Homeopathic Research Proposition

Title

A pilot study: does the homeopathic nosode Variolinum alleviate pain symptoms in patients diagnosed with post-herpetic neuralgia (PHN)?

Abstract

PHN is a common condition affecting about 1 in 5 people in the UK. PHN can be a debilitating condition extending from 2 weeks to years. Presently there is no cure and PHN patients are reliant on long-term drugs to manage pain and associated conditions such as depression; though the Herpes Zoster vaccine has been produced to reduce the risk of developing shingles in people over 60 in the UK. This pilot study is designed to examine if the homeopathic nosode Variolinum, a natural, chemical-free remedy, can be used to alleviate PHN pain so as to reduce the burden of PHN on the the individual, the NHS and society as a whole. The use of chemical-free remedy may offer an alternative pain relief to patients who are already on complex medicine regimes, especially the elderly population. This pilot study will be a double-blind randomised placebo controlled study involving volunteers who will be selected based on an inclusion & exclusion criteria so that confounding factors such as neuropathic pain other than PHN are excluded. Both the volunteers and the Study Co-ordinator will be blind and the analysis will be evaluated by the Principal Investigator.

Aims and Objectives

The aim of this pilot study is to evaluate if Variolinum 12c can alleviate PHN pain in patients diagnosed with PHN within 7 days of treatment using the following measures:

Primary Outcome Measures relating to pain intensity, descriptions and impact using the Short Form McGill Pain Questionnaire-2 (IMMPACT. 2009):

• mean change from SF-MPQ-2 Sensory and Affective Scores.
• mean change from Baseline in SF-MPQ-2 Visual Analog Scale
• mean change from Baseline in SF-MPQ-2 Current Pain Intensity

Secondary Outcome Measures relating to the patient quality of life:

• Mean change from Baseline in EQ-5D Questionnaire

Search Criteria

Systematic reviews, meta-analyses, randomised controlled trials, cohort studies and protocols were search and the search sources included PubMed, Cochrane Library, Science Direct, CAM-QUEST and Wellcome Library. Articles were searched using the following keywords wherever occurring in the text: “post herpetic neuralgia”, “Variolinum”, “nosodes”, “neuropathic pain” and “neuropathic pain scales”. Refer to Appendix A for Search Criteria and Databases.

Background and Literature Review

According to the Herpes Viruses Association (HVA 2014), in England and Wales, over 50% of the 194,000 people diagnosed with shingles each year are affected by PHN. The definition of PHN is yet to be agreed and the most recent definitions include differentiations based on pain durations (Niv and Maltsman-Tseikhin 2005): 

• acute herpetic neuralgia is where pain is present within 30 days from the onset of Herpes Zoster rash;
• subacute herpetic neuralgia is where pain is present between 30 and 120 days from the onset of Herpes Zoster rash; and
• post herpetic neuralgia is where pain persists after 120 days of Herpes Zoster rash onset.

According to the Shingle Support Society (2014), the pain associated with PHN are burning, stabbing, shooting sensations, which may be accompanied by intense itching or allodynia where the lightest touch on the skin creates painful sensations. Various neuropathic pain scales such as LANSS, NPQ, DN4 and many others have been developed and each of these covers a range of different pain symptoms as outlined by Mindruta et al (2012). Nalamachu and Morley-Forster (2013) state that PHN pain can be prolonged and debilitating, severely compromising the patient’s quality of life. 

The comprehensive review undertaken by Tontodonati et al (2012) concluded that as the detailed pathophysiological mechanisms of PHN were yet to be developed, treatment of PHN remained unsatisfactory. Patients on opioids, tricyclic antidepressants, anticonvulsants and lidocaine patches are only partially effective or simply unsuccessful and they may find the side-effects of these drugs outweigh their benefits (Nalamachu and Morley-Forster 2013). A regional cost comparison undertaken by the NHS in 2007 indicated that the cost for a 28-day treatment of neuropathic pain including PHN typically ranged from £67.57 to £4.44 per patient with Lipocaine patch at the top end and Amitriptyline at the lowest (NHS Regional Drug and Therapeutics Centre 2007). Applying these figures with the HVA statistics of half of 194,000 new shingle-sufferers affected by PHN, the annual drug costs for neuropathic pain can range in the region of £78m to £5m depending on which drugs are prescribed more frequently. However, this crude calculation does not take into account of other costs such as GP consultation time, hospital treatment and the costs to wider society such as sick leave at work. It is widely recognised that PHN is a significant liability but data concerning the burden of PHN on individual patients, healthcare systems and wider society are lacking in the UK (Serpell et al. 2014). Research attempts were made to assess the economic burden but these were inconclusive and incomplete (Carroll et al. 2013). 

In search for alternatives, antiviral treatment was tested to evaluate its efficacy in treating PHN and Chen et al (2014) concluded that the evidence was inconclusive. Brisson et al. (2007) also argued previously that the expensive antiviral treatment was not cost-effective. Despite this lack of sound cost-benefit modelling, the development of a vaccine was considered investment-worthy to prevent shingle and PHN, given the prevalent of HHV-3 Variocella-zoster viral infection amongst PHN patients. The Shingle Prevention Study by Oxman et al. (2008) showed that the Zostavax vaccine was effective at reducing the incidence of herpes zoster infection and PHN by 51% and 66% respectively in adults ≥ 60 years of age. However, given the HVA statistics that over 50% of shingle sufferers develop PHN, it is arguable that the 66% is a statistically significant efficacy to sanction large-scale vaccination. Furthermore, uncertainty remains about the vaccine’s duration of protection against herpes zoster infection and PHN (Drolet 2013). Despite these research attempts, there is little relief for people already suffering from PHN and those who may still develop the condition after the initial vaccination, given the 66% success rate. Considering the unsatisfactory efficacy of these treatments and the approximate costs, there is a strong case to undertake further research in the prevention of PHN and to seek alternative treatment in therapies such as Acupuncture and Homeopathy.

In the field of alternative medicine, research has shown that traditional Acupuncture has proven to be effective in PHN pain relief (Li et al. 2014). In the homeopathic literature, there is a body of anecdotal evidence where homeopathic remedies were used to treat shingles and PHN by practicing doctors and homeopaths such as Burnett of the 19th century (Chitkara 2010).

Homeopathy is system of medicine developed in Germany by Samuel Hahnemann (1755-1843) and it has been widely used for over 200 years. It is based on the Law of Similars, the origin of which dates back to the Swiss physician Paracelsus (1493-1541), which purports that a substance that causes a set of symptoms in a health person is said to cure a sick person suffering from similar symptoms (Owen 2007). For example, one of the side effects of opioid analgesics is constipation and the homeopathic remedy Opium, i.e. an ultra-diluted dose of Opium that has been serially succussed (Hahnemann 1996), is said to be used for curing people suffering from constipation, amongst other symptoms. The term potency is used to quantify and express the level of dilution and succussion - the lower the potency, the less diluted is the remedy (Hahnemann 1996).

Whilst most homeopathic remedies are sourced from the plant and mineral kingdoms, some are sourced from the animal kingdom including humans. The group of remedies that are prepared using diseased tissues or substances from a human or animal source is called nosodes (Owen 2007). Studies such as Schuller's (2010) suggest that nosodes can lead to desirable changes in the treatment of rheumatic diseases. However, the method that Schuller used was not without controversy because the nosode was generated through the use of bioresonance machine rather than the traditional method of preparation using disease tissues. Further, the trial design lacked double-blind protocol to minimise the risk of bias. The homeopathic method used in this study was auto-isopathy (Watson 2004), where the patient’s own disease tissues, in this case the disease energy imprint of the patient, were used to make the nosode. Therefore, it is difficult to evaluate the reproducibility of such study.

Other studies such as idiopathic nephrotic case by Pinto (2009) stated that nosodes such as Tub. Koch., had played a pivotal role in the case treatment. As a range of homeopathic remedies were used in this study to achieve clinical results, it was difficult to attribute success to the one nosode and to what extent other remedies such as Apis mellifica had played a key role. With the highly specific conditions and individualised responses of this patient, it will be very difficult to repeat the treatment and demonstrate the efficacy of any single nosode. Nonetheless, the patient reactions to the remedies were well-documented and clear responses illustrate probable curative actions of homeopathic remedies. Similarly, cases 36 and 45 contained in van Woensel’s Classical Homeopathy Evidence Based Medicine (2011) also reported the use of nosodes with long term curative results. 

 

In addition to treating diseases, the homeopathic literature also purports the use of nosodes to prevent diseases (Shepherd 1967). A large scale study in Cuba had demonstrated how nosodes were used as prophylactics in preventing leptospirosis (Roinger and Jacobs 2010). Critics of this study have identified a number of confounding factors including, firstly, the lack of a controlled group though the intervention regions were geographically distinct from the rest of the Cuban population; and secondly, whether the natural receding course of the endemic coincided with the administration of the homeoprophylactic (BMJ 2012). Nevertheless, given the scale of this study and the use of homeoprophylactic may deserve further research.

These recent studies suggest that the anecdotal evidence accumulated in the homeopathic literature can provide probable hypotheses for clinical trials and case studies. These anecdotal evidence are potentially open to bias both from the clinicians and the subjects. Confounding factors other than the specific action of the treatment may have affected the outcome. Therefore, the purpose of this pilot study is to use the double-blind RCTs standard to assess validity of the anecdotal evidence where nosodes such as Variolinum developed from the Herpesviridae family (Vermeulen 2005), were used to treat shingles and PHN.

Variolinum is one of the homeopathic nosodes made from the contents of the ripened pustule of small pox (Vermeulen 2005). In low potencies, Variolinum was used by Burnett (Chitkara 2010), Sankaran (1996) and others to treat shingles, though these remain unproven. In the current homeopathic literature, Variolinum has been used for treating small pox, Herpes Zosters, shingles and other conditions (Murphy 2006). Apart from anecdotal evidence, to date, no studies or clinical trials have been conducted for Variolinum. 

The use of double-blind placebo-controlled RCT is to identify any causal relationship between an intervention and a treatment outcome. Systematic randomise allocation rules out factors which may skew the treatment outcome amongst groups of subjects. Double blinding ensures that bias, whether positive or negative, of the investigator and/or the subjects are excluded from the trial and thus presents a neutral platform of scientific investigation. 

Due to the need to filter out any possible confounding factors, selective eligibility are critical to trial feasibility and internal validity. However, the exclusion of certain patient populations may lead to impaired generalisability of results. For example, women, children, the elderly, and those with common medical conditions are often excluded from RCTs because of the risks of pregnancy, consent and medical complications respectively (GMC 2015 and MRC 2004). Such exclusions may impair the generalisability of RCT results (van Spall et al 2007).

Further, RCT does present ethical issues where the subjects may have to suspend their current treatment in a trial for an alternative treatment. This may result in at best, a temporary increase in the level of discomfort experienced and at worse deterioration of symptoms leading to permanent damage to their health. So it is important that the trial methods are designed with rigour to safeguard the welfare of volunteers and address any ethical issues.

Another ethical issue to be considered in this pilot study relates to the safety of nosodes. As the source material of nosodes is derived from infectious tissues, there is a perceived risk of infection and safety for public health when nosodes are used in patient treatment. According to the amended European Directive 2001/83/ EC, nosodes are deemed safe if their manufacturing methods comply with those as specified in the German Homeopathic Pharmacopoeia or the French patented process of tyndallisation (ECHAMP 2006). According to these methods, no infectious particle is left in the nosode in all potencies above 24X or 12C (ECHAMP 2006). 

Taking into account of these ethical issues, this pilot study can potentially provide grounds for further research for a more cost-effective treatment for PHN because the manufacturing costs of nosode is a fraction of that of the Zostavax vaccine. This is in line with the conclusion drawn by Matthiessen and Bornhöft (2011) that cost-effectiveness of Homeopathy was supported by extensive research  and long-term use monitor.

Method & Design

Setting

This study will be a investigator-originated study where the Principle Investigator (PI) will recruit a Study Co-ordinator, (SC) such as a Contract Research Organisation. The SC will co-ordinate the trial and be the blind administrator. This will be a single-centre study where volunteers will report to The Hale Clinic in London at the beginning and at the end of the trial. Volunteers will be recruited by the SC through the following organisations and social media websites:

• Shingles Support Society
• Trigeminal Neuralgia Association
• Macmillen Cancer Support

In addition, volunteers will be recruited with the assistance of the National Institute for Health Research (NIHR) in the UK, subject to the successful application of grant funding from the Research Funding Bodies listed by the Research Council for Complementary Medicine on their website, which includes but not limited to:

• Economic and Social Research Council
• British Homeopathic Association
• John Templeton Foundation
• Blackie Foundation Trust

The NIHR will advise on availability research support staff and suggest clinicians who may be interested in contributing to the study, based on their wide contact base in association with the NHS. The NIHR can also provide intelligence on the local patient population to facilitate the volunteer recruitment process and provide advice on the research governance and regulatory requirements that apply to the study (NIHR 2015).

Study Design

The pilot study will be a single-centre double-blind randomised placebo-controlled trial where participants will be given Variolinum 12c or the placebo for 7 days. The trial period is set for 7 days on:

• ethics ground - as the trial involves suspension of pain management medication, a short trial period is chosen to reduce the possible duration of increase pain; 
• technical ground - following the Law of Similars, if Variolinum is the matching remedy, its action will be apparent within 7 days; and
• practical ground - as attrition is a known problem, a short study will reduce the risk of participants losing interest and missing the intervention treatment due to other health complication, for example.

Up to 50 volunteers will be recruited based on the following inclusion and exclusion criteria:

Inclusion Criteria:

• A male or female aged 18 years or older at the time of study entry (i.e. when informed consent is signed);
• Subject who has been diagnosed with PHN - despite the definition set out in the Background and Literature Review where PHN is defined as pain persisting 120 days after the onset of herpes zoster, it is important to evaluate the efficacy of Variolinum in the more recent onset of PHN pain when nerve tissues damage begins to occur;
• Subject must have a baseline score of greater than 0 on the SF-MPQ-2 pain scale to demonstrate the presence of pain;

Exclusion Criteria:

• Previous vaccination against Herpes Zoster preceding the first dose of study verum or placebo;
• Acupuncture or other Complementary and Alternative Medicine treatment within the last 4 weeks before the trial; 
• Other diseases influencing the overall quality of life of the subject;
• Other conditions, such as skin conditions that affect dermatome, considered reasonable by the SC as to the disqualification of the individual from study participation;
• Subject who has any other severe pain that might confound assessment or self-evaluation of pain due to PHN;
• Subject who is taking oral analgesics (either opioid or non-opioid) or is receiving topical therapy such as the 5% topical lidocaine patch for the treatment of pain and is unwilling or unable to complete a washout period during which the patient will discontinue analgesic therapy or topical pain therapy. 
• Young people under the age of 18 are excluded because PHN is uncommon in children (Stankus 2000) and that they may have difficulty in understanding the survey and express their pain experience accurately.

The remaining population who passes this selection criteria will become the study population (n) and each participant will be asked to sign a consent form. The SC will generate a randomised number table which will be used to distribute the verum and the placebo blindly amongst the study population. Half of the study population will receive the verum and the other half will receive the placebo. Both the verum and the placebo will be prepared and supplied by Helios Homeopathic Pharmacy in accordance with the standards of the European Pharmacopoeia and the Directive 2001/83/EC, which applies to industrially produced medicinal products for human use (WHO 2009).

Each of the participants will be asked to complete two surveys under the guidance of the SC, these include:

• the 2009 Short Form McGill Pain Questionnaire-2 (SF-MPQ-2) and
• the EQ-5D survey which is a standardised and generic measure of health for clinical and economic appraisal, developed by the EuroQol Group (1990)

The SF-MPQ-2 is designed to measure neuropathic pain sensation, intensity and changes (Melzack 1975); whereas the EQ-5D is designed to evaluate the overall quality of life of patients. The completed surveys will form the baseline of the study. If the SC considers that that characteristics and heterogeneity in treatment groups as a result of chance imbalance of volunteers is of any importance, then, adjusted analysis will be used in the analysis as recommended by Altman (2005). 

According to the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT 2009), the SF-MPQ-2 includes three pain assessment and these are outlined below:

• the Sensory and Affective Scores - participants will be asked to score 22 descriptors of pain as well as sensation on a 4-point intensity scale (0 = none to 3 = severe). These will be added up in each subclass (sensory range 0-66); the higher scores, the higher intensity of pain.
• the Visual Analog Scale - participants will be asked to mark the intensity of pain felt. The scale comprises a line of 100 mm in length which ranges from   0 (no pain) to 100 mm (most intense pain). Distance from left-hand end of line will be measured and recorded on in mm - the higher the score, the more intense level of pain.
• Current Pain Intensity - Affective score ranges from 0-5. Higher scores indicate more severe pain (0 = no pain, 1 = mild, 2 = discomforting,                3 = distressing, 4 = horrible, 5 = excruciating).

Refer to Appendix B for a sample of SF-MPQ questionnaire.

The SF-MPQ-2 was chosen over other pain surveys for its excellent reliability and validity (Dworkin et al 2009) and its relevance to neuropathic pain; though other questionnaires such as the DN4 are simpler to use (Mindruta et al 2012).

The EQ-5D survey covers 5 aspects of health state, namely: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, therefore taking into account the patients’ quality of life (EuroQol Research Foundation 2015). These overall state of health indicators are measured on a scale from 0 to 1 where 0 represents death and 1 represents perfect health. The scoring rule for the EQ-5D also permits scores less than 0, implying that some health states may be worse than death (Oemar and Oppe, 2013).

Intervention

On Day 1 of the 7-day trial, each volunteer of the study population will be instructed to take the verum, Variolinum 12c pillule, or the placebo, blank sucrose pillule, twice a day for 7 days at home. Each participant then report back to the SC by the end of the trial period at the Hale Clinic where they will complete the surveys again, under the guidance of the SC. The potency 12c is chosen because:

• PHN patients often have low vitality and higher potency remedy requires higher vitality on the part of the patients in order to facilitate appropriate Healing action according to the Law of Similars;
• PHN patients are often on other conventional drugs due to wider chronic health issues and higher potency may bring forth aggravation of symptoms as the Variolinum action pushes from inside out according to Hering’s Law of Cure (Owen 2007);

The repeated dose for the same remedy is given because:

• homeopathy is likely to be new to the study population and remedies may be antidoted by unpredictable lifestyles such as excessive alcohol intake or other drug intervention;
• the intensity of pain may warrant repeated action of the Variolinum;
• the twice a day ‘rising and bedtime’ routine is easy to remember and convenient to implement by the volunteers.

During the 7-day trial, if a volunteer reports an increase of pain to a severe level on the SF-MPQ-2 questionnaire, where:

• the Sensory and Affective Scores totalled over 45 out of a maximum score of 66 or;
• the Visual Analog Scale reaches 70 mm out of a maximum score of 10 or; 
• Current Pain Intensity reaches 4 out of a maximum score of 5; 
• or 0.2 to

the SC will resume his/her pain management medication on ethics ground; though this subject will be recorded as a withdrawn candidate from the study population. Equally, if a participant fails to complete all of the questionnaires satisfactorily, he/she will be recorded as a lost to follow-up candidate. The SC will then collate the survey findings into two groups, namely Dataset A and Dataset B. For example, if n = 40 but only 36 participants return their surveys satisfactorily, Dataset A will include all pre-trial and post-trial findings whereas Dataset B will only include those of the 36 participants. As suggested by Dumville et al (2006), this will provide a clearer picture of the population not included in the analysis and thus highlight any potential attrition bias.

Outcome  Measures

Primary Outcome Measures:

• Mean change from Baseline in SF-MPQ-2 Sensory and Affective Scores.
• Mean change from Baseline in SF-MPQ-2 Visual Analog Scale
• Mean change from Baseline in SF-MPQ-2 Current Pain Intensity

Secondary Outcome Measures:

• Mean change from Baseline in EQ-5D Questionnaire

Statistical Analysis

Assuming there will be a level of attrition or lost to follow-up, both Dataset A and Dataset B will be analysed using the methods set our below in order to highlight any potential attrition bias. The two methods are: Change Score and analysis of covariance, ANCOVA (Altman 2005). The Change Score method is simple to use where treatment outcomes are measured by the difference in mean pain score between baseline and at endpoint for each group (Kane 2004). Alternatively, a change score can be calculated by subtracting the follow-up score from the baseline score. This method, however, does not take into account of chance imbalances at baseline. By way of an analogy, Egbewale (2012) likens this lack of adjustment to two athletes starting a 100m race at different points of the track. Egbewale (2012) therefore recommends that ANCOVA is a better approach in analysing RCT results where analysis of covariance adjusts each patient's follow-up score for his or her baseline score. ANCOVA analysis therefore has the advantage of being unaffected by baseline differences. The Principle Investigator will then analyse and cross-reference the four sets of data as shown in table below:

 

	Dataset A - fulfilling Intention-to-treat principle (Gupta 2011)	Dataset B
Change Score	Analysis No. 1	Analysis No. 3
ANCOVA	Analysis No. 2	Analysis No. 4

 

Limitations of Study

As this is a pilot study, the inherent limitation is the population size and therefore its limited representativeness and statistical significance. The selection criteria, whilst critical in ensuring internal validity of the trial, further reduces the applicability to real-life circumstances such as comorbidity and health complications are often experienced by PHN sufferers. One of the assumptions of RCT is that participants, provided they fulfil the selection criteria, are all equals; but as pointed out by Egbewale (2012), this is far from common and that chance imbalances within the baseline should be taken into account in order to establish an equal footing for valid comparisons. Interestingly, parallels can be drawn between this observation and the homeopathic principle of individualisation (Hahnemman 1996) where each person is to be treated individually. According to the Law of Similars, these very characteristic differences between individuals are what homeopathic remedies are to match in order to achieve positive treatment response (Hannemann 1996). By extension, therefore, RCTs for homeopathic remedies are likely to be limited to therapeutics in terms of scope and action.

Planning and Resources

Research Funding Bodies often have annual programmes where they accept research proposals, evaluate the applications and grant funding. The Principle Investigator will identify the likely funding sources and a deadline can be set for the pre-trial preparations. The National Institute for Health Research (NIHR 2015) sets out 5 clear steps as set out below, which are used to structure the planning and resourcing of the study in table below showing indicative timescales:

• Step 1: Research ideas
• Step 2: Study development & planning
• Step 3: Study start-up and set-up
• Step 4: Study recruitment & follow-up
• Step 5: Study closure

What	When	Who
Identifying funding source & associated application timeframe	Step 1: Research Ideas  (Month 1-3)	Principal Investigator
Prepare budget & costs plan	Step 1: Research Ideas  (Month 1-3)	Principal Investigator
Shortlist Contract Research Organisations	Step 1: Research Ideas  (Month 1-3)	Principal Investigator
Contact NIHR for Research Design Service	Step 1: Research Ideas  (Month 1-3)	Principal Investigator
Apply for funding based on Research Proposal	Step 2: Study Development & Planning (Month 4 if coincides with funding programmes accepting Research Proposal)	Principal Investigator
Prepare applications for regulatory and ethical approvals	Step 2: Study Development & Planning (Month 5-8)	Principal Investigator
Submit application for regulatory and ethical approvals	Step 2: Study Development & Planning (Month 9)	Principal Investigator
Appoint Contract Research Organisation, assuming funding becomes available after initial application at Month 4 and all necessary approvals granted by Month 12	Step 3: Study Development & Planning (Month 12)	Principal Investigator
Confirm location of study trial	Step 3: Study set-up and start-up (Month 13)	Contract Research Organisation
Advertise for trial and commence recruitment process	Step 3: Study set-up and start-up (Month 14-16)	Contract Research Organisation
Conduct Pilot Study	Step 4: Study recruitment and follow up	Contract Research Organisation
Write up study analysis	Step 5: Study Closure	Principal Investigator
Seek Peer Review	Step 5: Study Closure	Principal Investigator
Dissemination of findings in peer-reviewed journals	Step 5: Study Closure	Principal Investigator

 

Word Count:  4,203

 

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Appendix A - Search Criteria

 

Nosode 

Search Engine	Keyword Search	Papers	Search Date
Cochrane Library	nosodes	3	22 March 2015
Science Direct (CAMLIS)	nosodes	974	22 March 2015
Wellcome Library	nosodes	31	22 March 2015
PubMed	nosodes (Clinical Trials filter on)	188	22 March 2015
CAM-QUEST	nosodes	10	22 March 2015

 

Post Herpetic Neuralgia / Shingles

Search Engine	Keyword Search	Papers	Search Date
Cochrane Library	post herpetic neuralgia	2	22 March 2015
Science Direct (CAMLIS)	post herpetic neuralgia	4343	22 March 2015
Science Direct (CAMLIS)	post herpetic neuralgia + shingles	920	22 March 2015
PubMed	post herpetic neuralgia (Clinical Trials filter on)	329	22 March 2015
PubMed	post herpetic neuralgia + shingles (Clinical Trials filter on)	197	22 March 2015
Wellcome Library	post herpetic neuralgia	253	22 March 2015
Wellcome Library	post herpetic neuralgia + shingles	80	22 March 2015
CAM-QUEST	post herpetic neuralgia	2	22 March 2015
CAM-QUEST	post herpetic neuralgia + shingles	0	22 March 2015

Variolinum

Search Engine	Keyword Search	Papers	Search Date
Cochrane Library	variolinum	0	22 March 2015
Science Direct (CAMLIS)	variolinum	63	22 March 2015
Wellcome Library	variolinum	0	22 March 2015
PubMed	variolinum	0	22 March 2015
CAM-QUEST	variolinum	1	22 March 2015

 

Neuropathic Pain / Neuropathic Pain Scales

Search Engine	Keyword Search	Papers	Search Date
PubMed	neuropathic pain	1623	22 March 2015
PubMed	neuropathic pain scales	1973	22 March 2015

 

Appendix B

Short Form McGill Pain Questionnaire  - as SF-MPQ-2 is only available from purchase, SF-MPQ-1 is included here for illustrative purposes only (Melzack 1975).