Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads

Abstract

Background: Anesthetic requirement in redheads is exaggerated, suggesting that redheads may be especially sensitive to pain. Therefore, the authors tested the hypotheses that women with natural red hair are more sensitive to pain and that redheads are resistant to topical and subcutaneous lidocaine.

Methods: The authors evaluated pain sensitivity in red-haired (n = 30) or dark-haired (n = 30) women by determining the electrical current perception threshold, pain perception, and maximum pain tolerance with a Neurometer CPT/C (Neurotron, Inc., Baltimore, MD). They evaluated the analogous warm and cold temperature thresholds with the TSA-II Neurosensory Analyzer (Medoc Ltd., Minneapolis, MN). Volunteers were tested with both devices at baseline and with the Neurometer after 1-h exposure to 4% liposomal lidocaine and after subcutaneous injection of 1% lidocaine. Data are presented as medians (interquartile ranges).

Results: Current perception, pain perception, and pain tolerance thresholds were similar in the red-haired and dark-haired women at 2,000, 250, and 5 Hz. In contrast, redheads were more sensitive to cold pain perception (22.6 [15.1-26.1] vs. 12.6 [0-20] degrees C; P = 0.004), cold pain tolerance (6.0 [0-9.7] vs. 0.0 [0.0-2.0] degrees C; P = 0.001), and heat pain (46.3 [45.7-47.5] vs. 47.7 [46.6-48.7] degrees C; P = 0.009). Subcutaneous lidocaine was significantly less effective in redheads (e.g., pain tolerance threshold at 2,000-Hz stimulation in redheads was 11.0 [8.5-16.5] vs. > 20.0 (14.5 to > 20) mA in others; P = 0.005).

Conclusion: Red hair is the phenotype for mutations of the melanocortin-1 receptor. Results indicate that redheads are more sensitive to thermal pain and are resistant to the analgesic effects of subcutaneous lidocaine. Mutations of the melanocortin-1 receptor, or a consequence thereof, thus modulate pain sensitivity.

Fig. 1.

Pain Tolerance Thresholds to 2000-Hz, 250-Hz, or 5-Hz stimulation on the forearm of volunteers with dark hair (dark, solid lines) or red hair (pale, dashed lines). Three areas of the arm were tested: an untreated control area, an area treated with 4% liposomal lidocaine, and an area injected with 1 mL of 1% lidocaine. Data were plotted as Kaplan-Meier survival curves, and the curves were compared with Log-Rank tests. Y-axis represents the fraction of the study population still able to reach a particular threshold. The curves for the two groups were significantly different for all three frequencies on the area treated subcutaneously with lidocaine.