Confirmatory tests for neuropathic pain

What confirmatory tests are helpful in confirming the presence of a neuropathic pain condition?

Pain is a clinical diagnosis, but in the following conditions testing can be useful in confirming the presence of a lesion of the somatosensory system and thus more clearly establish the case for a neuropathic pain diagnosis:

  • • Painful distal symmetric polyneuropathy: While typically a distinct clinical syndrome, in some cases the clinical presentation is less compelling and diagnostic confirmation of the presence of a neuropathy is helpful.
    • • Nerve conduction studies (NCS) can only demonstrate the presence of a large fiber neuropathy, which, in isolation, is often not painful; however, insofar as both large and small fibers are commonly affected in painful distal symmetric polyneuropathy, NCS are a good initial examination.
    • • NCS are, essentially by definition, normal in a pure small fiber neuropathy. The most commonly utilized confirmatory test for the presence of pathology in small myelinated and unmyelinated fibers is skin biopsy for epidermal nerve fiber (ENF) density measurement. There is a generally good correlation between a reduction in ENF density and other clinical indicators of neuropathy. Reduction in ENF density, in combination with clinical evidence of either punctate or thermal sensory loss, has been included as a criterion in a proposed “gold standard” for the diagnosis of small fiber neuropathy. A 3-mm punch biopsy is used and several laboratories are available for processing and reporting results.
    • • Tests of sudomotor function are also sometimes used to confirm small fiber neuropathy, as denervation of cutaneous sweat glands is common in small fiber neuropathy. Such tests include quantitative sudomotor axon reflex test (QSART) and thermoregulatory sweat test (TST).
    • • In patients with diabetes or other conditions in which a mild subclinical neuropathy is common, ENF density or tests of sudomotor function are likely to be abnormal in most patients, and therefore are less useful in demonstrating a cause for pain.
  • • Posttraumatic neuropathy and other focal, painful neuropathies: If there is clinical uncertainty regarding the presence of a nerve lesion, NCS can be useful if they are available for the nerve in question. In many cases, however, there is not an established NCS for the nerve in question. In such cases a skin biopsy for ENF density can be useful. If normal values are not established for the body region of interest, bilateral biopsies can be performed and a substantial side-to-side asymmetry in ENF density can be taken as supportive evidence of a nerve lesion.
  • • Central pain states: In poststroke pain and neuropathic pain from myelopathy or spinal cord injury, imaging has almost always been performed in the acute phase of the injury.

Quantitative sensory testing (QST) can be a useful adjunct to the neurological examination in postulated neuropathic pain states. QST is used to quantify sensory and pain thresholds to thermal or vibratory stimuli. While the term is usually applied to testing performed with specialized equipment, in its broader sense it can refer to any quantitation of sensory thresholds. QST provides supportive evidence of a somatosensory deficit and can also demonstrate allodynia, hyperalgesia, and hyperpathia, which are all clinical features of neuropathic pain; however, it does not localize the deficit or provide pathologic or neurophysiologic confirmation of a lesion in the somatosensory system.


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