Physiology of Pain Flashcards
Pain is different from all other senses because
the sensation is elicited by multiple stimuli
it preempts all other signals
these differences result in multiple alterations in the physiological functioning of the pain pathways
pain can be characterized as
fast pain
slow pain
fast pain
generally associated with the immediate injury
aka sharp pain
slow pain
often characterized as dull or achy
often occurs after the injury
Pain can be characterized by location
deep pain
muscle pain
visceral pain
somatic/cutaneous pain
again the characteristics of these forms of pain vary due to physiological and anatomical considerations
Sensory receptors
many are bare nerve endings with specialized ion channels that open in response to specific stimuli (i.e. thermoreceptors)
some sensory receptors show quite extensive morphological specilization
Sensing Noxious Stimuli - the nociceptors
Two types of fibers
bare nerve endings can be
A delta fibers
C fibers
A delta fibers
small sparsely myelinated, fast, sharp pain
C fibers
unmyelinated fibers associated with dull pain (slow pain)
Nociceptors must be able to detect
a wide variety of damaging stimuli
Types of Nociceptors
sensitive to both thermal and mechanical stimuli (most)
sensitive to only thermal
sensitive to only mechanical
silent/sleepin
Many mixed modality nociceptors also express a
mechanosensitibe Na channel (SCN9A or Na1.7)
Mutations in the nocicieptive Na channels lead to
an absence of pain sensation
paroxysmal pain syndrome
Mutations in the nocicieptive Na channels lead to
an absence of pain sensation
paroxysmal pain syndrome
Unlike other receptors, nociceptors express _________ which alter the sensitivity of the nociceptors to input
number of ligand gated receptors (in addition to the stimulus gated channels)
Ligand gated receptors for ______(4) are found on the nocicieptors to alter sensitivity
Substance P the kinins ATP H+ interestingly this collection of chemicals also exists in the spinal cord, where they also influence nociceptive inputs at those synapses
When ligands bind their ligand gated channels on the nociceptors,
they change the sensitivity of the nociceptors (usually increasing) and activate the silent receptors
The source of sensitivity-altering chemicals
activated nociceptors, the damaged tissue, and recruited WBC release these into the periphery as well as in the spinal cord.
There are multiple pathways to the brain
proprioceptive and discriminative touch
fast pain
slow pain
dorsal columns
spinothalamic tract
spinoreticulothalamic system
The NT released by nociceptive fibers
EAA (from A delta) acting primarily on non NMDA receptors
NT released by C fibers
Substance P
EAA
Nociceptors that travel with the spinoreticulothalamic pathway (slow pain) synapse on
what is this synapse important for
an interneruon in the spinal cord before crossing and ascending to the reticular formation
this synapse is the site of much modulation of spinal cord function
local (gate theory)
descending (opioid pathways)
Nociceptors that travel with the spinoreticulothalamic pathway (slow pain) synapse on
what is this synapse important for
an interneruon in the spinal cord before crossing and ascending to the reticular formation
this synapse is the site of much modulation of spinal cord function
local (gate theory)
descending (opioid pathways)
visceral afferent pain fibers travel with
autonomic nerves, rather than with either of the two spinal pathways already described
Unlike other senses, nociceptive input is distributed widely in the Cortex
insular cortex
post central gyrus
mediofrontal cortex
Pain and S1 and S2
S1 and S2 do receive input from the nociceptors and play a role in localizing the pain
Pain and the insular cortex
the insular cortex is particularly important in the interpretation of nociceptive inputs
processes information about the internal state of the body
contributes to the autonomic response to the pain
INTEGRATES ALL SIGNALS RELATED TO THE PAIN (ASYMBOLIA - occurs when insular cortex is lost)
Lesions in any one area
does not abolish the ability to experience pain, although the experience is changed
pan and the amygdala
many nociceptiv inputs go to the amygdala
this is particularly important for activating?producing the emotional components inherent in the sensation of pain
Visceral nociceptors, traveling with the autonomic nerves, have additional synapses within
the hypothalamus and the medulla - these form the basis of the physiological changes associated with visceral pain, including diaphoresis and altered BP
Visceral nociceptors, traveling with the autonomic nerves, have additional synapses within
the hypothalamus and the medulla - these form the basis of the physiological changes associated with visceral pain, including diaphoresis and altered BP
Gate theory based on
based in part on the observation that other somatic input can alleviate pain (rubbing the area)
Gate theory reminder
neurons traveling in the spinoreticulothalamic tract synapse on an interneuron within the spinal cord before ascending
Gate theory
Step 1 - activate an A beta fiber by the normal stimuli. The AB fiber has a branch that travels via the coral columns, but it ALSO BRANCHES WITHIN THE SPINAL CORD
Step 2 - the AB fiber releases EAA and activates an inhibitory interneuron in the spinal cord
Step 3 - the inhibitory interneuron releases glycine to inhibit the activity of the second order neuron in the pain pathway
End result - rubbing the area of skin activated by the AB fiber will reduce the sensation of pain
Basic idea of descending mechanisms of modification of painful inputs
use presynaptic inhibition to reduce activation of the second order nociceptive neuron in the spinal cord
Basic idea of descending mechanisms of modification of painful inputs
use presynaptic inhibition to reduce activation of the second order nociceptive neuron in the spinal cord
Descending modification of pain
Step 1 - neurons in the periaqueductal gray are activated by numerous inputs, including opiate, EAA and the cannibinoids
Step 2 - axons from the PAG neurons travel to the midline raphe nuclei and release ENKEPHALINS which activate the raphe neurons
Step 3 - axons from the raphe neurons travel to the spinal cord and release SEROTONIN, which activate inhibitory nterneurons, causing them to release opiates
Step 4 - the opiates released by the interneuron activate mu receptors on the presynaptic terminal of the C fiber
Step 5 - this produces pre-synaptic inhibition that reduces the release of substance P from the nociceptor and reduces pain transmission
