On Pain: Anatomy, Physiology, and Pathology of Nociception

Core Perspective

• Anatomy: how the body is built

• Physiology: how the body works

• Pathology: how the body breaks down, is injured, or is destroyed

Pain is central to pathology because nearly all diseases, injuries, and dysfunctions involve pain.

Why Pain Exists (Purpose of Pain)

Pain is not a flaw, it is a survival mechanism.

1. Warning System

• Alerts the body to tissue damage or potential injury

• Prompts withdrawal from harmful stimuli

2. Learning Mechanism

• Negative reinforcement prevents repeated injury

• Example: touching a hot stove once teaches avoidance

Clinical Insight

People with Congenital Insensitivity to Pain (a rare genetic disorder) cannot feel pain in the peripheral nervous system and are at high risk for:

• Burns

• Cuts

• Fractures

• Chronic injury without awareness

Pain is essential for survival.

Types of Sensory Receptors (Normal Sensation)

Before pain, we must understand normal sensation.

Mechanoreceptors

• Light touch (hair follicle movement)

• Pressure

• Proprioception (body position awareness)

Example:
You can touch your palm with eyes closed because muscle length receptors inform the brain of limb position.

Thermoreceptors

• Sense temperature within a normal physiological range

• Skin typically senses up to ~52°C (125°F) without tissue damage

Transition From Sensation to Pain

All sensory receptors operate within a safe range.

When stimuli exceed that range → pain receptors activate.

Nociceptors

• Activated by noxious stimuli

• Respond to:

  • Extreme heat or cold

  • Excessive pressure

  • Chemical irritation

  • Tissue damage

Pain begins when nociceptors fire.

Peripheral Nervous System: Pain Transmission

Neuron vs Nerve

• Neuron = single cell

• Nerve = bundle of neurons

Example: Ulnar Nerve

• Mixed nerve (sensory + motor)

• Supplies the pinky finger

Burning the pinky finger:

1. Nociceptor activates

2. Signal travels through the ulnar nerve

3. Enters the spinal cord

Spinal Cord Processing

The spinal cord is part of the Central Nervous System (CNS).

Key Site

• Substantia Gelatinosa (dorsal horn of spinal cord)

• First synapse between:

  • Primary nociceptor neuron

  • Secondary ascending neuron

This site is critical for pain modulation.

Ascending Pain Pathway (Brain Processing)

Step 1: Brainstem

Secondary neuron ascends through:

• Medulla oblongata

• Pons

• Midbrain

Step 2: Thalamus

• Acts as a sensory relay hub

• Distributes pain signals to:

  • Sensory cortex

  • Limbic system

  • Other processing centers

Cortical Awareness of Pain

Primary Somatosensory Cortex

• Located in the parietal lobe

• Just posterior to the central sulcus

• Organized somatotopically:

  • Each body part maps to a specific cortical region

Conscious awareness of pain occurs here (and partially in the thalamus).

Emotional Component of Pain

Amygdala (Limbic System)

• Processes negative emotions

• Generates distress, fear, and avoidance

Why this matters:

• Pain must be unpleasant to discourage repetition

• Positive pain response would be maladaptive

Pain Modulation (Descending Control)

Pain does not remain maximal indefinitely.

Peri-aqueductal Gray (PAG)

• Surrounds the cerebral aqueduct in the midbrain

• Receives signals from the thalamus

Descending Pathway

1. Thalamus signals PAG

2. PAG activates descending neurons

3. Signals return to the substantia gelatinosa

4. Endogenous opioids are released

Effect

• Inhibits nociceptive transmission

• Reduces perceived pain

The body produces its own painkillers (endorphins, enkephalins).

Ventricular System (Relevant Anatomy)

• Lateral ventricles (2)

• Third ventricle (between thalami)

• Fourth ventricle (between brainstem and cerebellum)

• Cerebral aqueduct connects 3rd to 4th ventricle

Cerebrospinal fluid (CSF):

• Produced in ventricles

• Cushions and protects the brain

Subjectivity of Pain

Pain is real, but subjective.

Phantom Limb Pain

• Occurs even when peripheral structures are gone

• Sensory cortex region remains active

• Brain-generated pain without peripheral input

Clinical Implication

Two people receiving the same injury will rate pain differently due to:

• Emotional state

• Prior experiences

• Cortical processing differences

Pain perception varies between individuals.

Key Takeaways

• Pain is a protective, adaptive mechanism

• It involves:

  • Peripheral nociceptors

  • Spinal processing

  • Brainstem transmission

  • Thalamic relay

  • Cortical awareness

  • Emotional interpretation

  • Descending modulation

• Pain is both physiological and psychological

• Despite extensive knowledge, pain perception remains incompletely understood

One-Line Summary

Pain is a complex sensory and emotional experience involving peripheral detection, central processing, emotional modulation, and endogenous control, essential for survival but uniquely subjective.