Written a few months ago, this look into endorphins was a submission for the Biochemical Society’s annual Science Writing competition – for the layperson. I can see some flaws, but figured I'd put it up on here for safe-keeping ;)

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Some of the biggest crimes committed today are hacking-related. Even this morning some of us Londoners picked up the Metro to find ‘radical Yorkshire lad hacking NHS, Sony and New International, digitally masquerading as a 16-year old girl’. Hardly surprising given the propensity for young people nowadays to engage in elaborate cross-gender identities (don’t scoff, we’re parodying a very different newspaper with that phrase), but it begs the question: Why do people do it at all? Why do they hack, commit criminal offences and risk a career-damaging spell in prison? Even the best of the hacking media darlings get a few hard knocks: Julian Assange’s media circus being one prime deterrent for even the “good” hacking in releasing classified government documents.

One hacking legend Kevin Mitnick explains it as akin to the convivial digital warfare: “I did get a huge endorphin rush when I was able to crack a system because it was like a video game”. Equally however, having retired from crime he notes that “I get the same endorphin rush today when I get into a client's system. I really feel good about it. So I get paid for what I did illegally years ago”. Do we gather from this that it isn’t the criminality that draws hacksters-to-be, but endorphins? The challenge of the chase? – What in general causes an endorphin release?

Let’s gather some more wool...

Endorphins are released by the pituitary gland, a tiny pea-sized organ in your brain protruding off your hypothalamus. This gland gives off 9 hormones to regulate your body’s homeostasis, including hormones such as oxytocin which plays a role in emotional bonding, trust and sexual arousal, and growth hormone which stimulates your growth and cell division¹. Endorphins are also essentially produced by hypothalamic neurons via a cleaved product of pro-opiomelanocortin, a rather complex gene that also produces sister peptides α-MSH and ACTH, regulating appetite/sexual behaviour and immune response respectively². Being the cultural buff, you will probably have heard the term “endorphin rush” in numerous films and books – the feeling of wellbeing and positivity that results from doing something difficult, dangerous or exciting. Equal to this, being an opioid peptide endorphin is produced following stressors such as pain, stress and even alcohol^{3 4}. It binds to opioid receptors much like morphine does, inhibiting key proteins involved in the transmission of pain. A vital addendum to this, β-endorphin, taking centre stage in the production “Endorphin” (TBA in all gothic West End dramas) binds at mu-opioid receptors in the central nervous system, inhibiting the chief neurotransmitter GABA and so creating the excess of dopamine that gives you a rush of pleasure¹.

As all who have been either willingly or forcibly ensconced into watching Legally Blonde will know, “Exercise produces endorphins; endorphins make you happy. Happy people don't shoot their husbands”: right? Perhaps – but how certain are we?

The stimulation and monitoring of endorphin production has through medical history been characteristically difficult – tapping into the brain and spinal cord for a ‘sample’ following a difficult or arduous ordeal can be both a risky and dangerous activity. Numerous studies have found a host of activities that produce β-endorphin, ranging from acupuncture⁵, endurance running and even laughter⁶ – this hormone regulates the relationship of pain and reward, and thus modulates our brain’s plasticity in learning, memory and motivation⁷. Describing their extent of action and influence is akin to finding every original granule of salt in a hot broth however; monitoring blood plasma for endorphin levels can be relatively easy, but going beyond the blood-brain barrier doesn’t entice human volunteers. Instead, scientists often have to rely on roundabout methods of evaluation, one of which in particular relates to our blonde Elle Woods’s exercise plan: the body’s pain management. Experiments in analgesia – that is, the reduction of pain - have shown that mice experience a reduction in pain and sensitivity to stress due to exercise directly as a consequence of β-endorphin production⁸. Using a roundabout method of engineering β-endorphin-deficient mice (roundabout doesn’t mean easier folks), Woods it seems had it right⁹ – Or, at least for mice.

Luckily while scientific research follows an oblique route, we still get results. One of the most exciting connections in the β-endorphin research world revolves around the mediation of stress, β-endorphin response and our immune system. Hans Selye, a pioneer in endocrinology in the early 1900’s said something that in truth is quite foretelling – “Every stress leaves an indelible scar, and the organism pays for its survival after a stressful situation by becoming a little older”. While we live in a world that is slowly demanding ever more productivity and juggling finesse, stress plays a significant role in changing our bodies on the micro scale. Stress has been shown not only to be a madness-inducing riot as evidenced by Jerry Springer’s extraordinary guests, but general neurophysiological stress has been shown to dampen our immune system, and promote progression and growth of cancerous cells⁷.

It might be surprising, but Molière’s vision of The Hypochondriac may be a deft and witty depiction of the irony of our own choices. Psychological factors and stresses play a keen role in how we alter our own endocrine and immune functions. While we’ve heard in the media that relieving stress helps cancer patients on chemotherapy to make dramatic improvements, it’s also true that reducing our general stress should decrease our likelihood of developing cancer⁷. β-endorphin has been shown to inhibit tumour progression¹⁰; it has been shown through neuron transplants to reduce prostate and breast cancer incidents^{11 7}.

While neuron transplants for humans aren’t yet a realistic future, we still have some proven sidesteps to our stress reduction and β-endorphin elevation. Exercise works wonders – not only for summer bathing suit opportunities, but to keep our organs functioning optimally on the cellular level. Laughter likewise has been shown to decrease our pain¹ and so likely produce β-endorphin: we experience the sensation of pain to a lesser degree when we are happy and laughing⁶. Perhaps this extends to all activities. Although we don’t have a conclusion embedded in β-endorphin research to prove what draws us to activities, be it hacking or reading biomolecular science journalism, we might have a strong biological basis for thought: If we feel a rush of dopamine when we’re doing it, it’s probably β-endorphin – if it’s β-endorphin, it’s probably good for our bodies, our stress levels and our health.

That’s a good enough biological excuse for me.

Ref:

1.                    Sprouse-Blum, A. S., Smith, G., Sugai, D. & Parsa, F. D. Understanding endorphins and their importance in pain management. Hawaii medical journal 69, 70–1 (2010).

2.                    Veening, J. G., Gerrits, P. O. & Barendregt, H. P. Volume transmission of beta-endorphin via the cerebrospinal fluid; a review. Fluids and barriers of the CNS 9, 16 (2012).

3.                    Grisel, J. E., Bartels, J. L., Allen, S. A. & Turgeon, V. L. Influence of β-Endorphin on Anxious Behavior in Mice: Interaction with EtOH. Psychopharmacology 200, 1–20 (2008).

4.                    Mice, D. B. A., Papachristou, N. & Lumeng, H. A. D. The Alcohol-Preferring C57BL / 6 Mice Present an Enhanced Sensitivity of the Hypothalamic fl-Endorphin System to Ethanol Than the Alcohol-Avoiding. J. of Pharmacology and Experimental Therapeutics 261, 788–794 (1992).

5.                    Lee, H. et al. Retraction: Substance P and beta-endorphin mediate electro-acupuncture induced analgesia in mouse cancer pain model. Journal of experimental & clinical cancer research : CR 28, 137 (2009).

6.                    Dunbar, R. I. M. et al. Social laughter is correlated with an elevated pain threshold. Proceedings. Biological sciences / The Royal Society 279, 1161–7 (2012).

7.                    Dipak K. Sarkar, Sengottuvelan Murugan, Changqing Zhang, and N. B. Regulation of cancer progression by β-endorphin neuron. Cancer Res 72, 836–840 (2013).

8.                  Parikh, D. et al. Stress-induced analgesia and endogenous opioid peptides: the importance of stress duration. Eur. J. Pharmacol 650, 563–567 (2010).

9.                    Howlett, T. a et al. Release of beta endorphin and met-enkephalin during exercise in normal women: response to training. British medical journal (Clinical research ed.) 288, 1950–2 (1984).

10.                 Sarkar, D. K., Zhang, C., Murugan, S., Dokur, M. & Nadka, I. Transplantation of β-endorphin neurons into the hypothalamus promotes immune function and restricts the growth and metastasis of mammary carcinoma. Cancer Res 71, 6282–6291 (2012).

11.                 Reuhl, K. et al. Cyclic adenosine monophosphate differentiated ␤ -endorphin neurons promote immune function. 105, 9105–9110 (2008).