Neuropathic pain is caused by damage or disease affecting the somatosensory nervous system and is characterized by abnormal sensations such as burning or stabbing pain. It is estimated to affect 7-8% of adults. Common causes include diabetes, shingles, HIV, cancer treatments and injuries. Diagnosis involves medical history, exams and tests to rule out other conditions. Treatment involves pharmacologic options like antidepressants, anticonvulsants and opioids as well as non-pharmacologic therapies. However, neuropathic pain is difficult to treat and a multidisciplinary approach combining several therapies is often needed to provide effective relief.

1. Neuropathic Pain : Management
in Non-Specialist Settings
By Tatenda Chikwetu

2. WHAT IS NEUROPATHIC PAIN?
• Pain caused by damage or disease
affecting the somatosensory nervous
system.
• Associated with abnormal sensations
(dysesthesia) or pain from normally non-
painful stimuli (allodynia).
• May be continuous and/or episodic
•Resemble stabbings or electric shocks.
•Burning or coldness, "pins and needles"
sensations, numbness and itching.

3. DEMOGRAPHICS
• 7–8% of adults currently have chronic pain with neuropathic
characteristics.
• 37% of people attending primary care clinics with chronic low
back have predominantly neuropathic pain.
• 26% of people with diabetes were found to have peripheral NP
which translates to some 47 million individuals
• 35% of HIV positive people across the world have NP, which
does not respond well to standard treatments.
• 40% of people have persistent pain after surgery, of which a
quarter of cases have neuropathic characteristics.
• Neuropathic postsurgical pain is more likely to be severe and
persistent than non-neuropathic postsurgical pain.
• Approximately 20% of people with cancer have cancer-related
neuropathic pain, as a result of either the disease or its
treatment.
• The lifetime incidence of shingles is around 25% of which 8%,
will develop chronic postherpetic neuralgia.

4. TYPES
• Central neuropathic pain/central pain
• Compression neuropathic pain
• Trigeminal neuralgia
• HIV-related neuropathy
• Mixed neuropathic pain
• Multiple sclerosis
• Neuropathic cancer pain
• Painful diabetic neuropathic pain
• Peripheral neuropathic pain
• Polyneuropathies
• Post-amputation pain/Phantom limb pain
• Post-herpetic neuralgia
• Post-stroke pain
• Post-operative neuropathic pain
• Spinal cord diseases
• Spinal cord injury

5. Causes
• Alcoholism. Poor diet can lead to vitamin deficiencies.
• Autoimmune diseases. SLE, rheumatoid arthritis, chronic inflammatory
demyelinating polyneuropathy and necrotizing vasculitis.
• Diabetes.
• Exposure to poisons. E.g. heavy metals or chemicals.
• Medications. Certain medications, e.g. cancer chemotherapy,
• Infections. Lyme , shingles, Epstein-Barr virus, hepatitis C, leprosy,
diphtheria and HIV.
• Inherited disorders. Hereditary neuropathies.
• Trauma or pressure on the nerve. E.g. motor vehicle accidents, falls or
sports injuries. Nerve pressure or repetitive movements
• Tumors. Polyneuropathy can arise as a result of some cancers related to
the body's immune response.
• Vitamin deficiencies. B vitamins including B-1, B-6 and B-12 — vitamin E
and niacin
• Bone marrow disorders. Abnormal protein in the blood, bone cancer,
lymphoma and amyloidosis.
• Other diseases. E.g. kidney disease, liver disease, connective tissue
disorders and an underactive thyroid (hypothyroidism).

6. Risk factors
• DM, especially poorly controlled DM
• Alcohol abuse
• Vitamin deficiencies, particularly B vitamins
• Infections e.g. Lyme disease, shingles, Epstein-Barr
virus, hepatitis C and HIV
• Autoimmune diseases, such as rheumatoid arthritis
and lupus, in which your immune system attacks your
own tissues
• Kidney, liver or thyroid disorders
• Exposure to toxins
• Repetitive motion e.g. CPS, bursitis, tendonitis, trigger
finger etc
• Family history of neuropathy

7. PATHOPHYSIOLOGY
Peripheral
• Nerve lesion and regeneration causing hypersensitivity, abnormal
excitability, and heightened sensitivity to chemical, thermal and
mechanical stimuli.
• Peripheral sensitization.
Central
• Spontaneous activity cause increased background activity, increased
responses to afferent impulses, including normally innocuous tactile
stimuli.
• Central sensitization.
• Loss of afferent inhibition.
• Hypoactivity of the descending antinociceptive systems or loss of
descending inhibition
• Peripheral nerve injury releasing proinflammatory cytokines and
glutamate
Cellular
• Altered expression of ion channels, changes in neurotransmitters and
their receptors as well as altered gene expression

9. Signs & Symptoms: Neuropathy
• Gradual onset of numbness, prickling or tingling in
your feet or hands, which can spread upward into
your legs and arms
• Sharp, jabbing, throbbing, freezing or burning pain
• Extreme sensitivity to touch
• Lack of coordination and falling
• Muscle weakness or paralysis
• Heat intolerance and altered sweating
• Bowel, bladder or digestive problems
• Changes in blood pressure, causing dizziness or
light-headedness

11. Diagnosis
• A full medical history. Symptoms, lifestyle,
exposure to toxins, drinking habits and a
family history of nervous system diseases.
• Neurological examination. Tendon reflexes,
muscle strength and tone, ability to feel
certain sensations, and posture and
coordination.
• Blood tests. Can detect vitamin deficiencies,
diabetes, abnormal immune function
• Imaging tests. CT or MRI scans can look for
herniated disks, tumors or other
abnormalities.

12. Diagnosis cont........
• Nerve function tests. Electromyography .
• Other nerve function tests. Autonomic reflex
screen that records how the autonomic nerve
fibers work, a sweat test, and sensory tests
that record how you feel touch, vibration,
cooling and heat.
• Nerve biopsy. Removing a small portion of a
a sensory nerve, to look for abnormalities.
• Skin biopsy. Removing a small portion of skin
to look for a reduction in nerve endings.

13. DESIRED TREATMENT OUTCOMES

14. Peripheral
neuropathic pain
Postherpetic neuralgia
and focal neuropathy
Lidocaine patch
yes no
yes
no
TCA
contraindication
Gabapentin /
pregabalin
yes
Tramadol, oxycodone
TCA
contraindication
TCA
(SNRI)
no
TCA
(SNRI)
Gabapentin /
pregabalin

15. Treatment Approach
• Pharmacologic
TCA & SNRI
Antiepleptics
Alpha-2-delta ligands
Opioids
Topical lidocaine
Sodium channel blockers
Botulinum Toxin A
• There is no evidence to support or refute
the use of oral NSAIDs to treat
neuropathic pain conditions.

16. Non Pharmacologic management
• Deep brain stimulation
• Motor cortex stimulation
• Physical therapy
• Working with a counsellor
• Relaxation therapy
• Massage therapy
• Acupuncture

17. Drugs that should be avoided in non
specialist settings
• Cannabis sativa extract
• Capsaicin patch
• Lacosamide
• Lamotrigine
• Levetiracetam
• Morphine
• Oxcarbazepine
• Topiramate
• Tramadol (long-term use)
• Venlafaxine.

20. Treatment Approach

21. Antidepressants
• SNRIs such as duloxetine, venlafaxine, and
milnacipran,
• TCAs such as amitriptyline, nortriptyline, and
desipramine
• TCAs and SNRIs are considered first-line medications
for NP except Trigeminal Neuralgia.
• Bupropion has also been found to have efficacy in the
treatment of neuropathic pain.
• S/Es include
• Blurred vision, Constipation, Dry mouth
• Drowsiness, Postural hypotension, Urine
retention
• Weight loss, Excessive sweating, Tremor
• Sexual dysfunction

22. Anticonvulsants
• Pregabalin and gabapentin may reduce pain
associated with diabetic neuropathy.
• Carbamazepine and oxcarbazepine are especially
effective in trigeminal neuralga.
• Gabapentin reduce symptoms of NP or fibromyalgia in
some people.
• Response differ between different people.
• Common Side Effects include
• Dizziness ,Drowsiness, Fatigue
• Nausea ,Tremor, Rash
• Weight gain

23. Cannabinoids
• Cannabis (weed, dagga, mbanje) and a
number of cannabinoid receptor agonists
appear to be effective for neuropathic pain.
• The predominant adverse effects are CNS
depression and cardiovascular effects—
which are mild and well tolerated
• Psychoactive side effects limit their use.
• S/Es include weight gain and possible
harmful psychological effects.

24. Dietary supplements
• Alpha lipoic acid (ALA) found to reduce the
various symptoms of peripheral diabetic
neuropathy.
• Vitamin B1 showed some efficacy in treating
neuropathy and various other diabetic
comorbidities.
• Vitamin B12, Niacin, Thiamine, Vitamin E,
Copper may also been helpful in nutritional
deficiency neuropathies

25. NMDA antagonism
• The N-methyl-D-aspartate (NMDA) receptor
seems to play a major role in NP
• NMDA antagonists e.g. ketamine and
dextromethorphan can alleviate neuropathic
pain and reverse opioid tolerance.
• Only a few NMDA antagonists are clinically
available
• Use is limited by a very short half life
(dextromethorphan), weak activity
(memantine) or unacceptable side effects
(ketamine).

26. Opioids
• Not considered first-line treatments for NP but remain
the most consistently effective class of drugs for this
condition.
• Opioids used include morphine , methadone ,
hydromorphone , levorphanol, transdermal fentanyl,
oxycodone, buprenorphine, tapentadol, and tramadol
• Some opioids, e.g. methadone and ketobemidone, also
possess NMDA antagonism
• S/E include Sedation, dizziness, nausea, vomiting,
• constipation, respiratory depression.
• physical dependence, tolerance, and
• Physical dependence and addiction may prevent proper
prescribing and adequate pain management

27. Topical agents
• In some forms of NP e.g. post-herpetic neuralgia, topical
application of local anesthetics such as lidocaine can
provide relief.
• Transdermal patches containing lidocaine are also
available .
• Topical applications of capsaicin, may cause
desensitization, or nociceptor inactivation.
• Capsaicin depletes substance P and also cause
reversible degeneration of epidermal nerve fibers.
• Transdermal Fentanyl may also help with pain relief
though tolerance may develop.

29. Side effects of drug
• S/E profiles may determine choice of
treatment esp long term therapies
• Some S/E are dose limiting (Antiepleptics,
alpha-2-delta ligands)
• Common CNS side effects include
drowsiness, euphoria, dysphoria : TCAs,
Antiepileptics, SNRIs, Opioids,
amphetamines etc
• Local S/Es like burning (topical agents e.g.
Capsaicin)

30. Conclusion
• Neuropathic pain can be very difficult to treat with only
some 40-60% of people achieving partial relief.
• Though treatment of the underlying pathophysiology
may not be possible, treatment of neuropathic pain is
• Unfortunately, neuropathic pain often responds poorly
to standard pain treatments and occasionally may get
worse instead of better over time.
• For some people, it can lead to serious disability.
• However a multidisciplinary approach that combines
therapies can be a very effective way to provide relief
from neuropathic pain.
• Choice of treatment depends on underlying condition,
response to drugs, side effect profile, price of the drug
etc