Neuropathy refers to diseases of the nerves and can cause sensory symptoms like numbness, tingling, and pain. Neuropathic pain is common and can be caused by medical conditions like diabetes or shingles. It affects 6-8% of the population. Symptoms include abnormal sensations in the affected areas and standard tests involve assessing responses to touch, pinpricks, vibration and temperature changes. Treatment involves both pharmacological options like pregabalin, duloxetine and gabapentin as well as non-pharmacological options like TENS, acupuncture and physical therapy. Newer treatments under investigation include botulinum toxin injections and the anticonvulsant lacosamide.

1. Neuropathy and
pain

2. NEUROPATHY
• Neuropathy means disease of one or more
nerves.
• Neuropathies can be sensory, motor or
autonomic.
• Sensory nerves tell us how things feel.
• Motor nerves stimulate muscle contraction
and initiate movement.
• Autonomic nerves control functions that our
bodies don’t consciously regulate, such as
breathing and heart rate.

3. IASP DEFINITION
• The IASP International Association
for the Study of Pain, defines pain
as an “unpleasant sensory and
emotional experience associated
with actual or potential tissue
damage, or described in terms of
such damage".

4. PREVALENCE
• The prevalence of neuropathic pain : 6% and 8%.
• Painful diabetic neuropathy : 16% and 26% of people with diabetes.
• Postherpetic neuralgia : 8% to 19% of people with herpes zoster when
defined as pain at one month after rash onset, and 8% when defined as
pain at three months after rash onset.
• The development of chronic pain after surgery is also fairly common, with
estimates of prevalence ranging from 10% to 50% after many common
operations. This pain is severe in between 2% and 10% of these patients,
and many of the clinical features closely resemble those of neuropathic
pain.
NICE clinical guidelines nov 2013

5. PATHOPHYSIOLOGY
K Bhanu management of neuropathic pain indian perspective chap 125

6. SYMPTOMS
• Numbness
• Burning
• Tingling
• Pain (shooting, sharp, cramping, deep, dull, pin/needle pricking)
• Weakness
• Muscle wasting
• Allodynia (Pain from a stimulus that does not normally evoke pain )
• Hyperalgesia (Exaggerated response to a normally painful stimulus)

7. CAUSES OF NEUROPATHIC
PAIN
1. Nutritional deficiency (vitamin
B12 mainly)
2. Diabetes
3. Alcohol
4. Smoking
5. Infections
6. High BP
7. Post-traumatic spinal cord injury
8. Cancer neuropathy
9. Exposure to toxin
10. Multiple sclerosis

8. PERIPHERAL CAUSES
Mononeuropathies and multiple
mononeuropathies:
• Diabetic mononeuropathy and amyotrophy.
• Trauma: painful scars, compression, transection
of a nerve, post thoracotomy.
• Neuralgic amyotrophy.
• Connective tissue disease.
Polyneuropathies:
• Metabolic/nutritional:
• Diabetic.
• Alcoholic.
• Amyloid.
• Pellagra.
• Beriberi.
Drugs/toxic:
• Nitrofurantoin.
• Isoniazid.
• Vincristine, cisplatin, arsenic.
• Disulfiram.
Infective:
• Acute inflammatory polyneuropathy (Guillain-
Barré syndrome).
• Chronic inflammatory demyelinating
polyneuropathy (CIDP).
• HIV.
Hereditary
Malignancy
Scadding J; Advances in Clinical Neuroscience and Rehabilitation
2003;3(2)

9. CENTRAL CAUSES
Spinal root/dorsal root ganglion:
• Prolapsed disc.
• Root avulsion.
• Trigeminal neuralgia., Postherpetic neuralgia
(herpes simplex or varicella zoster).
• Tumour
• Arachnoiditis.
Spinal cord
• Trauma
• Multiple sclerosis.
• Vascular: infarction, haemorrhage,
arteriovenous malformations.
• HIV and syphilis.
• Neural tube defect.
• Vitamin B12 deficiency.
Brainstem:
• Lateral medullary syndrome
• Multiple sclerosis
• Tumours
• Tuberculoma
Thalamus:
• Infarction.
• Tumours.
• Haemorrhage.
• Surgical lesions.
Subcortical and cortical:
• Infarction.
• Trauma.
• Arteriovenous malformation.
• Tumour.
Scadding J; Advances in Clinical Neuroscience and Rehabilitation
2003;3(2)

10. DIAGNOSTIC METHODS
A standardized examination of NP should include the following:
• Touch can be assessed by gently applying cotton wool to the skin
• Pain assessed by the response to sharp pin prick stimuli
• Deep pain by gentle pressure on muscle and joints
• Temperature: Cold and heat sensation—by measuring response to thermal
stimulus (metal objects at 20°C or 40°C)
• Vibration can be assessed by determining response to a tuning fork
• Abnormal temporal summation is the clinical equivalent of increasing
neuronal activity after repetitive noxious C fiber stimulation of more than 0.3
Hz.
• The responses should be graded as normal, increased or decreased.
• The stimulus evoked pain types are classified as hyperalgesic or allodynic.
K Bhanu management of neuropathic pain indian perspective chap 125

11. PAIN MEASUREMENT SCALES
Unidimensional scales
• Numeric rating scale (NRS) ]
• Visual analog scale (VAS)
Multidimensional scales
• Initial Pain Assessment Tool
Brief Pain Inventory (BPI)
• McGill Pain Questionnaire
(MPQ)

12. MECHANISM OF NEUROPATHIC
PAIN
• Uncontrolled neuronal firing after nerve injury is largely attributed to
increased expression of sodium channels.
• In addition to sodium channels, expression of voltage-gated calcium channels
is also increased following nerve injury. Calcium entry through voltage-gated
calcium channels is necessary for the release of substance P as well as
glutamate from injured peripheral nerves.
• Increased expression of the alpha-2-delta subunit of voltage-gated calcium
channels correlates with onset and duration of pain.
• Reduction in GABA, down regulation of GABA and Opioid receptors at dorsal
horn neurons occurs.

13. DIABETIC NEUROPATHY
American Diabetes Association (ADA) definition "the presence of
symptoms and/or signs of peripheral nerve dysfunction in people
with diabetes after exclusion of other causes"
Diabetic peripheral neuropathy and its evaluation in a clinical scenario:
A review Dixit S, Maiya A - J Postgrad Med 2014

14. CAUSES
• Metabolic factors, such as high blood glucose, long duration of
diabetes, abnormal blood fat levels, and possibly low levels of
insulin
• Neurovascular factors, leading to damage to the blood vessels that
carry oxygen and nutrients to nerves
• Autoimmune factors that cause inflammation in nerves
• Mechanical injury to nerves, such as carpal tunnel syndrome
• Inherited traits that increase susceptibility to nerve disease
• lifestyle factors, such as smoking or alcohol use
Diabetic Neuropathies: The Nerve Damage of Diabetes NIH 2009

15. CLASSIFICATION OF DIABETIC
NEUROPATHY
I. Peripheral neuropathy, the most common type of diabetic neuropathy, causes
pain or loss of feeling in the toes, feet, legs, hands, and arms.
II. Autonomic neuropathy : changes in digestion, bowel and bladder function,
sexual response, and perspiration. It can also affect the nerves that serve the
heart and control blood pressure, as well as nerves in the lungs and eyes.
Autonomic neuropathy can also cause hypoglycemia unawareness, a condition
in which people no longer experience the warning symptoms of low blood
glucose levels.
III. Proximal neuropathy : pain in the thighs, hips, or buttocks and leads to
weakness in the legs.
IV. Focal neuropathy : sudden weakness of one nerve or a group of nerves,
causing muscle weakness or pain. Any nerve in the body can be affected.
Diabetic Neuropathies: The Nerve Damage of Diabetes NIH 2009

17. CLINICAL SYMPTOMS OF DPN
• Sensory symptoms are usually worse at night when the patient is
trying to sleep.
• Often, patients with diabetic neuropathy state that movement,
walking, or standing lessens the pain.
• Balance problem is also increasingly common among people with
neuropathy.

19. MANAGEMENT OPTIONS

20. NONPHARMACOLOGICAL
THERAPY
• Transcutaneous electrical nerve stimulation, spinal
cord stimulation,
• Aromatherapy
• Acupuncture
K Bhanu management of neuropathic pain indian perspective chap 125

21. FDA APPROVED
MANAGEMENT
K Bhanu management of neuropathic pain indian perspective chap 125

22. RECENT ADVANCES IN
MANAGEMENT
BOTULINUM TOXIN:
• A potent neurotoxin used for the treatment of focal muscle
hyperactivity, may have analgesic effects possibly by acting on
neurogenic inflammation.
• Recent studies reported long-term efficacy of a series of
subcutaneous injections of BTX-A (100-200 units) injected into the
painful area in patients with mononeuropathies (mainly of traumatic
origin) associated with mechanical allodynia, and in patients with
diabetic painful polyneuropathies.
• The drug had an excellent safety profile with no systemic side effect
K Bhanu management of neuropathic pain indian perspective chap 125

23. RECENT ADVANCES IN
MANAGEMENT
LACOSAMIDE
• It is a antiepileptic medication that acts at voltage-gated sodium
channels.
• It has been studied extensively in painful DPN in addition to
epilepsy. Evidence of the efficacy of lacosamide in patients with
painful DPN has been provided in various controlled trials.
• So far Food and Drug Administration (FDA) has not approved this
drug for treatment of painful DPN.
K Bhanu management of neuropathic pain indian perspective chap 125

24. RECENT ADVANCES IN
MANAGEMENT
The various combinations found to be effective in several
controlled trials
• Extended release oxycodone and pregabalin
• Topical 5% lidocaine and pregabalin
• Sodium valproate and glyceryl nitrate therapy
• Moreover, analgesics can be combined with any of the first-
line medications.
K Bhanu management of neuropathic pain indian perspective chap 125