Redheads and anesthesia: Analyzing the differences in pain perception

For years, many have speculated that those with red hair, fair skin, or light-colored eyes may perceive pain differently, metabolize anesthetics more quickly, require larger doses of pain medication, experience higher levels of tactical sensitivity, or have increased anxiety associated with dental treatment. If these anecdotal observations have true scientific merit, can we or should we alter our delivery of care to improve the patient’s overall experience?

As the daughter of a redhead, I have personally experienced odd sensitivities through the years. Several of my six siblings have as well. Is there a genetic predisposition in my family? All of us have light eyes and are brunettes with red highlights, or are redheads. Based on DNA analysis, our heritage is predominately Irish, Scottish, English, and northwestern European, so we certainly qualify from a genetic perspective. In writing this article, I simply wanted to know more about this complicated subject from both a personal perspective and how to better understand and manage pain from a patient perspective.

The goal of this article was to find research support for what so many have observed through the years. Over the past 25 years, research studies involving human pigmentation have sought to determine if those with red hair perceive pain differently. Some research studies report differences for those with red hair as compared to dark-haired subjects, while other studies do not find a difference between redheads and the general population. The question is, does genetics play a role in how redheads perceive or experience pain? And if there is a difference, what can we do to help patients have a more pleasant dental experience?

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A recent mutation—understanding the genetics

The original ancestral coloring for humans was black hair and brown eyes.¹ Eumelanin is the default black-brown color that results in dark hair colors. Red hair is a variant of the melanocortin-1 receptor gene (MC1R). This functional change allows melanocytes to produce the red-yellow pheomelanin.² Scientists speculate this variant is a relatively recent occurrence, estimating red hair showed up in the genetic pool between 5,000 and 20,000 years ago.¹

The MC1R gene is recessive. Red hair is an indication that the person inherited the MC1R gene from both parents. If a person inherits the gene from only one parent, the gene for a more dominant, darker hair color will predominate. But the dark-haired person will still possess the same genetic characteristics and predispositions of redheads without exhibiting red hair.¹

Red hair is the most uncommon hair color in the world, and although redheads are found in all parts of the world, the highest concentrations are found in Britain, Scotland, and Ireland, with a large proportion in other northern European countries. The largest percentage of redheads is found in Scotland and represents 20% of the total population.¹ Both male and female redheads carry this genetic predisposition, but twice as many are women.¹

Hair color, skin tone, eye color

The color intensity of a person’s red hair is a measure of how much pigment is found in the hair shaft. Red hair is a general color classification that follows a wide spectrum ranging from very light to very dark. Descriptions of red hair run the gamut from strawberry blond on the light side to midrange tones that include actual carrot color, ginger hues, and vibrant auburn. The darkest red hues are deep mahogany.¹

Skin tone, freckles, and eye colors are closely associated with red hair. Typically, redheads have very fair skin, and often freckle easily. Due to low levels of melanin, redheads have a higher risk of sunburn and a significantly higher risk for developing melanoma.¹ The predominant eye color in the world is brown. While blue is not common, green is the rarest color.¹

Research gems—rough and polished

The research about redheads and pain perception is literally all over the map. The studies range from small clinical trials to large, randomized trials. Some contain objective findings, while others are based on subjective reports from redheaded subjects. Here are the key points gleaned from seven studies that focused on pain control issues. Like so many other research areas, it appears difficult to come to one solid conclusion.

• Female redheads were more sensitive to both heat and cold temperature variations and more resistant to the analgesic effects of both topical and subcutaneous lidocaine when compared to women with dark hair.³
• There was no difference between redheaded females and those with blond/dark hair with regard to pain from either heat or pressure after the application of a topical capsaicin cream, but redheaded females experienced a statistically significant smaller analgesic area.⁴
• Female redheads with bright red hair have increased inhaled anesthetic requirements compared to women with dark hair.⁵
• There was no significant difference in recovery times, pain scores, or quality of recovery for redheaded men or women receiving general anesthesia compared to those with black, brown, or blond hair.⁶
• Redheads did not differ from those with black or brown hair for recovery ratio time to eye-opening for general anesthesia.⁶
• Subjects who carry the MC1R red-hair variant have increased sensitivity to opioid analgesics, implying redheads may need lower doses of opioid pain medications.^7-9

There were even fewer studies about emotional factors that surround the perception of pain. Three studies dealt with dental anxiety, fear of pain, and avoiding dental care and revealed the following information. Two utilized the Corah Dental Anxiety Questionnaire to determine a subject’s anxiety level.¹⁰

• Participants with MC1R variants reported significantly higher levels of dental-care-related anxiety and fear of dental pain, and they were more than twice as likely to avoid dental care than those without the variants.¹¹
• Women with red hair and dark-haired women with MC1R variations reported significantly higher levels of dental anxiety than subjects who did not have MC1R gene variants, but there was no difference in the efficacy of the inferior alveolar nerve (IAN) block.¹²
• Eye color was not a predictor among white women for injection pain produced from oral lidocaine infiltration.¹³

What do we do now?

Even though the current literature does not reveal conclusive associations or connections, two things come to mind. First, people are simply not looking for excuses to come to the dental office, so when they do complain about how treatment feels or express reluctance, it is important to believe what they are saying. Second, it is entirely possible that the right studies have not been designed or conducted, or that researchers do not have the sufficient tools to quantify subtle discrepancies or differences between study subjects.

In the end, we need to listen to patients and treat them accordingly. People want to be free of pain and discomfort. Can we use the Corah Dental Anxiety Scale to help quantify their fears and then treatment plan accordingly? If they need anesthesia, then unless there is a medical contraindication, we should not be reluctant to provide that service.

Are you willing to ask someone their favorite flavor of ice cream? If they look shocked or shudder, and say they can’t tolerate the cold, you might consider a diagnosis of dentinal hypersensitivity. There are ample chairside desensitizers—such as arginine bicarbonate, NovaMin, fluoride varnish, chlorhexidine-thymol varnish, and hydroxyapatite preparations—that can provide comfort. Can you help your patients find an effective home remineralization protocol?

As prevention specialists, we also are in the position to advise those with fair skin to utilize sunblock preparations, have regular dermatologic examinations, and get unusual skin discrepancies evaluated immediately.

So rather than complain about those impossibly sensitive patients, let’s become their newest heroes. Listen to their experiences carefully and acknowledge their concerns. If they showed up for their appointment, they want dental care. We can be their best new hope of having a dental visit that is not full of angst for all involved. And if you are lucky, these patients may just turn out to be your favorite ones. 

Editor's note: This article appeared in the February 2022 print edition of RDH.

References

1. Frost P, Kleisner K, Flegr J. Health status by gender, hair color, and eye color: red-haired women are the most divergent. PLoS One. 2017;12(12):e0190238. doi:10.1371/journal.pone.0190238
2. Ha T, Rees JL. Red hair—a desirable mutation? J Cosmet Dermatol. 2002;1(2):62-65. doi:10.1046/j.1473-2165.2002.00036.x
3. Liem EB, Joiner TV, Tsueda K, Sessler DI. Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads. Anesthesiology. 2005;102(3):509-514. doi:10.1097/00000542-200503000-00006
4. Andresen T, Lunden D, Drewes AM, Arendt-Nielsen L. Pain sensitivity and experimentally induced sensitisation in red haired females. Scand J Pain. 2011;2(1):3-6. doi:10.1016/j.sjpain.2010.08.005
5. Liem EB, Lin CM, Suleman MI, et al. Anesthetic requirement is increased in redheads. Anesthesiology. 2004;101(2):279-283. doi:10.1097/00000542-200408000-00006
6. Myles PS, Buchanan FF, Bain CR. The effect of hair colour on anaesthetic requirements and recovery time after surgery. Anaesth Intensive Care. 2012;40(4):683-689. doi:10.1177/0310057X1204000415
7. Gradwohl SC, Aranake A, Abdallah AB, et al. Intraoperative awareness risk, anesthetic sensitivity, and anesthetic management for patients with natural red hair: a matched cohort study. Can J Anaesth. 2015;62(4):345-355. doi:10.1007/s12630-014-0305-8
8. Bryant E. Study finds link between red hair and pain threshold. National Institutes of Health. April 20, 2021. Accessed October 21, 2021. https://www.nih.gov/news-events/nih-research-matters/study-finds-link-between-red-hair-pain-threshold
9. Robinson KC, Kemény LV, Fell GL, et al. Reduced MC4R signaling alters nociceptive thresholds associated with red hair. Sci Adv. 2021;7(14):eabd1310. doi:10.1126/sciadv.abd1310
10. Binkley CJ, Beacham A, Neace W, Gregg RG, Liem EB, Sessler DI. Genetic variations associated with red hair color and fear of dental pain, anxiety regarding dental care and avoidance of dental care. J Am Dent Assoc. 2009;140(7):896-905. doi:10.14219/jada.archive.2009.0283
11. Droll B, Drum M, Nusstein J, Reader A, Beck M. Anesthetic efficacy of the inferior alveolar nerve block in red-haired women. J Endod. 2012;38(12):1564-1569. doi:10.1016/j.joen.2012.08.014
12. Clarke JH, Rustvold S. Norman Corah’s Dental Questionnaire. Corah’s Dental Anxiety Scale, Revised (DAS-R) - Dental Fear Central. Oregon Health Sciences University School of Dentistry. dentalfearcentral.org. 1993. Updated 1998. Accessed October 31, 2021. https://www.yumpu.com/en/document/read/51477465/corahs-dental-anxiety-scale-revised-das-r-dental-fear-central
13. Hyde J, Fowler S, Drum M, Reader A, Nusstein J, Beck M. Is eye color related to dental injection pain? A prospective, randomized, single-blind study. J Endod. 2018;44(5):734-737. doi:10.1016/j.joen.2018.01.009