Measures of cutaneous pain perception and nociceptor density: More than skin deep

Medical students learn early that skin, the body’s largest organ, functions as a barrier. Not historically emphasized, however, is the fact that this barrier is studded with extraordinarily complex machinery to enable sophisticated exploration and interpretation of one’s surroundings. A family of cutaneous organs faithfully transduces information regarding contact with the skin into electrical signals that are transmitted to the central nervous system via modality-specific axons. Through firing patterns and a series of integrated amplification and modulation steps, the organism is provided critical information about mechanical, thermal, and even chemical properties of the near environment. The experience of pain effectively alerts us to stimuli that have the potential to damage tissues, and those cutaneous receptors that initiate this process are referred to as nociceptors. The study of cutaneous thermal perception is believed to have originated with Blix, who devised an ingenious thermal sensory testing device and, starting in 1882, reported his findings of nonuniform cutaneous thermal perception, suggesting that cold and warm are transduced by different cutaneous receptors. Goldscheider extended Blix’s observations in a remarkably detailed publication illustrated with photographs and schematic drawings of findings in human skin and observed that “the skin contains a netlike system of receptive points, forming a mosaic of sensation points of various qualities: cold, warmth, pressure, and pain points. The sensory points belonging to a given quality are not at all arranged as one might expect, in a more or less uniform distribution, but are very nonuniform—here a densely packed group, there a gap. This is true especially of the temperature points. All the qualities together, although, fit into a common orderliness, a recognizable complete system. This realization of the nature of the arrangement of the sensory points may well assist microscopic demonstration of the end organs associated with the sensory nerves. ” Hence, Goldscheider predicted a convergence of cutaneous psychophysical testing with anatomic investigations of cutaneous innervation. In this issue of the Journal, Davies et al. add to the now extensive body of literature predicted by Goldscheider by reporting normative data for suprathreshold thermal pain perception and epidermal nerve density across body sites and adult age groups. Efforts to quantitatively measure heat-pain developed in the early 20th century, culminating in the development of the “dolorimeter” by Hardy, Wolff, and Goodell. They used a radiant heat source and standardized the duration of exposure, aperture, and skin absorption characteristics by painting the skin with India ink. Using this and other tools to quantify stimuli and perceptual responses in heat-pain and other modalities, these researchers performed groundbreaking work in what is now known as quantitative sensory testing (QST), compiled in their 1952 book. Although the term QST is generally applied to automated methods used in research, quantitative sensory testing is commonly done in the clinic, whether with Rydel–Seiffer vibration scores, timed vibration perception testing, or mapping of sensory deficits with fixed mechanical or thermal stimuli. Today, automated thermal QST is usually performed using a contact heat thermode with a surface temperature that can be modified rapidly and accurately by passing current through a Peltier element. Automated thermal QST enables considerable precision in standardizing the stimulus; however, a wide variety of stimulation protocols and psychophysical testing paradigms remain in use. The most notable difference between QST protocols is the choice between method of limits and method of levels testing. Method of limits testing asks the subject to identify the moment the target perception (such as warmth, coolness, or thermal pain) is perceived during a continuous ramp stimulus, whereas method of levels testing provides a ramp stimulus to a target temperature, and only when that is complete is the subject asked to indicate whether the stimulus was perceived. Method of limits testing is reaction-time-dependent; that is, any delay between the moment of perception and the report of perception artifactually raises the Disclosures: Dr Walk is affiliated with the laboratory of William R. Kennedy at the University of Minnesota. Correspondence to: D. Walk; e-mail: walkx001@umn.edu