PAIN !!! DENT/OBHS 131 Neuroscience 2009. Pain…. Is a submodality of somatosensation Is the perception of unpleasant or aversive stimulation (sensory.

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