merskey H, Bogduk N (Eds), Classification of Chronic Pain. IASP Press, 1994. 15. Mobbs e al. Peripheral nerve stimulation for the treatment of chronic pain. J Clin Neuroscience. 2007; 14:216-221. 16. Moulin DE, et al. Pharmacologic management of chronic neuropathic pain: Consensus statement and guidelines from the Canadian Pain Society. 17. Norrbrink Budh C, et al. A comprehensive pain management program comprising educational. Cognitive, and behavioral interventions for Neuropathic pain following spinal cord injury. J Rehab Med. 2006; 38:172-80. 18. Sindrup SH, Jensen TS. Pharmacologic treatment of pain in poly-neuropathy. Pain. 1999; 83:389-400. 19. Sundaraj SR et al. Spinalcord stimulation: a seve-year audit. J Clin Neuroscience. 2005; 12(3):264-70. 20. WATAG Guidelines for the treatment of Neuropathic pain. Dept Health, WA Government c/o PO Box X2213, Perth, Western Australia. 6847. 21. Werhagen L, Hultling C, Molander C. The prevalence of neuropathic pain after non-traumatic spinal cord lesion. Spinal Cord (2007); 45:609-615.  

Source: http://www.fpmx.com.au/pdf/AustPainSoc%20neuropathic%20pain%20guides.pdf

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