L15: Nociception

Question 1

What kind of receptors are activated when there are harmful stimuli being applied to skin or subcutaneous tissues? Where are these cell bodies located?

Answer 1

Nociceptors -cell bodies (like the somatosensory recepotrs) are located in the dorsal root and trigeminal ganglia

Question 2

Which receptors are considered the least differentiated sensory receptors in the skin?

Answer 2

Nociceptors exist as free nerve endings that do not have peripheral structures that transduce & filter peripheral stimuli

Question 3

Pain in humans is mediated by different classes of nociceptive afferent fibers? List & describe them

Answer 3

1) thermal or mechanical nociceptors contributes to “first pain”
- small-diameter
- thinly myelinated Aδ fibers
- conduct at 5-30 m/s
- activation is associated with sharp, pricking pain
2) Polymodal nociceptors lead to “second pain”
- small-diameter
- unmyelinated C fibers
- conduct slow at 0.5-2 m/s
- activation is associated with a variety of high-intensity mechanical, chemical, and hot or cold stimuli

Question 4

T/F: Nociceptors begin to discharge when there’s a stimulus.

Answer 4

False -nociceptors begin to discharge only when the stimulus is intense enough to cause damage

Question 5

In general, when the stimulus is intense enough to activate Aδ fibers (“first pain”) in a peripheral nerve, a tingling sensation is reported. When will you feel sharp pain?

Answer 5

If the stimulation is intense enough, you can feel sharp pain.

Question 6

First, a stimulus intense enough to activate Aδ fibers will cause a tingling sensation. If the stimulus is intense enough, it can result in sharp pain. When the stimulus intensity is increased further, what other receptors can be activated and what kind of feeling results?

Answer 6

If the stimulus intensity is increased further, the C fibers are activated resulting in a duller, longer-lasting sensation of pain. This duller, longer-lasting sensation of pain is referred to as “second pain.”

Question 7

Is it possible to selectively anesthetize C fibers and Aδ fibers?

Answer 7

Yes.

Question 8

What is vanilloid receptor TrpV1? What activates this receptor?

Answer 8

It is a receptor that is found in both C and Aδ fibers and is a Na+ voltage gated channel. It is activated by capsaicin, heat, acids and anandamide.

Question 9

What is endovanilloids?

Answer 9

It mimics the vanilloid receptor TrpV1 (found in both C and Aδ fibers)

Question 10

What is hyperalgesia?

Answer 10

Enhanced sensitivity and responsitivity to stimulation of the area in and around the damaged tissue.

Question 11

When peripheral tissues are damaged, is the sensation of pain in response to following stimuli enhanced or depressed?

Answer 11

Enhanced leading to hyperalgesia

Question 12

What is happening on the molecular level that peripheral damage leads to hyperalgesia?

Answer 12

When tissue is damaged, it releases various substances, such as bradykinin, histamine, prostaglandins that will enhance the responsiveness of nociceptive endings.

Question 13

When nociceptors are electrically stimulated, it causes a local release of substances (e.g. substance P) that results in

Answer 13

vasodilation, swelling and the release of histamine from mast cells. Histamine will enhance the responsiveness of nociceptive endings, which partially accounts for the phenomenon of hyperalgesia in areas post-injury.

Question 14

Can local pain be sensed when nociceptive pathways are damaged?

Answer 14

Yes, pain can arise spontaneously in the absence of activity in nociceptors.

Question 15

Brachial Plexus avulsion is an example of loss of afferent input from the periphery to the spinal cord, but pain is still felt. Explain the pain found in these patients.

Answer 15

These patients feel a burning pain in the dermatomes corresponding to the denervated area. The pain is due to hyperactivity of dorsal horn neurons in the deafferented region of the cord.

Question 16

Both C & Aδ nociceptive fibers enter spinal cord via the dorsal roots. They split upon entering the spinal cord. Branches of these axons ascend and descend for a few segments as part of which tract?

Answer 16

dorsolateral tract aka lissaur’s tract

Question 17

In the gray matter of the spinal cord, there are layers (I - IX). Nociceptive fibers terminate primarily in which layers?

Answer 17

Lamina I & II in the superficial dorsal horn

**some Aδ fibers fibers project more deeply into lamina V

Question 18

Why are lamina I neurons (in gray matter of spinal cord) termed nociceptive specific (NS) neurons?

Answer 18

b/c they contain a high density of projection neurons that process pain information, and are excited solely by C and Aδ fibers.

Question 19

Lamina V neurons (in gray matter of spinal cord) are known as wide dynamic range (WDR) neurons. Why are they called WDR neurons?

Answer 19

b/c these neurons contain input from both mechanoreceptors & nociceptors, responding to both somatosensory and noxious stimuli. WDR neurons have much bigger receptive fields than do nociceptive specific neurons.

Question 20

What is referred pain?

Answer 20

displacement of pain from a visceral structure to a somatic area of the body b/c of convergence of visceral & cutaneous nociceptors onto the same dorsal horn projection neurons.

Question 21

Explain “phantom limb” and “phantom pain”

Answer 21

the limb is no longer there (e.g. amputated), but the person still senses it b/c cortical input still exists for that limb. Thus, if one believes it’s there, then one can feel “phantom pain,” which is hard to treat.

Question 22

Briefly summarize how nociceptive info from body & face is conveyed to the primary somatosensory cortex (post-central gyrus).

Answer 22

• pain info from the body ascends to the primary somatosensory cortex by first entering dorsal root and crossing over at the level of the spinal cord. It will ascend to the thalamus as the anterolateral tract and synapse at the VPL of the thalamus, before being projected to post-central gyrus
• pain info from the face will pass trigeminal ganglion and descends to synapse at the spinal nucleus of V before ascending to the thalamus as the spinal tract of V and synapsing at the VPM before going to post-central gyrus.

Question 23

If large areas of the somatosensory cortex is damaged, will it result in impaired responses to noxious stimuli or loss of pain?

Answer 23

No, clinical studies have shown that damage to large areas of the somatosensory cortex does not result in impaired responses to noxious stimuli or loss of pain.

Question 24

Explain the condition of dissociated sensory loss following a spinal cord injury.

Answer 24

• since epicritic info (mechanosensation: touch, pressure, vibration, position sense) ascends ipsilaterally before descussating in the medulla; spinal cord injury will cause ipsilateral loss of sensation
• anterolateral pathway carrying protopathic (nociceptive info) decussates in the spinal cord; spinal cord injury will cause contralateral loss of pain sensation.

hence, dissociated sensory loss involves a loss of epicritic info on the same side of the spinal cord lesion and a contralateral loss of pain info. There will also be a zone of complete loss above the epicritis loss due to bth nociceptive and epicritic fibers enter spinal cord.

Question 25

Explain the descending pain modulatory system.

Answer 25

It is a way to modulate pain in which one does not feel pain until later. It is shown that if you electrically stimulate parts of the brainstem (nucleus raphe magnus in medulla), it will inhibit nociceptive neurons b/c they make inhibitory connections in spinal cord dorsal horn (laminas I, II, and V)

Question 26

What happens when the descending pain modulatory system is damaged?

Answer 26

body loses the ability to modulate pain

Question 27

Regions in the descending pain modulatory system contain what types of neuropeptides?

Answer 27

endogenous opiod peptides & their receptors exist in regions of the descending pain modulatory system.

Question 28

When patients are given morphine (opiod agonists), which pathway is this drug affecting?

Answer 28

the descending pain modulatory system binding to opiod receptors, helping modulate pain.

Question 29

In the superficial dorsal horn, there are enkephalin containing interneurons close to nociceptive afferents (primary sensory neurons), and to dendrites of the dorsal horn neurons that receive the nociceptive afferent input. There are opiate receptors on both the terminals of the nociceptive afferents & the dendrites of postsynaptic neurons. How do opiates regulate nociceptive transmission?

Answer 29

opiates and opiod peptides regulate nociceptive transmission in part by inhibiting the release of glutamate, substance P and other transmitters from the sensory neurons. Opiates also act post-synaptically at afferent synapses to suppress the nociceptive dorsal horn neurons.

*opiates modulate nociceptive transmission at the level of the primary afferent synapse by a combo of pre- and post-synaptic actions.

Question 30

Modulation of nociception at the level of the spinal cord occurs as a result of

Answer 30

both presynaptic and postsynaptic actions.