How does the mind tell you what [pain] is going on within? This question could be rephrased as this: of all the internal processes, how, [when, and why also] does the mind bring a pain sensation to attention? So, there are processes and there is attention, so to speak. Now, what does attention mean? The article below is an exploration of conceptual brain science using advances in pain medicine.
There is a recent [June 4, 2025] paper in PNAS, The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels, stating that:
“Paracetamol (e.g., Tylenol or Panadol) is one of the most widely used pain relievers, yet its mechanism of action remains unclear. While previous studies have focused on the effect of its active metabolite AM404 on the central nervous system (CNS), our research reveals that sensory neurons in the peripheral nervous system can also generate AM404. We demonstrate that AM404 inhibits pain-specific sodium channels in nociceptive neurons, effectively reducing normal and inflammatory pain. These findings provide insights into paracetamol’s peripheral mechanisms of action and highlight the potential of AM404 as a pain-selective local anesthetic, offering broader implications for pain management strategies.”
There is a recent [June 26, 2025] The Works in Progress Newsletter, The first non-opioid painkiller: Journavx was approved this year. Why did it take so long to develop?, stating that, “Opioids alleviate pain by acting on one of the three main opioid receptors, mu (μ) opioid receptors, which are distributed throughout the central nervous system, particularly in the brain. When opioids bind to the brain’s mu receptors, this suppresses incoming pain signals from the damaged site’s nociceptors, preventing the brain from creating the sensation of pain even when tissue damage is present.
Unlike opioids, which act within the central nervous system, Journavx does not meaningfully interact with the brain. Instead, it targets a specific sodium ion channel found almost exclusively on peripheral nociceptors, the pain-sensing neurons throughout your body. Ion channels, whether sodium, potassium, or calcium, are like tiny doors embedded in the neuron’s membrane: when a door opens, ions rush in or out and the neuron fires, sending an electrical signal to the next cell.
Three sodium channels are found primarily on nociceptors: NaV1.7, NaV1.8, and NaV1.9. Suzetrigine selectively blocks NaV1.8, which stops nociceptors from sending pain signals to the brain. Rather than preventing your brain from receiving pain signals, as opioids do, it prevents your neurons from transmitting them.”
A Brain Science Model of Pain
Pain-sensing neurons [or nociceptive neurons (or nociceptors)] are said to transmit pain signals. However, what is the form of a pain sensation? What is the architecture of a pain stimulus? What gets constructed [as pain] for signals to transmit? Why do signals have the capability to transmit pain? What happens at intervals of transmission, before termination in the brain?
Neurons are said to communicate using electrical and chemical signals. Electrical signals are underscored by ions, including sodium. Chemical signals are molecules, commonly referred to as neurotransmitters, among others. But, how can electrical and chemical signals transmit what they did not construct? How can they transmit what they cannot construct? How can they transmit a construction that cannot exist in their kind?
Simply, signals cannot be for transmission [or communication] if signals are unable to make [or sustain] what they are transmitting, refuting the term communication subspace. If receptors are targeted, and ions or molecules are induced or inhibited, then ions or molecules must be responsible for the structure of the sensation, conceptually. So, pain is a construct of ions and molecules, conceptually.
Why is this plausible? There is no function of neurons — for human survival — that does not involve their firing [ions] or transmission [molecules]. Neurons do not function for human existence, without them. [Neurons also function for human existence in the world (not just as cells or being cells). Why would neurons need to communicate using signals for their own survival, as cells, if other cells do not need similar signals to survive, or what would neurons be saying with signals for the purpose of being neurons?].
What it would look like if neurons were constructing pain or other sensations would be that they would be changing shape, or they would be moving towards the brain, or aligning in some form, building towards the brain. Signals are not sending the messages of pain for neurons because neurons cannot [maybe] do these [shaping, moving, or aligning], but signals are the basis for the sensations, while neurons act as the boulevard. [It would also be disruptive for neurons to shape, move, or align towards the brain, for different sensations].
This means that the configuration of pain — as a sensation or a feeling — is specified electrochemically. So, electrical and chemical signals are configurators. If signals were communicating what neurons constructed, they would not be effective because they would have to get inspections along the way to the brain [for accuracy] to avoid dampening [since they would be remote from the source].
But if they [signals] were communicating what they constructed, they would be interacting, transporting, and sustaining what they bear until they terminate where it is interpreted [or say where it fits], conceptually.
In the central and peripheral nervous systems, neurons are often in clusters: nuclei and ganglia, respectively. It is theorized that electrical and chemical signals are in sets [or loops] in those clusters. It is in those sets that they configure functions specifically. It is where they also distribute summaries of what they configured to other sets, interacting along the way such that, without an appropriate fit, there is no interpretation [accurate or not], so they have to keep going until they terminate at the sets [they can] fit. [An interpretation may fit, but not be accurate for a sensation, like the sight or smell or something, initially].
Simply, as electrical configurators travel through sets, they keep interacting with chemical configurators, but are only able to stop when they arrive at the set that fits what they bear [like pins of a plug into a socket]. This is why the brain is important because it holds several termination sets for signals arriving from within [itself] and across the body.
Functions [like feelings] are specific configurations of electrical and chemical signals. Attributes of functions are obtained by the states of the configurators [or assemblers] at the time of the interactions. So, attention — for example — is an attribute. It is obtained by the intensity of electrical configurators on chemical configurators. It is also obtained by a large volume of chemical configurators in one set. Or, a specific chemical configurator, say, glutamate.
Other attributes are self or subjectivity obtained by volume variation of chemical configurators, from side to side. Or, the end-to-end interactions of electrical configurators with chemical configurators. There is also intent and others. Attention of pain is possible because of the increased intensity that sodium ions add to electrical configurators. Also, the outcome of pain is an angular displacement of the set [of configurators] for pain, conceptually.
In general, as established in biology, sensations [touch, sight, sound, taste, smell] arrive by chemical signals that trigger electrical signals. It is postulated here that chemical configurators take specifications [off sensations] that electrical configurators swipe summaries from. Simply, there are displacements of molecules into configurations [to define sensations] that then allow ionic configurations to form and seek where to fit them. Chemical configurators take specifications from sensations. Electrical configurators seek to find where to fit those, resulting in the motion that terminates in the brain. This conceptually redefines sensory transduction.
Since sets often contain numerous chemical configurators, inducing or inhibiting one could affect other sets, resulting in side effects of medications. The same applies to some sodium channels, with their pain configuration and sodium ions for other functions.
According to The Works in Progress Newsletter, “Crucially, opioids don’t just kill pain: they also incite pleasure. When the mu opioid receptors present in the reward center of the brain are activated, this reduces the secretion of a neurotransmitter called GABA, which works to inhibit dopamine-producing neurons. As GABA release declines, dopamine spikes, lighting up the reward center and inducing pleasure.”
It is theorized here that [attention for] pleasure [as an experience] is a combination of chemical configurators in a set, not just of [one:] dopamine. It is possible that a dopamine spike results in attention for that set, since it may be the most dopamine available across sets in that instance. So, pleasure is theorized to be a result of the interactions of electrical configurators and chemical configurators, with attributes that might make it result in prioritization or attention of the set.
Also, the path or sequence [an attribute] made for relay to the pleasure set could be prepared to receive relays, such that the alert of its preparation becomes a craving that leads to addiction. So, while pleasure is said to be a set [of neuroconfigurators interacting and their attributes], addiction is sometimes a result of an attribute [sequences] asking for passage to the pleasure set, conceptually.
The future of pain medicine also depends on theoretical neuroscience, just like psychiatry, neurotechnology, AI, and others, with a brain theorem for how the mind works and how to prospect better care, globally.
This article was written for WHN by David Stephen, who currently does research in conceptual brain science with a focus on the electrical and chemical signals for how they mechanize the human mind, with implications for mental health, disorders, neurotechnology, consciousness, learning, artificial intelligence, and nurture. He was a visiting scholar in medical entomology at the University of Illinois at Urbana-Champaign, IL. He did computer vision research at Rovira i Virgili University, Tarragona.
As with anything you read on the internet, this article should not be construed as medical advice; please talk to your doctor or primary care provider before changing your wellness routine. WHN does not agree or disagree with any of the materials posted. This article is not intended to provide a medical diagnosis, recommendation, treatment, or endorsement.
Opinion Disclaimer: The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy of WHN/A4M. Any content provided by guest authors is of their own opinion and is not intended to malign any religion, ethnic group, club, organization, company, individual, or anyone or anything else. These statements have not been evaluated by the Food and Drug Administration.
