Do we understand the non-subjective mechanisms behind pleasure and pain?

Question

If we are to view pleasure and pain as being essentially synonymous with the more mechanistic concept of reward and punishment (i.e. as a part of learning and motivation system) then do we understand how this actually occurs at a neurobiological level? At least in "lower" animals, pain seems to simply cause an aversion response. Pain motivates the animal to stop whatever it was doing (possibly stopping the pain), and to avoid in the future repeating similar responses to those that preceded (and therefore were possibly causal toward) the incident that caused pain.

This sort of thing is not that hard to replicate in computational models, so it is clearly nothing magical. Obviously, the subjective "experience" of pleasure and pain gets more into philosophy of mind and that's not what I am asking about. I am only concerned about the mechanism which can explain outwardly observable behavior -- especially in simpler animals -- such as the basic stimulus-response-reward/punishment learning that a mouse or bird can do.

Do we understand the mechanism by which a pain signal causes the brain to suppress recently followed decision paths, and a pleasure signal causes the brain to reinforce them? Or is this still completely mysterious at this time?

Answer 1

I think part of the answer to your question is going to include the dopamine "reward" pathway in the basal ganglia. In particular, a leading theory of dopaminergic function is the predictive reward error or reinforcement learning hypothesis. In this theory, dopamine neurons signal expectations about the outcome of particular stimuli.

Some key experiments are outlined in Schultz, 1998 (PDF). First, an unexpected reward elicits a short activity increase in dopamine neurons. Second, if a conditioned stimulus (CS) precedes the reward, the dopamine neuron fires in response to the CS but not the reward. That is, the dopamine signal is now a predictive reward signal. Third, if the CS is presented and then the reward does not occur, the response to the CS occurs but the dopamine neuron depresses activity immediately after the reward should have happened.

So the theory goes that dopamine neurons are not simply saying whether a reward has occurred, but rather as a learning signal that adjusts predictions about rewards. If an unpredicted reward occurs, the neuron signals a positive error ("Oops, that was a reward I should know about!"). If a predicted reward occurs, the neuron signals no error at the time of the reward ("shrug, I knew that was going to happen"). If a predicted reward does not occur, the neuron signals a negative error ("Aw shucks, guess that bell doesn't mean food after all.").

A somewhat updated revision of the theory is outlined in a review by Redgrave and Gurney, 2006 (PDF). Importantly, they note that dopamine neurons suppress their activity in response to noxious stimuli (the pain aspect of your question). They also raise some tough questions about how exactly this dopamine signal interacts with other parts of the brain to mediate the learning suggested in the theory.

As with basically all neurobiology theory, a full understanding of how this signal that we detect in individual neurons translates into a coherent behavioral response program is a long ways away. But the basal ganglia, in general, are sometimes thought of as an action selection system (or "decision path" selection to use your words), so the ability of dopamine neurons to signal expectations is relevant.

Answer 2

Neurobiology is not my field of expertise, but this paper seems relevant:

Kent C. Berridge, Chao-Yi Ho, Jocelyn M. Richard, Alexandra G. DiFeliceantonio (2010) The tempted brain eats: Pleasure and desire circuits in obesity and eating disorders. Brain Research, 1350, 43-64.

What we eat, when and how much, all are influenced by brain reward mechanisms that generate “liking” and “wanting” for foods. As a corollary, dysfunction in reward circuits might contribute to the recent rise of obesity and eating disorders. Here we assess brain mechanisms known to generate “liking” and “wanting” for foods and evaluate their interaction with regulatory mechanisms of hunger and satiety, relevant to clinical issues. “Liking” mechanisms include hedonic circuits that connect together cubic-millimeter hotspots in forebrain limbic structures such as nucleus accumbens and ventral pallidum (where opioid/endocannabinoid/orexin signals can amplify sensory pleasure). “Wanting” mechanisms include larger opioid networks in nucleus accumbens, striatum, and amygdala that extend beyond the hedonic hotspots, as well as mesolimbic dopamine systems, and corticolimbic glutamate signals that interact with those systems. We focus on ways in which these brain reward circuits might participate in obesity or in eating disorders.

You may also be interested in these two book chapters:

Smith, Kyle, Stephen V. Mahler, Susana Pecina, and Kent C. Berridge. “Hedonic Hotspots: Generating Sensory Pleasure in the Brain.” In Pleasures of the Brain, edited by Morten L. Kringelbach and Kent C. Berridge, 27–49. New York: Oxford University Press, 2009.

A vital question concerning sensory pleasure is how brain mechanisms cause stimuli to become pleasurable and liked. Pleasure is not an intrinsic feature of any stimulus, but instead refl ects an affective evaluation added to the stimulus by the brain. That is, as Frijda expresses it (Frijda, this volume; Frijda, 2006), a pleasure gloss or hedonic value must be actively ‘painted’ on sweet or other sensations to make them pleasant. Brain mechanisms of pleasure, whatever they are, must take a mere sensory signal and transform it into a hedonic and ‘liked’ reward.

Finding the brain mechanisms responsible for painting a pleasure gloss is a major challenge for affective neuroscience (Barrett and Wager, 2006; Berridge, 2003b; Damasio, 1999; Davidson, this volume; Davidson and Irwin, 1999; Kringelbach, 2005; Kringelbach, this volume; LeDoux, 1996; Panksepp, 1991; Peciña et al., 2006). Fortunately, progress on fi nding hedonic generators in the brain is being made. In this chapter we focus specifi cally on the neuroanatomical hedonic hotspots in the brain where neurochemical signals actually contribute causally to the generation of pleasure.

Aldridge, J. Wayne, and Kent C. Berridge. “Neural Coding of Pleasure: ‘Rose-tinted Glasses’ of the Ventral Pallidum.” In Pleasures of the Brain, edited by Morten L. Kringelbach and Kent C. Berridge, 62–72. New York: Oxford University Press, 2009.

Pleasure is not a sensation. What is it then? Nico Frijda's answer in the "pleasure questions" section of this book (which he suggested a number of years ago) epitomizes an emerging consensus among many psychologists and neuroscientists (Frijda, Chapter 6, this book). He notes that pleasure "is a 'pleasantness gloss' added to whatever is pleasant". [...]

Here we ask: how is a "pleasure gloss" encoded in brain activity? Where in the brain is this glossing operation performed and how does it work? Is it possible for neuroscientists to recognize the signature patterns of neural activity that represent a pleasure gloss? These are difficult questions that are only beginning to be addressed. The "pleasure gloss" metaphor, applied to the transformation of neural signals for a stimulus, is like a varnish that is applied on top of a dull object to transform it into a shiny one. Adding hedonic tone to the signal passed on to downstream structures, the neural gloss effectively gives the entire brain a "rose-tinted" hedonic perception of the stimulus as pleasant.

In the context of neural firing signals, our idea is that a particular pattern of neuronal spikes or action potentials in crucial neurons may apply a glaze of pleasure on what might otherwise be an ordinary sensation or action signal.

Answer 3

To add to yamad's answer (which is pretty good), for about a decade, the way pain was thought to lower the effect of rewards is by tonic release of dopamine; in contrast, pleasure/reward triggers phasic release of dopamine. If you want an (imperfect) electrical analogy, the tonic release is the "DC" level and phasic are transients or spikes on top of that. More correctly:

Tonic dopamine activity refers to the level of extrasynaptic dopamine that is present at a steady-state concentration in the extracellular space. [...]

Importantly, tonic dopamine levels regulate the responsiveness of the phasic dopamine system to salient environmental cues: high tonic dopamine attenuates phasic dopamine release whereas low tonic dopamine facilitates phasic dopamine firing. The level of tonic dopamine in the limbic striatum is in turn modulated by corticostriatal and hippocampal afferents and homeostasis

Increased tonic dopamine is known to result from prolonged stress or pain, a mechanism that might have evolved to ensure rest and low activity levels during injury.

And among the refs cited in support of that is a (pretty highly cited) experiment of Floresco et al. (2003):

we report dissociable regulation of dopamine neuron discharge by two separate afferent systems in rats; inhibition of pallidal afferents selectively increased the population activity of dopamine neurons, whereas activation of pedunculopontine inputs increased burst firing. Only the increase in population activity increased ventral striatal dopamine efflux. After blockade of dopamine reuptake, however, enhanced bursting increased dopamine efflux three times more than did enhanced population activity. These results provide insight into multiple regulatory systems that modulate dopamine system function: burst firing induces massive synaptic dopamine release, which is rapidly removed by reuptake before escaping the synaptic cleft, whereas increased population activity modulates tonic extrasynaptic dopamine levels that are less influenced by reuptake.

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That was the view circa 2008. A 2016 review paints a fairly different picture (citing only post-2009 primary studies for this update):

Recent studies suggest that dopamine neurons in the VTA [ventral tegmental area] and SN [substantia nigra] form a heterogeneous population tuned to either (or both) aversive or rewarding stimuli.

The heterogeneity of dopamine neurons in response to aversive and rewarding stimuli suggests that they serve unique functional roles. Cells activated by reward and inhibited by punishment are well suited to code motivational valence, whereas neurons activated by both rewarding and punishing stimuli are likely to code motivational salience [stimulus awareness]. Neurons coding motivational valence [whether the stimulus is positive or negative in value] would provide a signal for reward seeking, evaluation, and value learning, in line with current theories on the role of dopamine in reward processing. In contrast, neurons coding motivational salience would provide a signal for detection and prediction of highly important events independent of valence, pursuant to dopamine's role in salience processing. These distinct aspects of dopamine neurotransmission might be neuroanatomically separate: dopaminergic neurons coding motivational valence have been found more commonly in the ventromedial SN and lateral VTA with projections to nucleus accumbens [NAc] shell, whereas neurons coding motivational salience are more often reported in the dorsolateral SN with projections to the nucleus accumbens core.

It's anybody's guess if this is the correct/complete picture. Time will tell.

The primary evidence for this updated view seems mostly based (in order of the number of citations) on 3 papers:

• Matsumoto and Hikosaka, "Two types of dopamine neuron distinctly convey positive and negative motivational signals", Nature 2009;
• Brischoux et al., "Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli", PNAS 2009
• Lammel et al., "Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli", Neuron 2011

One open problem remains though: how are pain and pleasure balanced by the brain? For example, we expect that an organism could tolerate mild pain in order to reap a reward. Where is this balancing decision made? A tentative answer comes from the authors of the aforementioned review, who in a newer (2017) empirical study found that the decision area in this case is the medial orbitofrontal cortex:

Alas this latter study used monetary rewards, so it's not terribly clear how well its result applies to lower species.

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And on a really interesting [for me] research side, in some species dopmamine signaling not only alters behavior but induces morphological changes in response to the environment; examples include both predator (e.g. Echinoid larvae) and prey (e.g. Daphnia) changing their morphology in reaction to prey/predators via dompamine-mediated pathways. Although not obviously related to predator/prey behavior, but to the wider environment; dopamine mediates myopia (eye growth) in humans and other species.

Finally, I only focused on the highlighted question at the end of the questotion-body. Your title question is actually substantially broader.

Just with respect to the rewarding side: liking and wanting are thought to have substantially different neurobiological circuitry, cf. the [highly cited] review of Berridge et al. (2009) (whose closely related work Kaj's answer indicated).

A similarly extensive line of work exists with respect to pain (i.e., the aversive side), e.g. see Baliki and Apkarian (2015) "Nociception, Pain, Negative Moods, and Behavior Selection".