CLINICAL GUIDELINE

Chronic Non Malignant Pain

Neuropathic Pain Guidelines,
GGC

A guideline is intended to assist healthcare professionals in the choice of disease-specific treatments.

Clinical judgement should be exercised on the applicability of any guideline, influenced by individual patient
characteristics. Clinicians should be mindful of the potential for harmful polypharmacy and increased
susceptibility to adverse drug reactions in patients with multiple morbidities or frailty.

If, after discussion with the patient or carer, there are good reasons for not following a guideline, it is good
practice to record these and communicate them to others involved in the care of the patient.

Version Number: 7 (3)

Does this version include
Yes
changes to clinical advice:
th
Date Approved: 11 March 2020
th
Date of Next Review: 18 September 2022

Lead Author: Colin Rae

Approval Group: Medicines Utilisation Subcommittee of ADTC

Important Note:

The Intranet version of this document is the only version that is maintained.
Any printed copies should therefore be viewed as ‘Uncontrolled’ and as such, may not necessarily contain the
latest updates and amendments.
 Contents

Introduction Page 2

Cannibinoid statement Page 3

Step 1 Treatments – Amitriptyline and/or Gabapentin Page 4

Step 2 Treatment – Pregabilin Page 5

Step 3 Treatments – Duloxetine and Carbamazepine Page 6

Topical Treatments Page 8

Treatment of Post Herpetic Neuralgia Page 9

Treatment of Trigeminal Neuralgia Page 9

When to Refer Page 10

Appendix 1 – NNTs Page 11

Appendix 2 – Renal Impariment Page 12

Appendix 3 – Referral criteria Page 13

Appendix 4 – Flare Up management Page 15

Appendix 5 – Potential signs of abuse Page 16

1
What is neuropathic pain?
It is: “Pain caused by a lesion or disease of the somatosensory nervous system.”
Signs and symptoms

• Burning
• Electric shocks
• Numbness
• Tingling
• Shooting/stabbing
Consider possibility of serious underlying pathology and refer for investigation as indicated.
NEUROPATHIC PAIN ASSESSMENT
Many Neuropathic Pain scoring tools e.g. LANSS are available for primary care use. The
IASP criteria of “Possible”, “Probable” and “Definite” NP might be easier to use.
This classifies the pain depending on whether the patient describes pain in an anatomically
plausible distribution of a nerve, has corresponding findings on examination in that same
distribution, and then a confirmatory diagnostic test to respectively satisfy those three
definitions in sequence. First line treatment can be initiated for possible neuropathic pain. If
possible criteria is not satisfied it is unlikely to be neuropathic pain.
Example: for radicular leg pain
Possible=pain in a specific dermatome
Probable= signs in that dermatome e.g. straight leg raise
Definite= an MRI showing nerve impingement at that level

Examples of Neuropathic Pain

• Post herpetic neuralgia (PHN)

• Peripheral neuropathy (e.g. diabetic, alcohol related, cancer/chemotherapy related)
• Trigeminal neuralgia (TN)
• Nerve root pain
• Post surgical
• Phantom limb pain

Complex Regional Pain Syndrome (CRPS) Info

• “CRPS is a neuropathic pain condition that occurs in a limb or body region and
should be considered when there is a disproportionate pain response to the initial
injury and a mixture of sensory, vasomotor, sudomotor or trophic changes.”
• Link to 2018 Tx pathway statement (RCPE)
https://www.rcplondon.ac.uk/guidelines-policy/complex-regional-pain-syndrome-
adults

2
Prescribing drugs for neuropathic pain

Before prescribing
1. Establish diagnosis and explain implications and chronicity to patient, and importance
of compliance with treatment.
2. Assess pain and function, and if it is helpful use e.g. Brief Pain Inventory to aid,
taking into account psychosocial factors.
3. Consider non-medication therapies physical and psychological therapies along with
lifestyle changes if relevant. GG&C Health and Wellbeing Directory has a wide
variety of resources.
4. Consider potential side effects/interaction from these drugs.
5. Assess risk of abuse/dependence if considering gabapentin/pregabalin (Class C
substances; see Appendix 5).

Initiating a trial
Talk to patient about treatment plan
a. Choice of drug.
b. Set realistic goals: 30% reduction in pain or 30% improvement in function.
c. Discuss benefits and side effects (and that side effects may improve with
time).
d. Discuss trial period including dose titration and the titration process.
e. Start low and go slow.
f. Discuss when this medication should be discontinued.
g. Plan review appointment – review 2-4 weeks after initiation, then allow 4
weeks of maximum tolerated dose before effects judged.
h. If one drug is not effective, wean and discontinue and choose alternative
option. If it is partially effective, consider adding a second drug rather than
substituting.
i. Check that patient understands.

Should treatment continue?

Arrange regular review of pain and function and side effects
a. For all patients who are benefiting, review the need to continue treatment
with periodic trial of reduction every 6 -12 months; agree on flare-up
management (Appendix 4).
b. For all patients who are not benefiting, wean and discontinue medication.
c. For patients who are at risk of abusing medication, consider increased
supervision e.g. instalment dispensing.
d. For all patients who are abusing medication, wean and discontinue the
medication.

Cannabinoid statement
• “There is insufficient clinical and research evidence to support the use of cannabinoid
drugs in the treatment of neuropathic pain. The use of medicinal cannabis for chronic
pain conditions is not recommended at this time.”

3
Step 1 Treatments – Amitriptyline and/or Gabapentin
There is stepwise guidance on the chronic pain website www.paindata.org
There is no strong evidence to choose one Step 1 drug over the other; this depends on
patient factors and prescriber experience. If the first agent chosen is not effective, then a
drug from the alternative class may be used either as sole agent or in combination.

• It is paramount to explain to patients with neuropathic pain prior to initiating any drug
that a realistic treatment aim would be a 30% reduction in pain rather than complete
cure.
• Regular review of symptoms and side effects should be conducted on all neuropathic
agents, particularly with Gabapentin and Pregabalin given the abuse potential and
scheduling of gabapentinoids as controlled substances.
• Periodic trial reduction should also be considered with review at least every 6 – 12
months.

Amitriptyline (PIL)
• Imipramine or nortriptyline can be prescribed instead if sedation or hypotension is a
problem. Both have the same dose and titration schedule to amitriptyline.
• Use most cost effective product.
• Neuropathic pain is an unlicensed although recognised indication for all three drugs.

In frail and elderly:

Start with 10mg in frail, elderly and increase in 10mg increments every 3-7 days to maximum
of 50mg per day.

In younger patients:
Start with 10-25mg and increase in steps of 25mg every 3-7 days to 100mg maximum per
day

Managing side effects:

To minimise morning sedation or hangover effects take at night or take medication 12hrs
before the patient scheduled wake up time.
Nortriptyline may be less sedating than amitriptyline; consider prior to amitriptyline in eldery
patients.

Dose adjustment/caution:
Use lower dose if the patient is already on an alternative antidepressant e.g. Amitriptyline
25mg per day.
Caution should be exercised in patients taking other serotonergic drugs such as SSRI’s and
Tramadol for the potential of Serotonin excess and Serotonin Syndrome.

When to stop trial:

If no benefit at 6-8 weeks of maximum tolerated dose.

Ongoing review:
Review the need to continue treatment with periodic trial of reduction every 6-12months.
Advice on weaning is in the drug patient information leaflets and refer to section on
‘Prescribing drugs for neuropathic pain’.

Gabapentin (PIL)

4
In adults:
Start at 300mg at night and increase in 300mg increments at weekly intervals aiming for a
dose of between 1200mg and 1800mg daily. Doses of up to 3600mg in 24 hours have been
used, where beneficial and tolerated.

In frail patients:
Start with 100mg at night in frail, elderly and increase by the same amount weekly. Titrate to
effect, but not above 1800mg per day

In renal failure:
Use lower dose and refer to BNF. Appendix 2.

When to stop trial:

If no benefit at 6-8 weeks of maximum tolerated dose.

Ongoing review:
Review the need to continue treatment with periodic trial of reduction every 6-12months and
refer to section on ‘Prescribing drugs for neuropathic pain’.

Carbamazepine – (PIL) can be used as first line treatment in classical Trigeminal Neuralgia
(TN) – see below.

Step 2 Treatment

Pregabalin (PIL) is an alternative in patients who have found no benefit from, or have not
tolerated conventional first or second line agents(as per Scottish Medicines Consortium
(SMC) restriction) i.e. gabapentin or amitriptyline.

In adults:
Start at dose of 75mg twice a day; Titrate up to a maximum dose of 300mg twice a day using
the most cost effective preparation. (One capsule twice daily is always the most cost
effective regimen).

In frail/elderly:
75mg once daily ; Titrate up to a maximum dose of 300mg twice a day using the most cost
effective preparation. (One capsule twice daily is always the most cost effective regimen).

When to stop trial:

If no benefit at 6-8 weeks of maximum tolerated dose.

Ongoing review:
Review the need to continue treatment with periodic trial of reduction every 6-12months and
refer to section on ‘Prescribing drugs for neuropathic pain’.

5
SWITCHING FROM GABAPENTIN TO PREGABALIN OR VICE VERSA

There are different ways of switching between pregabalin and gabapentin. Below is a
method for direct switching between the two drugs, which does not involve cross-titration.

If considering switching a patient from Gabapentin to Pregabalin, or vice-versa, the following

equivalence is suggested with Pregabalin roughly six times more potent than Gabapentin:

Total daily dose of Gabapentin Total daily dose of Pregabalin

0-900mg 150mg

901-1500mg 225mg

1501-2100mg 300mg

2101-2700mg 450mg

Above 2700mg 600mg

One drug should be discontinued after a final evening dose, with the new drug commenced
the following morning.

Pregabalin and Gabapentin risk of abuse and dependence

Since the last guideline was produced the potential for abuse and dependence has been
recognised in patients being treated with Gabapentin and Pregabalin.
This has resulted in these medications being controlled under the Misuse of Drugs act 1971
as class C substances and scheduled under the Misuse of Drugs Regulations 2001 as
Schedule 3.
1. Before prescribing patients should be assessed for risk of abuse/dependence
2. Patients already taking Pregabalin or Gabapentin should be observed for signs of
abuse/dependence including drug seeking behaviour, dose escalation or
development of tolerance.
3. Patients should understand the risks associated with these medications which also
include potentially fatal interactions with other sedative medication including opioids
and alcohol.
4. Prescribers should report any adverse reactions to these medications on a Yellow
Card including cases of abuse or dependence.

These medications are not subject to safe custody requirements, but it is illegal to be in
possession of either Pregabalin or Gabapentin without a current prescription.

6
Step 3 Treatment

Duloxetine (PIL) –
This has been accepted by the SMC for painful diabetic neuropathy and is restricted to
initiation by prescribers experienced in the management of diabetic peripheral neuropathic
pain as a second or third therapy. Duloxetine is licensed in the UK at a maximum dose of
120mg a day for the treatment of diabetic peripheral neuropathic pain. However most
sources recommend a dose of 60mg a day, as there is no evidence that doses higher than
60 mg confer additional significant benefit.

• Start with 30mg per day for two weeks and titrate up to a max of 60mg per day.
• Maximum dose to be given in divided doses.

Side effect:
In contrast to gabapentinoids, the side effect profile is more one of appetite suppression than
weight gain commonly seen with the latter. This may be beneficially harnessed in some
patients e.g. overweight diabetics.

If patient is benefiting from the medication but experiencing nausea, consider concurrent
prescription of a formulary-approved anti-emetic.

When to stop trial

• Use for an 8 week trial, allowing 4 weeks at max tolerated dose, discontinue if
inadequate response.
• If to be discontinued dose should be reduced over 1-2 weeks to minimise withdrawal
effects.

Ongoing review:
Review the need to continue treatment with periodic trial of reduction every 3 months and
refer to section on ‘Prescribing drugs for neuropathic pain’.

Cautions/ MHRA warnings

MHRA warn of a risk of suicidal ideation and request a review every 3 months for signs of
depression/suicidal ideation.
Duloxetine can cause hypertensive crisis so if patient already has hypertension and/or
cardiac disease the BP monitoring should be performed especially during the first month and
duloxetine should be avoided if patient has uncontrolled hypertension.

Carbamazepine (can be used as first line treatment for Trigeminal Neuralgia)

Dosing:
Initial dose of 100-200mg daily, increasing slowly in increments of 100-200mg at weekly
intervals
Usual maintenance dose range 600-1200mg in 24 hours
Maximum dose of 1600mg per day.

Monitoring:

7
Pre-treatment blood testing for leucopaenia (10% of patients), liver derangement and
hyponatraemia is required. Repeat testing should be carried out two weeks after initiation,
then monthly intervals for the first three months and based on clinical need thereafter.
Prescribers should have an awareness of the potential for suicidal ideation which has been
described (frequency unknown)

When to stop trial:

If no benefit at 6-8 weeks of maximum tolerated dose.

Ongoing review:
Review the need to continue treatment with periodic trial of reduction every 6-12months

8
Other treatments- only use if Steps 1-3 have failed

Topical treatments
Lidocaine 5% Medicated Plasters (PIL)
When to use:
This is restricted to patients who are intolerant of first line therapies for post-herpetic
neuralgia or where these therapies have been ineffective. Use for other indications remains
non-Formulary.
How to use:
The lidocaine plaster should be worn once daily for 12 hours on and 12 hours off.
Use the least number of plasters required for effective treatment.
The plasters may be cut into smaller sizes with scissors if required in order to minimise
wastage.
In total, not more than three plasters should be used at the same time.
When to stop trial:
Treatment should be re-evaluated 2 – 4 weeks after initiation - discontinued if they do not
demonstrate a 30% improvement in baseline pain scores and/or function

Ongoing review:
Studies have shown that the number of plasters can decrease over time. Patients should be
reviewed at 6-12 monthly intervals to see if amount of plaster can be reduced or if the
plaster-free period can be extended.

Capsaicin 0.075% cream (PIL) can be used for people with localised neuropathic pain who
wish to avoid, or cannot tolerate, oral treatments. Evidence of efficacy is poor, but side
effects are minimal. Period trial of cessations should be considered.

Opioids
There is a limited role for opioids in chronic non-malignant pain
Tramadol and potent Opioids – Follow local NHS GG&C Opioid guidelines

9
Treatment of Post Herpetic Neuralgia
Offer self-management advice:

• Wear loose clothing or cotton fabrics, as these will usually cause the least irritation
• Consider protecting sensitive areas by applying a protective layer (such as cling film
or a plastic wound dressing).
• Consider frequent application of cold packs, unless this causes pain (allodynia).
Offer analgesia to manage pain:

• Offer paracetamol with or without codeine if the person's pain is mild or moderate,
and there are no contraindications
• If pain remains uncontrolled, treat with standard oral anti-neuropathic medication as
per Steps 1-3.
• Consider prescribing capsaicin cream if pain is mild or as an adjunct to oral therapy if
pain is severe
• Consider lidocaine 5% plasters. This is restricted to patients who are intolerant of first
line therapies for post-herpetic neuralgia or where these therapies have been
ineffective. Use for other indications remains non-Formulary.
Consider referral to pain services if pain is unresponsive to treatment or significantly limits
their participation in daily activities.

Treatment of Trigeminal Neuralgia

Use Carbamazepine 1st line
Dosing:
Initial dose of 100-200mg daily, increasing slowly in increments of 100-200mg at weekly
intervals
Usual maintenance dose range 600-1200mg in 24 hours
Maximum dose of 1600mg per day.

Monitoring:
Pre-treatment blood testing FBC, U&Es and LFTs for leucopenia (10% of patients), liver
derangement and hyponatraemia is required. Repeat testing should be carried out two
weeks after initiation, then monthly intervals for the first three months and based on clinical
need thereafter. Frodo .Prescribers should have an awareness of the potential for suicidal
ideation which has been described (frequency unknown).

When to stop trial: if no benefit at 6-8 weeks of maximum tolerated dose.

Ongoing review: Review the need to continue treatment with periodic trial of reduction every
6-12months.
Caution: Not advised for use in moderate to severe renal impairment.
If there is inadequate response, treatment is not tolerated or in the presence of red flag
symptoms consider early referral for specialist advice, for example neurosurgery.

10
When to refer
Consider referral to pain services and/or other condition specific specialists if the person has
severe pain or their pain significantly limits their lifestyle, daily activities (including sleep
disturbances and participation), or their underlying health condition has deteriorated.
The patient should also be ready and willing to engage with multi-disciplinary approach to
managing their pain.
Follow referral criteria in Appendix 3 and the Chronic Pain Primary Care Guidelines

11
Appendix 1
NNT’s

A recent meta-analysis of the pharmacotherapy for neuropathic pain in adults showed that
outcomes were relatively modest. Trials were included with treatments lasting longer than 3
weeks’ duration and achieved 50% pain relief with the following Numbers Needed to Treat
(NNT) and Numbers Needed to Harm (NNH). 1 The table is based on meta-analysis from
Finnerup NB et al.

Drug Number Needed to Number Needed to Quality of final

Treat Harm evidence
Tricyclic antidepressants 3.6 ( 95% CI 3.0-4.4) 13·4 (9·3–24·4) Moderate
(TCA)
Serotonin-noradrenaline 6.4 (95% CI 5.2-8.4) 11·8 (9·5–15·2) High
re-uptake inhibitor (SNRI)
antidepressants
duloxetine and
venlafaxine
Pregabalin 7.7 (95% CI 6.5-9.4) 13·9 (11·6–17·4) High
Gabapentin 7.2(95% CI 5.0-8.3) 25·6 (15·3–78·6) High
and 31.9 for ER
preps
Topical lidocaine No information No information Low
Capsacin 8% 10·6 (7·4–19) No information High

Results of this meta-analysis showed that the efficacy of systemic drug treatments was
generally not dependent on the aetiology of the underlying disorder. The authors of the
meta-analysis propose first line use for TCAs, SNRIs, pregabalin and gabapentin in
neuropathic pain; a weak recommendation for lidocaine patches, capsaicin patches as
second line; and a weak recommendation for strong opioids (particularly oxycodone and
morphine) as third line.

1
Finnerup NB et al 2015. Pharmacotherapy for neuropathic pain in adults a systematic review and meta-
analysis

12
Appendix 2
Renal impairment
NB – Patients with renal impairment should have their dose of gabapentin or
pregabalin reduced per BNF recommendation below.

eGFR (mLs per minute per Total daily gabapentin dose mg ( to be administered in three
1.73m2 divided doses)
50-79 600-1800
30-49 300-900
15-29 150mg- 600mg (150mg daily dose to be given as 300mg in
three divided doses on alternate days)
<15a 150mg- 300mg (150mg daily dose to be given as 300mg in
three divided doses on alternate days)
a. For patients with creatinine clearance <15 ml/min, the daily dose should be reduced in proportion to creatinine clearance (e.g.,
patients with a creatinine clearance of 7.5 ml/min should receive one-half the daily dose that patients with a creatinine clearance of 15
ml/min receive).

eGFR (mLs per minute per Total daily pregabalin dose

1.73m2 Starting daily dose Maximum daily dose
30-60 75mg 300mg ( in two or three
divided doses)
15-30 25-50mg 150mg ( in two divided doses
or as a single daily dose)
<15 25mg 75mg ( as a single daily dose)

Amitriptyline-No dose change suggested in renal impairment

Duloxetine-No dosage adjustment is necessary for patients with mild or moderate renal
dysfunction (creatinine clearance 30 to 80 ml/min).Duloxetine must not be used in patients
with severe renal impairment (creatinine clearance <30 ml/min)
Lidocaine plasters- The plaster should be used with caution in patients with severe cardiac
impairment, severe renal impairment or severe hepatic impairment.

13
Appendix 3
Greater Glasgow and Clyde Pain Management Service Referral
Criteria.

MISSION STATEMENT
'The pain management service provides multidisciplinary knowledge and skills to support
people living with chronic non malignant pain. Chronic pain, for which there is often no cure,
has a significant impact on quality of life. While we can and do optimise medical treatments,
the overall aim of our approach is to inform and support people living with chronic pain to
improve their quality of life. Those who adopt this supported self management approach
are often more motivated and confident to manage their pain, and improve their quality of
life’.

Referral criteria for patients with chronic non malignant pain

Patient resides within GG&C Health Board catchment area and is 18 years of age or over.
**

Pain has been present for more than 3 months with an adverse impact on quality of life.

Patient understands a cure may not be possible and that actively engaging in self
management is more likely to improve quality of life than relying on medications alone.

If the patient requires further investigation or treatment, for their painful condition, please
refer to the appropriate service before referring to the pain service (e.g. orthopaedics,
rheumatology).

Current GG&C Chronic Pain Management guidelines should be followed prior to referral
(This includes trials of appropriate medications and referral to MSK physiotherapy where
appropriate).
(If in doubt please discuss with a pain consultant).

Exclusion criteria
Patients currently being actively investigated or awaiting treatment for the same condition by
other specialties.

Patients with significant pre-existing mental health or addiction problems should be

considered for referral to an appropriate service prior to referral to the pain service.

(If in doubt, please discuss with a pain consultant).

14
 Re-referral
Patients should not be re-referred for the same pain problem if assessment and therapeutic
options have been exhausted.

**(Patients aged 16 or 17 may be considered following discussion with a consultant).

(Patients residing in Argyle and Bute CHP catchment can be referred but may not be able to
access the full GG&C service).

(If in doubt discuss prior to referral).

15
Appendix 4
Flare-up Management

Flare ups are common in people with chronic pain. Although flare ups are often distressing
and frightening, they rarely indicate new damage.

• Advise patient to continue taking medication as prescribed.

• If short term changes to the patient’s medication are required, then a management plan
needs to be agreed between the patient and the healthcare provider and be adhered to.
Return to normal medication when flare up has settled.
• Reduce exercise and normal activity, but maintaining some gentle activity as this is
important.
• Suggest patient ask others to help during the flare up and gradually get back to usual
levels of activity.
• Advise patient to learn deep breathing exercises and relaxation techniques. Check for
negative thoughts and "catastrophic" thinking. Hot water bottles, heat packs, electric
blankets, warm baths or Jacuzzis can sometimes help.
• Encourage the patient to eat regularly and have a few meals in the freezer that can be
heated up.
• Distraction is often helpful – TV, reading, having someone to talk to etc.
• Return to normal activities and exercise when flare up has settled.
• Encourage patient to develop a flare up management plan that works for them. They
should start the plan as soon as the flare up begins.

16
Appendix 5
Potential signs of misuse

***Appendix: risk of misuse assessment (including drug diversion). Not an exhaustive list.
1. History of substance misuse
2. Specific requests for prescription of Pregabalin or Gabapentin by patients
3. Request for Gabapentin or Pregabalin after release from the prison service
4. Repeated early prescription requests
5. Repeated reports of lost medication
6. Contact out of hours service for resupply of medication.
7. ‘Doctor shopping’ or online access for private prescription
8. Consider using the opioid risk tool (need link) to assess risk of problematic drug
use
9. Consider PADT tool for monitoring of treatment and problematic drug use.

17