Exteroception & Nocioception Flashcards
Short sensory axons
Allow receptor potential to spread to synaptic end of the cell by passive electronic transmission
Ex: Rod photoreceptors, auditory hair cells
Long sensory axons
Employ regenerative action potentials to carry info from the receptive ending to the synaptic release site in the spinal cord or brainstem
I.e. somatosensory receptors
How do rod photoreceptors detect light?
Rod photoreceptors have resting potentials ~-30-40mV due to resting cation conductance via cGMP-gated cation channels
Receptor TM protein rhodopsin binds light-activated 1-trans-retinal, inducing a conformational change in rhodoptsin to metarhodopsin; this stimulates a G-protein which activates cGMP phosphodiesterase; decreased cGMP causes closure of cGMP-gated cation channels, hyperpolarizing the cell; decreased NT release is interpreted by higher order neurons as a response to light
A-alpha afferents
Largest diameter
Fastest speed
Muscle spindle and tendon afferents
A-beta afferents
Intermediate size
Intermediate speed
Mechanical receptors of skin
A-delta afferents
Small size
Slow conducting speed
Sharp pain, cold temperature
C afferent fibers
Smallest diameter (0.2-1.5uM) Slowest speed (0.4-2m/sec) *Unmyelinated
Warm temperature, burning pain, itch, crude touch
Rapidly vs. slowly adapting receptors
Rapidly adapting receptors (Meissner, Pacinian) fire only one or a few action potentials when stimulated by steady touch, then stop firing
Slowly adapting receptors (Merckel, Ruffini) fire continuously when stimulated with steady touch
Receptive field
The area of the skin in which a mechanical stimulus elicits a response from the individual cell
Merkel’s Disks
Slowly adapting afferents with small receptive fields
Present at high density in the finger tips
Pacinian Corpuscle
Rapidly adapting afferents with large receptive fields; lie deep in the dermis and subcutaneous tissue
High sensitivity to skin deformation over a wide area, i.e. vibration
Meisner’s corpuscle
Rapidly adapting afferents with small receptive fields
Present at high density in the fingertips where they sense fine vibration
Ruffini’s (free nerve) endings
Slowly adapting afferents with large receptive fields; lie deep in the dermis and subcutaneous tissue
Evaluate information related to prolonged stretching of skin, i.e. grip
Hair follicles
Unmyelinated branches of axons spiral around hair follicles within the dermis; bending of the hair shaft activates the sensory terminals
Ventrobasal complex
Ventral posterolateral (VPL) nucleus + Ventral posteromedial (VPM) nucleus in the thalamus
VPL receives input from secondary neurons in the nucleus gracilis and nucleus cuneatus; VPM receives input from secondary neurons in the principal nucleus
Trigeminal mesencephalic nucleus
Houses the cell bodies of muscle spindle fibers in the muscles of mastication (proprioceptive afferents) and some mechanoreceptors of the mouth; these cells are the only population of proprioceptive afferents with centrally located cell bodies
Spinoreticular pathway
Afferent fibers running within the anterolateral system that convey pain input to the forebrain; elicits emotional/behavioral responses to pain via connections to the limbic system (cingulate gyrus)
Spinomesencephalic tract
Afferent fibers running within the anterolateral system that convey pain input to the midbrain periaqueductal gray (PAG)
What is the thermoneutral point?
~38 degrees Celcius; neither warmth nor cool sensed because cool and warm receptors have equal firing rates
Cool receptors - firing range & fiber type
Firing range: 10-37 degrees C
Cool receptors are mostly A-delta fibers
There are 10x more cool receptors than warm receptors
Warm receptors - firing range & fiber type
Firing range: 30-48 degrees C
Warm receptors are mostly C fibers
Polymodal receptors
Located on C fibers; activated by high intensity mechanical, chemical, or thermal stimuli
Includes VR-1 receptor
VR-1 receptor
Located on polymodal C fiber nerve endings; activated by capsaicin and moderate heat
What kinds of molecular receptors detect pain?
VR-1: detects capsaicin, H+, and heat
Acid-sensing ion channels (ASICs)
P2X - detect purines (ATP) from dead cells
Types of acute pain - first vs. second
First pain - immediate “alerting” pain; tolerable and well-localized; carried by lightly myelinated A-delta afferents
Second pain - delayed; throbbing and intolerable, poorly localized; carried by unmyelinated, slowly conducting C afferents
Mechanical nociceptors
Activated by intense pressure:
A-beta fibers are blocked first, then A-delta, then C fibers
Sensitizers
Lowers the nociceptor action potential threshold so that weaker stimuli, or even non painful stimuli, evoke pain; cause both allodynia and hyperalgesia
Substance P Prostaglandins ATP ACh 5-HT
Allodynia
Generation of pain by non-painful stimuli
Hyperalgesia
Increased response to painful stimulus
Mechanism of the triple response
Tissue damage releases proteases which activate bradykinin; bradykinin vasodilates (causing redness) and increases capillary permeability (causing edema ‘wheel’);
Bradykinin also activates nociceptors, causing pain via C fiber APs which travel centrally toward the cell body and peripherally toward neighboring skin regions; substance P is released from peripheral axon branches in a region surrounding the site of the wound
Substance P causes mild vasodilation (pink ‘flare’) and acts as a sensitizer so that nociceptors within the pink flair are activated more easily (hyperalgesia and allodynia)
Substance P - Mechanism of release and actions
Released both centrally (near the dorsal horn) and peripherally (in the skin) in response to repetitive stimulation of C fibers by some nociceptive activator (often Bradykinin)
Substance P is both a sensitizer and a vasodilator
Effects of Bradykinin
Nociceptor activation
Vasodilation
Increased capillary permeability
Mechanism of central sensitization
Repetitive stimulation of C fibers causes release of Glutamate onto post-synaptic AMPA and NMDA channels as well as release of Substance P onto post-synaptic NK1 channels; Substance P binding causes closure of K+ channels, leading to depolarization; depolarization causes influx of Ca2+ through VSCSs and activates PKC, which phosphorylates NMDA removing the requirement for depolarization
Now, the synapse is potentiated and a single stimulation may be sufficient to evoke a post-synaptic potential even without substance P release; this is hyperalgesia
Why does rubbing an injury make it feel better?
Rubbing activates non-nociceptive A-beta afferents which synapse on inhibitory interneurons in the dorsal horn; these interneurons synapse on second order neurons in the substantia gelatinosum which receive pain input from afferent C fibers
What is the role of the PAG in pain modulation?
Periaqueductal gray (PAG) neurons in the midbrain project to the Raphe Magnus in the medulla; Raphe cells project to the spinal cord via the dorsal lateral funiculus, where they release serotonin; serotonin activates inhibitory interneurons which release enkpahalin (an endogenous opiate) onto and inhibit the second-order neurons of the substantia gelatinosum which receive pain input from afferent C Fibers of the ALS pathway
Why are SSRIs used to treat pain?
SSRIs increase the amount of serotonin available in the spinal cord, where it activates inhibitory interneurons; these interneurons release enkphalin onto the second order neurons of the substantia gelatinosum, which receive pain input from afferent C fibers in the ALS pathway
What is the sprouting and re-wiring mechainsm of neuropathic pain?
Following nerve injury, A-beta afferents sprout and invade the territory of the substantia gelatinosa where they synapse on second-order neurons of the ALS pain pathway; now, non-noxious stimuli activates pain pathways
How are glial cells involved in neuropathic pain?
Neuronal damage releases ATP which binds purigenic receptors on microglial cells, stimulating them to secrete BDNF; BDNF down-regulates the potassium/chloride co-transporter (KCC2), which allows accumulation of Cl- within the cell resulting in a more depolarized value for ECl; now, activation of GABA receptors leads to depolarization and excitation, causing hyperalgesia
*Remember: this is a reversion to an embryonic state
Which cortical layer receives input from the thalamus in the PCML pathway?
IV
Which cortical layer projects to the thalamus?
VI
Which cortical layer projects to the basal ganglia, brainstem, and spinal cord?
V
Which cortical area receives input from muscle stretch receptors?
3a
Which cortical area receives input from cutaneous receptors?
3b
Where is myocardium pain referred to?
Upper chest wall, left arm and hand (angina)
Where is gallbladder pain referred to?
Scapula
Where is uretral pain referred to?
Lower abdominal wall
Where is bladder pain referred to?
Perineum
Where is appendix pain referred to?
Periumbilical anterior abdominal wall
Tabes dorsalis
Sequelae of neurosyphilia; damage to large diameter myelinated afferent fibers (A-beta) causes hyperalgesia by interfering with the normal ability of these fibers to stimulate inhibitory interneurons in the spinal cord
