Types of Pain, Mechanisms, Differential Diagnosis, Comparison and management of neuropathic and nociceptive pain

1. Nociceptive Vs Neuropathic Pain:
Differential Diagnosis and
Management
Dr. Pranav Bansal
Professor & Head
Department of Anaesthesiology
BPS Govt. Medical College for Women, Khanpur Kalan, Sonipat

2. What is Pain?
• Pain is a complex constellation of unpleasant sensory, emotional, psychological and
certain autonomic (involuntary) responses and behavioural reactions provoked by
tissue damage.

3. Types of Pain
Nociceptive
Somatic Visceral
Neuropathic
Peripheral Central
Mixed

4. Nociceptive Pain
• Most common type of pain
• Physiologic response when nociceptors respond to
noxious or potentially harmful stimuli.
• Protective role
• Transient duration
• May be acute or chronic
• May vary in intensity, quality & may be referred.

5. Mediators of Nociceptive Pain
• Nociceptors are specifically designed receptors to detect stimuli that may cause
harm to the body, which may be mechanical, chemical or thermal in nature.
• Aᵟ fibres mediate sharp localised pain
• C fibres mediate dull and burning pain

6. Nociceptive Pain
Nociceptive pain may be somatic or visceral in origin.
-Visceral pain: Originates in nociceptors located in the
hollow organs and smooth muscles; it is often referred. E.g.
Dysmenorrhea, gastritis, appendicitis or acute pancreatitis
-Somatic pain: Originates from musculoskeletal,
joint or cutaneous nociceptors and is often well
localized. E.g. Gout, osteoarthritis, skin incision
and trauma-induced pain.

7. What is neuropathic pain?

8. What is neuropathic pain?
• Chronic Pain disorders caused by a lesions in peripheral or central somatosensory
system
• Occurrence in 35% of chronic pain patients
• 5% of population suffer from neuropathic pain
• Varied presentation: Can be intermittent, constant, spontaneous or provoked
Peripheral Neuropathic Pain: In diabetic peripheral
neuropathy and postherpetic neuralgia
Central Neuropathic Pain: Associated with
stroke or spinal cord injury/ ischaemia.

9. Question 1:
• Neuropathic pain can be distinguished from nociceptive or
inflammatory pain by absence of which of the following feature:-
A. Transduction
B. Transmission
C. Modulation
D. Summation

10. Ans. 1 A
Transduction: In neuropathic pain,
peripheral nerve damage directly
affects the nervous system, resulting in
the generation of ectopic discharges
that bypasses transduction.

11. Common Causes of Neuropathic Pain
Neuropathic
Pain
COMMON CAUSES
Diabetes
Post-Herpetic
neuralgia (PHN)
Phantom limb pain
Causalgia/CRPS
Central Causes
Spinal Cord Injury
Spinal Cord
Ischemia
Post Stroke Pain
Multiple Sclerosis
Entrapment
syndromes
Compressive
lesions
Inflammatory
lesionsMetabolic
Renal failure
Anti-HIV drugs
B12 and folate
deficiencies
Trigeminal
neuralgia
Traumatic
injury
Vasculitis
Tumor Related
Infiltration
Chemotherapy
(vincristine,
cisplatin)
Irradiation
Lesions in peripheral nerves may cause mononeuropathy, polyneuropathy or plexopathy

12. Mechanisms of Neuropathic Pain
Peripheral Mechanisms
Sensitization of
Peripheral Nerves
Wind Up phenomenon
Epiphatic transmission
Phenotypic Switch
↑ Expression of Na+ &
Ca++ channels
Deafferentation Pain
Sympathetically
Medicated Pain/ CRPS
Central Mechanisms
Synaptic Plasticity
(Temporal & Spatial
Summation)
Disinhibition (GABA &
Glycine)

13. Question 2:
• The process by which adjacent uninjured nerve fibres become
excited is known as:
1. Wind up
2. Neuroplasticity
3. Central sensitisation
4. Ephaptic transmission

14. Ans. 2 D
• Ephaptic transmission is the process by which adjacent uninjured nerve
fibres become excited. Here, two independent nerves communicate with
each other through an artificial synapse, which often develops after
injury to the insulating myelin sheath that normally prevents crosstalk
between parallel nerves.

15. How is neuropathic pain manifested?

16. Question 3
• A 65 years old male patient presented to pain clinic with complaint of chronic
lower back pain associated with movement for the past 2 years, along with
numbness and tingling sensation in right lower limb. MRI lower back revealed
PIVD L4-L5 and L5-S1 associated with right lower limb radiculopathy. The patient
has taking various medications including NSAIDs/ multiple course of steroids/
opioids and physiotherapy with no relief.
According to the above case scenario what could be the type of pain?
A. Nociceptive
B. Neuropathic
C. Somatic
D. Mixed pain

17. Ans. 3 D
• Mixed Pain: Nociceptive/ inflammatory pain around the
low back area with movement, and neuropathic pain in
the distribution territory of the effected nerve root
(lower extremity).

18. Mixed Pain
Cases with both nociceptive and neuropathic type of pain
Herniated lumbar disc
patient with
radiculopathy
Malignant Tumor Pain Diabetic Foot Syndrome

19. Neuropathic Vs Nociceptive Pain

20. Difference between Neuropathic and Nociceptive Pain
Characteristics Nociceptive Pain Neuropathic Pain
Mechanism Physiologic activation
of peripheral nociceptors
Lesions in
somato-sensory system
Localization Local and referred
pain
Confined to innervations
territory of the nerves
Quality of
symptoms
Ordinary painful
sensation
New strange sensations
Description of pain Varied (Throbbing, aching,
pressure-like pain)
Burning, lancinating, tingling, associated
with numbness

21. Difference between Neuropathic and Nociceptive Pain
Characteristics Nociceptive Pain Neuropathic Pain
Duration of pain Resolves when damaged tissue
heals, but can be chronic
Almost always a chronic condition
Intensity Decreases with duration Increases with duration
Tactile allodynia Absent Present
Character Distal radiation less common;
proximal radiation more common
Distal radiation common
Hypersensitivity Uncommon Present
(Allodynia/ Hyperalgesia)

22. Difference between Neuropathic and Nociceptive Pain
Characteristics Nociceptive Pain Neuropathic Pain
Autonomic signs Uncommon Colour and temperature changes, swelling;
sudomotor (sweating) activity
Motor deficits May have pain induced weakness Present if a motor nerve is affected;
dystonia or spasticity with CNS and
peripheral lesions (such as CRPS)
Paroxysms Exacerbations less common and often
associated with activity
Exacerbations common and unpredictable
Response to
Analgesics
Good Poor Response
Opioid resistance
Use of tricyclic
Antidepressants
Not useful Useful

23. Symptoms of Neuropathic Pain
Positive Symptoms
due to excessive activity)
Negative Symptoms
(due to deficit of function)

24. Which Symptoms are more harmful
Positive or Negative ???

25. Hyperalgesia and Allodynia

26. Associated Co-morbidities with Neuropathic pain
Mental status
changes/ Crying
Disability/ Changes in
activity patterns or
routines
Increased
confusion
Changes in
sleep periods
Irritability Appetite changes
Increased wandering

27. Diagnosing Neuropathic Pain is Challenging
Diagnostic
challenges
Multiple
complex
mechanisms
Diverse
symptoms
Difficulties in
communicating and
understanding
symptoms
Recognition
of
comorbidities

28. History is an initial Clues to Diagnosis
A thorough history to clarify the site of pain, radiation, precipitating events,
duration, character, pattern, intensity, aggravating and relieving factors and
associated symptoms.

29. The 3L approach to diagnosis
LISTEN
Patient verbal descriptors of
pain, questions and answers
LOOK
Sensory abnormalities
(skin and joints)
LOCATE
Nervous system lesion
or abnormality

30. LOOK
For the presence of sensory and/or physical abnormalities:
 First, inspect the painful body area and compare it with the
corresponding healthy area for differences in colour, temperature,
sweating
 Then, conduct simple bedside tests to confirm sensory abnormalities
associated with neuropathic pain:
• Gauze or a piece of cotton wool
• Pinprick
• Pinch
• Thermal (hot or cold object)
• Pain when straight leg is raised

31. LISTEN
Recognizing Neuropathic Pain
Be alert for common verbal descriptors of neuropathic pain:
Burning Tingling Shooting Electric shock-like Numbness

32. LOCATE
Correlate the region of pain to the lesion/dysfunction in the nervous system

33. Assessment of Nociceptive Pain
Simple pain scales: Useful for evaluation of Nociceptive pain
1. Visual Analogue Scale
2. Numerical Rating Scale
3. Verbal Rating Scale
4. Wong-Baker FACES Pain Rating Scale- Useful in children<7 years

34. Assessment of Pain
Useful for evaluation of chronic/ neuropathic pain
Includes pain intensity as well as mood, behavior, thoughts and beliefs,
physiological effects and their interaction with each other
 McGill Pain Questionnaire
 Brief Pain Inventory
 The Memorial Pain Assessment Card
 Neuropathic Pain Scale
 The Leeds Assessment of Neuropathic
Symptoms and Signs (LANSS)

35. Quantitative Sensory Testing for Neuropathic Pain
• Tests both the nociceptive and non-nociceptive systems in the
PNS & CNS
• Uses standardised mechanical and thermal stimuli (graded von
Frey hairs, 64Hz tuning fork, several pinprick stimuli, pressure
algometers, quantitative thermo-testing, etc.)
• Assesses a loss of function (minus signs) as well as a gain of
function (positive signs)
• Pain can be quantified in terms of Duration, Intensity, Threshold
for elicitation and Area involved.

36. Laboratory evaluation
To monitor:
1. Systemic response to treatment
2. Serum levels of primary analgesics and certain adjuvant medications such as
anticonvulsants.
• DNA and other specific biochemical tests for neuropathic pain disorders that
have a familial tendency or pattern of inheritance
• Nerve Biopsy: Direct and electron microscopic assessments of nerve tissue for
the definitive pathological diagnosis of neuropathy.

37. Specialized Tests
• Somatosensory-evoked potentials
• Triple-phase contrast bone scan as a tertiary way of testing for CRPS Type I /RSD
Electroneuromyography (ENMG) Nerve conduction studiesMRI scan

38. Goals of Treatment
Reduce
Pain
Treat underlying conditions/
Symptomatic Treatment
Reduce
Psychological
Stress
Improve
physical
functioning
Improve
quality of
life
Diagnosis
Prevention

39. Nociceptive Pain
Management
• The first line management
NSAIDS like paracetamol,
ibuprofen and aspirin.
• For more severe pain- Opioids as
tramadol, fentanyl may be
required
Neuropathic Pain
Management
• Combination of opioid analgesics,
antidepressants & anticonvulsants
• Non-pharmacological methods like
TENS, acupuncture.
• Invasive methods like sympathetic
blocks

40. International Guidelines for Neuropathic Pain Management
• NICE Guidelines (National Institute for Health Care
excellence), UK
• International Association for the Study of Pain the
European Federation of Neurological Societies (EFNS)
• Canadian Pain Society (CPS)
• Japan Society of Pain Clinicians

41. Pharmacological Management
Main classes of oral medication:
1. Serotonin/norepinephrine-modulating antidepressants/
TCA : Duloxetine, Amitriptyline, Nortriptyline
2. Sodium-channel blockers: Carbamazepine
3. Ca2+ channel alpha 2δ ligands: Gabapentin, pregablin
4. Opioids: Fentanyl, tramadol, oxycodone, morphine
5. NMDA receptor antagonist: Ketamine
6. Topical medications for patients with cutaneous
allodynia and hyperalgesia – Capsaicin and L.A.

42. Algorithm for pharmacotherapy of neuropathic pain according
to the guidelines of Japan Society of Pain Clinicians
General Guidelines
First Line Therapy
Tricyclic Antidepressants: Nortriptyline, Imipramine
Ca2+ channel α2δ ligands (Gabapentinoids):
Pregablin, Gabapentin
Second Line Therapy
SNRI: Duloxetine
Antiarrhythmic: Mexiline
Third-Line Therapy
Narcotic Analgesics: Morphine, Fentanyl,
Oxycodone, Tramdol Buprenorphine
Post-Herpetic Neuralgia
Extract of cutaneous tissue of rabbit
inoculated with vaccina virus
LA patch
Diabetic Polyneuropathy
SNRI: Duloxetine
Antiarrhythmic: Mexiline
Aldose Reductase Inhibitor: Epalrestat
Trigeminal Neuralgia
First Line Therapy: Carbamazepine
Second Line Therapy: Lamotrigine,
Baclofen

43. Question 4
• Which is the first line drug for
diabetic neuropathic pain?
A. Amitriptyline
B. Carbamezapine
C. Duloxetine
D. Pregablin

44. Ans 4. C
• Duloxetine and Venlaflaxine are newer
drugs that block serotonin and nor-
epinephrine uptake and have shown
promising results in diabetic
polyneuropathy.

45. Transdermal Fentanyl Delivery System (Ionsys)
• Needle free, patient activated system for in-hospital use
• Iontophoresis: Low intensity electrical field used to transport fentanyl across
skin into circulation
• Each double click delivers 40mcg over 10 min
• Used for 24 hours or 80 doses

46. Non pharmacological methods
Benefits:
 Reduce opioid requirement/side effects
 Attenuate activation of sympathoadrenal system
 May provide postoperative analgesia
 Devoid of any side effects
Methods
TENS
Acupuncture/Acupressure
Psychological Approaches
Mechanism
Spinal cord modulation
Endogenous enkephalins
Useful adjuvants to pharmacological therapy

47. Take home message
• Chronic pain can turn into neuropathic pain if inadequately
treated
• Differentiation of chronic nociceptive pain from neuropathic
pain is essential to guide proper therapy.
• A multimodal approach (including non-pharmacological)
targeting the various elements of pain should be tried in all
patients.
• Choice of drugs for various types of neuropathic pain may
varies according to different guidelines and underlying
condition of the patient