Determining the causes of
neuropathic pain is more than an epistemological exercise. At its essence, it is a quest to delineate mechanisms of dysfunction through which treatment strategies can be created that are effective in reducing, ameliorating, or eliminating symptomatology. To date, predictors of which patients will develop
neuropathic pain or who will respond to specific
therapies are lacking, and present
therapies have been developed mainly through trial and error. Our current inability to make therapeutically meaningful decisions based on ancillary test data is illustrated by the following: In a study specifically designed to assess the response of patients with painful distal sensory neuropathies to the 5%
lidocaine patch, no relationship between treatment response and distal leg skin biopsy, QST, or sensory nerve conduction study results could be established. From a mechanistic perspective, the hypothesis that the
lidocaine patch would be most effective in patients with relatively intact epidermal innervation, whose
neuropathic pain is presumed attributable to "irritable nociceptors," and least effective in patients with few surviving epidermal nociceptors, presumably with "
deafferentation pain," was unproven. The possible explanations are multiple and outside the scope of this review. However, these findings, coupled with the disparity in C-fiber subtype involvement in diabetic
small-fiber neuropathy, and the recently reported inability of
enzyme replacement therapy in
Fabry disease to influence intraepidermal innervation density, while having mixed effects on cold and warm QST thresholds, and beneficial effects on sudomotor findings, when therapeutic benefit was demonstrated, lead one to conclude that the specificity of ancillary testing in
neuropathic pain is inadequate at present, and reinforce the aforementioned caveats about inferential conclusions from indirect data. The diagnosis of
neuropathic pain mechanisms is in its nascent stages and ancillary testing remains "subordinate," "subsidiary," and "auxiliary" as defined in Webster's Third New International Dictionary. As a consequence of these difficulties, the recent approach by Bennett and his colleagues may have merit. They have hypothesized (and provide data in support) that
chronic pain can be more or less neuropathic on a spectrum between "likely," "possible," and "unlikely," based on patient responses on validated
neuropathic pain symptom scales, when compared with specialist
pain physician certainty of the presence of
neuropathic pain on a 100-mm visual analog scale. The symptoms most associated with
neuropathic pain were
dysesthesias, evoked
pain, paroxysmal
pain, thermal
pain, autonomic complaints, and descriptions of the
pain as being sharp, hot, or cold, with high sensitivity. Higher scores for these symptoms correlated with greater clinician certainty of the presence of
neuropathic pain mechanisms. Considering each individual patient's
chronic pain as being somewhere on a continuum between "purely nociceptive" and "purely neuropathic" may have diagnostic and therapeutic relevance by enhancing specificity, but this requires clinical confirmation. Thus, symptom assessment remains indispensable in the evaluation of
neuropathic pain, ancillary testing notwithstanding