pain !!! dent/obhs 131 neuroscience 2009. pain…. is a submodality of somatosensation is the...
TRANSCRIPT
PAIN!!!
DENT/OBHS 131Neuroscience
2009
Pain….
Is a submodality of somatosensation
Is the perception of unpleasant or aversive stimulation (sensory and emotional experience)
Warns of injury (physiological relevance)
Is highly individual and subjective
General topics
Brief review of somatosensationAnatomical pathwaysSubstance PNociceptorsGating theoryDescending controlOpioids / morphinePlacebo effects
Learning Objectives
Describe the course of the spinothalamic (and trigeminal) tract(s) from dermatome to cortex
Describe the types of fibers carrying pain information, including their relative conduction velocities, substances they release and where they terminate in the spinal cord and periphery
Discuss how the major types of nociceptors respond to damage / injury
Know that other ascending pathways are involved in pain transmission
Discuss the descending regulation of noxious information signaling
Explain how ascending pain information is “gated” in the spinal cord
Dual ascending sensory pathways
Dorsal columns / ML
Anterolateral system Several distinct pathways convey different aspects
of pain - see later e.g. spinothalamic -
awareness and location of pain
Small DRG processes enter the cord:,Afferents
Lissauer’stract
Superficial layers of dorsal horn
Ventral White Commissure (VWC) III
Sub P
synapse in the substantia gelatinosa,then cross in the VWC and ascend.
Pain and temperature
Learning Objective #2
Describe the types of fibers carrying pain information, including their relative conduction velocities, substances they release and where they terminate in the spinal cord and periphery
C fibers use two transmitters:substance P and glutamate
Substance P released with strong stimuli
Act to enhance and prolong the action of glutamate acting on AMPA receptors
Afferent termination in dorsal horn
Many nociceptive fibers terminate in layer I (marginal layer) and II (substantia gelatinosa) of dorsal horn of spinal cord
Some pain and non-noxious sensory (e.g., proprioception) into other layers (including ventral horn - important for reflexes)
Conduction velocities
Nociceptive afferents in peripheral nerve
Fast sharp pain and slow dull burning pain
myelination & axon diameter
Nociceptors are free nerve endings
Learning Objective #3
Discuss how the major types of nociceptors respond to damage / injury
Harmful stimuli activate nociceptorsNociceptors are peripheral free endings of primary sensory DRG and trigeminal ganglia neurons
Membrane contains receptors Classes (all located in skin and deep tissues)
Thermal - extreme temperatures – A fibers Mechanical - intense pressure – A fibers - sharp pain Polymodal - intense mechanical, chemical or thermal stimuli – C fibers (unmyelinated) – dull burning
Nociceptors
Chemical nociceptors
3. vasodilation / extravasation (neurogenic inflammation)
1. Damaged cells (endothelial / platelets) - release chemicals:activate & sensitize (HYPERALGESIA)free nerve endings
arachidonic acidcyclo-oxygenase(ASPIRIN)
2. local & central effects
Thermal nociceptors… …..are a separate group (interestingly including the heat-sensitive capsaicin receptor ) and are members of the transient receptor potential (TRP) gene family (non-selective cation channel)
Activated by extreme temp: < 5 C or > 45 C
Pain & Temperature (STT) pictured are “normal” thermoreceptors (also free nerve endings)
Mechanical nociceptors……
…….are activated by very strong stimuli
Sensitization of nociceptors
Pain pathways sensitize!!!!!
After tissue damage, the sensation to pain to subsequent stimuli is increased at primary site of injury
Occurs in primary and secondary (surrounding) areas Thresholds decrease or magnitude of pain from
suprathreshold stimuli increases - HYPERALGESIA Painful response to otherwise innocuous mechanical
stimulus - ALLODYNIA With severe persistent injury, C fibers fire
repetitively or “wind up” resulting in increased glutamate release in spinal cord that activates NMDA receptors – synaptic plasticity
Learning Objective #1
Describe the course of the spinothalamic (and trigeminal) tract(s) from dermatome to cortex
Spinothalamic
Cross Direct to
multiple thalamus
Pain pathways through thalamus
VPL / VPM (neospinothalamic) receive nociceptive specific and other sensory inputs spinothalamic tract (STT & TTT) project to primary somatosensory cortex neurons have small receptive fields - injury location
Intralaminar complex (paleospinalthalamic)
receive nociceptive specific inputs Includes projections from the spinoreticulothalamic
tract diffuse cortical projections
Learning Objective #4
Know that other ascending pathways are involved in pain transmission
Ascending pain pathways
Spinoreticular tract; to reticular formation of pons / medulla (level of attention); and onto thalamus
Spinomesencephalic tract; to mesencephalic reticulum, lateral periqaueductal grey in midbrain; and on to hypothalamus and limbic system (emotion and memory integration)
Spinoreticular
Collaterals - medulla
Synapses - pons Spinoreticulotha
lamic tract
Spinomesencephalic
Synapse - midbrain Descending control
Learning Objective #5
Discuss the descending regulation of noxious information signaling
Direct stimulation of PAG - specifically reduces sensation of pain
Descending control
NA (opioids)
5-HT
opioids
Descending pathways can regulate relay of nociceptive information in the spinal cord
Other transmitters
Local circuit interneurons…..
…in the spinal cord:
integration of ascending and descending information to modulate nociception
Placebo effect
Learning Objective #6
Explain how ascending pain information is “gated” in the spinal cord
Gating control hypothesis of pain
Cortical representation of pain
VPL / VPM project to primary somatosensory cortex and then to secondary somatosensory cortex: Awareness, location and “intensity” of pain
Medial thalamus projects to anterior insular cortex: Autonomic / visceral component of pain
Intralaminar nuclei of medial thalamus projects to anterior cingulate cortex (limbic association cortex): Emotional component of pain (circuit of Papez)
Referred pain
Convergence of somatic and visceral afferents on lamina V
Silent nociceptors: normally not active but firing threshold reduced by various insults