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and aim Pain sensitivity has been linked to the melanocortin-1 receptor (MC1R) gene. A mutation in MC1R can result in pale skin and red hair in humans and may modulate pain responses in general. Human studies have shown that women with non-functional MC1R's were sensitive to experimental induced cold and heat pain. A study demonstrated that females with red hair required higher dose of anesthesia than females with dark hair to experience analgesia to electrical stimulation. Moreover, women expressing non-functional MC1Rs display greater analgesia from opioid analgesia. If redheads in general respond differently to pain and analgesics, this is of clinical importance. The aim of this study was therefore to investigate pain sensitivity and experimentally induced sensitisation in red haired females. Method Twenty healthy females with pale skin and red hair (mean age 32 years, range 20-55) and 20 healthy females with blond/dark hair (mean age 31 years, range 20-51) participated in this study. The pain tolerance thresholds to heat and pressure stimulation were determined. Hyperalgesia was induced experimentally by applying 0.075% topical capsaicin cream for 30 min. The secondary pin-prick hyperalgesic area was estimated with a calibrated filament (von Frey hair, 15 g) and the area of allodynia by a soft brush. This was done 0, 30, 60, and 90 min after cream removal. Results Neither heat nor pressure pain tolerance thresholds were changed in the two groups. The secondary pin-prick hyperalgesic areas were significantly smaller for red haired females than blond/dark haired females (P = 0.014). There were no significant differences in the allodynic areas. Discussion As the secondary hyperalgesic response evoked by topical capsaicin is a central phenomenon, the observed smaller pin-prick hyperalgesic area in the red haired females could indicate a central role of MCRs in development or maintenance of hyperalgesia. Central involvement of MC1Rs or dysfunction of peripheral MC1Rs activating central MC4Rs has been suggested to influence pain sensitivity. The difference observed between red haired and non-red haired females may have implications for pain management regimens as compounds interacting with sensitisation such as NMDA-antagonists or alpha-2-delta-ligands may exert different types of action in people with MC1R mutation. Conclusion The present study showed that red haired females were less sensitive to topical capsaicin induced pin-prick hyperalgesia compared with blond/dark haired females. Implications The smaller hyperalgesic area in redheads could be a manifestation of central anti-hyperalgesic involvement of MCRs and could have an influence on the treatment of pain as well as in studies investigating anti-hyperalgesic drugs.

Pain sensitivity and experimentally induced sensitisation in red haired females