Quick discrimination of A(delta) and C fiber mediated pain based on three verbal descriptors

Abstract

Background: A(δ) and C fibers are the major pain-conducting nerve fibers, activate only partly the same brain areas, and are differently involved in pain syndromes. Whether a stimulus excites predominantly A(δ) or C fibers is a commonly asked question in basic pain research but a quick test was lacking so far.

Methodology/principal findings: Of 77 verbal descriptors of pain sensations, "pricking", "dull" and "pressing" distinguished best (95% cases correctly) between A(δ) fiber mediated (punctate pressure produced by means of von Frey hairs) and C fiber mediated (blunt pressure) pain, applied to healthy volunteers in experiment 1. The sensation was assigned to A(δ) fibers when "pricking" but neither "dull" nor "pressing" were chosen, and to C fibers when the sum of the selections of "dull" or "pressing" was greater than that of the selection of "pricking". In experiment 2, with an independent cohort, the three-descriptor questionnaire achieved sensitivity and specificity above 0.95 for distinguishing fiber preferential non-mechanical induced pain (laser heat, exciting A(δ) fibers, and 5-Hz electric stimulation, exciting C fibers).

Conclusion: A three-item verbal rating test using the words "pricking", "dull", and "pressing" may provide sufficient information to characterize a pain sensation evoked by a physical stimulus as transmitted via A(δ) or via C fibers. It meets the criteria of a screening test by being easy to administer, taking little time, being comfortable in handling, and inexpensive while providing high specificity for relevant information.

Figure 1. Choices of descriptors of the pain stimuli, summed across 20 subjects (A_δ selectivity more to the left, C fiber selectivity right).

The colored bars indicate the three discriminators found to provide a questionnaire that distinguishes between A_δ and C fiber mediated pain (blue = “pricking”, green = “pressing”, red = “dull”, as specified in Figure 2).

Figure 2. Cumulative presentation of the selections of the three discriminators found to provide a questionnaire that distinguishes between A_δ and C fiber mediated pain.

Left: presentation separately for the four pain models and standardized at 100% of the ratings for each model. Right: presentation of the selections of the three discriminators, pooled for predominately A_δ fiber mediated pain sensations evoked with von Frey hair puntuate pressure stimuli or with laser heat stimuli and C fiber mediated pain sensations evoked with blunt pressure stimuli or with 5-Hz electrical stimuli.

Figure 3. Odds ratios.

Odds ratios, calculated as (A · D)/(B · C), where A is the number of selections of the descriptor for C fiber pain, B the total number of presentations of C- fiber pain minus A, C the number of selection of the descriptor for A_δ fiber pain, and D the total number of presentations of A_δ pain minus C, and 95% confidence intervals, calculated as odds ratio±1.96 · (1/A+1/B+1/C+1/D)^0.5, of the selections of the descriptors for C fiber mediated pain (pooled ratings of blunt mechanical pressure and 5-Hz electrical stimuli) and the number of selections of the descriptors for A_δ mediated pain (pooled ratings of punctate mechanical pressure and laser heat), sorted from top to bottom for decreasing selectivity for C fibers and increasing selectivity for A_δ fibers. The descriptors used in the questionnaire test (Figure 2) are marked in bold letters and thicker lines. Odds ratios and the corresponding p-values resulting from χ² statistics are indicated at the right of the descriptors. Please note that the 10 descriptors that were never used are excluded and therefore, the total number of displayed descriptors is 67.