The Paradox of Pain: Deconstructing Sensation and Suffering in the Human Brain

Section 1: The Paradox of the Insensate Brain: An Introduction to Painless Surgery

The human brain, the intricate three-pound organ responsible for orchestrating every sensation, thought, and emotion, harbors a profound paradox: it is the sole generator of pain, yet it cannot feel pain itself.

This fundamental principle of neuroscience, while seemingly counterintuitive, is rooted in a simple anatomical fact.

The brain parenchyma, the functional tissue composed of neurons and glial cells, completely lacks the specialized sensory nerve fibers known as nociceptors.¹

These receptors, which are distributed throughout the skin, muscles, joints, and certain organs, are designed to detect potentially harmful stimuli and initiate the signals that the brain ultimately interprets as pain.⁴

Their absence within the brain tissue itself means that the organ of perception is, in a direct physical sense, insensate.⁶

The Ultimate Demonstration: Awake Craniotomy

Nowhere is this paradox more vividly and compellingly demonstrated than in the clinical practice of awake craniotomy.²

This remarkable surgical procedure allows neurosurgeons to operate directly on a patient’s brain while they are conscious and communicative.

The patient is typically sedated for the initial, potentially painful parts of the procedure, such as the scalp incision and the creation of an opening in the skull (the craniotomy itself).⁷

However, once the brain is exposed, the sedation is lightened, and the patient is awakened.

At this stage, the surgeon can manipulate, probe, and even resect brain tissue without causing any direct pain to the patient.²

First-hand accounts from individuals who have undergone this procedure offer powerful, humanizing evidence of the brain’s insensate nature.

Patients often describe the experience not as frightening or painful, but as surreal and even fascinating.

One patient recalled the hours-long procedure as “kind of fun,” stating, “I remember the whole surgery”.⁷

Another, when awakened on the operating table, had no sensation of the ongoing surgery and had to ask where the surgeon was, only to be told, “I am right here,” as he continued to operate on her brain.¹⁰

While the brain manipulation is painless, patients can experience discomfort from other sources, such as the pressure of the head clamp used for stabilization, which is managed with local anesthetics and sedation.¹¹

This clinical reality creates a perfect, contained illustration of the report’s central theme: pain originates not in the brain parenchyma but in its surrounding and supporting structures.

The patient’s body becomes a live map of pain-sensitive versus insensitive tissues, validating the anatomical distinctions that underpin our understanding of head pain.

Mapping “Eloquent” Brain Tissue

The decision to perform an awake craniotomy is not arbitrary; it is a functional necessity driven by the brain’s complex organization.

The brain is not a homogenous mass but is functionally segregated, with specific regions—termed “eloquent” cortex—governing critical functions like language, motor control, and sensory perception.⁷

When a tumor or epileptic focus is located near these eloquent areas, the surgeon faces the immense challenge of maximizing its removal while preserving the patient’s neurological function and quality of life.⁹

Awake surgery transforms the operating room into a laboratory for real-time functional localization.

By keeping the patient awake, the surgical team can create a precise functional map of the individual’s brain.

The surgeon uses a small electrical probe to painlessly stimulate the surface of the cortex at various points.⁷

Simultaneously, a neuropsychologist or other team member engages the patient in tasks—asking them to speak, count, identify pictures, or move a limb.¹⁰

If stimulating a particular spot causes a temporary disruption, such as a halt in speech or an inability to name an object, that area is marked and carefully avoided during resection.¹³

This constant feedback allows the surgeon to navigate the delicate landscape of the brain with unparalleled precision.

Patients have been known to sing “Happy Birthday” or discuss their college courses while the tumor is being removed, their chatter providing the crucial data stream that guides the surgeon’s hands.⁷

This procedure, therefore, is more than just a surgical curiosity; it is a live demonstration of the brain’s functional architecture.

It moves the discussion beyond the simple absence of pain receptors to a positive affirmation of the brain’s role as a complex, functionally segregated organ.

The procedure isn’t just about what the brain doesn’t do (feel pain), but about what it does do (control speech and movement), and how this can be observed directly.

Synthesizing the Paradox

The image of a patient calmly conversing with their surgeon while their brain is exposed is the ultimate testament to the foundational paradox of pain perception.¹⁴

The organ that constructs the entirety of our perceived world, from the softest touch to the most excruciating agony, is itself numb to physical injury.

This fact dismantles the intuitive notion that pain resides at the site of injury.

It forces a deeper inquiry: If the brain doesn’t hurt, what does? And if pain is not an intrinsic property of tissue, what, then, is it? The answers lie in deconstructing the very concepts of sensation and suffering, a journey that begins with the distinction between a raw signal and a subjective experience.

Section 2: Deconstructing Pain: Nociception, Pathways, and Perception

To understand why a headache hurts or how a phantom limb can ache, one must first grasp the critical scientific distinction between nociception and pain.

These terms are often used interchangeably in common parlance, but in neuroscience, they represent two distinct, albeit related, phenomena.

This distinction provides the essential framework for comprehending the brain’s role as the creator, rather than a mere receiver, of the pain experience.

Nociception vs. Pain: A Foundational Distinction

The International Association for the Study of Pain (IASP) provides formal definitions that are crucial for clarity.

Nociception is defined as “the neural process of encoding noxious stimuli”.¹⁵

It is an objective, physiological event—a data stream initiated by specialized sensors in the body that signals actual or potential tissue damage.

Its consequences can be autonomic (like a rise in blood pressure) or reflexive (like pulling a hand away from a hot surface), but it does not, in itself, imply the conscious feeling of pain.¹⁵

In contrast, pain is defined as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”.¹⁵

Pain is a perception—a subjective, personal, and conscious experience constructed by the brain.

It is always influenced by a host of biological, psychological, and social factors.²

The most important takeaway from these definitions is that nociception and pain are not equivalent and can be dissociated.

One can exist without the other.¹⁵

For instance, a patient under general anesthesia exhibits nociceptive responses to surgical incision (e.g., increased heart rate), but because the brain’s processing centers are suppressed, they do not experience pain.

Conversely, some individuals with neuropathic conditions, such as phantom limb pain, can experience excruciating pain in the complete absence of nociceptive input from the periphery.¹⁵

This dissociation is the cornerstone of modern pain science, reframing pain not as a raw sensation passively relayed to the brain, but as an active, interpretive output

of the brain.

The brain is not a simple radio receiving a signal; it is a complex processor that takes the nociceptive data stream, filters it through the lenses of memory, emotion, and context, and then generates a final, subjective output called “pain.”

The Journey of a Signal: From Stimulus to Spinal Cord

The entire process begins in the body’s tissues with the activation of nociceptors.

These are the free nerve endings of specialized primary afferent neurons located in the skin, muscles, joints, and the linings of some internal organs.¹

They are designed to respond to noxious—that is, potentially or actually tissue-damaging—stimuli.

This initial step is called

transduction, where the energy of the stimulus (be it mechanical, thermal, or chemical) is converted into an electrical signal, or action potential.¹⁸

Once transduced, this electrical signal begins its journey to the central nervous system in a process called transmission.

The signal travels along the axon of the primary afferent neuron.

These neurons are not all the same; they fall into two main categories that are responsible for the different qualities of pain we experience ⁵:

• Aδ (A-delta) fibers: These fibers are thinly myelinated, which allows them to conduct nerve impulses relatively quickly, at speeds of approximately 5 to 30 meters per second. They are responsible for mediating the initial, sharp, stinging, and well-localized sensation often called “first pain.” They allow for a rapid response to injury.⁵
• C-fibers: These fibers are unmyelinated and have a much smaller diameter, resulting in slower conduction velocities of 0.4 to 1.4 meters per second. They are responsible for the delayed, dull, burning, aching, and more diffuse sensation known as “second pain,” which often follows the initial sharp pain.⁵

This dual-fiber system provides an elegant neuroanatomical explanation for a universally understood sensory experience.

The common human phenomenon of feeling an immediate, sharp “ouch” after an injury (like stubbing a toe), followed moments later by a persistent, throbbing ache, is a direct perceptual consequence of these two different nerve fibers delivering their signals to the spinal cord at different speeds.

This makes the abstract concept of distinct nerve fiber types tangible and relatable to lived experience.

The cell bodies of these nociceptive neurons are clustered in ganglia located just outside the central nervous system: the dorsal root ganglia alongside the spinal cord for signals from the body, and the trigeminal ganglion for signals from the head and face.⁵

Ascending to the Brain: The Spinothalamic Tract

When the nociceptive signal arrives at the spinal cord, the primary afferent neuron terminates in the dorsal horn, the gray matter at the back of the spinal cord.

Here, it releases neurotransmitters, such as glutamate and substance P, to communicate with and activate second-order neurons.²¹

The axons of these second-order neurons then perform a crucial maneuver: they decussate, or cross over to the opposite side of the spinal cord.

From there, they ascend toward the brain, primarily within a major pathway known as the spinothalamic tract.²⁰

This crossing explains a fundamental principle of neural organization: sensory information from the right side of the body is processed by the left hemisphere of the brain, and vice versa.²⁴

Perception: The Brain Takes Over

The ascending nociceptive signals travel up the spinothalamic tract through the brainstem and arrive at the thalamus, a critical relay station deep within the brain.³

The thalamus acts like a switchboard, sorting the incoming signals and directing them to a distributed network of higher brain centers.²

It is only when these higher centers process the information that the raw nociceptive signal is transformed into the conscious, subjective, and multifaceted experience of pain.

This final, crucial step of perception is not the end of a simple linear pathway but the beginning of a complex symphony of neural activity across the brain, which will be explored in detail later in this report.

Section 3: The Anatomy of Head Pain: When the Brain’s Protectors Hurt

The resolution to the paradox of the unfeeling brain causing the feeling of a headache lies in the anatomy surrounding it.

While the brain parenchyma is insensate, it is encased within a cranium lined with multiple structures that are richly supplied with nociceptors.

The pain of a headache does not originate from the brain’s neurons but from the activation of these pain-sensitive “guards” that protect it.³

The distribution of these nociceptors is not random; it forms a highly sensitive protective perimeter.

Pain arising from these structures serves as a crucial alarm system, warning of potentially harmful processes like inflammation (meningitis), vascular distress (aneurysm), or increased intracranial pressure, effectively protecting the vital organ within.

The pain is a signal

about the brain’s environment, not from the brain itself.

The Protective Layers: The Meninges

The brain and spinal cord are enveloped in three protective membranes known as the meninges.

These layers are a primary source of intracranial pain.³

• Dura Mater: This is the outermost and toughest of the three layers, lining the inside of the skull. The dura mater is densely innervated with nociceptive fibers, particularly in and around the large blood vessels it contains, such as the dural venous sinuses and the middle meningeal artery.⁴ Mechanical traction, chemical irritation, or inflammation of the dura is a well-established cause of significant headache pain.²⁹
• Arachnoid Mater: Located beneath the dura, the arachnoid is a thin, web-like membrane. It is generally considered to be avascular (lacking blood vessels) and devoid of nerve endings, and thus is not a source of pain.²⁷
• Pia Mater: This is the most delicate and innermost layer, adhering closely to the surface of the brain and following its every contour. For over 70 years, the pia mater was considered, like the brain itself, to be insensitive to pain.³⁰ However, this long-held dogma has been challenged by recent research. Studies conducted during awake craniotomies have shown that direct electrical stimulation of the pia mater and its associated nutrient vessels can, in fact, trigger localized pain sensations in conscious patients.³⁰ This finding suggests that the pia mater may also be involved in headache pathophysiology, representing an exciting and evolving area of neuroscience that refines our understanding of intracranial pain sources.

The Vascular System: Blood Vessels

In addition to the vessels within the dura, the large arteries and veins at the base of the brain are pain-sensitive structures.²⁹

The network of arteries that includes the Circle of Willis, along with the major intracranial venous sinuses, are innervated by nociceptive fibers.

Dilation, stretching, or inflammation of these blood vessels can trigger pain signals, a mechanism implicated in vascular headaches like migraine.⁴

For example, conditions that cause vasodilation, such as fever or exposure to certain drugs like nitrates, can lead to a “toxic vascular headache”.²⁹

Extracranial Structures

A significant portion of headache pain originates from structures outside the skull entirely.²⁹

• Muscles and Fascia: The pericranial muscles—those of the scalp, face, jaw, and neck—are a major source of pain signals, particularly in the most common type of headache, the tension-type headache.⁴ Excessive or sustained contraction of these muscles, often related to stress or poor posture, can activate embedded nociceptors. This pain is frequently described in evocative terms, such as a “tightening band” or a “vise-like” pressure around the head.²⁹ The muscles of mastication (chewing), such as the temporalis and masseter, can also contribute to headache pain, especially in individuals with temporomandibular joint (TMJ) disorders.³²
• Scalp and Periosteum: The skin of the scalp and the periosteum—the thin, fibrous membrane that covers the surface of the skull bones—are both richly supplied with pain receptors and can be sources of head pain.³

The Nerve Hubs: Trigeminal and Cervical Nerves

The nociceptive signals generated by all the aforementioned structures—meninges, blood vessels, muscles, and scalp—do not travel to the brain randomly.

They are collected and transmitted by two main nerve systems:

• Trigeminal Nerve (Cranial Nerve V): This large cranial nerve is the principal sensory conduit for the face and the anterior two-thirds of the head. Crucially, its first and largest branch, the ophthalmic division (V1), provides the primary sensory innervation to the pain-sensitive structures within the front part of the cranium, including the supratentorial dura mater and its associated blood vessels.²⁸ This anatomical arrangement explains why irritation of the dura often results in pain that is “referred” to the regions supplied by the V1 branch, namely the forehead and around the eye.
• Upper Cervical Nerves (C1, C2, C3): The sensory roots of the first three cervical spinal nerves provide innervation to the structures at the back of the head (occipital region) and the upper neck.³²

The Convergence Point: The Trigeminocervical Complex (TCC)

Perhaps the most critical piece of the anatomical puzzle for understanding head pain is the Trigeminocervical Complex (TCC).

This is a region of gray matter located in the upper cervical spinal cord and lower brainstem where the sensory nerve fibers from both the trigeminal nerve and the upper cervical nerves converge and synapse on second-order neurons.³¹

The TCC acts as a “Grand Central Station” for head and neck pain signals.

This convergence of inputs from anatomically distinct areas is the neuroanatomical basis for the phenomenon of referred pain in headaches.³⁴

Because signals from the neck, face, and intracranial dura all converge on the same pool of second-order neurons in the TCC, the brain, upon receiving the signal from these neurons, can have difficulty distinguishing the original source.

This explains many clinically observed phenomena: why irritation of the upper neck joints (cervicogenic headache) can be perceived as pain in the forehead ²⁵, why neck muscle tension can feel like a headache, and why the intense pain of a migraine originating from dural inflammation is often accompanied by neck stiffness and tenderness.

The TCC is the anatomical substrate that links these seemingly disparate regions, creating the complex and often confusing tapestry of headache symptoms.

Table 1: Pain Sensitivity of Cranial and Intracranial Structures

Structure	Pain Sensitivity	Innervating Nerves	Clinical Relevance
Brain Parenchyma	No	N/A	Site of awake brain surgery; insensate to direct stimulation.
Dura Mater	Yes	Trigeminal Nerve (V1, V2, V3), Vagus N., Upper Cervical N.	Primary source of pain in migraines and other intracranial pathologies.
Pia Mater	Debated	Trigeminal Nerve	Traditionally thought insensitive; recent evidence suggests it may be pain-sensitive.
Arachnoid Mater	No	N/A	Avascular and non-innervated; not a source of pain.
Cranial Blood Vessels	Yes	Trigeminal Nerve	Dilation and inflammation contribute to vascular and migraine headaches.
Scalp Muscles	Yes	Trigeminal N., Upper Cervical N.	Primary source of pain in tension-type headaches.
Periosteum (Skull)	Yes	Trigeminal N., Upper Cervical N.	Can contribute to pain from external pressure or injury.
Scalp Skin	Yes	Trigeminal N., Upper Cervical N.	Sensitive to touch, temperature, and injury.

Section 4: The Neurovascular Engine of Migraine and Primary Headaches

Having established the anatomical sources of head pain, the focus now shifts to the complex pathophysiology of primary headache disorders.

These are not mere symptoms but are neurological diseases in their own right, arising from dysfunction within the brain’s pain-processing systems rather than from an obvious structural lesion like a tumor or injury.²⁵

Migraine serves as the archetypal and most-studied example, and its investigation has revealed a sophisticated interplay between nerves and blood vessels that drives its debilitating attacks.

This scientific understanding has not only demystified the condition but has also paved the way for revolutionary treatments that have transformed the lives of millions.

Beyond a Simple Headache: Defining Primary vs. Secondary Headaches

It is essential to first distinguish between primary and secondary headaches.

Secondary headaches are those caused by an underlying medical condition.

The headache is a symptom of something else, which could range from a relatively benign sinus infection or fever to a life-threatening condition like meningitis, a brain tumor, or a ruptured aneurysm.²⁵

In contrast,

primary headaches are the disorder itself.

The three most common types are migraine, tension-type headache, and cluster headache.²⁵

While they have distinct clinical profiles, they share a common feature: they are disorders of brain function, not brain structure.

The Modern View of Migraine: A Neurovascular Disorder

The scientific understanding of migraine has undergone a significant evolution.

An older, purely vascular theory proposed that migraines were caused by an initial constriction of cerebral blood vessels (leading to aura) followed by a rebound dilation (leading to pain).⁴⁰

While changes in blood flow do occur and may contribute to the pain, they are now understood to be a consequence, not the primary cause, of the attack.⁴⁰

The current, more comprehensive model centers on the Trigeminovascular System (TVS), viewing migraine as a complex neurovascular disorder.³⁷

This system comprises the trigeminal nerve endings that innervate the pain-sensitive blood vessels and dura mater of the cranium.²⁸

A migraine attack is believed to be initiated by the activation of this system.

This activation leads to a process called

neurogenic inflammation.

The activated trigeminal nerve endings release a cocktail of inflammatory neuropeptides directly onto the blood vessels they supply.²⁸

The most critical of these peptides are

Substance P and, most notably, Calcitonin Gene-Related Peptide (CGRP).³⁵

These neuropeptides have powerful effects: they cause the meningeal blood vessels to dilate and become “leaky,” allowing plasma proteins to seep into the surrounding tissue.²⁸

This creates a sterile (non-infectious) inflammatory environment that further irritates and sensitizes the nociceptive nerve endings of the trigeminal system.

This sensitization lowers their firing threshold, making them hyperexcitable and contributing directly to the characteristic throbbing pain of a migraine.³⁷

The pivotal role of CGRP in this cascade has been validated by the remarkable success of new classes of migraine medications—including the triptans (which inhibit CGRP release) and the newer monoclonal antibodies and “gepants” (which block CGRP or its receptor)—that specifically target this pathway.²⁸

This journey from a simple vascular model to a complex neuroinflammatory one, culminating in highly effective targeted therapies, stands as a powerful case study in medical progress.

Central and Peripheral Sensitization: The Making of a Migraine Attack

A migraine is not a static event but a dynamic process that evolves over hours or days, driven by progressive sensitization of the nervous system.

• Cortical Spreading Depression (CSD): In the roughly one-quarter of migraine sufferers who experience aura, the attack is often preceded by a phenomenon known as CSD.²⁵ This is a slow-moving wave of intense neuronal hyperactivity, followed by a period of sustained neural silence, that creeps across the surface of the cerebral cortex at a rate of 2-3 mm per minute. CSD is the neurophysiological correlate of the aura, with the wave’s path across the visual or somatosensory cortex determining the nature of the symptoms (e.g., flashing lights, tingling sensations). This dramatic electrical event is a powerful trigger for the activation of the trigeminovascular system, initiating the cascade of neurogenic inflammation.³⁷
• Peripheral Sensitization: As neurogenic inflammation takes hold in the meninges, the peripheral trigeminal nociceptors become increasingly sensitized. Their thresholds for activation drop, and they begin to fire more readily.³⁷ This state of peripheral sensitization is responsible for the signature throbbing or pulsating quality of migraine pain, which is characteristically worsened by routine physical activities that cause minor shifts in intracranial pressure, such as coughing, bending over, or even just walking.³⁷
• Central Sensitization: If the barrage of nociceptive signals from the periphery continues unabated, the second-order neurons within the Trigeminocervical Complex (TCC) can also become hyperexcitable. This is central sensitization. The neurons’ resting state becomes more “depolarized,” making them hair-trigger responsive to any input.³⁷ The clinical manifestation of this state is
  cutaneous allodynia, a bizarre and distressing symptom where normally innocuous stimuli become painful.³⁵ For someone in the throes of an allodynic migraine, the light touch of clothing, the pressure of eyeglasses, the act of combing hair, or even a gentle breeze on the face can be experienced as intensely painful. Allodynia is not a psychological overreaction; it is the direct, perceivable consequence of this specific neurobiological change in the central nervous system. Understanding this link helps to de-stigmatize the symptom and validate the patient’s report of this strange experience.

Differentiating Primary Headaches

While migraine is the most complex, other primary headaches have distinct features:

• Tension-Type Headache (TTH): The most prevalent primary headache, TTH is typically characterized by a bilateral, non-pulsating, pressing or tightening sensation of mild to moderate intensity, often described as a “hatband”.²⁹ It is not usually accompanied by nausea or vomiting. While the mechanisms are less understood than migraine, they are strongly associated with increased tenderness in the pericranial muscles, suggesting that activation of nociceptors in these muscles is a key factor.⁴
• Cluster Headache: This is a rare but excruciatingly severe headache disorder. Attacks are strictly unilateral, centered around the eye or temple, with an intense, boring, or burning quality.²⁹ They are relatively short-lived (15-180 minutes) but occur in clusters, with patients experiencing multiple attacks per day for weeks or months, followed by periods of remission. The pain is accompanied by prominent ipsilateral (same-sided) autonomic symptoms, such as a red, tearing eye, nasal congestion, and facial sweating.²⁹ The cyclical nature of cluster headache points to the involvement of the hypothalamus, the brain’s master clock, in addition to the activation of the trigeminal system.³⁷

The Lived Experience: Narratives of Chronic Pain

Scientific descriptions of pathophysiology cannot fully capture the human toll of these disorders, especially when they become chronic.

Personal narratives from those living with chronic migraine and headache reveal a reality of profound disability and struggle.

Patients describe the pain as “unbearable” and “excruciating,” a relentless force that forces them to retreat from life, abandoning careers, education, and social engagement.⁴²

One woman recalls spending three years essentially confined to her bed, with windows covered in tinfoil because light was so painful.⁴²

A common theme is the “invisibility” of the illness.

Because there are no outward signs, sufferers often face stigma and a lack of empathy.

They are told it’s “just a headache” or that they are exaggerating, leading to feelings of isolation and frustration.⁴²

The journey to an accurate diagnosis and effective treatment can be arduous, with many feeling dismissed or misdiagnosed by the medical system.⁴⁶

Living with a chronic, unpredictable condition requires immense energy and careful planning.

Many adopt strategies like the “spoon theory,” where they must consciously budget their limited daily energy to avoid triggering a severe attack, a stark contrast to the spontaneity enjoyed by healthy individuals.⁴⁴

These stories underscore the devastating impact of primary headache disorders and highlight the urgent need for continued research, better treatments, and greater societal understanding.

Table 2: A Comparative Overview of Primary Headache Disorders

Feature	Migraine	Tension-Type Headache	Cluster Headache
Pain Quality	Throbbing, Pulsating	Pressing, Tightening, Band-like	Boring, Burning, Stabbing
Location	Typically Unilateral (one-sided)	Typically Bilateral (both sides)	Strictly Unilateral, Orbital/Temporal
Intensity	Moderate to Severe	Mild to Moderate	Excruciating, Severe
Duration	4 to 72 hours	30 minutes to 7 days	15 to 180 minutes (in clusters)
Associated Symptoms	Nausea, Vomiting, Photophobia (light sensitivity), Phonophobia (sound sensitivity), Aura (in some)	None, or mild photophobia/phonophobia	Ipsilateral Autonomic Symptoms (tearing, nasal congestion, eyelid drooping, facial sweating), Restlessness
Proposed Key Mechanism	Activation of Trigeminovascular System (TVS), CGRP release, Cortical Spreading Depression (CSD)	Pericranial muscle tenderness, Central sensitization mechanisms	Hypothalamic activation, TVS activation

Section 5: The Pain Matrix: How the Brain Constructs the Experience of Suffering

Once a nociceptive signal has ascended from the periphery and reached the thalamus, its journey is far from over.

It is at this stage that the signal is transformed from a simple “danger” alert into the rich, multifaceted, and deeply personal experience of pain.

This transformation does not occur in a single, discrete “pain center.” Instead, modern neuroscience has revealed that pain perception emerges from the coordinated activity of a distributed network of brain regions, often referred to as the “pain matrix” or “pain connectome”.⁵⁰

This network can be broadly divided into components that process different dimensions of the pain experience.

The Sensory-Discriminative Dimension: “What, Where, and How Much?”

This dimension of pain deals with its physical characteristics: its location on the body, its intensity, and its quality (e.g., sharp, dull, hot, cold).

It answers the “what, where, and how much” questions about the noxious stimulus.

This processing is largely handled by what is known as the lateral pain system.⁵⁴

• Thalamus: Functioning as the brain’s primary sensory relay station, specific nuclei within the thalamus receive the ascending signals from the spinothalamic tract. They sort this information and forward it to the appropriate areas of the cerebral cortex for further processing.³
• Primary and Secondary Somatosensory Cortices (S1/S2): Located in the parietal lobe, these cortical areas are crucial for the sensory-discriminative aspects of pain. They contain a detailed somatotopic map of the body (often visualized as the “homunculus”), which allows the brain to precisely localize the source of the pain.² Activity in these regions correlates with the perceived intensity of the painful stimulus.⁵¹

The Affective-Motivational Dimension: “How Unpleasant Is This?”

This is the emotional core of the pain experience—the unpleasantness, the anguish, the suffering that makes pain aversive and motivates us to escape or avoid its source.

This dimension is what separates the mere sensation of a stimulus from the feeling of being in pain.

It is primarily processed by the medial pain system, which involves several key limbic and cortical structures.⁵⁴

• Anterior Cingulate Cortex (ACC): This region, located deep in the frontal lobe, is consistently implicated in processing the affective, or emotional, quality of pain. It is less concerned with where the pain is and more with how unpleasant it is.⁵⁰ The ACC integrates the nociceptive information with emotional and motivational states, generating the experience of suffering.⁵⁴
• Insular Cortex (Insula): The insula is a region of cortex tucked away deep within the lateral sulcus of the brain. It plays a fundamental role in interoception—the sense of the physiological condition of the entire body. Its activation is critical for generating the subjective feeling and emotional awareness of pain, essentially linking the physical sensation to our internal bodily state.² The ACC and insula are so frequently co-activated during painful experiences that they are considered a core hub for pain affect.
• Limbic System (Amygdala, Hippocampus): These classic emotional centers are also integral to the pain matrix. The amygdala processes the fear, anxiety, and threat associated with pain, while the hippocampus is involved in forming and retrieving memories of painful experiences, which can influence future responses to pain.⁵⁰

The existence of these two parallel but interconnected systems—the lateral for sensation and the medial for affect—is the neurobiological basis for the clinical dissociation between “pain sensation” and “pain unpleasantness.” This explains why, for example, certain surgical interventions (like a cingulotomy, which targets the ACC) can dramatically reduce the emotional distress of intractable pain, leaving patients who report that they can still feel the stimulus but it no longer “bothers” them.⁵⁴

This is a profound insight into the nature of suffering, demonstrating that it has a distinct neural substrate that can be independently modulated.

The Cognitive-Evaluative Dimension: “What Does This Mean?”

Pain is not just a sensation and an emotion; it is also a cognitive experience.

The brain appraises the pain, places it in context, directs attention toward or away from it, and plans a behavioral response.

This higher-order processing is primarily the domain of the Prefrontal Cortex (PFC).²

The PFC exerts “top-down” control over the pain experience.

For example, the expectation of pain can amplify its perception, while distraction or a belief that the pain is not dangerous can diminish it.

The PFC’s involvement highlights that pain is not a simple bottom-up process but is constantly being shaped by our thoughts, beliefs, and attentional state.

Descending Modulation: The Brain’s Own Pain-Control System

The brain is not merely a passive recipient of pain signals; it possesses a powerful system for actively modulating them.

Descending pain modulatory pathways originate in higher brain centers, including the PFC and ACC, and project down to the brainstem, particularly to a region called the Periaqueductal Gray (PAG).²³

The PAG, in turn, projects to the

Rostral Ventral Medulla (RVM), which sends signals down to the dorsal horn of the spinal cord.⁵⁶

These descending pathways can either facilitate or, more commonly, inhibit the transmission of nociceptive signals from the first-order to the second-order neurons at the very first synapse in the spinal cord.²³

This mechanism, often described by the “gate control theory of pain,” can effectively “close the gate” on incoming pain signals, preventing them from ever reaching the brain for perception.

This system utilizes the body’s own analgesic chemicals, the

endogenous opioids (such as endorphins and enkephalins), and is the primary target for powerful pain-relieving drugs like morphine.²⁰

The traditional view of pain processing often depicted a simple, hierarchical path: signal travels to the thalamus, then to the somatosensory cortex (S1) for perception.

However, research has fundamentally challenged this.

Studies of patients with lesions that destroy the S1 cortex reveal that their capacity to evaluate the intensity of a painful stimulus remains almost completely intact.⁵²

Furthermore, functional imaging shows that multiple brain regions—including the secondary somatosensory cortex (S2), the insula, and the ACC—all show activity that correlates with perceived pain intensity.⁵²

This means that the conscious awareness of how much something hurts is not dependent on a single brain region but is a distributed, parallel computation.

This redundancy makes the pain system incredibly resilient.

Damage to one part does not abolish the perception, as other parallel pathways can still process the information.

This design ensures that a vital protective signal is not easily lost, but it also helps to explain the remarkable tenacity and persistence of chronic pain.

Table 3: The Brain’s Pain Matrix: Key Regions and Functions

Brain Region	Primary Role/Dimension	Specific Function
Somatosensory Cortex (S1/S2)	Sensory-Discriminative	Localizes pain on the body; determines its intensity and physical quality (sharp, hot, etc.).
Thalamus	Relay Station	Sorts and directs ascending sensory signals to various cortical and limbic areas.
Anterior Cingulate Cortex (ACC)	Affective-Motivational	Processes the emotional unpleasantness, distress, and suffering associated with pain.
Insular Cortex (Insula)	Affective-Motivational / Interoceptive	Integrates pain with the body’s internal physiological state; generates the subjective “feeling” of pain.
Prefrontal Cortex (PFC)	Cognitive-Evaluative	Manages attention, expectation, and appraisal of pain’s meaning; involved in top-down control.
Amygdala / Limbic System	Emotional Response	Mediates fear, anxiety, and the formation of negative memories associated with pain.
Periaqueductal Gray (PAG)	Descending Modulation	A key midbrain center that initiates top-down signals to inhibit ascending pain transmission.

Section 6: When the Map Is Not the Territory: Pain Without a Periphery

Perhaps the most compelling and definitive evidence that pain is a construct of the brain, rather than an intrinsic property of the body’s tissues, comes from the remarkable and often tragic phenomenon of phantom limb pain (PLP).

This condition, in which an individual experiences vivid, and often excruciating, pain in a body part that has been amputated, provides an unparalleled window into the brain’s role in generating perception in the absence of a physical source.⁵⁸

The Phenomenon of the Phantom Limb

Following the amputation of a limb, the vast majority of individuals continue to feel its presence.

This “phantom limb” is not a vague impression but a detailed, vivid sensation; they may feel the limb’s position, feel an itch on a non-existent finger, or even attempt to move it.⁵⁹

For many, these phantom sensations are accompanied by significant pain.

This is not a psychological delusion or a sign of mental illness; it is a real, tangible, and neurologically-driven perceptual experience.⁶⁰

The challenge in understanding and treating PLP is that the pain arises from a part of the body that, quite literally, no longer exists.⁶²

The Leading Theory: Maladaptive Cortical Reorganization

The most widely accepted explanation for PLP centers on the concept of brain plasticity—specifically, a form of it that becomes maladaptive.⁵⁹

The brain’s primary somatosensory and motor cortices contain highly organized somatotopic maps, where specific areas of cortex are dedicated to processing sensory information from, and controlling movement of, specific body parts.

This is often visualized as the cortical “homunculus”.⁵⁹

When a limb is amputated, the corresponding area on this cortical map is suddenly deprived of its normal stream of sensory input.

It becomes “silent” neural real estate.⁵⁸

In a process known as

cortical reorganization, this silent territory does not remain idle.

Instead, the representations of neighboring body parts on the cortical map begin to expand and “invade” the deprived area.⁶³

For an arm amputee, the cortical area for the face, which lies adjacent to the hand area on the map, may expand into the now-silent hand territory.⁵⁹

This rewiring creates a profound sensory mismatch.

Now, when the person is touched on the face, the sensory signals not only activate the original face cortex but also the newly re-purposed hand cortex.⁶³

This can lead to the bizarre experience of feeling a touch on the face as a sensation in the phantom hand.

The brain receives conflicting and nonsensical information—a signal that indicates the hand is being touched, but without any of the corresponding proprioceptive or visual confirmation.

It is hypothesized that this persistent conflict or “error signal” is interpreted by the brain’s pain-processing networks as pain.⁵⁹

In this sense, PLP can be understood as a “glitch” in the brain’s body representation software.

The brain’s internal body model, or “body schema,” fails to update correctly after the “hardware” (the limb) is removed.

The resulting conflict between the persistent software map and the absent hardware input generates a continuous stream of error signals that the brain experiences as pain.

Challenging and Refining the Theory

As with all areas of active science, the maladaptive plasticity theory is not without its challenges and refinements.

Some studies have shown that, contrary to the invasion model, the original representation of the missing hand can persist in the brain for decades after amputation, and that the degree of this persistence, rather than its takeover by neighbors, correlates with the intensity of phantom pain.⁵⁹

Other factors are also believed to contribute.

At the site of the amputation, damaged peripheral nerves can form tangled masses of axons called

neuromas, which can fire erratically and send chaotic signals up the spinal cord.⁶³

Additionally, some researchers propose that “pain memories” from the time of the injury or from pre-amputation pain can become wired into the brain’s circuitry, contributing to the phantom sensations.⁶³

It is likely that PLP is a complex condition arising from a combination of these peripheral, spinal, and cerebral mechanisms.⁶⁰

Therapies that “Trick” the Brain

Despite the complexities, the cortical reorganization theory is strongly supported by the success of therapies designed specifically to resolve the underlying sensory-motor conflict.

These treatments provide powerful evidence for the theory because they work by leveraging the brain’s own plasticity to “rewire” it in a more adaptive Way.

• Mirror Therapy: In this elegantly simple therapy, the patient places a mirror vertically on a table, hiding their amputated limb and reflecting their intact limb. When they look in the mirror and move their intact hand, they receive a powerful visual illusion that their phantom limb has been resurrected and is moving painlessly and under their control.⁶¹ This congruent visual feedback can “trick” the brain, resolve the sensory conflict, reduce the activity of the “error” signals, and thereby alleviate the pain.
• Brain-Machine Interfaces (BMIs) and Virtual Reality: More advanced therapies use technology to achieve a similar goal. Electrodes can read the brain’s motor intent to move the phantom hand. This decoded signal is then used to control a robotic prosthetic or a virtual hand on a screen.⁶⁵ By re-establishing a coherent link between the brain’s motor command and a corresponding sensory (visual) feedback, these therapies can induce a new, more adaptive form of plasticity, effectively training the brain out of its painful state.⁶⁶

The very existence of phantom limb pain, and the success of therapies that manipulate the brain’s perception of the body, provides the ultimate proof that pain is not a simple sensation from the periphery.

It is a rich, dynamic, and wholly brain-generated construct.

The brain creates the pain based on its internal maps, its memories, and the state of its own intricate wiring.

Neuroplasticity, the very mechanism that allows us to learn and adapt, is revealed to be a double-edged sword: it can lead to the intractable suffering of PLP, but it can also be therapeutically harnessed to guide the brain back toward a painless state, offering a hopeful and dynamic view of recovery from neurological injury.

Section 7: The Overlap of Hurt: The Neurology of Physical and Emotional Pain

The brain’s construction of pain extends beyond the realm of physical injury.

One of the most profound discoveries in modern neuroscience is the significant and clinically crucial overlap between the neural circuits that process physical pain and those that process emotional and social distress.

This finding provides a concrete biological basis for the deep connection between bodily suffering and emotional anguish, revealing that, at the level of the brain, “hurt” is a common currency.⁶⁷

A Shared Neural Currency for Pain

Neuroimaging studies have consistently revealed a striking fact: when people experience emotional pain—such as the sting of social rejection, the grief of a loss, or the ache of a “broken heart”—the same areas of the brain become active as when they experience physical pain.⁶⁸

Specifically, the

anterior cingulate cortex (ACC) and the anterior insula, the core components of the brain’s affective pain system (the medial system), are robustly activated by both types of aversive experience.⁵⁴

This shared neural substrate suggests that the brain did not evolve an entirely new system to process the pain of social threats.

Instead, from an evolutionary perspective, it was more efficient to co-opt the ancient, powerful alarm system already in place for physical threats.⁶⁹

For a profoundly social species like humans, threats to social connection—ostracism, rejection, exclusion—were historically as dangerous to survival and procreation as physical injury.

By processing social pain through the same affective circuitry as physical pain, the brain ensures that these social threats are taken just as seriously, generating a powerful motivation to maintain the social bonds crucial for survival.⁶⁹

This provides a deep biological reason why our language is filled with metaphors that conflate the two: we speak of “hurt feelings,” a “crushing” disappointment, or a “heart-wrenching” loss because, in the brain, the experience of suffering is fundamentally similar.⁶⁷

Experimental Evidence

The evidence for this overlap is not merely correlational.

Clever experiments have demonstrated a causal link.

In seminal fMRI studies, participants playing a virtual ball-tossing game who were then deliberately excluded by the other “players” showed increased activity in the ACC and insula, the same regions that light up in response to a painful heat stimulus.⁶⁸

Even more compellingly, this shared pathway can be modulated by common analgesics.

A landmark study found that participants who took a daily dose of acetaminophen (Tylenol), a standard over-the-counter painkiller, reported less subjective emotional pain from social rejection compared to a placebo group.

Furthermore, this subjective report was mirrored in their brain activity: the acetaminophen group showed blunted activation in the ACC and insula in response to the social exclusion.⁶⁹

The fact that a drug designed to treat physical pain can also reduce emotional pain provides powerful evidence that the two experiences rely on common neurochemical mechanisms.

The Clinical Implications: The Vicious Cycle of Pain and Mood

This neural overlap is not an academic curiosity; it has profound implications for clinical medicine and mental health.

It provides a clear neurobiological explanation for the extremely high rate of comorbidity between chronic pain conditions and mood disorders like depression and anxiety.⁶⁷

The relationship is a vicious, bidirectional cycle.

On one hand, chronic physical pain constantly bombards the affective pain circuitry (the ACC and insula), which is deeply interconnected with brain regions that regulate mood.

This sustained, aversive input can disrupt normal mood regulation, leading to the development of depression and anxiety.⁷¹

Researchers have identified specific circuits that link pain to

anhedonia, the inability to experience pleasure, which is a core symptom of depression.

They found that pain can suppress the activity of dopamine neurons in the brain’s reward pathway, providing a direct neurochemical link between the presence of pain and the loss of motivation and pleasure.⁷⁰

Conversely, a negative emotional state can powerfully amplify the perception of physical pain.

Stress, anxiety, and depression can lower the pain threshold and increase pain sensitivity by altering the “top-down” modulation of pain signals.⁶⁷

The emotional state acts as a volume knob for the pain experience.

This understanding underscores the critical need for an integrated, biopsychosocial approach to treatment.

Effectively managing chronic pain often requires addressing the co-existing emotional and psychological distress, and, conversely, treating depression and anxiety can lead to significant improvements in pain management.⁶⁷

The shared circuitry may also be a cornerstone of empathy.

When we witness another person in pain, our own pain matrix, particularly the ACC and insula, can become partially activated.

This suggests that empathy is not just a cognitive understanding but an embodied simulation, allowing us to feel a shadow of another’s suffering and motivating compassionate behavior.⁵³

Section 8: A Synthesis of Sensation and Suffering: The Brain as the Sole Organ of Pain

This exploration began with a simple question born from a paradox: if the brain is the organ of perception, why can it not feel pain? The journey to the answer has traversed the intricate pathways of the nervous system, from the specialized sensors in the skin to the complex, distributed networks of the cerebral cortex.

In synthesizing the evidence, a clear and profound conclusion emerges: the brain, while itself insensate, is the sole and ultimate organ of pain.

Revisiting the Paradox

The initial paradox is resolved by understanding the brain’s architecture and the nature of neural signaling.

The brain tissue itself is devoid of nociceptors because it is protected by a perimeter of highly sensitive “guards”—the meninges, blood vessels, muscles, and skin of the head and neck.

These structures are equipped with the necessary sensors to detect threats to the brain’s integrity, such as inflammation, pressure, or vascular distress.

When activated, these guards do not send “pain” to the brain; they send objective, electrochemical signals—nociception—along dedicated neural highways like the trigeminal nerve and ascending spinal tracts.

Pain is not the message that is sent; it is the interpretation of the message upon its arrival.

Pain as a Brain-Generated Construct

The central thesis of modern pain science, and of this report, is that pain is not a raw sensation that travels unimpeded from the periphery to a passive receiver in the brain.

It is a complex, multidimensional, and entirely subjective experience that is actively constructed by the brain.

The evidence for this constructive view is overwhelming.

The brain takes the raw nociceptive data stream and integrates it with a vast array of other information, processing it through multiple, parallel networks that correspond to the different dimensions of the experience:

• The Sensory Dimension (“What and Where”): The somatosensory cortex analyzes the physical characteristics of the stimulus, giving pain its location, intensity, and quality.
• The Emotional Dimension (“How Bad”): The limbic system, particularly the anterior cingulate cortex and insula, imbues the sensation with its unpleasant, aversive quality, generating the experience of suffering.
• The Cognitive Dimension (“What it Means”): The prefrontal cortex appraises the context, directs attention, and draws on memory and expectation to modulate the final perception.

The Definitive Evidence

Two key lines of evidence presented in this report stand as definitive proof of pain’s cerebral origin.

First, the phenomenon of phantom limb pain demonstrates, unequivocally, that the brain can generate the complete and excruciating experience of pain in the utter absence of a physical source.

The pain is not in the non-existent limb; it is in the brain’s internal map of that limb, a product of maladaptive plasticity and sensory-motor conflict.

If the brain can create pain without a body part, then pain must be a product of the brain, not the body part.

Second, the neural overlap between physical and emotional pain reveals that the quality of suffering is a product of specific brain networks, namely the affective pain matrix.

The fact that the sting of social rejection and the ache of a physical injury are processed by the same core regions—and can even be palliated by the same analgesic medication—shows that “hurt” is a state of the brain that can be triggered by both physical and purely psychological events.

Final Conclusion: The Unification of Sensation and Suffering

Ultimately, every pain we can experience—from the sharp sting of a paper cut to the throbbing agony of a migraine, from the dull ache of an old injury to the profound anguish of a broken heart—is a neurobiological event.

It is a perception created, modulated, and experienced exclusively within the intricate networks of the human brain.

The brain is the final arbiter, the sole interpreter, and the exclusive stage upon which the entire drama of pain unfolds.

This understanding is far from a mere academic exercise.

It has profound implications.

It validates the experiences of those with “invisible” conditions like chronic migraine or fibromyalgia, confirming that their suffering is biologically real even without an obvious peripheral injury.

It explains why psychological and social factors are not just reactions to pain but are integral components of the pain experience itself, necessitating holistic, biopsychosocial approaches to treatment.

Finally, by revealing the deep connection between our own suffering and that of others, it provides a powerful neurobiological foundation for empathy and compassion.

To understand that pain is a construct of the brain is to understand the profound power of this organ to create our reality, and to appreciate the shared human experience of suffering in all its forms.

Works cited

1. www.brainfacts.org, accessed on August 8, 2025, https://www.brainfacts.org/ask-an-expert/if-the-brain-cant-feel-pain-why-do-i-get-headaches#:~:text=These%20specialized%20fibers%20%E2%80%94%20which%20are,located%20in%20brain%20tissue%20itself.
2. Why Doesn’t the Brain Have Nociceptors? – BrainFacts.org, accessed on August 8, 2025, https://www.brainfacts.org/thinking-sensing-and-behaving/pain/2021/why-doesnt-the-brain-have-nociceptors-020321
3. Can the Brain Itself Feel Pain? – Brainline.org, accessed on August 8, 2025, https://www.brainline.org/author/brian-greenwald/qa/can-brain-itself-feel-pain
4. If the brain can’t feel pain, why do I get headaches? – BrainFacts, accessed on August 8, 2025, https://www.brainfacts.org/ask-an-expert/if-the-brain-cant-feel-pain-why-do-i-get-headaches
5. Nociceptors: the sensors of the pain pathway – PMC – PubMed Central, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC2964977/
6. www.ninds.nih.gov, accessed on August 8, 2025, https://www.ninds.nih.gov/health-information/disorders/headache#:~:text=The%20brain%20itself%20doesn’t,that%20message%20to%20the%20brain.
7. Makenzi’s story, Low-grade Glioma, awake craniotomy | Mayfield Brain & Spine, accessed on August 8, 2025, https://mayfieldclinic.com/mc_hope/story_makenzi.htm
8. Awake Craniotomy | Expert Surgeon – Aaron Cohen-Gadol, MD, accessed on August 8, 2025, https://www.aaroncohen-gadol.com/en/patients/craniotomy/awake-craniotomy
9. Wide Awake Brain Surgery – Time Magazine, accessed on August 8, 2025, https://time.com/awake-brain-surgery/
10. I Was Awake During My Brain Surgery, accessed on August 8, 2025, https://neurosurgery.weillcornell.org/patient-story/i-was-awake-during-my-brain-surgery
11. Awake craniotomy – Neurosciences Journal, accessed on August 8, 2025, https://nsj.org.sa/content/20/3/248
12. The Top 10 facts you need to know about Awake Craniotomy, accessed on August 8, 2025, https://jmsma.scholasticahq.com/article/37294-the-top-10-facts-you-need-to-know-about-awake-craniotomy
13. During Awake Craniotomy, Patient Sang Her Way Through Brain Surgery | NYU Langone News, accessed on August 8, 2025, https://nyulangone.org/news/during-awake-craniotomy-patient-sang-her-way-through-brain-surgery
14. Patient and Neurosurgeon Discuss Awake Craniotomies – Moffitt Cancer Center, accessed on August 8, 2025, https://www.moffitt.org/endeavor/archive/patient-and-neurosurgeon-discuss-awake-craniotomies/
15. Nociception versus Pain | Pain Management Education at UCSF, accessed on August 8, 2025, https://pain.ucsf.edu/understanding-pain-pain-basics/nociception-versus-pain
16. Pain or nociception? Subjective experience mediates the effects of, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5901905/
17. Pain Principles (Section 2, Chapter 6) Neuroscience Online, accessed on August 8, 2025, https://nba.uth.tmc.edu/neuroscience/m/s2/chapter06.html
18. Nociceptive Pain: What It Is, Causes, Treatment & Types – Cleveland Clinic, accessed on August 8, 2025, https://my.clevelandclinic.org/health/symptoms/nociceptive-pain
19. Anatomy And Neurobiology Of Pain – DUNE – University of New England, accessed on August 8, 2025, https://dune.une.edu/cgi/viewcontent.cgi?article=1018&context=biomed_facpubs
20. Pain Pathways – TeachMePhysiology, accessed on August 8, 2025, https://teachmephysiology.com/nervous-system/sensory-system/pain-pathway/
21. Pain and Nociception – Introduction to Neuroscience, accessed on August 8, 2025, https://openbooks.lib.msu.edu/introneuroscience1/chapter/pain/
22. The Anatomy and Physiology of Pain – Pain and Disability – NCBI Bookshelf, accessed on August 8, 2025, https://www.ncbi.nlm.nih.gov/books/NBK219252/
23. What are pain pathways (nociceptive pathways)? – Dr.Oracle AI, accessed on August 8, 2025, https://www.droracle.ai/articles/55081/what-is-pain-pathways
24. Nociceptors – An Introduction to Pain – YouTube, accessed on August 8, 2025, https://www.youtube.com/watch?v=fUKlpuz2VTs
25. Understanding Headaches and Migraines | Brain Institute – OHSU, accessed on August 8, 2025, https://www.ohsu.edu/brain-institute/understanding-headaches-and-migraines
26. If we have no pain receptors in our brain, then how do we get headaches and migraines?, accessed on August 8, 2025, https://www.reddit.com/r/askscience/comments/35rw5c/if_we_have_no_pain_receptors_in_our_brain_then/
27. Meninges: What They Are & Function – Cleveland Clinic, accessed on August 8, 2025, https://my.clevelandclinic.org/health/articles/22266-meninges
28. Meningeal Mechanisms and the Migraine Connection – PMC, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11412714/
29. Headache – Clinical Methods – NCBI Bookshelf, accessed on August 8, 2025, https://www.ncbi.nlm.nih.gov/books/NBK377/
30. Migraine: Regions of the Brain We Thought Felt No Pain – Salle de presse de l’Inserm, accessed on August 8, 2025, https://presse.inserm.fr/en/migraine-regions-of-the-brain-we-thought-felt-no-pain/58062/
31. The anatomy of head pain – PubMed, accessed on August 8, 2025, https://pubmed.ncbi.nlm.nih.gov/38043970/
32. Anatomy of a Headache – Precision Chiropractic Vermont, accessed on August 8, 2025, https://www.precisionchirovt.com/news/blog/migraine-headache/anatomy-of-a-headache
33. Physical therapy in Reading, Sinking Spring, Wernersville, Berks county for Headaches, accessed on August 8, 2025, https://www.southmountainpt.com/Injuries-Conditions/Head/Headaches/a~8004/article.html
34. If the brain doesn’t feel pain, why do headaches hurt? | Live Science, accessed on August 8, 2025, https://www.livescience.com/if-the-brain-doesnt-feel-pain-why-do-headaches-hurt
35. The four causes of primary headaches | Medmastery, accessed on August 8, 2025, https://www.medmastery.com/guides/headaches-clinical-guide/etiology-primary-headaches-four-main-culprits
36. Pathophysiology of Headaches | Principles and Practice of Pain Medicine, 3e | AccessAnesthesiology, accessed on August 8, 2025, https://accessanesthesiology.mhmedical.com/content.aspx?bookid=1845§ionid=133686257
37. Current Understanding on Pain Mechanism in Migraine and Cluster Headache – PMC, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5018152/
38. This is the REAL reason headaches hurt – YouTube, accessed on August 8, 2025, https://www.youtube.com/shorts/oi6j2xytWpg
39. Brain aneurysm – Symptoms and causes – Mayo Clinic, accessed on August 8, 2025, https://www.mayoclinic.org/diseases-conditions/brain-aneurysm/symptoms-causes/syc-20361483
40. How a Migraine Happens | Johns Hopkins Medicine, accessed on August 8, 2025, https://www.hopkinsmedicine.org/health/conditions-and-diseases/headache/how-a-migraine-happens
41. Patients with tension headaches (Chapter 43) – Case Studies in Pain Management, accessed on August 8, 2025, https://www.cambridge.org/core/books/case-studies-in-pain-management/patients-with-tension-headaches/18AFB47C640E5E6AC24CF42D83292BD1
42. What I Wish People Knew About Living with Chronic Migraines – Jefferson Health, accessed on August 8, 2025, https://www.jeffersonhealth.org/your-health/living-well/what-i-wish-people-knew-about-living-with-chronic-migraines
43. My migraine journey, accessed on August 8, 2025, https://migrainetrust.org/my-migraine-journey/
44. Maddie’s Story: Medical Management of Chronic Migraine, accessed on August 8, 2025, https://www.chop.edu/stories/maddie-s-story-management-chronic-migraine
45. Living with chronic migraine: a qualitative study on female patients’ perspectives from a specialised headache clinic in Spain – PubMed Central, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5724120/
46. After Ten Years of Chronic Migraines, Kaitlin Finally Gets Her Life Back – UT Health Austin, accessed on August 8, 2025, https://uthealthaustin.org/blog/pediatric-headache-success-story
47. Why women suffer more from migraines and why doctors often ignore their pain, accessed on August 8, 2025, https://timesofindia.indiatimes.com/life-style/health-fitness/health-news/why-women-suffer-more-from-migraines-and-why-doctors-often-ignore-their-pain/articleshow/123116421.cms
48. Case Study: Severe Headache in a Young Woman – Women’s Healthcare, accessed on August 8, 2025, https://www.npwomenshealthcare.com/case-study-severe-headache-in-a-young-woman/
49. The lived experience of chronic headache: a systematic review and synthesis of the qualitative literature – PMC, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5778309/
50. pmc.ncbi.nlm.nih.gov, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6650904/#:~:text=Brain%20structures%2C%20including%20the%20primary,16%2C17%2C18%5D.
51. Chronic Pain and the Brain – Physiopedia, accessed on August 8, 2025, https://www.physio-pedia.com/Chronic_Pain_and_the_Brain
52. Pain Intensity Processing Within the Human Brain: A Bilateral, Distributed Mechanism, accessed on August 8, 2025, https://journals.physiology.org/doi/10.1152/jn.1999.82.4.1934
53. Neuroanatomy S3 E4: Pain #neuroanatomy #ubcmedicine – YouTube, accessed on August 8, 2025, https://www.youtube.com/watch?v=GJOb-FOXd2c
54. Pain and Emotion: A Biopsychosocial Review of Recent Research – PMC – PubMed Central, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC3152687/
55. Pain processing in the brain: What changes with chronic pain – YouTube, accessed on August 8, 2025, https://www.youtube.com/watch?v=8Y2G40-9mUc
56. Chronic Pain: Structural and Functional Changes in Brain Structures and Associated Negative Affective States – PubMed Central, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6650904/
57. The Neurology of Pain: How Our Brains Interpret Pain, accessed on August 8, 2025, https://premierneurologycenter.com/blog/the-neurology-of-pain-how-our-brains-interpret-pain/
58. Phantom Limb Pain | TxBDC | UT Dallas, accessed on August 8, 2025, https://txbdc.utdallas.edu/research/phantom-limb-pain/
59. Solving Phantom Limb Pain – Science is Getting Closer, accessed on August 8, 2025, https://www.ndcn.ox.ac.uk/news/solving-phantom-limb-pain-2013-science-is-getting-closer
60. What neuroimaging has taught us about phantom limb pain – PMC – PubMed Central, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8933774/
61. Phantom Limb Pain: What It Is, Causes, Treatment & Prevention – Cleveland Clinic, accessed on August 8, 2025, https://my.clevelandclinic.org/health/diseases/12092-phantom-limb-pain
62. Rethinking the role of the brain in driving phantom pain, accessed on August 8, 2025, https://www.iasp-pain.org/publications/relief-news/article/brain-and-phantom-pain/
63. The Neural Basis of Phantom Limb Pain – Grey Matters Journal, accessed on August 8, 2025, https://greymattersjournal.org/the-neural-basis-of-phantom-limb-pain/
64. 2-Minute Neuroscience: Phantom Limb – YouTube, accessed on August 8, 2025, https://www.youtube.com/watch?v=GYxksqaLBxc
65. Neural basis of induced phantom limb pain relief – PMC – PubMed Central, accessed on August 8, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6492189/
66. Cause of phantom limb pain in amputees, and potential treatment, identified, accessed on August 8, 2025, https://www.cam.ac.uk/research/news/cause-of-phantom-limb-pain-in-amputees-and-potential-treatment-identified
67. The Connection Between Emotional and Physical Pain – Dakota Family Services, accessed on August 8, 2025, https://dakotafamilyservices.org/resources/blog/archive/connection-between-emotional-and-physical-pain/
68. Emotional and Physical Pain Activate Similar Brain Regions – Psychology Today, accessed on August 8, 2025, https://www.psychologytoday.com/us/blog/body-sense/201204/emotional-and-physical-pain-activate-similar-brain-regions
69. On the surprising neuroscience of emotional pain – YouTube, accessed on August 8, 2025, https://www.youtube.com/watch?v=LBw0iqo5U2k
70. Emotional aspects of chronic pain isolated in brain circuitry, accessed on August 8, 2025, https://hopecenter.wustl.edu/emotional-aspects-of-chronic-pain-isolated-in-brain-circuitry/
71. Emotional aspects of chronic pain isolated in brain circuitry – WashU Medicine, accessed on August 8, 2025, https://medicine.washu.edu/news/emotional-aspects-of-chronic-pain-isolated-in-brain-circuitry/