It's taken an army of mice (and a group of clever Canadian researchers) to crack open an old sexual chestnut and get at the meat inside: For women, "Not tonight dear, I have a headache" is not a passive-aggressive rebuff to a mate's sexual invitation (not always, at least). It's a biological phenomenon with deep evolutionary roots.
Even for females who've never watched a 1950s movie or been schooled in the art of sexual gamesmanship, bodily pain puts a serious damper on sexual desire, new research has revealed.
And pain reduction can help restore libido squelched by physical discomfort (which suggests that fetching an analgesic and a glass of water might be a better strategy than sulking or wheedling).
In the new study, the libido-busting effect of pain was not seen in male mice, who sought to mate with females whether or not the males (or their potential female partners) were in pain.
Pain made a female mouse significantly less receptive to mating irrespective of where the hurt was: in the cheek, tail, hind legs or genitals.
For males, even a pain in the penis did not dampen the urge to have sex.
Over aeons and across species, that gender-specific response to pain has likely served to reduce reproduction under circumstances that are less-than-ideal for a potential offspring's survival.
A mother in pain, after all, is a mother whose full attention and physical strength may not be available to nurture her babies and protect them from predators.
Males were less likely to be tending a brood and more likely to be off looking for another chance to spread their genetic material. So standing down for physical pain would have served no evolutionary purpose.
The study, published in the Journal of Neuroscience, gleaned these insights by gauging the responses of sexually compatible pairs of mice to injections of agents that are known to induce inflammation in rodents - the food additive carrageenan and zymosan.
In some pairs, the female got the hurt-shot; in other pairs, it was the male. To rule out the possibility that mating was disrupted by specific discomforts - a hurting rear paw or a pain in the genitals, for instance - the researchers injected the pain-inducing shots in a number of different bodily sites.
They chemically ensured that the female mice would be sexually appealing to male mice.
And then, they left the pairs of mice in a cage that would let the smaller female mouse stay and mate with the male or withdraw to an adjoining room to be by herself.
Once they established that females in pain were far more likely to mate than those without pain, the researchers set about exploring what, if anything, helped.
To some female mice, they administered the analgesic pregabalin, a drug for chronic nerve pain better known by its commercial name, Lyrica.
To others, they administered "pro-sexual" agents - apomorphine and melanotan-2 - known to rev up sexual behaviour in rodents (although not, reliably, in human females).
The Lyrica was no aphrodisiac. It didn't promote an increase in sexual activity among female mice that were not in pain. But among those who were, it not only killed the pain, it also reversed the libido-killing effect of that pain.
The two rodent aphrodisiacs also made females in pain more receptive to males, leading researchers to suggest that, for those looking to develop and test an effective "pink Viagra," a good test of effectiveness might be how well it restores libido in women with chronic pain.