Neurobiology of pain

Question 1

What is pain and how is it defined?

Answer 1

Pain is an unpleasant sensory and emotional experience often associated with actual or potential tissue damage. It can exist without a physical cause (e.g., phantom limb pain) and is influenced by biological, psychological, and social factors.

Question 2

What are the features of Aδ fibers in pain transmission?

Answer 2

Aδ fibers are myelinated for fast conduction, transmit sharp and localized pain, and release only glutamate at the dorsal root ganglion.

Question 3

What are the features of C fibers in pain transmission?

Answer 3

C fibers are unmyelinated (slow), transmit dull, aching, and poorly localized pain, and release Substance P, CGRP, and glutamate.

Question 4

What is pain transduction and how does it occur?

Answer 4

Pain transduction is the conversion of noxious stimuli into electrical activity. Tissue injury releases inflammatory mediators that activate ion channels on nociceptors, leading to action potential generation.

Question 5

What neurotransmitters are involved in pain transmission at the spinal cord?

Answer 5

Glutamate (activates AMPA/NMDA), Substance P (activates NK1 receptors), and CGRP (causes vasodilation/inflammation).

Question 6

What are the three stages of pain signaling?

Answer 6

Transduction (stimulus → electrical signal), Transmission (signal travels through neurons), Modulation (signal enhanced or suppressed).

Question 7

Describe the steps of the ascending pain pathway.

Answer 7

1. Nociceptors detect injury. 2. Signal travels to DRG. 3. First-order neurons synapse in dorsal horn. 4. Second-order neurons decussate and ascend via the spinothalamic tract. 5. Thalamus relays signal to the somatosensory cortex via third-order neurons.

Question 8

Describe the detailed process of the ascending pain pathway.

Answer 8

1. Peripheral injury activates nociceptors. 2. Signal sent to DRG, releases glutamate & Substance P. 3. Second-order neurons in dorsal horn activated. 4. Signal decussates and travels via spinothalamic tract to thalamus. 5. Thalamus relays signal to somatosensory cortex → conscious pain perception.

Question 9

What is the descending pain modulation pathway?

Answer 9

1. Brain regions activate the PAG. 2. PAG activates RVM. 3. RVM sends serotonergic and noradrenergic signals to dorsal horn. 4. Interneurons release enkephalins & GABA → inhibit pain transmission.

Question 10

Describe the detailed process of the descending pain pathway.

Answer 10

1. Cortex, amygdala, and hippocampus activate PAG. 2. PAG stimulates RVM. 3. RVM sends serotonin & noradrenaline to dorsal horn. 4. Interneurons release GABA (Cl⁻ influx) & enkephalins (K⁺ efflux via μ-opioid receptors) → inhibit ascending pain signals.

Question 11

What is inflammatory pain and how does it occur?

Answer 11

Caused by tissue damage, mediated by COX pathway and inflammatory mediators (e.g., prostaglandins, bradykinin), leads to hyperalgesia and allodynia.

Question 12

What is neuropathic pain and how does it occur?

Answer 12

Arises from nervous system injury/dysfunction. Involves upregulated NaV1.8 channels, ectopic firing, and central sensitization. Lacks protective function.

Question 13

What is the Gate Control Theory of Pain?

Answer 13

Non-nociceptive Aβ fibers activate inhibitory interneurons in the dorsal horn, releasing GABA & enkephalins, which suppress pain signals from Aδ & C fibers (“closing the gate”).

Question 14

What is central sensitization?

Answer 14

A state of heightened spinal cord excitability due to repeated stimulation. Driven by NMDA receptor activity and neuropeptides. Leads to hyperalgesia and allodynia.