Why do redheads experience more pain?

You have just administered a full inferior alveolar nerve block. You wait the standard five to 10 minutes, confirm soft tissue anesthesia, and pick up your instrument. The patient flinches. You reinject. You wait again. The patient winces again. You and the patient become frustrated. Sound familiar? If that patient had red hair, this scenario is not a failure of technique; it is a failure to account for pharmacogenomics.

Redheads represent fewer than 2% of the global population, yet they are disproportionately represented among patients who require supplemental anesthesia, report higher postoperative pain, and—according to published data—are more than twice as likely to avoid dental care altogether.¹ The question is not whether the redheaded patient experiences pain differently. The question is: does your clinical protocol account for it?

The answer, for most practitioners, is no. Understanding the mechanism behind this phenomenon and its specific dental implications is not merely academic; it is needed for informed, patient-centered care.

The MC1R gene: Where pigment meets pain

Red hair is not simply a cosmetic trait. It is the phenotypic expression of a functional variant in the melanocortin 1 receptor (MC1R) gene, located on chromosome 16. In individuals with intact MC1R function, melanocytes predominantly produce eumelanin or the dark pigment responsible for brown and black hair. A loss-of-function variant in MC1R shifts melanocyte output toward pheomelanin, the red-gold pigment responsible for red hair, fair skin, and freckling.

What is less commonly appreciated in clinical practice is that MC1R receptors are not confined to the surface of melanocytes. They are also expressed in brain glial cells and neurons of the ventral periaqueductal gray, neural elements central to the modulation of pain pathways.² In other words, the gene that gives patients their copper-colored hair is the same gene that governs how their nervous system processes nociceptive pain signals.

In red-haired mice carrying the MC1R variant, loss of receptor function decreases proopiomelanocortin (POMC). This is a precursor hormone which is cleaved into alpha-melanocyte-stimulating hormone (α-MSH), which activates the pain-sensitizing MC4R receptor, and beta-endorphin, which activates the pain-inhibiting OPRM1 opioid receptor.

The reduction in α-MSH caused by MC1R loss of function disproportionately tips the balance toward OPRM1-mediated opioid signaling. The result is an elevated basal nociceptive threshold in the red-haired background.³

Redheads are not simply “pain sensitive.” Their pain pharmacology and processing is different, context-dependent, and modality-specific. Simply put, redheads process pain differently.

Pain modality matters: The redhead is not a uniform phenotype

The MC1R variant does not produce uniform hyperalgesia. It produces a divergent pain profile—along these four main mechanisms:

• Thermal pain (heat/cold): Redheads demonstrate significantly increased sensitivity. Individuals with red hair have heightened responses to both heat and cold stimuli compared to dark-haired counterparts. This has direct implications for dental procedures involving thermal pulp testing, irrigation temperature, and intraoral soft tissue laser manipulation.
• Electrical and prick pain: Studies indicate a higher pain tolerance to electrical stimulation and mechanical stimuli such as pinprick sensation. The elevated opioid appears to confer a degree of protection from these stimulus types.
• Local anesthetic efficacy: Redheads demonstrate significantly reduced analgesic response to subcutaneously administered local anesthetics, including lidocaine, compared to dark-haired individuals, even when controlling for injection technique and dosage.
• Opioid responsiveness: In contrast to their resistance to local anesthetics, redheads show increased sensitivity to opioid analgesics. Redheaded patients often achieve effective postoperative analgesia at lower opioid doses.⁴

The NIH has characterized this succinctly: redheads may require higher doses of some pain-killing medications like NSAIDS, yet respond more effectively to opioids, requiring lower doses. These are not contradictory findings. They are two pharmacological pathways governed by the same upstream genetic variant.

Dentistry and the redhead: A documented problem

The dental chair is where the MC1R phenotype becomes most clinically consequential. Three specific areas demand attention: local anesthetic resistance, dental anxiety and avoidance behavior, and general anesthetic requirements.

No. 1: Local anesthetic resistance

In one study that enrolled 30 red-haired and 30 dark-haired women, pain sensitivity was evaluated using standardized electrical and thermal stimulation devices, as well as the analgesic efficacy of both topical and subcutaneous lidocaine.

The results produced one finding that practitioners rarely discuss: topical liposomal lidocaine (4%) showed no statistically significant difference between the two groups. This is an important clinical nuance. The resistance is not to lidocaine as a molecule; it is specifically to subcutaneous lidocaine, which is precisely the route of delivery used for dental nerve blocks and infiltration anesthesia.

When subcutaneous local lidocaine was administered, pain tolerance thresholds in the redheaded group were measured 50% less than those of dark-haired subjects. Across all three nerve fiber frequencies in this study, subcutaneous lidocaine was significantly less effective in the red-haired group.²

The authors concluded that redheads may ultimately achieve adequate analgesia, but they require more anesthetic to get there. The practitioner who administers a standard dose and moves forward has not “delivered” anesthesia to the redheaded patient. They have delivered an insufficient dose and are operating on a patient who may still be partially sensate.

On the thermal side of the same study, redheads were twice as sensitive to cold pain perception and cold pain tolerance and demonstrated a lower threshold for heat pain tolerance. Electrical stimulation thresholds, by contrast, showed no significant group differences at baseline.

Practical implications for the redheaded patient undergoing periodontal or implant surgery: increase local anesthetic volume and concentration where clinically appropriate, allow extended waiting periods before probing for anesthesia, employ supplemental intraligamentary (PDL) or intraosseous injection when blocks appear incomplete, and discuss expectations with the patient preoperatively. The patient who flinches during a technically perfect block is not being dramatic. They are telling you something pharmacogenomically true.

No. 2: Dental anxiety and avoidance

A study published in the Journal of the American Dental Association, enrolled 144 participants—67 natural redheads and 77 dark-haired controls—and assessed dental anxiety, fear of dental pain, and avoidance behavior.¹ Participants with MC1R gene variants reported significantly more dental care-related anxiety and fear of dental pain than those without variants, and were more than twice as likely to avoid dental care entirely, even after controlling for general trait anxiety and sex.

Redheads who have experienced inadequate anesthesia in prior appointments, which the literature confirms is common, develop a conditioned fear response based on documented, repeated experience of procedural pain. This cycle has real consequences for periodontal disease prevalence and implant treatment access in this patient population as these patients are most likely to avoid dental appointments.

Another article identified red hair as one of five validated predictors of postoperative dental pain, noting that redheads are more likely to experience pain after dental procedures and demonstrate a diminished response to local anesthesia, and that mutations of the MC1R receptor modulate pain sensitivity.

No. 3: General anesthesia requirements

For redheaded patients requiring IV sedation or general anesthesia for oral surgical procedures, the data parallel the local anesthetic findings. Studies have demonstrated that red-haired women required approximately 19%–20% more volatile anesthetic (desflurane) than dark-haired women to prevent movement in response to supramaximal electrical stimulation. Animal models confirm the finding: MC1R knockout mice required greater minimum alveolar concentration (MAC) to achieve equivalent anesthetic depth compared to wild-type controls.

Importantly, propofol pharmacodynamics do not appear to be affected by MC1R status, suggesting the resistance is specific to volatile anesthetic agents rather than IV sedatives broadly. This distinction should inform sedation planning for the oral surgical and periodontal patient.

Postoperative pain management: Recalibrating the protocol

The postoperative period presents a clinical paradox for the redheaded patient. They are more likely to experience elevated postoperative pain, consistent with data showing that incomplete intraoperative analgesia predicts worse postoperative pain scores, yet they are also more responsive to opioid analgesics, achieving effective pain relief at lower doses.⁵

Three practical implications follow:

• Do not underprescribe postoperative analgesia based on the assumption that the patient’s elevated basal pain threshold will protect them. Thermal sensitivity and local anesthetic failure predict real postoperative discomfort.
• Do not overprescribe opioids based on the assumption that more is better. The heightened OPRM1 sensitivity in redheaded patients means standard or lower doses may achieve adequate analgesia while reducing adverse effect risk.
• Maximize nonopioid perioperative strategies, including preprocedural NSAIDs, corticosteroid prophylaxis where appropriate, and long-acting local anesthetics such as bupivacaine or liposomal bupivacaine for postsurgical nerve blockade.

The emerging literature on MC1R and pain is moving toward personalized, pharmacogenomically informed protocols. In the near term, the practitioner who identifies the redheaded patient preoperatively and adjusts their anesthetic and analgesic approach accordingly is already practicing a more precise version of dentistry than the practitioner who does not.

Conclusion

The MC1R gene variant that produces the red hair phenotype operates simultaneously across the melanocyte and the nociceptive system, yielding a patient who is more resistant to subcutaneously administered local anesthetics, more sensitive to thermal pain, more prone to dental anxiety and avoidance, and paradoxically more responsive to opioid analgesics.

Editor’s note: This article originally appeared in Perio-Implant Advisory, a chairside resource for dentists and hygienists that focuses on periodontal- and implant-related issues. Read more articles and subscribe to the newsletter.

References

1. 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
2. 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
3. Robinson KC, Kemény LV, Fell GL, et al. Reduced MC4R signaling alters nociceptive thresholds associated with red hair. Sci Adv. 2024;7(14):eabd1310. doi:10.1126/sciadv.abd1310
4. Bryant E. Study finds link between red hair and pain threshold. NIH National Institutes of Health. April 20, 2021. https://www.nih.gov/news-events/nih-research-matters/study-finds-link-between-red-hair-pain-threshold
5. Froum S. Dental pain: can we predict who has a higher risk prior to treatment? Perio-Implant Advisory. February 7, 2022. https://www.perioimplantadvisory.com/periodontics/oral-medicine-anesthetics-and-oral-systemic-connection/article/16412197/dental-pain-predicting-postoperative-pain-prior-to-the-procedure