Pain and Nociception Unlocking The Gate Control Theory

With Alaa CattaehDiagrams created with Biorender.com

Template created using Canva

Contents

Pain vs Nociception

1

Modulation

5

Phases of Nociception

2

Transduction

3

Transmission

4

What is Pain? Pain vs Nociception

• A psychological state• An unpleasant sensory and emotional experience

associated with actual or potential tissue damage• Can occur without obvious tissue injury

What is Nociception?• Information indicating tissue damage • Process through which potentially damaging stimuli are detected• A noxious stimulus activates a particular set of sensory nerve cells

TRANDUCTION• Exposure to noxious stimuli activates

nociceptors and produces an action potential

TRANSMISSION• AP travels along fibres from point of

transduction to dorsal horn of spinal cord and subsequently to the brain.

PERCEPTION• Conscious & emotional experience of

discomfort and pain

1

2

3

The 4 Phases of NociceptionPhases of

Nociception

MODULATION• The response• Inhibition of nociceptive impulses• Release of endogenous opioids

4

SBAAmirah accidently cut her hand with scissors as she was crafting. She felt a sharp scratch around her finger, but the unpleasant sensation only lasted few seconds. Outline the correct order of Amirah’s nociceptive phases during that time.

• Transmission, Transduction, Modulation, Perception• Transmission, Transduction, Perception, Modulation• Transduction, Transmission, Perception, Modulation• Transduction, Transmission, Modulation, Perception

Transduction

Transduction

How Nociceptors are StimulatedWhat is a nociceptor?A ‘pain receptor’ which is a sensory neuron that responds to damaging or potentially damaging stimuli by sending “possible threat” signals to the spinal cord and the brain.

What stimuli activate the nociceptors?Intense mechanical stimuli

Irritant chemical stimuliThermal stimuliProstaglandins

Inflammatory mediators

Once nociceptors become activated they produce an action potential.Substance P (a neuropeptide) is released when nociceptive axons carry high frequency trains of action potentials.

Transduction

Nociceptor

Cell Damage

Substance P

Transduction

What is Substance P?A polypeptide acting as a neurotransmitter a neuromodulator

Where is it released?Released from nociceptive sensory nerves at both dendritic end and axon terminals• Dorsal horn of spinal cord (synaptic transmission)• Periphery (dendritic terminals) at site of injury

Functions:• Substance P is one of the neurotransmitters

found in CNS that propagates pain.• Vasodilation• Increase in nerve fibre sensitization• Induces mast cells to release 5HT and

histamine → inflammation

Substance P

Dendritic end

Substance P Mast

Cell

The Nerve Fibers A-delta (Aδ) fibres:• Rapid onset sharp pain• Thin & myelinated axon (AP travels

5-35 m/s)• Small receptive field – well localized

pain• High threshold mechanoreceptors

C fibres:• Slow longer lasting dull throbbing pain• Thin & unmyelinated axon (AP travels

0.5-2 m/s)• Pain is poorly localized• Polymodal

Transduction

A-beta (Aβ) fibres: • Light touch & vibration• Wide & myelinated axon (AP 35-75 m/s)

SBANadia is learning about the different functions of substance P. When it’s released at the site of injury, substance P can lead to inflammation causing the injured area to appear red and swollen.

How can substance P trigger an inflammatory response?

• It activates macrophages• It causes vasoconstriction• It activates mast cells• It releases histamine

SBAMichael was hanging a picture frame up his wall when suddenly one of the nails fell down and he stepped on it.He immediately felt an intense sharp pain in his foot and started to scream.

This sharp onset of pain was caused by which nerve fibre?

• A-beta fibre• A-delta fibre• B fibre• C fibre• D fibre

Pain Transmission

Transmission

The Pathway of Pain Transmission

The spinothalamic pathway:

1. 1st order sensory neurone enters dorsal horn of spinal cord and synapses with 2nd order neurone at substantia gelatinosa

2. 2nd order neurone decussates within the spinal cord and travels via the lateral spinothalamic tract to the thalamus

3. 2nd order neurone synapses with 3rd

order neurone which carries the sensory signals to the primary sensory cortex

Transmission

Break time!Let's take a 2-3 minute break to recharge...

Any questions? Drop them in the Q&A!

Pain Modulation

Modulation

The Gate Control Theory of Pain (Melzack & Wall 1965)

• Nociceptive signals travel via the spinothalamic pathway to reach the brain where the thalamus first labels the sensation as ‘pain’.

• The theory suggests that the spinal cord contains a neurological "gate" that either blocks pain signals or allows them to continue on to the brain.

• It describes how non-noxious input can override the pain signals and close the gate to prevent them from travelling to the central nervous system.

What is the “gate”?

This is the substantia gelatinosa in the dorsal horn of the spinal

cord which contains inhibitory neurons acting as guards that can

close the gate and block the spinothalamic transmission of pain Modulation

How Non-Noxious Input Suppresses Pain Transmission

Modulation

How Non-Painful Input Closes Gate to Painful Input

Pain signals can be interrupted in the substantia gelatinosa

of the spinal cord, which acts as a gate:

• When you rub the site of pain, A-beta fibres are activated by

touch and produce an AP traveling faster than A-delta and C

nociceptive fibres

• The touch sensory neurone synapses with an inhibitory

interneuron in the substantia gelatinosa which is in contact with

both nociceptive and touch sensory fibres

• The inhibitory interneurone inhibits the nociceptive fibres

carrying the pain signal by preventing the release of substance P

How does the inhibitory interneuron inhibit nociceptive transmission?

Enkephalin

Opioid

receptor

Ca2+

Channel

K+

Channel

C fibre

Inhibitory

interneuron

2nd order

neurone• The inhibitory interneuron

releases enkephalins which bind

to opioid receptors

• This closes Ca2+ channels in the

pre-synaptic nociceptive fiber

meaning that vesicles containing

Substance P neurotransmitter

cannot be released

• This also opens K+ channels in

post-synaptic 2nd order neuron

causing hyperpolarization (makes

it less excitable) and therefore

reduces pain signal transmission

K+

Substance P

Modulation

SBAYoung Chloe was running in the park but accidently fell off and injured her knee. She attempted to lessen the pain by rubbing the bruised area.This stimulated A-beta fibres which in turn activated inhibitory interneurons to release enkephalins causing hyperpolarization of neurons and therefore reduction of pain transmission.

How was hyperpolarization achieved?

• Closure of Ca2+ channels• Opening of Ca2+ channels• Closure of K+ channels• Opening of K+ channels

Descending Pathways that Block Pain Transmission

Modulation

Once the signal from the spinothalamic pathway reaches

the somatosensory cortex, it triggers the descending pain

modulation pathway:

• The main pathway is thought to involve neurons that project from

the Periaqueductal gray (PAG) to serotonin-producing neurons of

the medulla oblongata (raphe nuclei).

• The activated raphe nuclei neurons project down to the dorsal

horn of the spinal cord where they release serotonin which binds

to interneurons in substantia gelatinosa.

• Interneurons release endogenous opioid neurotransmitters that

bind to mu opioid receptors on the incoming nociceptive fibres.

• Activation of opioid receptors produces hyperpolarization of the

neurons, which result in the inhibition of firing and the release of

substance P thereby blocking pain transmission.

SBAUnlike the gate control theory, where closing the gate is stimulated by non-noxious input, descending pain suppression is activated by noxious stimulation because that excites neurons in the nucleus reticularis gigantocellularis which innervate the PAG.

Where is the PAG found?

• Midbrain• Medulla• Dorsal horn• Substantia gelatinosa• Dorsolateral faniculus

Summary

Transduction• Noxious stimuli activate

nociceptors resulting in an AP

• Nociceptors release substance P

• Substance P is a neurotransmitter and a neuromodulator

Transmission• 1st order neurone synapses

with 2nd order neuronewhich travels via lateral spinothalamic tract to synapse with 3rd order neurone at thalamus

• 3rd order neurone carries signal to somatosensory cortex

ModulationGate Control Theory:• A-beta fibers stimulated

by touch activate inhibitory interneurons

• Close the gate

Descending Pain Suppression Theory:• PAG and raphe nucleus

stimulation produces analgesia.

1 2 3

Additional Resources

DCML pathway inhibits

Spinothalamic pain transmission:

https://youtu.be/oQLFfvGM7nI

Mechanisms of pain modulation:

https://nba.uth.tmc.edu/neuroscie

nce/s2/chapter08.html

Pain transduction:

https://youtu.be/lEQyLR6UBW0

Additional Resources

ECG and limb leads: https://button-bubbler-50c.notion.site/ECG-and-Limb-Leads-

c318019e1f9c4e41a20e275fd8e8d671

Regulation of appetite and digestion: https://www.notion.so/Regulation-of-Appetite-and-Digestion-

517d09feb16c4bd8bfb508e4504d8289

Differential diagnosis of dementia: https://button-bubbler-50c.notion.site/Differential-Diagnoses-of-Dementia-

b7ee72bbb67f4760bd29c6bb76e2d20f

Here are links to some of the learning resources I made if you’re interested ☺

Email: cattaeha@cardiff.ac.uk

Referenceshttps://en.wikipedia.org/wiki/Substance_P

http://faculty.washington.edu/chudler/cv.html

https://teachmeanatomy.info/neuroanatomy/pathways/ascending-tracts-sensory/

https://en.wikipedia.org/wiki/Gate_control_theory

https://nba.uth.tmc.edu/neuroscience/s2/chapter08.html

https://www.youtube.com/watch?v=xkMP4eXp1Oc

Michael-Titus, A. et al. 2010. 5 - PAIN AND ANALGESIA. In: Michael-Titus, A. et al.

eds. The Nervous System (Second Edition). Churchill Livingstone, pp. 79-104.

Diagrams created with Biorender.com

Thank You!