Physiology of Pain

Question 1

Pain is different from all other senses because

Answer 1

the sensation is elicited by multiple stimuli
it preempts all other signals
these differences result in multiple alterations in the physiological functioning of the pain pathways

Question 2

pain can be characterized as

Answer 2

fast pain

slow pain

Question 3

fast pain

Answer 3

generally associated with the immediate injury

aka sharp pain

Question 4

slow pain

Answer 4

often characterized as dull or achy

often occurs after the injury

Question 5

Pain can be characterized by location

Answer 5

deep pain
muscle pain
visceral pain
somatic/cutaneous pain

again the characteristics of these forms of pain vary due to physiological and anatomical considerations

Question 6

Sensory receptors

Answer 6

many are bare nerve endings with specialized ion channels that open in response to specific stimuli (i.e. thermoreceptors)
some sensory receptors show quite extensive morphological specilization

Question 7

Sensing Noxious Stimuli - the nociceptors

Two types of fibers

Answer 7

bare nerve endings can be
A delta fibers
C fibers

Question 8

A delta fibers

Answer 8

small sparsely myelinated, fast, sharp pain

Question 9

C fibers

Answer 9

unmyelinated fibers associated with dull pain (slow pain)

Question 10

Nociceptors must be able to detect

Answer 10

a wide variety of damaging stimuli

Question 11

Types of Nociceptors

Answer 11

sensitive to both thermal and mechanical stimuli (most)
sensitive to only thermal
sensitive to only mechanical
silent/sleepin

Question 12

Many mixed modality nociceptors also express a

Answer 12

mechanosensitibe Na channel (SCN9A or Na1.7)

Question 13

Mutations in the nocicieptive Na channels lead to

Answer 13

an absence of pain sensation

paroxysmal pain syndrome

Question 14

Mutations in the nocicieptive Na channels lead to

Answer 14

an absence of pain sensation

paroxysmal pain syndrome

Question 15

Unlike other receptors, nociceptors express _________ which alter the sensitivity of the nociceptors to input

Answer 15

number of ligand gated receptors (in addition to the stimulus gated channels)

Question 16

Ligand gated receptors for ______(4) are found on the nocicieptors to alter sensitivity

Answer 16

Substance P
the kinins
ATP
H+
interestingly this collection of chemicals also exists in the spinal cord, where they also influence nociceptive inputs at those synapses

Question 17

When ligands bind their ligand gated channels on the nociceptors,

Answer 17

they change the sensitivity of the nociceptors (usually increasing) and activate the silent receptors

Question 18

The source of sensitivity-altering chemicals

Answer 18

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

Question 19

There are multiple pathways to the brain
proprioceptive and discriminative touch
fast pain
slow pain

Answer 19

dorsal columns
spinothalamic tract
spinoreticulothalamic system

Question 20

The NT released by nociceptive fibers

Answer 20

EAA (from A delta) acting primarily on non NMDA receptors

Question 21

NT released by C fibers

Answer 21

Substance P

EAA

Question 22

Nociceptors that travel with the spinoreticulothalamic pathway (slow pain) synapse on
what is this synapse important for

Answer 22

an interneruon in the spinal cord before crossing and ascending to the reticular formation

this synapse is the site of much modulation of spinal cord function
local (gate theory)
descending (opioid pathways)

Question 23

Nociceptors that travel with the spinoreticulothalamic pathway (slow pain) synapse on
what is this synapse important for

Answer 23

an interneruon in the spinal cord before crossing and ascending to the reticular formation

this synapse is the site of much modulation of spinal cord function
local (gate theory)
descending (opioid pathways)

Question 24

visceral afferent pain fibers travel with

Answer 24

autonomic nerves, rather than with either of the two spinal pathways already described

Question 25

Unlike other senses, nociceptive input is distributed widely in the Cortex

Answer 25

insular cortex post central gyrus mediofrontal cortex

Question 26

Pain and S1 and S2

Answer 26

S1 and S2 do receive input from the nociceptors and play a role in localizing the pain

Question 27

Pain and the insular cortex

Answer 27

the insular cortex is particularly important in the interpretation of nociceptive inputs 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 - occurs when insular cortex is lost)

Question 28

Lesions in any one area

Answer 28

does not abolish the ability to experience pain, although the experience is changed

Question 29

pan and the amygdala

Answer 29

many nociceptiv inputs go to the amygdala | this is particularly important for activating?producing the emotional components inherent in the sensation of pain

Question 30

Visceral nociceptors, traveling with the autonomic nerves, have additional synapses within

Answer 30

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

Question 31

Visceral nociceptors, traveling with the autonomic nerves, have additional synapses within

Answer 31

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

Question 32

Gate theory based on

Answer 32

based in part on the observation that other somatic input can alleviate pain (rubbing the area)

Question 33

Gate theory reminder

Answer 33

neurons traveling in the spinoreticulothalamic tract synapse on an interneuron within the spinal cord before ascending

Question 34

Gate theory

Answer 34

Step 1 - activate an A beta fiber by the normal stimuli. The AB fiber has a branch that travels via the coral columns, but it ALSO BRANCHES WITHIN THE SPINAL CORD Step 2 - the AB fiber releases EAA and activates an inhibitory interneuron in the spinal cord Step 3 - the inhibitory interneuron releases glycine to inhibit the activity of the second order neuron in the pain pathway End result - rubbing the area of skin activated by the AB fiber will reduce the sensation of pain

Question 35

Basic idea of descending mechanisms of modification of painful inputs

Answer 35

use presynaptic inhibition to reduce activation of the second order nociceptive neuron in the spinal cord

Question 36

Basic idea of descending mechanisms of modification of painful inputs

Answer 36

use presynaptic inhibition to reduce activation of the second order nociceptive neuron in the spinal cord

Question 37

Descending modification of pain

Answer 37

Step 1 - neurons in the periaqueductal gray are activated by numerous inputs, including opiate, EAA and the cannibinoids Step 2 - axons from the PAG neurons travel to the midline raphe nuclei and release ENKEPHALINS which activate the raphe neurons Step 3 - axons from the raphe neurons travel to the spinal cord and release SEROTONIN, which activate inhibitory nterneurons, causing them to release opiates Step 4 - the opiates released by the interneuron activate mu receptors on the presynaptic terminal of the C fiber Step 5 - this produces pre-synaptic inhibition that reduces the release of substance P from the nociceptor and reduces pain transmission