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A number of laboratory tests are critically important in the quest to diagnose presence or absence of organic neuropathic dysfunction and to establish the relevance of such to the subjective pain complaints. However, none of these tests has absolute diagnostic value and their results must be interpreted in the light of the clinical picture. Conventional electrophysiology evaluates function of large caliber afferent and motor fibers leaving the function of small caliber afferent fibers unexplored, and cannot explore the basis for positive sensory phenomena. The quantitative somatosensory thermotest is the best test available to explore function of small caliber afferents. It allows documentation of positive sensory phenomena in the form of thermal hyperalgesia. Because it is a psychophysical test, it lacks localizing value. Thermography sensitively detects and precisely delineates areas of cutaneous thermal change of neural origin. Three types of diagnostic neurologic blocks are used in the clinic: compression-ischemia, local anesthetic and sympathetic blocks. Although they may provide important information about the pathophysiology of pain and hyperalgesias, adequate placebo control is of the essence because chronic neuropathic pain patients may express a high incidence of placebo response.

The quantitative somatosensory thermotest (QST) assesses the function of afferent channels concerned with sensory submodalities served by small calibre fibres. Measured ramps of ascending or descending temperature are applied to the skin through a Peltier contact thermode, and detection thresholds are recorded as the subject signals the onset of a particular sensation. The present study describes underlying principles, methodological aspects and normal reference values for the QST. In patients, measurement of thresholds for cold sensation, warm sensation, cold-induced pain and heat-induced pain, applied to 465 individuals, yielded 13 abnormal patterns segregated into three main groups: (i) thermal (cold or warm) hypoaesthesia; (ii) thermal hyperalgesia (abnormally reduced threshold for cold and/or heat induced pain); (iii) thermal hypoaesthesia combined with thermal hyperalgesia. Critical analysis of these results yielded a number of observations of general relevance: (i) thermal specific (warm or cold) hypoaesthesia and thermal (heat or cold) hyperalgesia may occur in the absence of hypoaesthesia for tactile submodalities served by large calibre afferents; (ii) cold hypoaesthesia and warm hypoaesthesia may dissociate from each other; (iii) thermal pain hyperalgesias may occur in the absence of hypoaesthesias for specific cold or warm sensations; (iv) cold hyperalgesia and heat hyperalgesia may dissociate from each other. Thus, a negative routine sensory examination and unimpaired sensory nerve action potentials do not exclude possible somatosensory dysfunction. Furthermore, while most methods of sensory testing only document normality or deficit, the QST permits additional documentation of hyperalgesia, a positive sensory phenomenon that implies unusual pathophysiologies such as sensitization of receptors, central hyperexcitability, disinhibition or, possibly, ectopic nerve impulse discharge. This psychophysical test does not specify the level within afferent channels, between skin and brainmind, where the abnormality resides. It is recommended that the QST for all four thermal specific and thermal pain functions be incorporated in routine neurological assessment.

While the pure sensation of cold is evoked by activation of a specific set of afferent channels, an additional set is believed to be activated by noxious low-temperature stimuli evoking cold pain. At primary afferent level, the channels concerned with the cold fraction of cold pain are served by myelinated A delta cold-specific fibres, whereas those concerned with the pain fraction are served by unmyelinated C nociceptors. In the present study, interaction between the two types of afferent input underlying cold pain was investigated by selectively blocking conduction in myelinated fibres. When doing so to the point of abolishing cold sensation, ramps of low-temperature stimuli eventually evoked a first sensation of burning pain. In addition to, and contemporaneous with, this change in quality, a significant decrease in pain threshold (reduction in required stimulus energy) was recorded when applying a noxious low-temperature stimulus. Such exaggeration in magnitude of low temperature-induced pain and the unmasking of its burning quality by A fibre block imply release of central sensory transmission due to removal of inhibitory primary afferent input. Myelinated fibres transmitting either tactile, cold sensations or both could exert this inhibition. Previous evidence of suppression of pain by low-temperature stimuli indicates that it is the cold-specific input that normally exerts this central gating on nociceptor input. The present results may also offer an explanation for the occurrence of a syndrome of burning pain on cold exposure in neuropathic patients with impaired ability to perceive cold.

Elementary sensations of definable quality were evoked by intraneural electrical stimulation of sensory units through tungsten microelectrodes inserted in the median nerve of awake human subjects. The most commonly reported sensations were tapping, pressure, dull pain and sharp pain, which correlated with recording from RA units, SA I units, C nociceptors and A delta nociceptors, respectively. All sensations were projected more often to the fingertips than to the palm. The multifocal projections of sensations recruited by excitation of small groups of neighbouring nerve fibres were significantly more scattered in space than anticipated if these fibres had preserved an orderly intraneural map, implying lack of somatotopy in the nerve. Mean projected field sizes were 3.4 mm2 for sharp pain, 9.2 mm2 for tapping/vibration, 29.3 mm2 for pressure and 35.4 mm2 for dull pain, and in addition the latter two showed a rising size gradient from fingertip to palm. Consideration of projected field size as a variable in discriminative touch suggests that input from RA units and A delta nociceptors may be of importance in stimulus localization, while SA I units may play an additional role in two point discrimination.

The accuracy of the cerebral localisation function from the input of single mechanoreceptive units was studied in the hand and forearm of human subjects by means of microneurography and intraneural microstimulation (INMS). The mean distance separating the projected field of a sensation evoked by INMS at liminal amplitude from the receptive field of the activated unit (interfield distance, or IFD) was found to vary from 2.6 mm for SA I units in the fingertips to 23.4 mm for SA I units in the forearm. A less pronounced proximodistal IFD gradient was found for quickly adapting units. IFD values for each skin region were comparable with those obtained by a point localisation test directly on the skin. This indicates that functional gradients exist for inputs from single mechanoreceptive units, and that stimulus localisation hardly improves when numerous units are coactivated.