Nociception

Question 1

nociception vs pain

Answer 1

• nociception is the system that perceives tissue damage

- pain is a psychological perception

Question 2

nociceptors

Answer 2

• peripheral free nerve endings
• stimulated in response to harmful stimuli to the skin or subQ tissues
• cell bodies in dorsal root and trigeminal ganglia

Question 3

nociceptors 2

Answer 3

• least differentiated of the sensory receptors in the skin
• free nerve endings with no peripheral structures to transduce and filter
• pain is mediated by different classes:
• thermal/mechanical via ad fibers, 5-30m/s, myelinated- sharp, pricking pain
• polymodal-C fibers, 0.5-2 m/s- high intensity chemical, mechanica, and hot/cold
• a noxious stimulation activates the nociceptor by depolarizing the membrane of the sensory ending, only when stimulus is intense enough

Question 4

early vs late

Answer 4

1. if stimulus intensity activates ad fibers, tingling sensation reported, then sharp pain
2. if it is increased further, it activates C fibers for a duller, long lasting pain
3. can be separated by anesthetic blocking experiments and selectively anesthetizing C and ad fibers

Question 5

TrpV1 receptor

Answer 5

• agonist is capsacin, vanilloid receptor
• heat, acids, anandamide
• endovanilloids- mimics
• respond to endogenous chemical signals similar to capsaicin that are released with peripheral injury
• receptors for transducing mechanical and chemical tissue damage are less understoof
• candidates are other members of Trp family and ASIC channels
• AP Na voltage gated channels

Question 6

hyperalgesia

Answer 6

• when peripheral tissues are damaged, the sensation of pain in response to subsequent stimuli is enhanced
• hyperalgesia is the enhanced sensitivity and responsitivity to stimulation of the area in and around damaged tissue
• point of injury vs flare

Question 7

injury and sensitization

Answer 7

• causes released of a number of substances that activate and stabilize nociceptors
• bradykinin, histamine, prostaglandins enhance the responsiveness of nociceptors
• electrical activity in nociceptors stimulates substance P and causes vasodilation, swelling, and release of histamine from mast cells
• aspirin and NSAIDs inhibit COX-prostaglandin syn

Question 8

entry to spinal cord

Answer 8

• local pain can be sensed even when nociceptive pathways are damaged
• pain due to injury of peripheral nerves is a clinical problem
• can get pain with loss of afferent input

Question 9

brachial plexus avulsion

Answer 9

• patients feel a burning pain in the dermatomes corresponding to the denervated area
• pain is though to result from hyperactivity of dorsal horn neurons in the deafferented region of the cord

Question 10

laminar organization

Answer 10

• central axons of nociceptive nerve cells enter at dorsal roots
• ad and C fibers split upon entering spinal cord
• branches of these axons ascend and descend for a few segments as part of dorsolateral, some axons synapse with neurons in dorsal horn –>
• nociceptive fibers terminate primarily in superficial dorsal horn ( lamina I and II)
• some Ad fibers go to lamina V
• these fibers synapse and cross to ascend

Question 11

nociceptor afferents

Answer 11

• terminate on dorsal horn projection neurons
• lamina I neurons have high density of projection neurons that process pain, excited soley by AD and C- nociceptive specific
• other projection neurons in lamina V receive input from mechano and noci- dynamic range neurons-respond to somatosensory and noxious- larger receptive fields
• fibers from nociception cross in anterior commissure

Question 12

visceral pain

Answer 12

• few neurons in the dorsal horn are specific to conveying visceral pain
• referred pain is the displacement of pain from a visceral structure to a somatic area of the body because of the convergence of visceral and cutaneous nociceptors onto the same dorsal horn projection neurons
• angina referred to upper chest wall and radiation of the arm, esophagus referred to chest wall
• ureter pain referred to lower abd and back
• bladder pain referred to perineum
• prostate pain with characteristic distribution above and below affected side

Question 13

phantom limb pain

Answer 13

• sensory information about phantom body parts can exist in the absence of peripheral input and such somatic information can also be accompanied by pain
• central mechanisms continue to operate into some level independent of information from periphery

Question 14

major pain pathways

Answer 14

1. nociceptive information from upper body and lower body are relayed to the brain by projection neurons that cross the midline and ascend all the way to the brainstem and thalamus in anterolateral spinothalamic pathway
2. nociceptive info from the face- axons from trigem ganglion cells and from ganglia associated with VII, IX, X carry info from facial nociceptors and thermoreceptors into the brainstem, cross at midline and ascend in trigeminothalamic tract
3. major targets- VPM from face and VPL from body-similar for mechanosensory-some discrimincation- albeit poor, essentially separate system
4. response properties of the two major divisions of the thalamus are similar to those of the projection neurons that synapse on them
5. SI receives nociceptive info from VPN, no order, damage does not impair responses

Question 15

major differences

Answer 15

• pain and temp cross and ascend opposite side of cord
• somatosensory ascends ipsi until caudal medualla
• loss on one side will cause lowered mechano on that side and lowered pain on other side
• dissociated sensory loss
• also an area missing because those fibers are taken out

Question 16

descending pain modulatory system

Answer 16

• brain stem stimulation was found to inhibit nociceptive neurons in the dorsal horn of the spinal cord
• neurons in PAG make excitatory connections in rostroventral medulla-raphe nucleus
• neurons in rostroventral medulla make inhibitory connections in laminae I, II, V (where afferents end)
• electrical stimulation in either site results in inhibition of dorsal horn neurons that respond to noxious stim
• experimentally induced lesions of the dorsolateral funiculus abolished this effect
• opiates in the same regions produced analgesia
• endogenous opioid peptides exist and their receptors are located in the places above

Question 17

interactions

Answer 17

• descending axons from serotonergic and noradrenergic neurons from the nucleus raphe magnus contact dendrites of spinothalamic tract
• also connect with local (in dorsal horn) enkephalin containing inhibitory neurons
• the descending inhibition of spinothalamic tract mediated by the activation of the enkephalin interneurons
• see picture
• norepi (or serotonin) inhibits nociceptive receptor, also activates an opioid for additional inhibition

Question 18

whole picture

Answer 18

1. superficial dorsal horn contains lots of enkephalin and dynorphin containing interneurons close to terminals of nociceptive afferents and to the dendrites of dorsal horn neurons that receive noci afferents
   - opioid receptors on nociceptive afferents and dendrites of DR neurons
   - inhibit noci by stopping glutamate, substance P, other transmitters
   - transmitter release suppressed by activation of opioid receptors
   - also suppress dorsal horn neurons (in addition to noci afferents)
2. combo of pre and post synaptic actions