Week 3 - Nociception

Question 1

what is the difference between pain and nociception?

Answer 1

pain is a conscious, emotional, psychological perception associated with noxious stimuli

nociception is any process in PNS or CNS associated with noxious or highly-unplesant stimulus

both pathways rely on different sets of structures

Question 2

what are nociceptors? what are they activated by?

Answer 2

peripheral endings of primary sensory neurons whose cell bodies are located in dorsal root and trigeminal ganglia (like somatosensory receptors)
-harmful stimuli applied to skin or subcutaneous tissue

Question 3

how do nociceptors differ from mechanoreceptors and other sensory receptors on skin?

Answer 3

least differentiated sensory receptors on skin

-exist as free nerve endings that don’t have peripheral structures that transduce and filter peripheral stimuli

Question 4

what are the 2 types of nociceptors that mediate pain? what kind of fibers do they have? what are they activated by?

Answer 4

thermal/mechanical - small diameter, thinly myelinated A-delta fibers that conduct at 5-30 m/s
-activation associated with sharp, pricking pain
polymodal - small-diameter, unmyelinated C fibers that conduct at 0.5-2 m/s
-activated by high-intensity mechanical, chemical, and hot (over 45 C) or cold stimuli

Question 5

how does a noxious stimulus activate a nociceptor?

Answer 5

depolarizing membrane of a sensory ending

• mechanisms of which are unknown
• nociceptors discharge only when stimulus is intense enough to cause damage

Question 6

what does “noxious” mean?

Answer 6

high intensity and potentially tissue damaging or life threatening

Question 7

what is the “first and second” pain? what happens if stimulation is intense enough?

Answer 7

stimulus intensity has to be raised to a level to activate corresponding fibers

1st: A-delta fibers in peripheral nerve = tingling
- if stimulation is intense enough, there is sharp pain
2nd: C fiber axons activated if stimulus intensity is increased further = duller, longer-lasting sensation of pain

Question 8

can A-delta and C-fibers be separated?

Answer 8

yes, by anesthetic blocking experiments

-can selective anesthetize C and A-delta fibers

Question 9

what is the receptor on both C and A-delta fibers? what is it activated by? how are APs triggered?

Answer 9

vanilloid receptor TrpV1

• activated by stimuli like capsaicin, head, acids, and anandamine (endogenous cannabanoid receptor stimulus)
• respond to endogenous chemicals similar to capsaicin that are released with peripheral injury
• AP Na+ voltage gated channels

Question 10

what is hyperalgesia?

Answer 10

enhanced sensitivity and responsivity to stimulation of area in and around damaged tissue

• so if burn point A, near point B and C, all 3 of them will have decreased threshold sensitivity
• AKA if peripheral tissues are damaged, sensation of pain in response to subsequent stimuli is enhanced

Question 11

what causes hyperalgesia?

Answer 11

sensitization of nociceptors by various substances released when tissue is damaged

• release of bradykinin, histamine, prostaglandins, and other agents from site of injury enhances responsiveness of nociceptive endings
• electrical activity in nociceptors stimulates local release of chemical substances that cause vasodilation, swelling, and release of histamine from mast cells

Question 12

how do aspirin and other NSAIDs act?

Answer 12

inhibit cyclooxygenase (for biosynthesis of prostaglandins)

Question 13

can pain be sensed if nociceptive pathways are damaged?

Answer 13

yes, pain can arise spontaneously in absence of activity in nociceptors
-pain due to peripheral nerves is important clinical problem with several etiologies

Question 14

what is brachial plexus avulsion an example of? what is the pain from?

Answer 14

referred pain when nociceptive pathways are damaged; patients feel burning pain in dermatomes corresponding to denervated area (dorsal roots have been torn away)
-pain is from hyperactivity of dorsal horn neurons in deafferented region of cord

Question 15

where do most nociceptive fibers terminate?

Answer 15

superficial dorsal horn (lamina I and II) projection neurons

-some A-delta nociceptive fibers project more deeply into lamina V

Question 16

what do lamina I neurons contain? what are they called?

Answer 16

high density of projection neurons that process pain information
-excited solely by A-delta and C nociceptive fibers, thus called nociceptive specific (NS) projection neurons

Question 17

what kind of input do lamina V neurons receive?

Answer 17

both mechanoreceptors and nociceptors, thus called wide dynamic range neurons (WDR)

• respond to both somatosensory and noxious stimuli
• have much larger receptive fields than NS neurons

Question 18

in general, where do mechanoreceptor A-alpha, A-beta fibers, and nociceptor A-delta and C fibers synapse?

Answer 18

A-alpha/beta = lamina IV
A-delta = lamina I and V
C = lamina II

Question 19

what is referred pain?

Answer 19

displacement of pain from visceral structure (organ) to a somatic area of the body b/c fo convergence of visceral and cutaneous cociceptors onto same dorsal horn projection neurons

Question 20

where is anginal pain referred to?

Answer 20

upper chest wall and radiation of arm

Question 21

where is esophageal pain referred to?

Answer 21

chest wall

Question 22

where is ureteral pain referred to?

Answer 22

lower abdomen and back (happens if passing a kidney stone)

Question 23

where is bladder pain referred to?

Answer 23

perineum

Question 24

where is prostate pain referred to?

Answer 24

characteristic distribution above and below affected side

Question 25

how is nociceptive input from lower and upper body (excluding face) relayed to brain?

Answer 25

projection neurons that cross midline and ascend all the way to brainstem and thalamus in anterolateral spinothalamic pathway

Question 26

how is nociceptive input from face relayed to brain?

Answer 26

axons from trigeminal ganglion cells and VII, IX, and X ganglia carry info from facial nociceptors and thermoreceptors into brainstem, cross midline, and ascend trigeminothalamic tract

Question 27

what is the major target nuclei of ascending pain and temperature axons?

Answer 27

ventral posterior nuclear complex of thalamus, esp. VPM (face) and VPL (rest of body)

• similar arrangement for mechanosensory and noxious stimuli responsible for discriminative aspects of pain
• although close together, comprise separate systems

Question 28

what doe the somatosensory cortex receive from VPN of thalamus?

Answer 28

nociceptive information

• no orderly arrangement of input to cortex similar to tactile inputs
• clinical studies indicate damage to large areas of somatosensory cortex doesn’t cause impaired responses to noxious stimuli or loss of pain

Question 29

what are the zones of loss if there’s a lesion in the spinal cord?

Answer 29

1. right next to it is zone of complete loss of sensation
2. reduced epicritic/somatosensory sense below ipsilaterally
3. reduced nocioception below contralaterally

referred to dissociated sensory loss

Question 30

what happens to the dorsal horn of the spinal cord if brain stem is stimulated?

• what do experimentally induced lesions of dorsolateral funiculus do?
• what does administration of low doses of opiates do?

Answer 30

brain stem stimulation inhibits nociceptive neurons in dorsal horn of spinal cord

• neurons in periaqueductal gray matter make excitatory connections in rostroventral medulla
• neurons in rostroventral medulla make inhibitory connections in laminae of I, II, and V of dorsal horn (also termination of nociceptive afferent neurons)
• electrical stimulation in either site causes inhibition of dorsal horn neurons that respond to noxious stimulation
• experimentally induced lesions of DF (pathway carrying descending info) abolished effect of electrical stimulation
• opiates directly into same specific regions produced powerful analgesia

Question 31

what are the interactions between primary afferents, interneurons, and descending neurons in dorsal horn?

Answer 31

descending axons of serotonergic and noradrenergic neurons from nucleus raphe magnus contact dendrites of spinothalamic tract neurons and local enkephalin-containing inhibitory interneurons in superficial dorsal horn
-descending inhibition of spinothalamic tract neurons is mediated by activation of enkephalin interneurons in dorsal horn

Question 32

where is the nucleus raphe magnus?

Answer 32

the rostroventral medulla (where PAG neurons make excitatory connections)

Question 33

what does the superficial dorsal horn contain?

Answer 33

high density of enkephalin- and dynorphin-containing interneurons close to terminals of cocicceptive afferents, and to the dendrites of the dorsal horn neurons that receive nociceptive afferent input

Question 34

where are opiate receptors located?

Answer 34

terminals of nociceptive afferents and on the dendrites of postsynaptic neurons

Question 35

how do opiates and opioid peptides regulate nociceptive transmission?

Answer 35

inhibit release of glutamate, substance P, and other transmitters from sensory neurons
-opiates also act possynaptically at afferent synapses to suppress activity of nociceptive dorsal horn neurons