Neuropathic Pain

Background

Pain is very common and when properly recognized , it can easily be assessed and simply treated. Many effective medications and established guidelines are available.

There are two main types of pain: nociceptive pain and neuropathic pain but the focus of this paper is neuropathic pain.

Definition and classification

The International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”.Nociceptive pain is pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors. e.g. arthritis, fracture, burns. This pain occurs with a normally functioning somatosensory nervous system.Neuropathic pain is pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system1. Neuropathic pain can be from the central nervous system or peripheral nervous system origin, e.g. painful diabetic peripheral neuropathy, radiculopathy, post herpetic neuralgia, central thalamic pain.

Anatomy, Physiology and Pathology

Central pain locations are the spinal cord, brainstem, thalamus, cortical/subcortical, and peripheral pain locations arecranial nerves, nerve roots and peripheral nerves.

Pain sensation begins in the periphery of the nervous system, sensed by specialized nociceptors that are the nerve terminals of the primary afferent fibers. The pain signal is then transmitted to the dorsal horn of the spinal column and transmitted through the central nervous system (CNS) where it is processed and interpreted in the somatosensory cerebral cortex. Modulation (augmentation or suppression) of this pathway is done by major descending inhibitory pathways which travel from the brainstem down the spinal cord to the dorsal horn.

Disease, injury, or dysfunction of the central or peripheral nervous system with anatomical or chemical changes lead to abnormal neural discharges producing pain through peripheral nerve hyper excitability, loss of central pain inhibitory controls, and central sensitization.

Common causes of Neuropathic pain

Central

• Central poststroke pain
• Multiple sclerosis
• Spinal cord injuryPeripheral
• Trigeminal neuralgia
• Post-herpetic neuralgia
• Carpal tunnel syndrome
• Spinal nerve root pain (radiculopathy)
• Diabetic peripheral neuropathy
• Other polyneuropathies e.g. HIV, alcoholism, amyloid, drugs, idiopathic
• Vasculitis
• Complex regional pain syndrome
• Phantom limb

Symptoms and terminology

Positive symptoms: burning or shooting pain, pins and needles or tingling, burning, paraesthetic, lancinating, electric like, shooting, deep dull aching
Negative symptoms – numbness

• Paraesthesia: Abnormal sensations (spontaneous or evoked)
• Dysaesthesias: Unpleasant abnormal sensations (spontaneous or evoked)
• Allodynia: Pain in response to non-painful stimuli
• Hyperalgesia: Increased pain in response to painful stimuli
• Hypoalgesia: Diminished pain in response to a normally painful stimulus
• Analgesia: Absence of pain in response to a normally painful stimulus
• Hypoaesthesia: diminished sensations to non painful stimulus
• Anaesthesia: total loss of sensations

Diagnostic workup

Diagnostic workup may include: clinical biochemistry, nerve conduction study to diagnose and localize lesions, and assess severity and outcome of various types of neuropathies, imaging and nerve biopsies.

Assessment of pain

Practical assessment includes: severity assessment, classifying type and assessing other factors contributing to pain such as underlying cause or comorbidities, psychological (anger, anxiety, depression ) and social factors (lack of social supports). Severity assessment can be easily done by verbal rating scale (mild,moderate, severe) or (0 to 10 scale) but do not forget to assess pain at rest and on movement with functional activity score such as: no limitation, mild to moderate limitation, severe limitation,e.g., your patient has mild pain or no pain at all at rest but he/she may have severe pain on walking, affecting his mobility and work.This would be an example of lumbar spinal stenosis with radiculopathy causing neurogenic claudication. Types of pain can be acute (<6 months) or chronic (>6 months) and nociceptive or neuropathic pain or mixed (nociceptive and neuropathic). Assessment is helpful for determining treatment.²

Management

Non-pharmacological treatments involvephysical measures such as rest, physiotherapy, acupuncture, psychological measures such as reassurance.

Pharmacological treatments are often the mainstay of treatment. Different medicines work differently along the pain pathway and different combinations are sometimes necessary.

Targets for controlling neuropathic pain

• Block peripheral sensitization (local anesthetics, topical capsaicin Tricylic anti-depressants 9TCA), anticonvulsants)
• Block central sensitization (anticonvulsants, opioids, NMDA-receptor antagonists, TCA)
• Descending modulation (anticonvulsants, opioids, TCA)
• Modulate calcium channels at the alpha-2-delta subunit (pregabalin or gabapentin)
• Restore inhibitory neurotransmission GABA (anticonvulsants)
• Block sodium channels (carbamazepine)

AAN – American academy of Neurology
NICE – National Institute for Health and Care Excellence
EFNS – European Federation of Neurological Societies
TCA – Tricyclic antidepressants eg. Amitriptyline

Common case scenarios of neuropathic pain encountered in clinical practice

Case 1. A 65 years old woman with a 20 year history of diabetes mellitus with diabetic retinopathy and nephropathy presenting with pins and needles sensation in the soles of both feet which affect her sleep. This is a case of painful diabetic peripheral neuropathy. In addition to conducting nerve conduction study assessment and comprehensive diabetic care, we can prescribe pregabalin, gabapentin, duloxetine or amitriptyline.

Case 2: A 45 year oldwoman had herpes zoster on the right forehead a month ago and still suffering from severe burning, tingling, deep aching pain at same area. This is a case of post-herpetic neuralgia and we can prescribe gabapentin, pregabalin or amitriptyline, lidocaine plasters locally according to its severity and response.

Case 3: A 42 year old man with intense and unilateral electric shock like pain at left cheek without tooth or sinus problem and no sensory loss (numbness) at that area. This is a case of
trigeminal neuralgia and carbamazepine or oxcarbamazepine can be started with close monitoring for Steven-Johnson syndrome.

Case 4: A 51-year-old man recently had a fall and is now having back pain and problems walking with tingling pain shooting down his right lateral leg with weakness of right ankle and big toe dorsiflexion, and persistent numbness at dorsum and sole of right foot. This is a case of right L5 radiculopathy. He will need nerve conduction study and electromyogram and MRI of his lumbar spine to confirm the diagnosis. In addition to non-pharmacological treatments such as: rest not more than three days, physiotherapy, psychological support and surgical treatment (e.g. prolapsed disc), pharmacological treatments (e.g.paracetamol and/or NSAIDs for nociceptive back pain) and amitriptyline, pregabalin, gabapentin or duloxetine, infiltration of epidural steroids for relief of acute pain.

Case 5: A 60 year old hypertensive man and chronic smoker, presented with left hemiparesis and left hemiesthesia of sudden onset. CT scan reveals right thalamic infarct. This is a case of central thalamic pain due to lacunar infarct at right thalamus. In addition to stroke management, patient needs amitriptyline, pregabalin or gabapentin.

Conclusion

Pain is due to a direct consequence of a lesion or disease affecting the somato-sensory system. Neuropathic pain can be due to central and peripheral causes. Treatment options are pharmacological, non pharmacological, interventional management and a multidisciplinary approach. The aim is to improve, recognize, assess and treat pain. We hope that careful recognition, proper assessment and appropriate control of pain can decrease suffering, offer better sleep and mobilization and lessen psychological impact such as depression and anxiety. It will subsequently help enable the patient to participate in family matters and work, leading to increased work output and decreased burden on the family and society.

References

1. International Association for the study of pain. ISAP Taxonomy. Pain terms. Dec. 2014, Updated 2017 .
   Available at https://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698
2. Morriss W, Goucke R, Huggins L, O’Connor M. Essential pain management, EPM UK workshop manual: 2017.
3. Bril, V., England, J., Franklin, G.M., Backonja, M., Cohen, J., Del Toro, D., Feldman, E., Iverson, D.J., Perkins, B., Russell, J.W. and Zochodne, D. Evidence-based guideline: treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation.Neurology. 2011;76(20):1758–1765.
4. Attal N, Cruccu G, Baron RA, Haanpää M, Hansson P, Jensen TS, Nurmikko T. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. European journal of neurology. 2010 ;17(9):1113-88.
5. Kalso E, Aldington DJ, Moore RA. Drugs for neuropathic pain in adults: pharmacologic management in non-specialist settings. British Medical Journal. 2013; 19: 347-73.

Ohnmar¹, Kyaw Phyo Hlaing², Yan Lynn Aung³, Win Min Thit⁴

1. Associate Professor, Department of Neurology, University of Medicine 1
2. Specialist assistant Surgeon, Department of Neurology, Yangon General Hospital
3. Consultant Neurologist, Department of Neurology, Yangon General Hospital
4. Professor/Head, Department of Neurology, University of Medicine 1

Primary author’s information:
Dr.Ohnmar, Associate Professor, Department of Neurology, University of Medicine 1.
M.B.B.S (Ygn), M.Med.Sc (Int Med), MRCP (UK), FRCP (Edin), Dr.MedSc (Neurology), Fellowship in Neuromuscular (NNI, Singapore)
dr.maohmar@gmail.com, Phone: 095198124