Friday, August 19, 2011

Redheads and Pain: A Recap

Hello My Redheaded Lovelies!

I just had a post published on How to Be a Redhead that recaps all of my posts on Redheads and Pain. I'm re-posting the more long winded version below in case you prefer EXCRUCIATING detail (no pun intended, it's genetic from my Dad). The next How to Be a Redhead post will be about Nutritional and Lifestyle Recommendations for Pain.

Enjoy!
Carolbetty

-----
I’ve been researching redheads and pain for a few years and have written about it on my blog Blessed with Red: The Redheads Guide to Thrive. It’s a very confusing and complicated topic, and every time I read over a study that I’ve read dozens of times before, I always seem to understand something new.

I also learn from my readers – thank you!

I’m going to try to synthesize and summarize everything I’ve learned so far about redheads and pain in the following.

To recap my last post The Red Hair Factory, you may recall us previously discussing a hormone called alpha melanocyte-stimulating hormone (α-MSH). It is the message sent out by the brain (the CEO) and skin melanocyte cells (pigment factories) in response to exposure to the sun (environmental demand). Under normal conditions, α-MSH binds to the melanocortin 1 receptor (MCIR) on skin melanocyte cells and relays the message over the MC1R intercom for the melanosomes (assembly lines) to begin the skin tanning process; however, for us redheads, the MC1R intercom doesn’t function or its function is significantly reduced, the message doesn’t get through, and this is why we burn.

BUT the hormone messenger α-MSH is a multi-tasking fiend!

It doesn't only play a role in pigment and hair color production. It also binds with other receptors to modulate pain. In the central nervous system, different hormones work together to create balance in the perception of pain: α-MSH increases sensitivity to pain via other melanocortin receptors, MC3R and MC4R, while opiates decrease sensitivity to pain via opioid receptors.

Now, unlike the MC1R gene, the MC3R and MC4R genes are not affected at all by the red hair mutation and more than likely work just fine in most redheads. It is postulated that because of the malfunctioning MC1R gene in redheads that there is a negative feedback loop to the pituitary in the brain which causes an overproduction of α-MSH in the central nervous system. The excess α-MSH acts on MC3R and MC4R which in essence overpowers the opiate hormones and receptors. In summary, the theory is that there is a hormonal imbalance in redheads that causes an increased sensitivity to pain.

Redheads and Pain Studies: A History

But how do you test to find out if redheads have more α-MSH pumping in their veins than non-redheads? Apparently, testing α-MSH is expensive and difficult due to circadian rhythms. As far as I know it has never been done….yet.

And what exactly does “sensitivity” to pain mean? How do you isolate and measure pain in an experiment? There are several studies on redheads and pain that I reference below. Some of them refer to the following different thresholds for pain:

-Perception or Sensory: When one initially senses or perceives a stimulus such as heat, cold, or an electrical current (I feel it, but no pain….yet).

-Pain Perception: This is the first point where a stimulus actually begins to cause pain (OK this is starting to hurt……).

-Pain Tolerance: This is the maximum level of pain that a person can tolerate from a stimulus (I can’t take it anymore!!!!! Stop now!!!!).

Study 1:
Pain Sensitivity Differences Between the Sexes and Between Redheads and Non-Redheads (2003)


In 2003, a study was conducted by Jeffrey Mogil and his colleagues that concluded there are significant differences in pain modulation between men and women. The study also concluded that there may be a genetic factor in pain modulation because the narcotic drug pentazocine had a greater analgesic (or pain reducing effect) on the female redhead participants than on other participants.

But how and why? It was postulated that pentazocine not only stimulates opioid receptors in the central nervous system which reduce pain, but that it may also inhibit the pain increasing effect of α-MSH by blocking it from binding with MC3R and MC4R, receptors that increase pain.

One of my readers wondered whether differences in drug metabolism could possibly account for different responses to drugs (as opposed to differences in pain perception or tolerance). The idea is that some people may metabolize certain drugs faster than others, and therefore will require more of it or less of it than others. That is a great question that could apply to this study and to the ones referenced below, and I do not have an answer for it. Does anybody know?

It is also important to note that the media can often misinterpret information. At an August 2005 press briefing, Professor Ian Jackson of the Medical Research Council’s Human Genetics Unit in Edinburgh was misquoted in a press release that stated Mogil’s study demonstrated that redheads have a “higher pain tolerance.” The press release failed to reference the fact the female redhead participants who demonstrated this effect were completely drugged up on pentazocine!

More simply put, if you are a hot female redhead in desperate need of a narcotic, you might get a better fix on penatazocine than any other type of drug. I'm joking, of course! I do not advocate drug use, as the adverse affects of pentazocine are similar to that of morphine. Also, as with many other narcotics, pentazocine is addictive.

Study 2:
Redheads Require More Anesthesia in Surgery (2004)


For many years, anesthesiologists have anecdotally observed that redheads required more anesthesia in surgery. In 2004, Dr. Edwin Liem and his colleagues at the University of Louisville, Kentucky, decided to put this theory to the test. They conducted controlled scientific experiments that confirmed that female redheads require 19 percent more anesthesia in surgery. Because of Mogil’s study above, Dr. Liem decided to only include female participants in his experiment. The desflurane anesthesia was inhaled by participants and they were monitored for gross involuntary movement of the legs and arms after being stimulated by electrical current. The amount of desflurane was adjusted according to their reaction. Overall, female redheads required 19% more anesthesia than female non-redheads.

Please note that this effect may not be the case for all female redheads so it is important that you discuss these findings with your physician if you ever have the need for a surgical procedure.

Study 3:
Redheads Have Increased Sensitivity to Thermal Pain and a Reduced Effectiveness of Injected Lidocaine


After his first study above, Dr. Liem was flooded with responses from redheads stating that their anesthesia had failed them or that they required unusually large does of local anesthetics to modulate their pain. In 2005, he and his colleagues decided to design another experiment to test whether redheads were more sensitive to pain than non-redheads and whether redheads were resistant to the local anesthetic lidocaine, either when applied topically or when injected. Again, to control for the differences of pain modulation between the sexes, he only included female participants in the study.

His results were as follows:

-Using electrical stimulation, there was no statistical difference between redheads and non-redheads regarding initial perception of the electrical current, pain perception, or pain tolerance.

-Redheads were more sensitive to cold pain than non-redheads, both in terms of cold pain perception and cold pain tolerance.

-Redheads were more sensitive to heat pain tolerance; but heat pain perception was not statistically different between the two groups.

-The local anesthetic lidocaine was less effective in redheads than non-redheads when it was injected (subcutaneous lidocaine); but there was no statistical difference between the two groups when it was applied topically (liposomal lidocaine).

Please note that this effect may not be the case for all female redheads so it is important that you discuss these findings with your physician or dentist if you ever have the need for a procedure that requires the use of lidocaine.

Study 4:
Redheads and Fear of Dental Pain, Anxiety Regarding Dental Care, and Avoidance of Dental Care (2009)


On August 6, 2009, an article appeared in the New York Times called The Pain of Being a Redhead by Tara Parker-Popeimes. It highlighted a new study which appeared in The Journal of the American Dental Association. This article brought the whole redhead and pain issue to the forefront again. Participants in the study completed surveys that measured “general and dental care–specific anxiety, fear of dental pain, and previous dental care avoidance.” The authors tested the participants’ blood samples to detect gene variants associated with natural red hair color. As expected, most redhead participants had the MC1R red hair variants (65 out of 67), but interestingly enough 20 out of 77 dark haired participants also had MC1R red hair variants – that is one-fourth! The conclusion was that participants with MC1R red hair variants, including redheads and non-redheads, reported significantly more dental care-related anxiety, fear of dental pain, and avoidance of dental care, even when the authors adjusted for general anxiety and sex.

It should be noted that this study is somewhat different than Dr. Liem’s studies as it did not attempt to measure pain itself. It used surveys to measure the participant’s anxiety about dental care and dental pain and compared it to genetic MC1R red hair variant results. While any anxiety about dental care is most likely due to painful past experiences, apparently anxiety and phobia about dental care in itself can also be a factor in increased sensitivity to dental pain.

Study 5? (well sort of):
Mythbusters: No Pain, No Gain


In Season 8 of Mythbusters, there was an episode entitled No Pain, No Gain that aired on April 20, 2010. Mythbusters is filmed in the San Francisco Bay Area where I live, and I could have totally participated in this episode if I had been paying better attention -- I’m so disappointed that I missed it! Jamie and Adam’s goal was to test three pain myths:

-Women Tolerate Pain Better than Men
-Swearing Increases Tolerance to Pain
-Redheads Have a Lower Pain Tolerance

First, they visited Stanford University to determine what pain testing methods they would use for their experiment:

1. Heat pain tolerance
2. Electrical pain tolerance
3. Capsaicin pain tolerance - the active ingredient in spicy hot chili peppers
4. Cold pain tolerance

They settled on testing cold pain tolerance by setting up a contraption that would measure the amount of time that a person could tolerate leaving their hand in ice water. They maintained the water as close to 1 degree centigrade as possible by adding salt and monitoring it with a thermometer. While they asked participants when they first started to perceive pain, their experiment results only focused on the amount of time until pain tolerance was achieved.

Myth: Women Tolerate Pain Better than Men
CONFIRMED!

On average, women could tolerate cold pain for 100.4 seconds, while men could only tolerate it 84.3 seconds. Apparently, women who had previously given natural childbirth without anesthetics were the ones to pull the average up. Hello! Of course!

Myth: Swearing Increases Tolerance to Pain
CONFIRMED!

On average, the five subjects could tolerate about 30% more cold pain when they swore than when they didn't swear (is this why I swear like a sailor?) However, since the same five subjects immersed their same hands during the non-swearing sessions as they did for the swearing sessions afterward, I wonder if the thermal nociceptors (pain sensory receptors) in their hands might have habituated and adapted naturally. When winter comes, we all have to habituate to it. The same temperature doesn't seem so cold the second or third time around, does it? Hmmmmm……pondering.

AND LAST BUT NOT LEAST......

Myth: Redheads Have a Lower Pain Tolerance
BUSTED! In fact, possibly the reverse???

On average, non-redheads tolerated 79.1 seconds of cold pain, while the redheads could tolerate 132.2 seconds of cold pain. Jamie was very proud that his redhead-kind are such bad-asses and so am I!

So the redhead myth being busted brings up some interesting questions as it contradicts what we read above in Dr. Liem’s experiments which indicated that redheads were more sensitive to cold pain perception and cold pain tolerance. The discrepancy between Dr. Liem’s experiments and Mythbusters’ experiment may be related to:

-Equipment and Methods: Dr. Liem’s equipment was likely more sophisticated. Also, in Dr. Liem’s first experiment, the participants were completely unconscious; whereas, in Mythbusters, the participants were conscious and it was almost a game or dare to beat the clock. Oh how us redheads love to live up to a challenge or a dare - that is when we are conscious of it!

-Type of Pain Tested: Dr. Liem tested electrical and thermal pain, while Mythbusters only tested thermal pain. Dr. Liem also measured pain perception and pain tolerance. While Mythbusters asked about pain perception, they only measured or published pain tolerance results.

-Sex: Dr. Liem limited his study to female redheads because of the differences in pain pathways between the sexes; whereas Mythbusters tested both male and female redheads. Could male redheads have pulled the average up?

I think one Mythbuster participant put it nicely when he said “I think it is a myth. I think we may feel it faster than other people, but I think we can stand it just as well, if not better.” Well said!