CNS: Nociception/Pain (Exam 2 Material)

What are nociception and nociceptors?

Nociception:

• The nervous system’s detection and processing of potentially harmful stimuli (noxious stimuli)

• Produces sensory signals that can trigger the perception of pain

• Protective mechanism: Helps organisms detect and avoid harmful stimuli, improving survival

Nociceptors → Pain receptors

• Free nerve endings of sensory neurons located in the periphery, including the skin

• Detect potentially harmful stimuli and transmit signals toward the CNS

• Innervate the skin = supply the skin with sensory nerves

What are three types of stimuli that activate nociceptors?

How does nociception work

What is the neuronal pathway of nociception?

Nociception: Harmful stimuli are detected in the body and transmitted to the brain through 3 orders of sensory neurons.

1. First-order sensory neuron (Body → Spinal Cord)

• Nociceptors detect potentially harmful stimuli

• Cell body located in the dorsal root ganglion (DRG) outside the spinal cord

• The axon enters the dorsal horn of the spinal cord and releases glutamate, activating the second-order neuron

  • Glutamate is an excitatory neurotransmitter that activates the second-order neuron, allowing the pain-related signal to continue toward the brain.

2. Second-order sensory neuron (Spinal Cord → Thalamus)

• Located in the dorsal horn of the spinal cord

• Its axon crosses crosses to the opposite side of the spinal cord before ascending to the brain

• Ascends through the spinal cord and brainstem to the thalamus, where it synapses with the third-order neuron

  • For example, a painful stimulus on your right hand is transmitted through a pathway that crosses to the left side of the spinal cord and ascends toward the left thalamus and somatosensory cortex.

3. Third-order sensory neuron (Thalamus → cortex)

• Cell body is located in the thalamus

• Projects to the somatosensory cortex in the parietal lobe

• Allows the brain to identify the location and intensity of the painful stimulus

What is the difference between the spinothalamic and trigeminothalamic pathways? 🟠

1. Spinothalamic pathway (Body → Brain)

• Coverage Area: Transmits nociceptive (pain) signals originating from the trunk and limbs.

• First-Order Neurons: Primary nociceptor fibers carry signals from peripheral receptors, with their cell bodies located in the dorsal root ganglion.

• Level of Decussation (Crossing Over): Secondary pain fibers decussate (cross to the opposite side) immediately at the level of entry in the spinal cord (shown at lumbar level A and cervical level B).

• Ascending Path: Signals ascend through the spinothalamic tract via the caudal medulla (C) up to the thalamus.

• Thalamic Relay & Destination: Synapses in the Ventral Posterior Lateral (VPL) nucleus of the thalamus before projecting to the primary somatosensory cortex (D).

2. Trigeminothalamic pathway (Face → Brain)

• Coverage Area: Transmits nociceptive signals originating from the face, scalp, and head.

• First-Order Neurons: Carried by cranial nerve V (Trigeminal nerve) with primary cell bodies in the trigeminal ganglion.

• Level of Decussation (Crossing Over): Nociceptive fibers descend to synapse in the spinal trigeminal nucleus located in the caudal medulla (A), where secondary pain fibers decussate.

• Ascending Path: Ascends through the brainstem via the pons (B) up to the thalamus.

• Thalamic Relay & Destination: Synapses in the Ventral Posterior Medial (VPM) nucleus of the thalamus (C) before projecting to the somatosensory cortex.

What is the difference between Nociception vs Touch?

• Nociception: Detects harmful pressure

• Touch: Detects light pressure

Describe the dorsal column system (touch).

• First order neuron enters at dorsal root and ascends to medulla in dorsal columns

• Synapses on a second-order neuron on the same side in medulla

• Second order neuron decussates (crosses) in brainstem (medulla)

What are the two types of dissociated sensory loss?

• Imagine right side of spinal cord is where lesion occurs

• Ipsilateral = same side of injury

  • Decreased touch sensation: These signals travel up that same side of the spinal cord before crossing in the medulla, so the injury blocks them

  • Normal pain sensation: These signals cross to the opposite side shortly after entering the spinal cord so they travel upward on the undamaged side

• Contralateral = opposite side of injury

  • Normal touch sensation: These signals travel up on the opposite side of the injury, so they don’t get blocked

  • Decreased pain sensation: These signals cross to the opposite side or to the side of the injury so that means that they get blocked by the lesion

What is referred pain?

• Feeling of pain at a site separate from where an injury is located

• The brain is improperly processing pain input from an interal organ as body pain

What are some examples of referred pain?

• The perception of pain in the shoulders or medial aspect of the left arm is a sign of a heart attack

• Liver injury may present as pain the shoulder blades

• Lung cancer sometimes causes shoulder pain

• Kidney stones can cause pain the lower back, abdomen, and sides

• “Brain freeze” from drinking cold liquids too quickly is a form of referred pain

What occurs during normal pain signaling? What happens when the Naᵥ1.7 sodium channel gene is mutated? What are the diseases associated with these mutations?

Normal Pain Signaling: When a nociceptor detects a harmful stimulus:

1. The nociceptor is stimulated

2. Voltage-gating Na⁺ channels open → Na⁺ enters, causing depolarization

3. Voltage-gated K⁺ channels open → K⁺ exits, helping repolarize the neuron

4. Action potentials travel along the sensory neuron to transmit pain signals toward the CNS

What happens if Naᵥ1.7 is mutated?

• Loss of function: Naᵥ1.7 cannot function properly → nociceptors have difficulty generating action potentials

  • Result: Congenital insensitivity to pain

• Gain of function: Naᵥ1.7 becomes overactive → nociceptors fire too easily

  • Result: Extreme pain

Diseases associated with these mutations

• Congenital insensitivity to pain: Individuals are born unable to perceive physical pain because pain signals are not transmitted normally

• Paroxysmal extreme pain disorder: Episodes of severe pain due to overactive Naᵥ1.7 channels

• Primary erythromelalgia: Episodes of burning pain, redness, and warmth, typically in the hands and feet

What is the difference between nociceptive pain and neuropathic pain?

• Nociceptive pain: Pain from physical damage to the body

  • Pain goes away as injury heals

  • Responsive to opiates

• Neuropathic pain: Pain caused by neurological damage or dysfunction

  • Pain is chronic without a specific stimulus or injury

  • Phantom limb pain

  • Chronic low back pain

  • Can be caused by many disorders

What are the symptoms of neuropathic pain?

• Allodynia: Non-injurious tactile stimuli that cause the sensation of pain

• Hyperalgia: Abnormally heightened perception and increased persistence of pain

  • Sharp, shooting, searing or stabbing pain

  • Tingling sensations

  • Numbness

  • Extreme sensitivity to touch

  • Insensitivity to heat or cold

  • Muscle weakness

  • Worse pain at night