Physiology Of Pain

Question 1

Describe fast pain

Answer 1

Generally associated with immediate injury

Sharp pain

Question 2

Describe slow pain

Answer 2

Often characterized as dull or achy

Often occurs after injury

Question 3

Describe Adelta fibers

Answer 3

Bare nerve ending
Small, sparsely myelinated
Fast, sharp pain

Question 4

Describe C fibers

Answer 4

Bare nerve ending

Unmyelinated fibers associated with dull pain (slow pain)

Question 5

What are types of nociceptors?

Answer 5

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

Question 6

Describe silent nociceptors

Answer 6

Not activated by first injury

Sensitized by first injury, so if injury occurs again in same area, they are activated

Question 7

Describe mutations in mechanosensitive Na+ channel SCN9A (Na1.7)

Answer 7

Inactivation of channel leads to complete absence of pain. (Other sensations like temperature are normal)
Altered inactivation of the channel can lead to paroxysmal extreme pain syndrome. Rectal, ocular, or submandibular pain bouts occur.

Question 8

Unlike other receptors, nociceptors express a number of ligand-gated receptors (in addition to the stimulus-gated channels), which alter the sensitivity of the nociceptors to input. What are the substances? Importance? Sources?

Answer 8

Substances: Substance P, kinins (bradykinin), ATP, H+
This collection of chemicals also exists in the spinal cord, where they also influence nociceptive inputs at those synapses.
When these chemicals bind to their receptors, they change the sensitivity of the nociceptors (usually increasing) and activate silent nociceptors.
Activated nociceptors, damaged tissue, recruited white blood cells release these substances in the periphery and spinal cord.

Question 9

What is the neurotransmitter released from nociceptors?

Answer 9

EAA (from Adelta fibers) into spinal cord

EAA acts primarily on non-NMDA receptors

Question 10

What is the neurotransmitter released by C fibers?

Answer 10

For low levels of pain, EAA is released
For more intense stimulation, substance P becomes dominant effect
Substance P binds to neurokinin A receptors and elicits slow epsp that adds onto EAA standard epsp

Question 11

Hw does capsaicin work for pain relief?

Answer 11

Causes substance P to be released from C fibers
Extensive release of substance P exhausts the cells’ supply of vesicles containing substance P
This leads to synaptic fatigue and temporary pain relief until the neurons can make new vesicles
In neonates, large doses of capsaicin can cause permanent depltion of substance P and loss of slow pain

Question 12

Nociceptors that travel with the spinoreticulothalamic pathway (slow pain) synapse on an interneuron in the spinal cord before crossing and ascending to the reticular formation. What is the importance of this synapse?

Answer 12

Site of much modulation of the spinal cord function:
Local (gate theory)
Descending (opioid pathways)

Question 13

What do visceral afferents travel with?

Answer 13

Autonomic nerves, rather than the spinothalamic or spinoreticulothalamic tracts

Question 14

Describe the spinothalamic tract

Answer 14

Controls fast pain (Adelta fibers)
Fibers ascend and will synapse in ventral posterior nucleus of thalamus
Then to cortex

Question 15

Describe spinoreticulothalamic tract

Answer 15

Control slow pain (C fibers)
ascend to medulla and synapse in reticular formation
Synapse in intralaminar nucleus of thalamus
Then to cortex

Question 16

What is an important difference between nociceptive input and other sensory inputs?

Answer 16

Nociceptive input is distributed widely in the cortex

Question 17

Describe S1 and S2 involvement with pain

Answer 17

Help localize the pain

Damage to S1/S2 does not impair ability to feel pain

Question 18

Describe the role of insular cortex with nociceptive inputs

Answer 18

Receives inputs from medial nuclei and ventroposterior medial nucleus
Processes information about internal state of the body
Contributes to the autonomic response to pain
integrates all signals related to pain

Question 19

Describe asymbolia

Answer 19

Caused by lesion of insular cortex
Pain is perceived, and sharp and dull pain can be distinguished
However, no appropriate emotional response

Question 20

What is the importance of the amygdala and nociception?

Answer 20

Many nociceptive inputs go to the amygdala

Important for activating/producing emotional components inherent in sensation of pain

Question 21

Visceral nociceptors, traveling with autonomics, have additional synapses within the hypothalamus and medulla. What do these additional synapses do?

Answer 21

Form basis of physiological changes associated with visceral pain, including diaphoresis and altered blood pressure

Question 22

How does the body modify nociceptive inputs?

Answer 22

Peripheral mech: Input from other cutaneous receptors that also reduces ability of primary afferent to activate second order neuron
Central mech: descending influences that reduce ability of primary afferent to activate second order neuron

Question 23

Describe gate theory of pain

Answer 23

Activate Abeta fiber (large, myelinated, fine touch or vibration) by normal stimuli (rubbing the area). Abeta fiber has a branch that travels via dorsal columns and a branch to the spinal cord
Abeta fiber releases EAA and activates inhibitory interneuron in spinal cord
Inhibitory interneuron releases glycine that activates chloride conductance.
This hyperpolarizes the second order neuron in the pain pathway
This increases the number of action potentials needed from C fibers to activate the second order neuron
This means fewer action potentials from second order neuron, so perceived as less pain
End result: rubbing area of skin activated by Abeta fiber will reduce sensation of pain

Question 24

Describe descending influences that modify pain

Answer 24

Neurons in the periaqueductal gray (PAG) are activated by numerous inputs, including opiate, EAA, and cannibinoids
Axons from PAG neurons travel and release enkephalins in the midline raphe nuclei to activate those neurons
Axons from raphe nuclei neurons travel to spinal cord and release serotonin, which activates inhibitory interneurons
Inhibitory interneurons release enkephalins or dynorphins (NOT GABA), which activate mu receptors on the presynaptic terminal of the C fiber
This causes hyperpolarization due to K+ efflux
This produces presynaptic inhibition that reduces the release of substance P from the nociceptor and reduces pain transmission

Question 25

Describe deep pain

Answer 25

Associated with periosteum, ligaments
Usually dull, achyy
Few Adelta fibers
Many C fibers
Associated with muscle spasm

Question 26

Describe muscle pain

Answer 26

Cause: usually injury or ischemia during contraction
Both group III and IV fibers present
Get both fast and slow pain

Question 27

Describe visceral pain

Answer 27

Poorly localized
Few receptors (almost all Group IV)
Stretch receptors (distension)
Often referred

Question 28

Describe referred pain

Answer 28

Identifying exact location of a stimulus requires experience on part of brain
Visceral pain is not experienced enough to process properly
There is also convergence of fibers in spinal cord
End result: visceral pain can be referred to different places
Ex: heart attack referred to left arm, left shoulder, and jaw

Question 29

How is pain different from all other senses?

Answer 29

Sensation is elicited by multiple signals
It preempts all other signals
Theses differences result in multiple alteration in physiological functioning of pain pathways