By Yash Kulkarni

“One feels inclined to say that the intention that man should be ‘happy’ is not included in the plan of ‘Creation.’ “

–Sigmund Freud, Civilization, and Its Discontents, 1930

Sigmund Freud is indeed right; one cannot know the true meaning of pleasure (happiness) unless and until one hasn’t known what pain is. For instance, a well satisfied person cannot experience the pleasure of having food, which a hungry person can. Happiness is a feeling of contrast; the more happiness you have, the less you experience it. Humans are not meant to be happy continuously, our biology shunts us from attaining the state of perpetual happiness. What exactly goes on in the brain, that forbids us from eternal happiness? Is it possible to experience continual happiness?

Happiness is a very broad term, but in the sense of biology, happiness can be defined as a delightful sensation driven via the release of biochemical substances (e.g., neurotransmitters – serotonin, dopamine, or hormones – oxytocin, etc.) directly into the blood stream or by rapid signaling of excitatory currents. Happiness brings in together various biological systems to work in tandem (e.g. nervous, limbic, and cardiovascular system) upon a hedonic, or pleasant, sensation. The science of happiness is as ancient as it seems. Two different aspects of happiness are quite well known, namely hedonia (pleasure in the most fundamental things) and eudaimonia (life well lived/meaningful life)¹. So, what exactly happens inside of the brain when stimulated by a hedonic or pleasant stimulus?

In the brain there are regions defined as ‘hedonic hotspots’ where the pleasure circuitry is considered to reside. Hedonic hotspots are also referred to as pleasure generators. Several cortical and subcortical regions of the brain act as the hedonic hotspots that drive the ‘liking’ reaction in the brain¹. Even though the hedonic hotspots are separated from each other, they interact with one another upon a hedonic stimulus (e.g. food). Once in the active stage hedonic hotspots account for a pleasure reaction². Recently two subcortical brain regions, were shown to be key focuses of the pleasure circuitry³. Firstly, the habenula, a group of nerve cells present close to the pineal gland, has an influence on the sleep-wake cycle and mood. The habenula has shown a considerate anatomical, physiological, and functional significance (mainly in the reward seeking and anhedonic behavior) as depicted in the figure 1³. Secondly, the nucleus accumbens where most of the hedonic hotspots reside, is a basal forebrain region popular for its role in the reward-circuit and is an important component of the mesolimbic pathway (dopamine pathway) playing a vital role in the pleasure circuitry⁴.

The hedonic hotspots (such as the nucleus accumbens and habenula) in humans are capable of generating and enhancing a ‘liking’ reaction with respect to a sensory stimulus such as a sweet taste, drugs (e.g., opioids and endocannabinoids), or any other neurochemical modulators. The ‘liking’ reaction is driven by a motivational process known as ‘wanting’ reaction that makes the stimulus more attractive. The ‘wanting’ reaction accounts for the reward circuitry, including the dopamine related pathways⁴.

Apart from the reward circuitry there also exists a pain network, which consists of several cortical regions including the somatosensory cortex and the dorsal anterior cingulate cortex (figure 2). The dorsal anterior cingulate cortex is associated with the psychological aspects of pain while the somatosensory cortex is associated with the physical pain⁵. On further research, it was found that pain and pleasure are correlated to each other, not just anatomically but also neurochemically⁶. Two main neurotransmitter systems govern the pleasure-pain circuitry – the opioid and the dopamine systems. The opioid system is necessary for hedonic feelings. Some opioids found in the nucleus accumbens enhance the pleasantness of hedonic stimuli while reducing the aversiveness of pain or any negative stimuli, while other opioids in the same region are responsible for inducing aversiveness but reducing pain⁶. The dopamine system increases the motivation, but not the pleasure, of performing a pleasant task (e.g. eating palatable food). Thus, dopamine prepares oneself for the hedonic experience also known as the ‘wanting’ reaction⁶. Phasic dopamine (large amount of dopamine release) increases opioid level while tonic dopamine (small amount of dopamine release) decreases opioid level (figure 3). Conversely, opioids can also regulate the dopamine signaling⁶. Thus, dopamine and opioid release systems are directly linked to the reward expectancy, pleasure, and pain.⁶

Thus, it is evident that pain and pleasure are interdependent, either anatomically due to the overlapping hedonic and anhedonic sites (e.g., in the nucleus accumbens) or neurochemically due to the correlation between dopamine and opioid signaling. Dopamine accounts for the reward system instigating the further release of opioids which accounts for the hedonic pleasure⁷. Even though pain and pleasure are correlated, it is still not clear how chronic pain affects the ability to enjoy rewards and enhance pleasure. Therefore, eternal happiness may not exist, not just because it may seem daunting to achieve but because it is our own neurobiology that makes pain inevitable. Although continual happiness might not be the reality of our lives, we still can strive to make our lives happier by overcoming the pain that our biology and environment impose on us.

TL:DR

• Hedonic hotspots (pleasure generators) are anatomical sites in the brain where pleasure circuitry resides. The habenula and nucleus accumbens are prime focuses in the pleasure and pain related pathways.
• Neurotransmitters like dopamine and opioids develop an interdependence between reward, pleasure, and pain pathways.
• Correlation between the pleasure and pain pathways via neurotransmitters and anatomy makes it inevitable to avert pain. Thus, eternal happiness might not exist.

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References

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2.        Moccia, L., Mazza, M., Nicola, M. di & Janiri, L. The experience of pleasure: A perspective between neuroscience and psychoanalysis. Frontiers in Human Neuroscience vol. 12 Preprint at https://doi.org/10.3389/fnhum.2018.00359 (2018).

3.        Loonen, A. J. M. & Ivanova, S. A. Circuits Regulating Pleasure and Happiness – Focus on Potential Biomarkers for Circuitry including the Habenuloid Complex. Acta Neuropsychiatrica Preprint at https://doi.org/10.1017/neu.2022.15 (2022).

4.        Kringelbach, M. L. & Berridge, K. C. The Neuroscience of Happiness and Pleasure.

5.        König, M. et al. Quantum spin hall insulator state in HgTe quantum wells. Science (1979) 318, 766–770 (2007).

6.        Siri Leknes & Irene Tracey. A common neurobiology for pain and pleasure. Nature reviews vol. 9 Preprint at doi:10.1038/nrn2333 (2008).

7.        Navratilova, E. et al. Positive emotions and brain reward circuits in chronic pain. Journal of Comparative Neurology vol. 524 1646–1652 Preprint at https://doi.org/10.1002/cne.23968 (2016).