Pain

Pain (recap from before):

  • Part of the somatosensory system

  • Information can be discriminative (specific) and non-discriminative (broad/general)

  • There are many different types of perception (exteroception, mechanoreception, thermoreception, nociception, proprioception and introception)

  • Information can be either cutaneous (skin) or deep in the body (muscles, etc)


Pain is a major type of non-discriminative somatic information. Pain can come from both deep and cutaneous structures. We know more about cutaneous (skin) nociceptors than about deep nociceptors.


Pain is important is it alerts us to things in the environment that may harm our bodies. It is also among the most debilitating conditions as it often persists, recurs and can be crippling. Chronic pain also affects a large number of people (10-30% adults in Europe).


Pain has 3 components. The experience of pain depends on:

  1. Sensory coding of the stimuli

  2. Motivational/affect component: whether your brain wants to attend to the input or is otherwise occupied.

Eg. In moments of high stress, you may not notice a bee stinging you.

  1. Cognitive/cultural component: whether your brain has learned to ignore that input

At Easter in the Philippines, people crucify themselves and claim to feel no pain.


Pain is not just peripheral sensations being transmitted to a passive brain and being interpreted as pain. Pain depends on peripheral input and whether the brain wants to attend to it yet. This means the sensory processing of pain in the brain can be modulated by other brain systems.


Nociceptors are pain receptors. Like other somatic sensations, nociception originates from specialised nerve-fibre endings. Noxious stimuli are changed to electrical impulses at the peripheral free endings of the A-delta and C classes of nerve fibres. Free nerve endings mean there are no special accessory structures associated with the terminals.


Nociceptors are slow but plentiful. C fibres are unmyelinated and A-delta are thinly myelinated. C-fibres are the slowest conducting nerve fibres.

This is because the brain doesn’t need to know about pain quickly. This is because pain isn’t common if you learn from noxious experiences. Since changing the fibres to be faster requires energy, there is no evolutionary advantage for doing this for rare events.\

Nociceptors are the most abundant of the somatic receptors (showing how they are still important). They are 9x as dense as touch receptors and 15x for thermoreceptors.


Nociceptors are classified into 4 classes:

  1. Sensitive to temperature (different for hot pain and cold pain)

  2. Sensitive to mechanical stimuli

  3. For mechanical and thermal stimuli

  4. For mechanical, thermal and chemical stimuli, or Wide Dynamic Range nociceptors.


Nociceptors are specialised to respond to stimuli only at injurious levels. Nociceptors respond to the same stimuli as other cutaneous receptors, but only at stimulus levels outside the normal range (levels that can harm). There is then a systematic increase in responses depending on the intensity of damaging stimuli.


Different ion channels change (transduce) the effects of different noxious agents. Specific receptors/ion channels are sensitive to heat, mechanical stimuli, proton ( H+ in acids) and cold. In all cases, there is a net depolarization (positve charge, usually Na+), that ascites the nociceptor afferent neurons.
One of the most commonly involved ion channels in pain (and best understood) is the TRPV1 channel (also in normal temperature sensations and part of TRP superfamily of ion channels).

TRPV1 allows cations to move, leading to depolarization of the cell, and eventually, the production of action potentials. TRPV1 is activated at >43*C. TRPV2 is activated at >52*C.

TPRV1 can also bind to the chemical, capsaicin (in chillies), allyl isothiocyanate (in mustard/wasabi) and allicin (garlic). That’s why some foods are spicy.

The activation to TRPV1 leads to painful, burning sensations of heat and pain. Opening the TRPV1 channel leads to a Ca++ influx, leading to a release of Ca++ from internal stores in the cell. Excess Ca++ leads to many effects, with the later ones being detrimental (see below).




Pain ratings for heat parallel changes in firing rates of A-delta nerve fibres.

The responses of nociceptors match well with human judgements about pain. We can see this if we compare the train of action potentials to a person’s judgement of the pain (see graph on the right). The graph shows that both measures of heat pain increase in a very similar manner, suggesting that our perceptions of heat pain are strongly dependent of the number of Action Potentials in the nerve fibre (pain also depends on affective and cognitive components tho).




Fast and slow pain sensations exist due to the different conduction rates of the A-delta and C pain nerve fibres. Since A-delta is lightly myelinated and slightly thicker than the C nerve fibre, it transmits information faster than C, meaning that their inputs arrive at different times in the CNS. This means for some body parts, pain sensations have 2 components: a initial fast, sharp pain and a slow, dull pain.


Tissue injury results in changes at the site of damage. These include:

  1. Allodynia: Where non painful stimuli are felt as painful (normal/no pain feels painful)

Eg. Touching a finger may feel painful

  1. Primary Hyperalgesia: Where painful stimuli cause more intense pain. (mild pain feels like intense pain)

Eg. Squeezing a finger may feel like intense pain


Allodynia and primary hyperalgesia are caused by changes to the endings of nociceptor nerve fibres (when damaged), due to chemicals released from the damaged skin, leading to the receptors becoming more sensitive. This correlates to the fact that we too become more sensitive to harmful stimuli when applied to a region that has previously been injured.

Damage to tissues releases inflammatory agents (eg, histamine) from cells into the damaged tissues. This causes the swelling of local blood vessels. A by-product of this is fluid leakage out of the blood vessels to cause swelling in the tissue itself.

The ion channel TRPV1 is activated by the stretch caused by local fluid accumulation/swelling. Tissue damage causes the release of chemicals, sensitising TRPV1 ion channels.