BIOL 2480 - Pain

Pain: unpleasant sensory experience associated with

damage

Detection of pain is called

Detection of pain is called

Detection of pain is called nociception but this is different from

Perception of pain, perception is more psychological

•Categories of pain:

Persistent and Chronic

Persistent-

-short term. Alerts body to problem

Chronic -

long lasting but difficult to treat

Nociceptive - activation of

nociceptors

Neuropathic -

•direct injury to nerves

Pain - Unpleasant sensory experience associated with

actual or potential tissue damage

Detection is done by binding of stimuli by

peripheral free nerve endings called nociceptors

Perception of pain is done by brain after

integration and elaboration of sensory input

Persistent pain serves a purpose - to alert body that something is

wrong and needs to be fixed

examples of neuropathic: Neuralgia - pain that occurs when a nerve is

irritated of inflamed.

Postherpetic neuralgia - virus

invades

Chronic pain serves no useful purpose and is often

difficult to assess & treat

Pain doesn't cause damage, but is associated with

damage

•Neuropathic - direct injury to nerves, then sends signals to

brain for pain response

-Chronic - long lasting but difficult to treat, no actual damage, cant find a reason for

pain, no enflamed nerve/receptor

Pain receptors: called

Nociceptors

Receptors are specialized

free nerve endings

4 types of pain receptors- all

•ionotropic (Na+ & Ca2+)

Free nerve endings (circled) are very

highly branched

There are different types of nociceptors but all work essentially the same way, they are just activated by

different stimuli.

Like mechanoreceptors, nociceptors arise from DRG with one branch

cutaneous and one to spinal cord

Overall nerve conductance is SLOWER in

nociceptors than in mechanoreceptors

Overall nerve conductance is SLOWER in nociceptors than in mechanoreceptors because nociceptors are either

lightly myelinated or completely unmyelinated.

There are different conductance velocities in

different types of nociceptors

All nociceptors have relatively high

threshold of activation

The four basic types of nociceptors often get stimulated together and are distributed extensively, both

deep & superficial

The four basic types of nociceptors often get stimulated together and are distributed extensively, both deep & superficial. All are activated by

ion channel opening, letting in Na+ and Ca2+

mechanoreceptors - AB fibre, being more

specialized, slower

Mechanical nociceptor, Ad fibre

medium fast, slightly myelinated

Nociceptors and touch receptors both have

•cell bodies in the dorsal root ganglion (DRG)

Nociceptors sent one axonal ending to

periphery and one to spinal cord or brainstem

Axons are either

lightly myelinated a-delta fibers or unmyelinated C fibers

Mechanoreceptors are more heavily

myelinated A-beta fibers

4 basic types of nociceptors, 1)

1.Thermal nociceptors

1.Thermal nociceptors

Only activated by

temperature extremes

1.Thermal nociceptors

-Only activated by temperature extremes

Afferents are

-myelinated Adelta fibers

5-10 m/s

Thermal nociceptors are only activated by temp extremes, being completely quiet until

temp increases past some critical level.

Figure shows responses of nociceptors & normal thermoreceptors to increased heat. Bottom graph shows that as temp increases, get gradual response of normal thermoreceptor up to

plateau and then magnitude stays same.

Nociceptor is completely quiet until 43 deg and then get increased resp with

increased temp. 45 deg is avg pain threshold for hot, get similar response down around 5 degrees.

Thermoreceptor fires more AP with increased stimulus intensity but then levels off. Nociceptor doesn't fire until

43 deg and then keeps firing with more stimulation.

2. Mechanical nociceptors

Only activated by

intense pressure

Mechanical nociceptors

-Only activated by intense pressure

Afferents are

-small myelinated Adelta fibers (lightly myelinated)

-5-10 m/s

Mechanical nociceptors are the same speed as

temperature receptors

Polymodal nociceptors

Activated by

many stimuli

Polymodal nociceptors

-Activated by many stimuli

Afferents are

-small unmyelinated C fibers

-< 1 m/s

Polymodal nociceptors, takes longer to

reach spinal cord due to not being myelinated

4. "Silent" nociceptors, is important for

sensitization

4. "Silent" nociceptors, is important for sensitization, doesn't usually fire, changes in

inflammation cause it to fire

Mechanical - need

intense pressure

Mechanical - need intense pressure. Same kind of fibers as

thermal. Relatively quick conductance

Polymodal - can be stimulated by

mechanical, chemical, or thermal stimuli. Notice conductance is much slower than other 2, Due to non-myelination

Silent - Visceral. Usually quiet (so don't react to mechanical or chemical contact normally) but can get greatly reduced threshold due to

inflammation or chemical insult. May be important for sensitization.

Body nociceptors first synapse in

spinal cord

Face (Trigeminal) nociceptors first synapse in

medulla

For body, DRG neurons form synapse in spinal cord (cervical for upper body, lumbar for lower). From spinal cord axon travels all the way up to

thalamus along spinothalamic tract and ends in thalamus.

From thalamus get innervation and goes to cerebral cortex (primary somatic sensory cortex) mostly (spinothalamic is main one but there is also one that goes to other parts of

medulla and one going to midbrain)

For face, travels along trigeminal, just like for mechano. These DRG first synapse in

medulla, go to thalamus and then to cerebrum

Pain gives off a

•compound action potential made up of first pain and second pain.

First you feel

touch (A-beta)

First you feel touch (A-beta), THEN you feel

pain (A-delta and C).

First you feel touch (A-beta), THEN you feel pain (A-delta and C). Complex

action potential

Compound AP of a nerve represents

summated APs of all the component axons in the nerve.

Compound AP of a nerve represents summated APs of all the component axons in the nerve. Can be more than just the

sum of the parts.

Many axons send inputs into the nerves going to

the brain.

First you feel mechanoreceptor inputs, then

nociceptors kick in.

First pain is Adelta fibers from

unimodal (heat, mechano).

First pain is Adelta fibers from unimodal (heat, mechano). These are

first pricks of pain you feel.

Myelinated go faster but not as fast as

straight mechano

Myelinated go faster but not as fast as straight mechano. Next get

polymodal C fibers

Next get polymodal C fibers. Dull ache you feel after

1st prick.

Can selectively block

C or Adelta fibers and block 1st or 2nd pain

Both mechanosensors and nociceptors integrate inputs to

projection neurons, which go to brain.

Dorsal horn of spinal cord is in layers. Projection neurons take input from dorsal horn and send it on to

next neuron in chain. (medulla, thalamus, or midbrain)

Main projection neuron in layer 1 gets direct input from

Adelta fiber

Main projection neuron in layer 1 gets direct input from Adelta fiber and indirect from

C fiber via interneuron in layer II

Other layers have other neurons that

feed back in.

Layer V neuron gets input from

AB and from Adelta.

This layer V neuron sends dendrites to axon of interneuron which can modify

response of layer I.

•Why does my swollen ankle hurt?

Chemical stimuli affect

nociceptor activation after injury.

- Nociceptors can also release signals to

change inflammatory response

This is a type of hyperalgesia, Each orginate from different cells but all act to decrease

threshold of activation of nociceptors.

Each orginate from different cells but all act to decrease threshold of activation of nociceptors. Some can actually

activate nociceptors directly.

Histamine - will directly activate

polymodal receptors

ATP gets released from damaged endothelial cells and can

sensitize nociceptors directly or in conjunction with others

Prostaglandins also get released during damage and can make

receptors more sensitive

Aspirin can block

prostaglandin synthesis

Bradykinins activate kinases that phosporylate

ion channels, making them more sensitive

Substance P & CGRP are neuroactive peptides that can be released from

DRG axons directly, directly increasing the swelling response

ATP, Prostaglandin, Serotonin, Histamine, go to neuron, which then causes release of

substance P and CGRP when signal goes to spinal cord

So why does the left arm hurt during a heart attack?

Referred pain

Referred pain - Pain felt in part of body other than

actual source

visceral and somatic inputs converge in

spinal cord

Many internal nociceptors innervate the same dorsal horn neurons as

peripheral nociceptors so brain thinks pain is coming from periphery.

In case of heart, some of the heart nociceptors innervate the same neurons as those

on chest or left arm.

Few visceral nociceptors innervate a

single dorsal horn neuron

If Dr. knows enough, he can use patients peripheral pains as symptom of larger problem.

Prostate manifests as right leg pain, esophagous manifests as chest and throat pain.

Defined: stimuli that were once ignored by

•nociceptors now activate them.