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


CONCLUSIONS
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.
Liem
Edwin B
EB
Outcomes Research Institute and Department of Anesthesiology and Perioperative Medicine, Louisville, Kentucky 40202, USA.
Joiner
Teresa V
TV
Tsueda
Kentaro
K
Sessler
Daniel I
DI
D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology*; D005260:Female; D006200:Hair Color / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology*; D009154:Mutation; D017288:Pain Threshold; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*
D000779:Anesthetics, Local; D044102:Receptor, Melanocortin, Type 1; D008012:Lidocaine
Pain. 1996 Nov;68(1):141-50
9252009
Annu Rev Genet. 2003;37:67-90
14616056
Muscle Nerve. 1997 Nov;20(11):1468-9
9342169
Anesth Analg. 2004 Jan;98(1):248-51, table of contents
14693629
Anesthesiology. 2004 Aug;101(2):544-6
15277941
Anesthesiology. 2000 Nov;93(5):1245-54; discussion 6A
11046213
Anesth Analg. 1998 Oct;87(4):885-9
9768788
Anesthesiology. 2004 Aug;101(2):279-83
15277908
Psychosom Med. 1997 Sep-Oct;59(5):512-20
9316184
Eur J Pharmacol. 1999 Jun 30;375(1-3):295-310
10443584
Hum Mol Genet. 2001 Oct 1;10(21):2397-402
11689486
Pain. 2001 May;92(1-2):229-34
11323144
Anesthesiology. 2003 Nov;99(5):1189-97
14576558
Biochem Mol Biol Int. 1996 Feb;38(1):73-80
8932521
Ann N Y Acad Sci. 2003 Jun;994:348-58
12851335
Cell Mol Life Sci. 2001 Mar;58(3):434-41
11315190
Neurosci Biobehav Rev. 2000 Jun;24(4):485-501
10817845
Anesthesiology. 1990 Apr;72(4):711-34
2157353
Nat Genet. 1995 Nov;11(3):328-30
7581459
Clin Pharmacol Ther. 2003 Jan;73(1):107-21
12545149
Pain Pract. 2001 Jan;1(1):53-60
17129284
Psychosom Med. 2002 Jul-Aug;64(4):621-6
12140352
Annu Rev Neurosci. 1984;7:309-38
6143527
Science. 1994 Sep 16;265(5179):1724-8
8085162
Biochem Biophys Res Commun. 1999 Jul 5;260(2):488-91
10403794
Anesthesiology. 2004 May;100(5):1263-70
15114226
Pain. 2002 Jun;97(3):195-201
12044616
QJM. 1999 Mar;92(3):125-31
10326071
J Neurosci. 2000 Nov 1;20(21):8131-7
11050135
Pain. 1994 Sep;58(3):403-11
7838590
Pain. 2002 May;97(1-2):163-9
12031789
Neuroreport. 1995 Nov 13;6(16):2193-6
8595200
Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4867-72
12663858
Anesthesiology. 1995 Jan;82(1):60-3
7832336
J Neurol Neurosurg Psychiatry. 1989 Apr;52(4):502-11
2738593
Anesth Analg. 2002 May;94(5):1259-62, table of contents
11973201