Physiology Of Pain

Front 1

What are A-delta fibers?

Back 1

Small, sparsely myelinated
Fast, sharp pain

Front 2

What are C fibers?

Back 2

Unmyelinated fibers associated with dull pain (slow pain)

Front 3

What are the different types of nociceptors sensitive to?

Back 3

Sensitive to both thermal and mechanical stimuli (majority)
Sensitive to only thermal stimuli
Sensitive to only mechanical stimuli
Silent/sleeping

Front 4

What channel do many mixed modality nociceptors also express and what happens when there are mutations in the channel?

Back 4

Mechanosensitive Na+ channel (SCN9A or Nav1.7)
Mutations in channel lead to an absence of pain sensation
Another class of mutation produces a paroxysmal pain syndrome

Front 5

What are the ligand-gated receptors that nociceptors also express?

Back 5

Include receptors for:
-Substance P
-the Kinins (e.g. bradykinin)
-ATP
-H+

This collection of chemicals also exists in the spinal cord, where they also influence nociceptive inputs at those synapses

Front 6

What is the source of substance P, the Kinins, ATP, and H+ that act at the ligand-gated receptors on nociceptors?

Back 6

Activated nociceptors, the damaged tissue, and recruited WBC release these into the periphery as well as in the spinal cord

Front 7

Which pathway to the brain is for fast pain and which is for slow pain?

Back 7

Spinothalamic tract - fast pain
Spinoreticulothalamic system - slow pain

Front 8

Which receptors do EAA from A-delta fibers primarily act on?

Back 8

non-NMDA receptors

Front 9

Which NTs are released by C fibers?

Back 9

Substance P - released as intensity of pain increases
EAA

Front 10

Nociceptors that travel with the spinoreticulothalamic pathway synapse on ___________ in the spinal cord before crossing and ascending to the reticular formation.

Back 10

an interneuron

Front 11

What do the visceral afferents travel with?

Back 11

Autonomic nerves
Rather than with either of the two spinal pathways

Front 12

T/F: Nociceptive input is narrowly distributed in the cortex.

Back 12

False.
Unlike other senses, nociceptive input is distributed widely
Distributed so widely that lesion of a specific area cannot get rid of pain, have to get rid of entire tract

Front 13

T/F: S1 and S2 receive input from nociceptors and play a role in localizing pain.

Back 13

True

Lesions here, can still feel pain but unable to tell where it is

Front 14

Why is the insular cortex important in interpretation of nociceptive inputs?

Back 14

Processes information about the internal state of the body
Contributes to the autonomic response to the pain
*Integrates all signals related to the pain (asymbolia)

If damaged, still feel pain but lack the emotional response

Front 15

Why is the amygdala important in interpretation of nociceptive signals?

Back 15

Important for activating/producing the emotional components inherent to the sensation of pain

Front 16

Where do visceral nociceptors that travel with the ANS have additional synapses?

Back 16

Within the hypothalamus and the medulla
These form the basis of the physiological changes associated with visceral pain, including diaphoresis and altered BP

Front 17

What is the gate theory of pain?

Back 17

Based on the observation that other somatic input can alleviate pain (rubbing the area)
Rubbing the area of skin activated by the A-beta fiber will reduce the sensation of pain

Front 18

What are the steps in the gate theory?

Back 18

1. Activate A-beta fiber by the normal stimuli. The A-beta fiber has a branch that travels via the dorsal columns, but also branches within the spinal cord
2. A-beta fiber releases EAA and activates inhibitory interneuron in the spinal cord
3. Inhibitory interneuron releases glycine to inhibit activity of second order neuron in the pain pathway

Front 19

What are the descending mechanisms for physiological modification of painful inputs?

Back 19

1. Neurons in periaqueductal gray are activated by numerous inputs, including opiate, EAA, and cannabinoids
2. Axons from PAG neurons travel to midline Raphe nuclei and release enkephalins, which activate raphe neurons
3. Axons from raphe neurons travel to spinal cord and release serotonin, activating inhibitory interneurons causing them to release opiates
4. Opiates activate mu receptors on presynaptic terminal of C fiber
5. Produces pre-synaptic inhibition that reduces release of substance P from nociceptor, reducing pain transmission

Front 20

How does a person get chronic pain?

Back 20

Chronic pain results from alterations at all levels of nociceptive system (receptors, spinal cord, higher CNS)
Changes resemble synaptic plasticity that produces learning and memory and involve changes that may be permanent
Changes may be initiated even if perception of initial injury prevented by general anesthesia

Front 21

What is chronic pain?

Back 21

State in which nociceptive input ceases to be correlated with physiological pain but is no longer protective in nature and no longer linked to an appropriate stimulus
Associated with:
-hyperalgesia (sensation of pain not correlated to degree of stimulation)
-allodynia (sensation of pain in response to non-noxious stimuli)

Front 22

How are the nociceptors sensitized in producing chronic pain?

Back 22

In response to tissue damage: H+, bradykinin, NGF
Interact with the nociceptors:
-Directly activate nociceptors
-Sensitive nociceptors (more AP every time)
-Activation of immune system - modulators then contribute
-Increase Substance P release from nociceptors

These create positive feedback that reinforces occurrence of pain

Front 23

How are non-nociceptive fibers recruited in producing chronic pain?

Back 23

A-beta fibers can be converted into nociceptors
Triggered by exposure to bradykinin, NGF, and H+ which alters protein expression in the A-beta fibers
Although fibers now expressing channels that make them nociceptive, they retain their physical characteristics -- low threshold!

Front 24

Take home message in production of chronic pain.

Back 24

Nociceptors become hyperactive (lower threshold) and may become spontaneously active
Allodynia results when A-beta fibers become nociceptive

Front 25

Since the chemicals are released with any damage, why do you not get chronic pain every time you experience an injury?

Back 25

The descending opioid inputs appear to be crucial in preventing this from happening anytime you experience pain
But with severe or persistent pain, the presynaptic inhibition is unable to keep the system down-regulated

Front 26

What is central hypersensitivity?

Back 26

Spinal mechanisms amplify low levels of afferent activity within the spinal cord
-Occur rapidly
-Induced even in animals with transected spinal cord
-Relies on synaptic plasticity
-Can occur even if higher CNS perception of pain blocked by general anesthesia