Tuesday, January 7, 2014

Endorphins and adrenaline - What science really says

The following is in response to this article

Which apparently was first posted here

Basically, the article claims that endorphins are released in discrete “loads” and that it takes the body about 10 min to replenish the load before it can release it again. Then it proposes a method in which the bottom is beaten hard at 10 min intervals to taken him or her to increasingly high endorphin “levels” until a state of stupefied bliss is achieved. It also makes some claims on how adrenaline release balances the endorphin release, and gives instructions on how to minimize adrenaline release and maximize endorphin release (which is supposed to be the goal).

There are two different issues with that article. The first one is that it claims that all this is based on science. The second issue is whether the states that it describes really can happen to a bottom during a SM scene. I will address here the first issue only. Concerning the second, there are abundant testimonies of altered states of consciousness occurring in bottoms during SM scenes. However, the physiological basis of those states of consciousness, their value and the best ways to achieve them are highly debatable.

PET images showing the areas of the brain where endorphins are released by pain: the prefrontal cortex (PFCTX), the anterior thalamus (A TH), the right anterior insula (INS), the hypothalamus (HYPO) and the amygdala (AMY). From Zubieta et al. (2001), Science 293: 311.
I am a neuroscientist who has been doing research on pain for several decades. In particular, I have been investigating endorphin release in rats. Based on my knowledge, I am going to argue that the article cited above has no scientific basis whatsoever. The issue of endorphin release is enormously complicated, so I am going to summarize here the points most relevant for this discussion.

The first thing I need to explain is the blood-brain barrier. Blood is highly toxic to neurons, so there is a barrier between the capillaries that supply the brain with oxygen and nutrients and the nervous tissue. Most substances cannot cross the blood brain barrier without the “permission” of the gate keepers cells that form it. In particular, endorphins, adrenaline and other hormones secreted into the blood do not cross the blood-brain barrier, which means that the amounts of endorphins and adrenaline in the blood have no effect whatsoever on the mind. These substances need to be released inside the brain to do anything to your mood or your consciousness.

Second, you may imagine the endorphins as forming a sort of soup that bathes the brain all over. That is completely wrong. Endorphins are released by very specific neural pathways and affect only very small brain areas. This means that the effect of the endorphins depend on where in the brain they are released. For example, endorphin release in a small area of the brain stem called the nucleus raphe magnus inhibits pain; their release in the nucleus accumbens produces a state of bliss mediated by dopamine; their release in the insula produce positive emotions, and so far and so forth.

Third, what I have been calling until now “endorphins” are really a collection of about 40 different peptides encoded by three different genes and classified into three different families: endorphins, enkephalins and dynorphins. The endorphins and enkephalins bind to mu opioid receptors and delta opioid receptors, whereas dynorphins bind to kappa opioid receptors. All three receptors produce analgesia (meaning “a decrease in pain”), but only mu and delta receptors produce euphoria (a sense of pleasure and well-being). Kappa receptors, on the contrary, produce dysphoria, a profoundly unpleasant sensation of being sick and unhappy. Therefore, not all “endorphin” release will lead to a state of bliss. Like endorphins and enkephalins, dynorphins are released by pain, particularly when is accompanied by distress. This can happen, for example, in an adverse social environment or in unpleasant situations over which we have no control.

Images showing where in the human brain endorphins decrease the unpleasantness of pain: the anterior cingulate cortex (A CING), the thalamus (THA) and the nucleus accumbens (N ACC). From Zubieta et al. (2001), Science 293: 311.
Now, going back to that post, it is not true that endorphins are released in “loads” and that it takes the body 10 min to replete the load once is released. From what I have said above you can deduct that this is an enormously naïve and simplistic view of what in reality is a tremendously complex system. The final effect on our state of consciousness and on our mood would depend on whether endorphins, enkephalins or dynorphins are released, and most important, where in the brain they are released. Since the levels of endorphins in the blood do not affect the brain, to study endorphin release we need to have a technique that would allow to detect them inside a living brain. As incredible as this may seem, it was actually done by a scientist named Jon-Kar Zubieta. Using positron emission tomography (PET), he is able to measure the binding of an opioid drug, carfentanil, to the mu opioid receptors. He published a number of papers using this technique (I list some of them at the end) that show where in the brain endorphins are released (actually, where they bind to the mu opioid receptor, displacing carfentanil) during pain or in some particular emotional states. Unfortunately, he did not study masochists being beaten into a pulp in a SM scene. There is no indication whatsoever in his studies that endorphins are released in “loads”, or that the loads need to be replenished every 10 min. This also does not agree with what we know about the mechanisms by which endorphins are synthesized and released.

What about adrenaline? Actually, the brain uses a similar compound instead, nor-adrenaline (often called nor-epinephrine or simply NE). NE does a lot of things in the brain - again, depending where it is released an which of its many receptors are activated. It is true, however, that NE released into the spinal cord inhibits pain. This is driven by a neuronal pathway that originates in several parts of the brain stem (the nuclei called A5, A7 and nucleus coeruleus) and then travels down the spinal cord. The A5, A7 and coeruleus nuclei are activated by stress in the fight/flight response, which is well-known to produce analgesia. So adrenaline can complement endorphins to reduce pain during an SM scene.

How all this applies to an SM scene is anybody’s guess. I don’t know of any scientific studies done on sadomasochists, although it would be fascinating to do them. But in view of the complexities of these systems, how much they vary from person to person and how strongly they are influenced by social interactions and the ambient, we can guess that there is no simple formula to induce the release of endorphins or adrenaline in a person. The top has to fly by the seat of his pants, read the bottom very carefully and stay on the safe side when inducing altered mind states on the bottom. We are playing with fire here, and even though things may seem to fine during a scene, nobody knows what unforeseen consequences it may have in the future.

Zubieta, J. K., Y. R. Smith, et al. (2001). Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science 293(5528): 311-315.

Mason P (1999) Central mechanisms of pain modulation. Curr Opin Neurobiol 9:436-441.

Hunt SP, Mantyh PW (2001) The molecular dynamics of pain control. Nat Rev Neurosci 2:83-91.

Zubieta JK, Smith YR, Bueller JA, Xu Y, Kilbourn MR, Jewett DM, Meyer CR, Koeppe RA, Stohler CS (2002) mu-opioid receptor-mediated antinociceptive responses differ in men and women. J Neurosci 22:5100-5107.

Zubieta JK, Ketter TA, Bueller JA, Xu Y, Kilbourn MR, Young EA, Koeppe RA (2003) Regulation of human affective responses by anterior cingulate and limbic mu-opioid neurotransmission. Arch Gen Psychiatry 60:1145-1153.

Apkarian AV, Bushnell MC, Treede RD, Zubieta JK (2005) Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 9:463-484.

Ribeiro SC, Kennedy SE, Smith YR, Stohler CS, Zubieta JK (2005) Interface of physical and emotional stress regulation through the endogenous opioid system and mu-opioid receptors. Prog Neuropsychopharmacol Biol Psychiatry 29:1264-1280.

Wager TD, Scott DJ, Zubieta JK (2007) Placebo effects on human mu-opioid activity during pain. Proc Natl Acad Sci U S A 104:11056-11061.

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