Tools for Assessing Neuropathic Pain

Citation: Cruccu G, Truini A ( Tools for Assessing Neuropathic Pain Giorgio Cruccu 0 1 Andrea Truini 0 1 0 Abbreviations: DN4, Douleur Neuropathique en 4 Questions; IENF, intra-epidermal nerve fibre; LANSS, Leeds Assessment of Neuropathic Symptoms and Signs; LEP , laser-evoked potential; NCS, nerve conduction study; NPQ, Neuropathic Pain Questionnaire; QST, quantitative sensory testing: SEP, somatosensory-evoked potential; StEP, Standardized Evaluation of Pain 1 1 Department of Neurological Sciences, La Sapienza University , Rome, Italy, 2 IRCCS San Raffaele Pisana, Rome , Italy According to the latest definition, the term neuropathic pain refers to pain arising as a direct consequence of a lesion or disease affecting the somatosensory system [1]. When physicians and researchers use the term assessment of neuropathic pain, they may be referring to two distinct types of assessment: (1) assessing pain intensity and quality and possibly their treatmentinduced changes, and (2) diagnosing neuropathic (as opposed to non-neuropathic) pain. Pain is a complex experience that depends strongly on cognitive, emotional, and educational influences. Hence the pressing need for tools that can measure pain objectively. We distinguish four different levels of ''objectivity'': (1) laboratory tests that use quantitative tools and measure an objective response; (2) quantitative sensory testing, a measure that despite using quantitative, graded stimuli inevitably relies on the patient's evaluation; (3) bedside examination, which relies on the physician's experience and the patient's ability and willingness to collaborate; and (4) pain questionnaires, tools that depend entirely on the patient. We review each of these in turn, drawing in part on our previous work in this field [2]. - Laboratory Tests for Diagnosing Neuropathic Pain Large-size, non-nociceptive afferents (i.e., those that do not carry pain) have a lower electrical threshold than small-size, nociceptive afferents. Unless special techniques are used, i.e., experimental blocks or stimulation of special organs (cornea, tooth pulp, glans), electrical stimuli unavoidably also excite large afferents, thus hindering nociceptive signals. Hence standard neurophysiological responses to electrical stimuli, such as nerve conduction studies (NCS; see Glossary) and somatosensory-evoked potentials (SEPs), can identify, locate, and quantify damage along the peripheral or central sensory Research in Translation discusses health interventions in the context of translation from basic to clinical research, or from clinical evidence to practice. pathways, but they do not assess nociceptive pathway function [2,3]. For many years researchers have tried numerous techniques for selectively activating pain afferents. The currently preferred approach uses laser stimulators to deliver radiant-heat pulses that selectively excite the free nerve endings (Ad and C) in the superficial skin layers. Consensus from over 200 studies now confirms that late laser-evoked potentials (Ad-LEPs) are nociceptive responses. Late LEPs are the easiest and most reliable neurophysiological tools for assessing nociceptive pathway function and are diagnostically useful in peripheral and central neuropathic pain [4,5]. In clinical practice, their main limitation is that they are currently available in too few centres [2,3]. Ultralate LEPs (related to C-fibre activation) are technically more difficult to record, and few studies have assessed their usefulness in patients with neuropathic pain [6]. Contact heat-evoked potentials are a recent development that still need clinical validation [7]. Painful neuropathies typically and preferentially involve small nerve fibres. Nerve biopsy may be unrewarding in the early detection of small-fibre neuropathy because small-fibre assessment is difficult and requires electron microscopy. Punch skin biopsy can quantify Ad and C nerve fibres by measuring the density of intra-epidermal nerve fibres (IENF). IENF loss has been shown in various neuropathies characterized by small-fibre axonal loss. Punch skin biopsy is easy to do, minimally invasive, and optimal for follow-up. Despite these advantages, it is useless in central pain and demyelinating neuropathy, and is currently available only in few research centres [8,9]. Quantitative Sensory Testing Quantitative sensory testing (QST) analyses perception in response to external stimuli of controlled intensity (Table 1). Detection and pain thresholds are determined by applying stimuli to the skin in an ascending and descending order of magnitude. Mechanical sensitivity for tactile stimuli is measured with plastic filaments that produce graded pressures, such as the von Frey hairs, pinprick sensation with weighted needles, and vibration sensitivity with an electronic vibrameter. Thermal perception and thermal pain are measured tifying mechanical and thermal allodynia and hyperalgesia in painful neuropathic syndromes, and has been used in pharmacological trials to assess treatment efficacy on provoked pains [2]. QST abnormalities, however, cannot provide conclusive evidence of neuropathic pain, because QST shows changes also in Piece of cotton wool Tuning fork (128 Hz) Wooden cocktail stick Von Frey filaments Laboratoryc Pinprick, sharp pain using a thermode, or other device that operates on the thermoelectric effect. QST has been used for the early diagnosis and follow-up of small-fibre neuropathy that cannot be assessed by standard NCS, and has proved useful in the early diagnosis of diabetic neuropathy. QST is also especially suitable for quan Six Key Papers in the Field Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, et al. (2008) Neuropathic pain: Redefinition and a grading system for clinical and research purposes. Neurology 70: 16301635. [1] The new definition of neuropathic pain and a proposed diagnostic flow-chart that helps to grade neuropathic pain as unlikely, possible, probable, and definite. Bennett MI, Attal N, Backonja MM, Baron R, Bouhassira D, et al. (2007) Using screening tools to identify neuropathic pain. Pain 127: 199203. [10] A review that brings together the main authors of all the modern screening tools for neuropathic pain and provides a pros-and-cons analysis. Chou R, Qaseem A, Snow V, Casey D, Cross JT Jr, et al. (2007) Diagnosis and treatment of low back pain: A joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med 147: 478491. These guidelines, specifically devoted to low back pain, face the problem of differentiating nociceptive and neuropathic pain components and recommend adequate methods. Rolke R, Baron R, Maier C, To lle TR, Treede RD, et al. (2006) Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values. Pain 123: 231 243. Although taking 30 min only, this is the most thorough and best validated (...truncated)