Posts Tagged ‘ pain ’

Pain on the Brain

Men and women experience pain in different ways, a new study shows.

"Aaaagh, my KORs are killing me!"

The behavior of opioids – chemicals that suppress pain – differs between men’s and women’s bodies. This is because the three main types of opioid receptors in the brain and spinal cord interact very differently, depending on whether their owner is a man or a woman.

See, scientists have known for years that certain kinds of narcotic analgesics – a certain class of pain relieving drugs – are much more effective on women then on men. It was hard to understand why, though, because both men and women have mu (MOR), delta (DOR), and kappa (KOR) opiate receptors – the three main kinds – and these receptors work in essentially the same way in either gender.

But now, scientists have found that the spinal cords of female animals have almost five times as many kappa-mu heterodimers – complex molecules formed by combining KORs and MORs (commonly called KOR/MOR heterodimers) – as those of males. And not only that – the number of KOR/MOR heterodimers climbs four times higher when a woman’s body is pumping with estrogen and progesterone – two hormones crucial for regulating female body chemistry:

Spinal synthesis of estrogen is critical to the processes [of forming and using KOR/MOR heterodimers], and blockade of either estrogen receptor (ER) α-, β-, or G-protein-coupled ER1 or progesterone receptor (PR) substantially reduces KOR/MOR and eliminates mediation by KOR of spinal morphine antinociception.

In other words, a squirt of estrogen causes a sharp increase in the number of KOR and MOR receptors that get formed. This is a Big Deal, because some previous research suggests that in men, KORs and the chemicals that activate them may actually promote pain – and that their attachment to a MOR converts them to part of a pain-relieving system:

The research suggests that kappa-mu opioid receptor heterodimers could function as a molecular switch that shifts the action of kappa-opioid receptors and endogenous chemicals that act on them from pain-promoting to pain-alleviating.

To figure out what was going on with all these receptors, a team led by Alan Gintzler, a SUNY biochemist, first did some research to show that KOR and MOR opioid receptors join to form KOR/MOR heterodimers, the Journal of Neuroscience reports. This research was the first step toward understanding how these receptors interacted in the body’s pain system.

For this new study, though, the scientists injected estrogen and progesterone into the spinal cords of test animals, and determined that both chemicals were critical for the formation or KOR/MOR heterodimers, and these heterodimers’ activity in suppressing pain, as opposed to spreading it.

This discovery could go a long way toward explaining why certain pain-suppressant drugs that target MORs and KORs – such as pentazocine and nalbuphine – work well on women, but poorly on men: in spinal cords that lack the KOR/MOR heterodimer, the drugs might be activating the lonely little KORs, which – without their MOR friends, would help promote pain instead of relieving it. How rude of them.

Anyway, this new data looks like it’ll provide some encouraging ideas for future pain relief research:

The activation of the kappa-opioid receptor within the kappa-mu-opioid receptor complex could provide a mechanism for recruiting the pain-relieving functions of spinal kappa-opioid receptors without also activating their pain-promoting functions.

The researchers also point out that doctors should talk with women about where they are in their menstrual cycle before prescribing them medications like these – when estrogen and progesterone levels drop, pain relievers might turn into pain promoters.

So the moral of the story is, if you’re a guy (or a women who’s low on estrogen), some things really are gonna hurt me more than they hurt you.

Pain and Transcendence

New research has begun unveiling the neurophysiological correlates of the benefits brought on by techniques like meditation.

Meditation outfit: wash with bleach only.

This side of neurophysiology is exploring a few related avenues. One of these is the study published in the journal Zygon, which analyzes cerebral functional changes associated with religious sensations such as “out-of-body” experiences (OBEs).

As it turns out, people who meditate to reach an OBE feeling share some intriguing aspects of brain function with patients who have undergone certain types of cerebral traumas. In particular, the left temporal lobe shows more activity – while activity decreases in the right temporal and parietal lobes, which are known for maintaining self/other distinctions:

The ability to connect with things beyond the [perceived] self, such as transcendent experiences, seems to occur for people who minimize right parietal functioning. This can be attained through cultural practices, such as intense meditation or prayer or because of a brain injury that impairs the functioning of the right parietal lobe. Either way, our study suggests that ‘selflessness’ is a neuropsychological foundation of spiritual experiences.

While this research is intriguing, it mainly represents an expansion on existing ideas – the ability of monks and nuns to modulate activity in the temporoparietal areas (and a few others) through prefrontal focus has been studied in fMRI research for years.

The new concept here is that similar “transcendent” changes may be induced by brain injury or disease – which lends weight to the long-held hypothesis that many famous religious leaders may have suffered from temporal lobe epilepsy.1

Meanwhile, other meditation-related studies are exploring a different set of outcomes and benefits. This research focuses on the technique of mindfulness meditation, which dates back several millennia, but is gaining increasing attention in cutting-edge psychotherapy:

Mindfulness is a state of active, open attention on the present. When you’re mindful, you observe your thoughts and feelings from a distance, without judging them good or bad.

For one example, a group of researchers at Wake Forest University took a class of volunteers through a mindfulness training program. After only a few days of training, the patients reported an average 57% reduction – not in their pain itself – but in their perception of its “unpleasantness“:

A brain scanner showed how the intervention worked. Learning to meditate altered brain activity in the very same regions, such as the insula and anterior cingulate cortex, that are targeted by next-generation pain medications. It’s as if the subjects were administering their own painkillers.

It’s also worth noting that the insular cortex (called the “insula” above) plays a major role in interoception – that is, the perception of one’s own interior states and feelings – and in one’s senses of self and personal agency. This region lights up with activity during both mindfulness and transcendental meditation.

As Jonah Lehrer points out in his article, pain itself is perhaps better understood as a mental state than a purely physical one. Our central nervous systems have the ability to flood themselves with soothing and uplifting chemicals like opiates, endorphins, and dopamine – and as we saw above, at least some of these abilities can be brought under our conscious control.

But I think there’s an even deeper truth coming to light here: many people have a tendency to seek an escape from themselves when the going gets tough – through drugs (prescription or otherwise), through distractions like TV or the Internet, or just by keeping their thoughts anywhere in the past and future, as long as they stay out of the present.

Now, none of those things is necessarily wrong in and of itself. But there’s no escaping the fact that we all have to fall back into ourselves at some point, and many people seem to fight that point off as long as possible.

It is wrong to think that misfortunes come from the east or from the west; they originate within one’s own mind. Therefore, it is foolish to guard against misfortunes from the external world and leave the inner mind uncontrolled.

Wouldn’t it be nicer if it already felt comfortable in there? If the interior of your mind joyfully welcomed you home?

What I’m saying is, it seems that these sorts of meditation practices focus not on muting our interior perceptions, but on coming to peace with them.


1. The novel Lying Awake by Mark Salzman provides a gripping (and admirably even-handed) exploration of this debate from the perspective of an increasingly skeptical nun.


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