In principle, could a brain be rewired to experience more pleasure and/or pain?

Question

I'm not sure if these are two separate questions, but I'm curious: in theory, could an existing adult mind/brain be modified to perceive pleasure/pain signals more intensely than otherwise? Without drastically changing the rest of the brain (i.e. while making sure that the brain is the same person; although this question is understandably complicated and potentially philosophical)?

As to the latter part of the question, the SCN9A gene might play a part. Maybe there exists a similar gene for pleasure?

(I made a post focusing on the genetic side on the biology SE. I think the questions are different enough for this to be acceptable, but it might be worth looking there to avoid duplicated effort.)

Answer 1

This is a difficult question to answer and likely can generate a variety of equally valid (or invalid) answers.

I thought to tackle this from a pathological vista - namely that of sensory processing sensitivity (SPS), which seemingly resembles your area of interest.

SPS can be defined as (Acevedo et al., 2018)

[A] genetically based trait associated with greater sensitivity and responsivity to environmental and social stimuli. [It] is characterized by greater empathy, awareness, responsivity and depth of processing to salient stimuli.

In their article the authors review the structural underpinnings as observed by fMRI scanning of SPS, alongside the brains of Autism Spectrum Disorder, Schizophrenia and Post-Traumatic Stress Disorder who also exhibit SPS alongside their other symptoms.

Common activated regions in all disease types were shown in the precentral gyrus.

SPS was associated with activity in reward processing centers (ventral tegmental area (VTA) and substantia nigra (SN), centers for regulation of bodily physiology and pain (hypothalamus and periaqueductal gray (PAG); self versus non-self recognition and empathy (inferior frontal gyrus (IFG) and insula), awareness and self reflection (temporoparietal junction (TPJ)) and self-control (prefrontal cortex (PFC)).

In terms of Autism Spectrum Disorder, Schizophrenia and Post-Traumatic Stress Disorder the authors continue with multiple brain regions that are activated commonly and uniquely with respect to SPS proper. I refer to the review referenced below for details.

I reckon, but am unsure, that re-wiring of the pathways or altering the structures themselves with, e.g., transcranial stimulation or with ablation techniques can emulate SPS symptoms, including pain and emotion processing. The practical ways to do this are difficult, given the complexity of the brain.

<sub>References
- Acevedo et al., Philos Trans R Soc Lond B Biol Sci (2018); 373(1744): 20170161</sub>

Answer 2

could an existing adult mind/brain be modified to perceive pleasure/pain signals more intensely than otherwise

It depends what you mean by "modified", but even without going to any genetic (or surgical, e.g. implants) modifications, the central mechanisms involved in pain can be sensitized merely by experience/exposure to a certain level of stimuli; see e.g. (fairly cited) review paper on central sensitization.

The nociceptor-induced sensitization of the somatosensory system is adaptive in that it makes the system hyperalert in conditions in which a risk of further damage is high, for example, immediately after exposure to an intense or damaging stimulus. This sensitization is the expression of use-dependent synaptic plasticity triggered in the central nervous system (CNS) by the nociceptor input and was the first example of central sensitization, discovered [in 1983]. Since then, we have learned that a number of different forms of functional, chemical, and structural plasticity can sensitize the central nociceptive system to produce pain hypersensitivity under both normal and pathological circumstances, some of which are persistent.

[...]

To induce central sensitization, the noxious stimulus must be intense, repeated, and sustained. Input from many fibers is required over tens of seconds; a single stimulus, such as a pinch, is insufficient. Peripheral tissue injury is not necessary, although the degree of noxious stimulation that produces frank tissue injury almost always induces central sensitization, so that the phenomenon is very prominent after post-traumatic or surgical injury.

The mechanism[s] by which this happens are on one hand very diverse as far as initiation, but seem to converge in one final pathway (dorsal horn neurons):

multiple different triggers can contribute to the establishment of this form of central sensitization: glutamate acting on NMDAR, but also on AMPAR and mGluR, the neuropeptides substance P and CGRP, the kinin bradykinin, as well as BDNF and NO. [...] The reason so many different transmitters, modulators, and their receptors are involved is that it is not their specific action that is important but rather that they are released directly from or induced in response to nociceptor afferent activity, and each can separately or together initiate the activation of those multiple intracellular signaling pathways that lead to the establishment of hyperexcitability in dorsal horn neurons [...]. In other words, there are many parallel inputs to dorsal horn neurons that can independently or cooperatively initiate central sensitization.

So that gives numerous potential [malevolent] pharmacological/genetic/physical interventions that could have the same (ultimate) effect of causing central sensitization to pain. And if you care about the practical details, you can read the experimental methods section of the papers cited in that review.

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As far as "pleasure" is concerned, there have been numerous studies on sensitization to drugs that have addictive potential. But in that area, things are more muddy because "behavioral sensitization" doesn't really separate the "like" and "want" components, which have some common pathways in the brain (the famous dopamine mesolimbic/NAc) but also distinct for various "likes" (e.g. those for sweet taste have been fairly well identified) and it seems it is mainly other neurotransmitters are mainly involved in the latter (e.g. MOR-receptor agonists, like endorphins and also orexin for taste. Things are complicated in that regard because merely eating something that does not subjectively register as pleasant will also release pretty much the same neurotransmitters; there are apparently subtle differences to consider in what regions of the brain where they are released.) Behaviorally studied, preferences can have many confounders besides actual "like"; see e.g. [amusing perhaps] controversy on sugars vs cocaine, which was even the stuff of tabloids some years back (as "cupcakes vs cocaine" or thereabout).

While sensitization of D2 [dopamine] receptors involved in the feedback loop of addiction is fairly well understood (e.g. see all the D2High research), I'm not sure there's been comparable effort to understand if there is easily and separately triggerable sensitization in receptors involved in e.g. sweet tasting, although in general, mu opioid receptors can be sensitized as well.