Module 3: Pain Introduction (afferent division)

What is nociception?

Pain → unpleasant sensation that is a critical part of the body’s defence system (alerts CNS to immediate physical harm)

• includes external and internal events

• can include perceived events that are observed.

There are pain receptors found in pretty much all parts of the body. These are called nociceptors. There are three distinct groups of nociceptors based on modality. What are they? What do nociceptors make up?

1. Mechanical Nociceptors

   • respond to physical damage

   • ex. crushing, cutting

2. Thermal Nociceptors

   • responds to temperature, especially heat

3. Chemical Nociceptors

   • responds to noxious chemicals, which are both external and internal to the body

Nociceptors are specialized nerve endings of the afferent nerve fibres called “pain fibres”.

We can categorize pain fibres into two categories based on their conduction speed. What are these two categories? Briefly describe each type of pain fibre.

1. Fast Pain Fibres (A-delta fibres)

   • responsible for responding to temperature and both chemical and mechanical stimuli.

   • perceived sensation of their activation = acute, sharp, or stabbing pain.

   • quick intense pain

2. Slow Pain Fibres (C fibres)

   • unmyelinated fibres

   • responsible for responding to chemical and mechanical stimuli, as well as temperature.

   • unlike A-delta fibres, polymodal receptors can be activated.

   • perceived sensation = burning, aching, throbbing, chronic pain

Bradykinin is commonly associated with the slow pain pathway. What is it?

A chemical activated by enzymes released from damaged cells. Once its activated, it directly stimulates nociceptors. As there’s no adaptation to the stimulus, nociceptors are stimulated until bradykinin is removed; explains the long lasting pain in slow pain pathway.

How does the brain generally process pain?

When an action potential reaches the end of an afferent pain fibre axon, it triggers the release of neurotransmitters, specifically, substance P and glutamate.

• substance P coexists with glutamate to activate the ascending pathways and transmit signals to higher levels for further processing.

We discussed that substance P and glutamate activate ascending pathways to transmit signals to higher levels for further processing. What areas of the brain are influenced by these neurotransmitters. Briefly describe how they influence these regions.

1. Hypothalamus/Limbic System

   • receives input from the thalamus and reticular formation.

   • allows for behavioural and emotional responses to pain stimuli.

2. Cortex

   • cortical somatosensory processing localizes pain to a discrete body region.

   • aka figures out where it is

3. Thalamus

   • perceives pain

4. Reticular Formation

   • increases level of alertness and awareness of painful stimulus

We’ve discussed that glutamate is released when an action potential reaches the end of the pain fibre and triggers signalling to higher cortical areas for further pain processing. But what is glutamate?

an amino acid that also functions as a neurotransmitter

• released by afferent pain nerve fibres to activate postsynaptic glutamate receptors on neurons in the spinal cord’s dorsal horn.

Glutamate has two actions depending on which type of receptor is activated: either an AMPA or NMDA receptor. What happens when either of these receptors are activated?

AMPA

• activation leads to permeability changes that can generate action potentials in dorsal horn neuron and send signals to higher brain regions

• as sodium enters the AMPA channel, depolarization occurs.

• only when a certain level of depolarization is reached, will the magnesium ion in the NMDA

NMDA

• once NMDA are activated, they allow calcium to enter the neuron

• which leads to activation of a 2nd messenger pathway that results in the neuron being more excitable than normal

**These two explain why injured areas are more sensitive to stimuli that doesn’t normally hurt → ex. clothes causing pain when they rub against a sunburn).

Pain fibres don’t adapt, so how is a signal stopped?

After an initial painful stimulus, theres a decrease perception of pain due to the CNS’s built in pain suppressing system: the endogenous analgesic system

How does the endogenous analgesic system work?

We centrally process pain and one consequence of this the activation of descending pathways.

• in turn they activate inhibitory neurons in the dorsal horn.

• Axons in these interneurons terminate on afferent fibre nerve terminals.

• they then release endogenous opiates that act on opiate receptors and result in suppression of neurotransmitters released from the afferent pain fibres

  • similarly exogenous opioids can activate the opioid to decrease the perception of pain

(endogenous opiate = substances produced by body to have painkilling effects)

(exogenous opioids = substances that aren’t produced by body and still have painkilling effects)

Now that you have learned how pain is perceived consciously, briefly describe what would occur if you stepped on a particularly sharp piece of Lego. What kind of receptor would be activated? How would you become consciously aware of this pain? How might this perception of pain be different if you were taking an exogenous opioid such as morphine?

• pain perceived at the source and travel up A-delta fibres.

• as the action potential reaches the end of the A-delta pain fibre, glutamate would be released.

• signal travels to the dorsal horn where AMPA receptors are activated.

• signal would travel to higher cortical areas:

  • reticular formation to increase alertness

  • thalamus to consciously perceive pain

  • cortex to localize pain to foot

  • hypothalamus allows for behavioural and emotional response

Morphine response

• activate the opioid receptors which suppress neurotransmitter from being released from A-delta fibres.

• decreases perception of pain.