Central and Peripheral Neuropathic Pain

Introduction

Neuropathic pain is a high-yield topic for the MCCQE1, falling under the domains of Neurology, Internal Medicine, and Family Medicine. It is defined by the International Association for the Study of Pain (IASP) as:

“Pain caused by a lesion or disease of the somatosensory system.”

Unlike nociceptive pain (which arises from actual or threatened tissue damage), neuropathic pain arises from the nervous system itself. For Canadian medical students, understanding the distinction between Central and Peripheral origins, as well as the Canadian Pain Society (CPS) guidelines for management, is crucial for the Medical Expert role within the CanMEDS framework.

MCCQE1 High-Yield Concept

Neuropathic pain is often resistant to standard analgesics (NSAIDs, Acetaminophen). Recognizing the descriptor words (burning, shooting, electric) is the key to switching your management algorithm to neuropathic agents.

Classification and Etiology

Neuropathic pain is broadly classified based on the anatomical location of the lesion.

Peripheral Neuropathic Pain

Peripheral Neuropathic Pain originates from lesions to the peripheral nervous system (nerve roots, plexus, or peripheral nerves). Common etiologies include:

Diabetic Polyneuropathy: The most common cause in Canada.
Post-Herpetic Neuralgia (PHN): Following a VZV reactivation (Shingles).
Trigeminal Neuralgia: Compression of CN V.
Chemotherapy-induced peripheral neuropathy: (e.g., Vincristine, Taxanes).
Traumatic nerve injury: Surgery or compression (e.g., Carpal Tunnel Syndrome).
HIV-associated neuropathy.

Clinical Presentation

Patients typically present with a combination of “positive” and “negative” symptoms.

Symptom Terminology

Understanding these terms is vital for describing findings in an OSCE or interpreting an MCQ stem.

Term	Definition	Clinical Example
Allodynia	Pain due to a stimulus that does not normally provoke pain.	Pain from bed sheets touching the feet.
Hyperalgesia	Increased pain from a stimulus that normally provokes pain.	Extreme pain from a mild pinprick.
Paresthesia	Abnormal sensation, whether spontaneous or evoked.	”Pins and needles” or tingling.
Dysesthesia	An unpleasant abnormal sensation.	Burning or shooting sensation.

🍁

Canadian Epidemiology Note: With the rising prevalence of Diabetes Mellitus in Canada (approx. 10% of the population), Diabetic Peripheral Neuropathy is the most frequently encountered form of neuropathic pain in primary care.

Diagnostic Approach

For the MCCQE1, follow a structured approach to diagnosis.

Step 1: Detailed History

Focus on the quality of pain using the OPQRST mnemonic.

Q (Quality): Look for keywords: Burning, Shooting, Electric-shock, Lancinating, Freezing.
Distribution: Is it dermatomal (Shingles)? Stocking-glove (Diabetes)? Hemibody (Stroke)?

Step 2: Physical Examination

Perform a focused neurological exam.

Light touch: Use a cotton wisp (test for anesthesia or allodynia).
Pinprick: Use a safety pin (test for hyperalgesia).
Vibration/Proprioception: 128 Hz tuning fork (dorsal column function).
Motor/Reflexes: Assess for associated motor deficits or hyporeflexia (LMN signs).

Step 3: Screening Tools

Use validated tools to support diagnosis.

DN4 (Douleur Neuropathique 4): A score of $\ge$ 4/10 suggests neuropathic pain.
LANSS (Leeds Assessment of Neuropathic Symptoms and Signs).

Step 4: Investigations

Rule out reversible causes, especially in peripheral neuropathy.

Labs: HbA1c (Diabetes), Vitamin B12 (deficiency), TSH (Hypothyroidism), SPEP (Paraproteinemia), Creatinine/Urea (Uremia).
Imaging: MRI of Spine/Brain (if central cause or radiculopathy suspected).
Electrophysiology: EMG/NCS (to localize the lesion and determine axonal vs. demyelinating).

Management Guidelines (Canadian Focus)

Management should align with the Canadian Pain Society (CPS) guidelines. The goal is often pain reduction (e.g., 30-50% improvement) and improved function, rather than complete pain elimination.

Pharmacological Management

General Principles

Start low and go slow (especially in the elderly).
Trial a medication for at least 2-4 weeks at a therapeutic dose before declaring failure.
Monotherapy is preferred initially; combination therapy is for partial responders.

First-Line Agents

Drug Class	Examples	Mechanism	Key Side Effects/Notes
Gabapentinoids	Gabapentin, Pregabalin	Bind $\alpha_2\delta$ subunit of voltage-gated Ca channels.	Dizziness, sedation, peripheral edema. Renally cleared (dose adjust).
Tricyclic Antidepressants (TCAs)	Amitriptyline, Nortriptyline	Inhibit reuptake of 5-HT and NE; Na channel blockade.	Anticholinergic (dry mouth, urinary retention), QT prolongation, orthostatic hypotension. Avoid in elderly.
SNRIs	Duloxetine, Venlafaxine	Inhibit reuptake of 5-HT and NE.	Nausea, hypertension (Venlafaxine). Duloxetine is approved for diabetic neuropathy and OA.

Second-Line Agents

Topical Agents: Lidocaine 5% patch (specifically for Post-Herpetic Neuralgia), Capsaicin cream.
Tramadol: Weak mu-opioid agonist + SNRI effect. (Note: Lower seizure threshold).

Third-Line Agents

Opioids: Morphine, Oxycodone, Hydromorphone.
Cannabinoids: Considered third/fourth line in Canadian guidelines.

⚠️

Critical Exception: For Trigeminal Neuralgia, the first-line treatment is Carbamazepine. Gabapentinoids and TCAs are less effective.

Non-Pharmacological Management

Physiotherapy: Desensitization techniques, TENS (Transcutaneous Electrical Nerve Stimulation).
Psychological: CBT (Cognitive Behavioral Therapy) for chronic pain coping.
Interventional: Nerve blocks, spinal cord stimulators (for refractory cases).

Canadian Guidelines & Public Health

Opioid Stewardship

Canada is currently facing an opioid crisis. The 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain strongly recommends:

Optimizing non-opioid pharmacotherapy and non-pharmacological therapy first.
If opioids are initiated, keep dosage $\le$ 90 mg morphine equivalents (MME) per day.
“Choosing Wisely Canada” recommends against using opioids as first-line therapy for neuropathic pain.

Access to Care

Wait times for specialized Pain Clinics in Canada can be long (6-12 months). Primary care management is essential during this period.

Key Points to Remember for MCCQE1

Distinguish Type: Is it Central (Stroke, MS) or Peripheral (Diabetes, Shingles)?
Vocabulary: “Burning,” “Electric,” “Shooting” = Neuropathic.
First-line Trio: TCAs, Gabapentinoids, SNRIs.
Trigeminal Neuralgia: Carbamazepine is the answer.
Elderly: Avoid Amitriptyline (Beers Criteria); prefer Nortriptyline or Gabapentin/Pregabalin (watch renal function).
Zoster: Treat acute shingles with antivirals to prevent PHN. Treat PHN with TCAs/Gabapentinoids.

Sample Question

Clinical Scenario

A 68-year-old male presents to his family physician with a 3-month history of intense burning and shooting pain in his feet, interfering with his sleep. He has a history of Type 2 Diabetes Mellitus (A1c 8.2%), Hypertension, and Benign Prostatic Hyperplasia (BPH). Physical examination reveals decreased sensation to monofilament testing and absent ankle jerks bilaterally. There is no evidence of foot ulcers. He is currently taking Metformin, Ramipril, and Tamsulosin.

Question

Which one of the following is the most appropriate initial pharmacological management for this patient’s pain?

Explanation

The correct answer is:

C. Pregabalin

Detailed Explanation: The patient presents with classic Diabetic Peripheral Neuropathy (burning/shooting pain, stocking distribution implied, sensory loss, absent reflexes).

Pregabalin (Option C): Gabapentinoids (Pregabalin/Gabapentin) are first-line agents for neuropathic pain according to Canadian Pain Society guidelines. They are generally well-tolerated, though renal dose adjustment may be necessary.
Amitriptyline (Option A): While TCAs are first-line for neuropathic pain, this patient has Benign Prostatic Hyperplasia (BPH). TCAs have strong anticholinergic side effects which can precipitate urinary retention in patients with BPH. Therefore, Pregabalin is a safer choice in this specific context.
Hydromorphone (Option B): Opioids are third-line agents for neuropathic pain and should be avoided as initial therapy due to the risk of dependence and side effects (Choosing Wisely Canada).
Indomethacin (Option D): NSAIDs are effective for nociceptive pain but are generally ineffective for neuropathic pain. Furthermore, NSAIDs pose a risk of renal injury in a diabetic, hypertensive patient.
Carbamazepine (Option E): This is the first-line treatment for Trigeminal Neuralgia, not diabetic neuropathy.

References

Canadian Pain Society. (2014). Pharmacological management of chronic neuropathic pain: Revised consensus statement from the Canadian Pain Society. Pain Research and Management.
Busse, J. W., et al. (2017). Guideline for opioid therapy and chronic noncancer pain. CMAJ.
Choosing Wisely Canada. (2023). Pain Medicine - Opioids. Link to Choosing Wisely
Medical Council of Canada. (2023). MCCQE Part I Objectives: Chronic Pain.
Public Health Agency of Canada. (2022). Diabetes in Canada: Highlights from the Canadian Chronic Disease Surveillance System.