Week 3 - Nociception Flashcards
what is the difference between pain and nociception?
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
what are nociceptors? what are they activated by?
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
how do nociceptors differ from mechanoreceptors and other sensory receptors on skin?
least differentiated sensory receptors on skin
-exist as free nerve endings that don’t have peripheral structures that transduce and filter peripheral stimuli
what are the 2 types of nociceptors that mediate pain? what kind of fibers do they have? what are they activated by?
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
how does a noxious stimulus activate a nociceptor?
depolarizing membrane of a sensory ending
- mechanisms of which are unknown
- nociceptors discharge only when stimulus is intense enough to cause damage
what does “noxious” mean?
high intensity and potentially tissue damaging or life threatening
what is the “first and second” pain? what happens if stimulation is intense enough?
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
can A-delta and C-fibers be separated?
yes, by anesthetic blocking experiments
-can selective anesthetize C and A-delta fibers
what is the receptor on both C and A-delta fibers? what is it activated by? how are APs triggered?
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
what is hyperalgesia?
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
what causes hyperalgesia?
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
how do aspirin and other NSAIDs act?
inhibit cyclooxygenase (for biosynthesis of prostaglandins)
can pain be sensed if nociceptive pathways are damaged?
yes, pain can arise spontaneously in absence of activity in nociceptors
-pain due to peripheral nerves is important clinical problem with several etiologies
what is brachial plexus avulsion an example of? what is the pain from?
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
where do most nociceptive fibers terminate?
superficial dorsal horn (lamina I and II) projection neurons
-some A-delta nociceptive fibers project more deeply into lamina V
what do lamina I neurons contain? what are they called?
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
what kind of input do lamina V neurons receive?
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
in general, where do mechanoreceptor A-alpha, A-beta fibers, and nociceptor A-delta and C fibers synapse?
A-alpha/beta = lamina IV A-delta = lamina I and V C = lamina II
what is referred pain?
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
where is anginal pain referred to?
upper chest wall and radiation of arm
where is esophageal pain referred to?
chest wall
where is ureteral pain referred to?
lower abdomen and back (happens if passing a kidney stone)
where is bladder pain referred to?
perineum
where is prostate pain referred to?
characteristic distribution above and below affected side
how is nociceptive input from lower and upper body (excluding face) relayed to brain?
projection neurons that cross midline and ascend all the way to brainstem and thalamus in anterolateral spinothalamic pathway
how is nociceptive input from face relayed to brain?
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
what is the major target nuclei of ascending pain and temperature axons?
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
what doe the somatosensory cortex receive from VPN of thalamus?
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
what are the zones of loss if there’s a lesion in the spinal cord?
- right next to it is zone of complete loss of sensation
- reduced epicritic/somatosensory sense below ipsilaterally
- reduced nocioception below contralaterally
referred to dissociated sensory loss
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?
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
what are the interactions between primary afferents, interneurons, and descending neurons in dorsal horn?
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
where is the nucleus raphe magnus?
the rostroventral medulla (where PAG neurons make excitatory connections)
what does the superficial dorsal horn contain?
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
where are opiate receptors located?
terminals of nociceptive afferents and on the dendrites of postsynaptic neurons
how do opiates and opioid peptides regulate nociceptive transmission?
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
