Nociception is to Pain as Fuel is to Fire
Nociception ≠ Pain
It is important not to confuse pain with the term nociception, as is so commonly done.
A great way to demonstrate the difference between nociception and pain is to compare it to the fire triangle.
So, what is the fire triangle?
The fire triangle
Firefighters are trained to utilize the “fire triangle” to understand the various components that make up a fire so they can most effectively extinguish said fire. All four components are needed for the fire to exist, so take away one of them and the fire is extinguished.
There are four main components that make up a fire:
Requirements for the Fire
Each of the four components have their own requirements and complexities:
Needs to be a combustible material, meaning it needs to be able to catch fire and burn easily.
The fuel stores what is referred to as potential energy, which when burned is released as heat .
Must to be enough oxygen to sustain the fire.
(This is why candle snuffers exist: they quickly “snuff” out the oxygen of the flame by not allowing air into the system, thus extinguishing the fire).
Has to be hot enough to raise the substance to its ignition temperature.
The Chemical Reaction:
To produce fire, a certain type of reaction must occur between the fuel and the oxygen.
Termed a combustion reaction, heat releases, making it exothermic, and oxygen is added, termed redox, leading to the burning of fire.
The four components can comprise of different materials:
- Solids: Wood, fibers, dust, plastic
- Liquids: flammable liquids such as gasoline, pentane, ethanol, benzene, acetone
- Gases: natural gas such as methane CH4
- The oxygen can produced by oxidizing agents.
- Solids: Ammonium nitrite
- Liquids: nitric acid, hydrogen peroxide, bleach, pool chemicals
- Gases: oxygen, chlorine, fluorine
Various heat sources exist:
- Engines, motors, electrical sources, open flames from the sun, frictions, compressions
- Heat, sparks, static electricity
Types of Fires
There are also different classes of fire, which all need to be managed differently depending on their components.
Class A: Burns on ordinary solid material
- Wood, paper, some plastics, cloth
Class B: Involve flammable liquids
- Petrol, oil, paraffin, alcohol, ether
Class C: Burn on flammable gases
- Methane, butane, propane
Class D: Ignite with metals
- Titanium, aluminum, magnesium, sodium, potassium
Class E: Caused by electrical sources
- Electrical apparatuses, equipment, wiring
Class F: Ignite with oils
- Cooking vegetable oils or fat
This is a post about pain and nociception… why am I talking about fire? Well…
Nociception is to the sensation of pain, akin to the way fuel is to fire.
The “Pain Triangle”
Like the fire triangle, there are four main components that make up pain
- Sensation (Nociception)
- Pain Experience
Similar to how different materials can cause different types of fires, different types of stimulus can cause different types of pain.
What exactly is nociception?
Nociception is a sensory mechanism that allows organisms to detect potentially tissue-damaging, or noxious stimuli.
Nociception helps protect an organism from further damage (Cox et al., 2006). It serves a crucial biological purpose by alerting an organism to environmental dangers, inducing the sensation of pain, reflex withdrawal, and complex behavioral and emotional responses.
More specifically, nociception is the process by which intense thermal, mechanical, or chemical stimuli are detected by a subpopulation of peripheral nerve fibers, called nociceptors (Ossipov, 2012).
A Simplified Definition
Nociception is the perception or sensation of potential tissue damage in response to a harmful stimuli.
A More In-Depth Definition
How Is Nociception Detected?
Noxious stimuli are detected by nociceptors, which are a subpopulation of specialized high-threshold primary sensory neurons (Lumpkin and Caterina, 2007). Once tissue damage occurs, the nociceptors will transfer signals to the spinal cord and then transmit the signal to the brain for higher-level processing.
Nociceptive Pain Pathway Steps
occurs when sensory receptor cells are stimulated by an energy source (i.e., heat, cold, touch, sound, light, etc.)
the process of transforming one form of energy to another (this occurs when chemical mediators have been released in response to the cell stimulation, creating second messengers from the reactions)
involves the process from the receptor to the final destination to the brain, usually occurring via three neurons (first order, second order, third order neurons)
the “ouch!!” moment. (i.e., the conscious awareness of pain.)
involves signals from the brain going back down the spinal cord to modify incoming impulses.
When does nociception occur?
Just like how heat must reach hot enough levels to raise the substance to its ignition temperature for a fire to burn, the intensity of the stimulus must be high enough to reach a noxious range for nociceptors to become activated and pain to be felt.
Different types of nociceptors
Fire can be fueled by different kinds of materials, and so too can pain be fueled by different kinds of nociceptors.
Vertebrates are animals who have a spinal cord, like you and me! Vertebrate nociceptors are characterized by “free” nerve endings that contact barrier epithelial tissues such as the skin, oral mucosa, or gut (Seol Hee Im.; Michael J. Galko 2011).The way they are built allows for the rapid sensory detection of high‐threshold stimuli capable of causing tissue damage.
There are two major classes of nociceptors:
Medium diameter myelinated (Aδ) afferents
Small diameter unmyelinated “C” fibers
Fast-conducting sensory nerves with myelinated axons.
- Larger diameter and thicker myelin sheaths increases conduction
- Aβ-fibers conduct touch signals from low-threshold mechanoreceptors with a velocity of 80 m/s and a diameter of 10 μm;
- Aδ-fibers have a diameter of 2.5 μm and conduct cold, noxious, and thermal signals at 12 m/s.
- The third and fastest conducting A-fiber is the Aα, which conducts proprioceptive information with a velocity of 120 m/s and a diameter of 20 μm.
- Slow-conducting unmyelinated thin sensory afferents with a diameter of 1 μm and a conduction velocity of approximately 1 m/s.
Unmyelinated C fibers
- The unmyelinated C fibers are also heterogeneous.
- Like the myelinated afferents, most C fibers are polymodal (ie they include a population that is both heat and mechanically sensitive (CMHs) (Perl, 2007)).
- Heat-responsive, mechanically insensitive, unmyelinated afferents (so-called silent nociceptors) develop mechanical sensitivity only in the setting of injury (Schmidt et al., 1995).
- These afferents are more responsive to chemical stimuli (capsaicin or histamine) compared to the CMHs
- Likely come into play when the chemical milieu of inflammation alters their properties.
- Subsets of these afferents are also responsive to a variety of itch-producing pruritogens.
Nociceptors can also be distinguished according to the type of potentially painful stimuli they respond to, for example:
Thermal: React to intense hot or cold temperatures, such as touching a hot candle flame.
- To heat (TRPV1)
- To cold (TRPM8)
Chemical: React to chemicals such as substance P or prostaglandins released following tissue damage or from external chemicals such as topical capsaicin.
- To acidic milieu (ASICs)
- To chemical irritants (TRPA1)
Mechanical: Activated when too much strain, stretch occurs to a muscle or tendon, respond only to intense mechanical stimulation such as stretching, cutting, pulling, or pinching.
Mechano-thermal: Like the name implies, these nociceptors respond to both mechanical and thermal stimuli.
Polymodal: respond to multiple types of stimuli, such as chemical, thermal, and mechanical.
Silent: Must first be activated by tissue inflammation before it can respond to chemical, thermal, or mechanical stimuli.
Nociceptors can be distinguished according to the where it is that they are located, for example:
- High threshold mechanonociceptors,
- Thermal nociceptors
- Chemical nociceptors
- Polymodal nociceptors
Joint and ligaments:
- High threshold mechanonociceptors
- Polymodal nociceptors
- “Silent nociceptors”
Visceral (located within an organ):
- Mechanical pressure nociceptors
- Temperature nociceptors
- Chemical nociceptors
- Silent nociceptors (the majority of the visceral nociceptors are silent)
The nociceptors differ in both the way they behave and what they comprise of on a molecular level. Each class of nociceptor is responsible for detecting different types of pain.
Why we need nociception
The functional significance of pain is shown by individuals who are born with defects in their nociceptive processing. Unfortunately, patients with congenital insensitivity to pain typically do not survive past their twenties (Basbaum et al., 2009) because their inability to perceive pain means they are more likely to suffer from an accumulation of injuries such as burns, bruises, sprains, and broken bones, wounds over time, leading to significant health complications (Al Amroh et al., 2020) .
Similar to how a fire needs fuel to burn, pain needs the sensation of nociception to occur.