The Reason Why Testosterone Increases Pain Threshold And Reduces Fear (Part 2)
The Reason Why Testosterone Increases Pain Threshold And Reduces Fear (Part 2)

The Reason Why Testosterone Increases Pain Threshold And Reduces Fear (Part 2)

Testosterone Increases Pain Threshold

For several years, evidence has accumulated indicating that T regulates pain perception in both males and females in humans, monkeys, rodents, and birds.  The use of pain studies is unethical in humans so a majority of the research is performed on rats.  There are several tests used in animals to determine pain threshold in rats. See Figure 1 for an explanation of the tests.  When you give animals a little T, they become like Marv from Sin City and say, “That’s all you got bitch….”  For example, when birds were given supplemental T, they left there feet in the hot water longer than control animals (6).  When you castrate a male rat- (this is scientific terminology for “cutting his balls off.”) he has pain threshold similar to that of female rats, but when you give him T his pain threshold increases (9, 18).  In addition, if you give female rats T, they increase pain threshold levels similar to those of male rats.  T reduces pain thru many biochemical pathways, but a main contributing hormone is that T has an effect on increasing serotonin levels- “that feel good hormone” which may explain the extreme feelings of pleasure and euphoria during steroid use.

It has documented that after intense stress, whether it is a physical or psychological stressor, T levels tend to decline in the plasma.  If the stressor is great enough, also it’s reduced in the brain and spinal cord.   When rats were administered a drug called formalin into their front paws (i.e. formalin causes immediate pain in rodents) they had a depletion of T in their brain and spinal cord that persisted 24 hrs after injection.  In contrast, the rats that were treated with good ole juice, there was a decrease in serum T levels but there was no elimination of T from the brain and spinal cord (12).   The depletion in brain T levels maybe a contributing factor of depression that can occur after steroid withdrawal.  Another study cut the “nads” off of rats and injected them with formalin, the rats showed significant signs of pain, however when rats were given T, they showed signs of pain but reactive response to pain was dampened (13).  Ok, one more rat torture study! When studying chronic pain in rats there is a surgery called a sciatic nerve resection (SNR)   The sciatic nerve is the largest single nerve in the body; it runs from each side of the lower spine through the rear and back of the thigh, and all the way down to foot, connecting the spinal cord with the leg and foot muscles.  A SNR involves cutting the sciatic nerve which leaves the rat with a limp leg.  The surgery pisses rats off and causes extreme pain, so they become like Hannibal Lecter and bite and scratch the self-mutilated dead leg, the phenomenon is called autotomy.  Rats that are neutered and have SNR chow down on their leg like a bodybuilder hitting the buffet after a heavy day of squats, however, when you give the rats some “sauce” there is a delay in the autotomy for about 4 weeks (14).

Mechanisms of Testosterone Mediated Pain Threshold: Clear as Mud. 

As you know, T can be converted into DHT by the enzyme 5α reductase, and DHT can be further converted into 3 α-androstanediol (3 α -diol).  Furthermore, T can be converted to estrogen as well.  So is it T causing these effects on pain threshold or a testosterone derivative? (i.e. estrogen, DHT, or 3 α -diol)  Edinger and Frye found that all three (i.e. T, DHT, and 3 α -diol) metabolites caused rats less anxiety and pain in a behavioral series of open tests (10).  It’s interesting that female rats also demonstrate reduced pain threshold when their ovaries are removed to make them estrogen deficient, yet replacement of estrogen causes their pain threshold to be increased (7).  It also of interest that when women are subjected to pain studies, they appear to have a higher pain threshold toward the beginning of their menstrual cycle when estrogen is the highest, pain threshold decreases during the later month when estrogen is lower (15).  Both T and estrogen are producing pain-suppressing effects, but the combination of both may provide a superior effect than either one by itself.  One study found that both T and estrogen were effective at increasing serotonin levels in the brain.  In the male rats, after 3 days of T administration there was a 50% elevation in firing rate of serotonin neurons (26).  Another study reported that if you castrate animals and give them T with an aromatase inhibitor the pain relieving effects are diminished (  ).  This increase in serotonin in the brain may explain why men and women have feelings of euphoria while on steroids.

When looking at the mechanisms at which T reduces pain, it stimulates a host of inhibitory neurotransmitters that tell the brain to stop firing painful impulses.  T has been shown to activate serotonin, GABA, and enkephalins, all of which are pain suppressing (4).  One scientist decided to get to the bottom of the whole T or its metabolites debate and injected normal and neutered male and female rats with either T or estrogen.  Interesting, the neutered male rats increased their pain threshold after T administration but not estrogen administration, whereas the in female rats, both estrogen and T increased pain threshold (16).   The male rats that were left with intact testes did not experience any additional pain threshold increases from additional T supplementation.  Thus T was far more effective than estrogen in reinstating both forms of analgesia in neutered rats, while generally failing to alter pain threshold in intact males. It should be of interest that the area of the brain that contains pain information called the periaqueductal gray has both androgen and estrogen receptors (10).  It could be speculated that since T can convert to estrogen the activation of both T and estrogen receptors has a synergistic effect compared to estrogen alone.

T is currently being researched as a pharmacological means to reducing pain in patients with rheumatoid arthritis. Rheumatoid arthritis is the result of an overactive immune system that causes inflammation of the joints, however T reduces pain is and also suppresses the immune system.  It has been documented that T may reduce the severity of pain by inhibiting inflammatory components (23).  Furthermore, in neutered rats that are administered a bacterial drug that causes inflammation similar to rheumatoid arthritis; the effects of the drug are completely reversed by T administration (24).  This may be the reason why men whom have rheumatoid arthritis may find substantial reductions in pain and inflammation after T administration (25).

Aging and Pain Threshold

Aging is associated with a host of aches, pains, and diseases that can make life miserable for us men.  We all make fun of the old geezer in movies who is screaming about his prostate is the size of a watermelon.  Well the joke is on us, every man if he lives long enough will eventually develop prostate cancer…it’s not a matter of if you develop it, it’s when you develop it.  Prostate cancer is a slow growing disease; so many doctors overlook it if the patient is too old.  As prostate cancer is the second leading cause of death among men, a common treatment for those men unlucky enough to develop prostate cancer is androgen deprivation therapy.   Androgen deprivation therapy involves drugs that suppress T levels, in fact androgen deprivation therapy is a potent form of testosterone therapy it is similar to orchiectomy (another work for not having testicles.)   When men are forced to take androgen deprivation therapy they experience physical symptoms just like post-menopausal women, they develop hot flashes and experience a loss of libido (19).  T is needed for general health and normal physical functioning; one of the primary symptoms of men on androgen deprivation therapy is a low quality of life.     It should be of no surprise that in addition to a poor quality of life, men’s pain threshold decreases as we age.  It could be due to a number neurochemical alteration but lowered T levels could be an additional mechanism.  For example, older male rats have reduced pain suppressing opiate receptors in the area of the brain controlling pain compared which younger rats (17).    Additionally, when older rats are subjected to pain studies they need more morphine to produce pain relief than younger rats.

Daredevil: The Man without Fear on Juice?

In addition to reducing pain, T has been shown to also reduce the fear response in males.  That should be of no surprise to men, that’s why your girlfriend jumps in your lap at scary movies.  In all mammals, females in general tend to be more fearful.  If you take castrate male rats, they elicit fear evoking responses similar to females (29).  That’s why we have to keep our T levels in the optimal range; nothing is more pathetic than a man jumping into his girlfriends lap during SAW!! So before puberty, if scientists expose rats to an open maze test (an open maze test is a measure of fear responses. The bolder an animal is, the further the animal will explore the maze) males and females have similar responses but after puberty when hormones start surging the males become bolder and explore while the females become timid (28).  So here is an interesting study demonstrating how T can decrease one’s level of fear.  Scientists took female cows and divided them into a control group or a T injected group and exposed them to a series of fear experiments (i.e. maze exploration, feeding in an unfamiliar area, surprise effect, ect.)  The female cattle exposed to T consistently demonstrated less signs of fear in all the experiments.  In addition, the cattle on T had lower heart rates and demonstrated lower cortisol responses throughout the entire study.  Another interesting side note, when the cattle did have the crap scared out of them they had a lower cortisol response than the control group (27).  Human studies are few but a single dosage of T elicits reductions in fear in women just like animals.  In one study, women were either given a placebo or were administered a single dosage of T.  Okay, this is where psychologists get a little weird.  They took women to a dimly lit cabin, with a device that administered shocks; they also wore an EMG for measuring brain activity.  The women were told they were going to be administered three shocks in increasing amplitude.  Based on EMG activity, the women that were administered T had a reduction in fear compared to the women who received nothing (34).

Conclusion

So how what is the evolutionary mechanism for testosterone leading to higher pain threshold?  In the wild, males have to compete with each other over females.  If higher T levels leads to more intensive fighting in males, it simultaneously increases the likelihood that the male will get injured and thus cause pain.  The function of pain is to alert the organism of injuries and should be avoided in the future. Nevertheless the perception of pain during aggressive attacks might decrease aggressive behavior and lead to that animal not passing on his genes.  It could be hypothesized that an additional role of T is to reduce pain threshold, as this would increase the willingness of an animal to fight with other animals and have successful reproduction.  It has been proposed that the decreased pain perception in conjunction with higher aggression and physical strength is the physiological basis for the “winner” effect in males.  So the million dollar question is, “Will taking supraphysiological dosages of T increase a person’s pain threshold above normal?  Human studies are lacking, but in rats it seems that T does decrease pain threshold but taking additional T won’t increase it further.  For example, Aloisi et al. (20) gave male and female rat’s supraphysiological dosages of T but only the females increased their pain threshold tolerance.  In human studies, a physiological dose of steroids may be helpful in treating painful conditions.  In one study, 16 male and 28 female patients experiencing moderately severe pain during episodes of sickle-cell disease were selected for a cross-over trial of low doses of steroids against saline solution. About 80% of the individuals on steroids’ had good responses and reductions in pain while the placebo group had no effect (21).  Another study reported that low-dose supplemental T treatment given to men with heart disease reduced chronic chest pain induced by exercise-exertion (22).  So keep on training hard, in addition to packing on some serious size you will have some additional benefits as a higher pain threshold and no fear!

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