Neuropathic%20pain Diagnosis

• History and clinical examination are required to confirm the presence of a neuropathic pain syndrome and also an important step in reaching an etiologic diagnosis for neuropathic pain
• Rapid and correct diagnosis of neuropathic pain should be done so that appropriate treatment can be started earlier

Common Neuropathic Pain Syndromes

Central Neuropathic Pain

• Pain may be burning, shooting, aching, or pricking and is often associated with dysesthesia, hyperalgesia or allodynia to brush or cold
• Seen among post-stroke, spinal cord injury and multiple sclerosis patients

Painful Diabetic Peripheral Neuropathy (DPN)

• Symmetrical sensory loss and burning, shooting, stabbing or severe deep aching pain of both lower extremities among patients with diabetes mellitus (DM)
  • Affects about 50% of patients with DM

• Pain may be accompanied by allodynia and hyperalgesia
• Symptoms may worsen at night

Postherpetic Neuralgia (PHN)

• Pain persisting for >3 months after herpes zoster skin lesions have healed
• Risk factors for developing PHN:
  • All patients >50 year with herpes zoster virus (HZV) infection
  • Patients with a greater degree of skin surface area involved and more severe pain at presentation of HZV infection
  • Patients with HZV ophthalmicus
  • Patients who experience sensory dysfunction on the affected dermatome
  • Painful prodrome prior to rash

• Patients at greatest risk for developing PHN should be offered antiviral treatment
• Diagnostic clinical features of PHN:
  • Pain localized to the dermatome affected by the herpes zoster rash
  • Pain may be described as burning, throbbing, sharp or shooting
  • Allodynia
  • Pain accompanying movement
  • Areas of scarring of hypopigmentation caused by herpes zoster rash
  • Presence of psychosocial stress

Trigeminal Neuralgia (TN)

• Characterized by intermittent unilateral facial pain following the unilateral sensory distribution of the trigeminal nerve, typically radiating to the maxillary or mandibular area
  • Ophthalmic division pain alone occurs in <5% of patients

• Pain is quite severe, stabbing electric shock-like sensation
• Pain may be brief and paroxysmal but may occur in multiple attacks several times a day, with no pain between episodes
• Typically with normal physical examination findings, although mild light touch or pin perception loss has been described in the central area of the face
• Average age of pain onset in idiopathic TN is usually the 6th decade of life, but may occur at any age
• Symptomatic or secondary TN tends to occur in younger patients
• Common triggers precipitating pain attack include light touch or vibration and activities such as shaving, face washing or chewing

Postsurgical Neuropathic Pain

• Peri-incisional sensory loss, pain and allodynia for >3 months after surgery; phantom pain following amputation or mastectomy

Human Immunodeficiency Virus (HIV)-Related Neuropathy

• Symmetrical painful paresthesias, most prominent in the toes and soles of the feet among HIV patients

Lumbosacral Radiculopathy (Herniated Intervertebral Disc)

• Lancinating pain radiating into the anterior thigh (L2/3) or lower leg (L4-S1) with motor weakness or sensory loss

Complex Regional Pain Syndrome

• Regional (eg limb) pain together with edema, cutaneous blood flow and sweating abnormalities

• Will help determine whether the character and distribution of pain follow the neuropathic criteria and whether a relevant lesion or disease in the nervous system is probably responsible for the pain

Pain Intensity

• Can be rated using a valid verbal, numerical or visual analog scale or Numeric Pain Rating Scale such as the Neuropathic Pain Scale and Neuropathic Pain Questionnaire
• Assessed at each visit to monitor therapeutic response

Description of Sensory Symptoms

• Quality of pain: burning, sharp, stabbing, cold, allodynia, hyperalgesia, spontaneous, dysesthesia, paresthesia
• Frequent non-painful sensations: pricking, tingling, aching, numbness, hypoesthesia, anesthesia, hypoalgesia, analgesia
• Sensory abnormalities and  pain paradoxically co-exist

Temporal Variation of Pain

• Pain usually becomes worse toward the end of the day
• Rule out a neoplastic process if pain progressively increases over the recent months

Functional Impact

• Impact on sleep, self-care, daily activities, work, social and sexual dysfunction, mood and suicidal ideas

Previous Treatment

• Usually resistant to medications [eg Paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs)]
• Adequate titrated doses of specific drugs should be determined and documented

Alcohol and Substance Abuse

• History of dependence disorders can affect decision about prescribing opioids and cannabinoids
• Consider interaction of sedatives and alcohol with other substances

Spontaneous Pain or Sensation

• Paresthesias (eg tingling, itching, sensation of something crawling on one’s skin, discomfort of one’s foot “falling asleep”)
• Dysesthesias (eg pricking, electric shock-like, burning or shooting pain)
• Phantom pain

Stimulus-Evoked Pain or Sensation

• Allodynia
• Hyperalgesia
• Hyperpathia
• Hypoesthesia/Anesthesia

• Allows integration of the patient’s current symptoms and localization of the involved elements of the nervous system
• Identifying pain localization, quality, intensity and pattern is essential
• Reveals the presence of negative (loss of function) and positive (hyperalgesia and/or allodynia) signs for sensory modalities affecting the somatosensory system and relevance to the underlying disease or lesion

Motor Examination

• May reveal motor weakness in the distribution of the involved nerve

Deep Tendon Reflex

• May be decreased or absent in the distribution of affected nerve

Sensibility Examination

• Reduced or absent light touch, pin prick, vibration responses and proprioception in the affected nerve territory
• Sensory disturbances can expand outside the area of nerve innervation
• Dynamic allodynia: pain arising from gentle brushing of skin with cotton ball
• Thermal allodynia: burning sensation due to an ice cube placed on the skin
• Hyperalgesia to a pin prick test
• Pain on leg lifting: irritation of lumbar nerve roots
• Myofascial trigger points: myofascial pain plus neuropathic pain

Skin Examination

• Changes in skin temp, color, sweating or hair growth (complex regional pain syndrome)
• Residual dermatomal scars persisting after herpes zoster infection
• Characteristic skin changes of DM

Ancillary Tests

• May be conducted to document the presence of a specific underlying neurologic disease or confirm a sensory lesion within the pain distribution

Laboratory Tests

• Quantitative means to measure objective response

Neurophysiological Testing

• Standard neurophysiological responses to an electrical stimulus can identify, localize and quantify damage along peripheral or central sensory pathways
• Pain-related evoked potential: Laser-evoked potentials are the easiest and most reliable methods for assessing function of the nociceptive and A-delta fiber pathways in patients with neuropathic pain
• Electromyography and Nerve Conduction Velocity (EMG/NCV): Provides objective evidence of nerve injury or dysfunction but primarily evaluates the large myelinated fibers thus small fiber neuropathy may not be ruled out if the result is normal
• Microneurography: Provides valuable information on the physiology and pathophysiology of all nerve fiber groups but this is not recommended as routine procedure for assessing patients with peripheral neuropathic pain 
• Pain-related reflexes: Diagnostically useful only for facial pains as in trigeminal pain disorders

Skin Biopsy

• Best tool for assessing neuropathies with distal loss of unmyelinated nerve fibers
• Recommended in patients with painful or burning feet of unknown origin and with clinical impression of small fiber dysfunction

Additional Tests to Identify Other Causes of Neuropathies

• Glucose tolerance test
• Thyroid function
• Vitamin B₁₂ levels
• CD4+ T-lymphocyte counts
• Lumbar puncture

Quantitative Sensory Testing

• Psychophysiological measure of perception in response to external stimuli of controlled intensity, which allows documentation of sensory profile
• Appropriate to quantify positive sensory phenomena like mechanical and thermal allodynia and hyperalgesia which may help characterize painful neuropathic syndromes and predict or monitor treatment effects

• Functional neuroimaging studies are encouraged in patients with neuropathic pain

• Facilitates specific diagnosis

• May help in the diagnosis of complex regional pain syndrome

• Measures cerebral blood flow or metabolic activity in defined brain regions

• Can identify small patches of inflammation in peripheral nerves
• Recommended as part of the initial work-up of patients with TN and is the 1st-line modality for diagnosing secondary TN

• Investigate local synaptic changes specifically associated with a given task or a particular stimulus by comparing statistically activated and controlled conditions

Screening and Assessment Tools

• The main advantage is to identify potential patients with neuropathic pain, particularly by non-specialists

Screening Tools

• Unidimensional scales
• McGill Pain Questionnaire
• Douleur Neuropathique en 4 (DN4) Questions
• ID-Pain
• Pain DETECT
• Leeds Assessment of Neuropathic Symptoms and Signs
• Standardized Evaluation of Pain
• Chinese Identification Pain Questionnaire

Assessment Questionnaires

• Brief Pain Inventory
• Neuropathic Pain Scale
• Neuropathic Pain Symptom Inventory