Temperature and Pain Flashcards
Know the pathways for processing of pain and temperature information.
sense in primary neuron →dorsal horn synapse →2nd order neuron decussates in cord → ascends in spinothalamic/spinoreticular tract → synapses on 3rd order neuron in brain → goes to sensory cortex or hypothalamus.
Where are pain and temperature information first detected?
Pain and temperature both have an axon that bifurcates, producing a receptor branch and a central axon (that enters the CNS) and are both detected by sensory endings. The sensory endings are free nerve endings not associated with other structures (such as pacinian corpuscles, merkel’s discs, etc).
Where does information first enter the central nervous system?
The afferent fibers have a cell body in a dorsal root ganglion, associated with a vertebral body, and the central axon enters the spinal cord at the appropriate cord level. In the dorsal horn, these primary neurons synapse on secondary neurons in the substantia gelatinosa.
How does the information get to the brain?
The axons then cross the midline of the spinal cord and ascend to the brain in the anterolateral system. The second order neurons convey information to the thalamus, which synapses with another neuron in the VPL thalamus. This 3rd order neuron projects to the somatosensory cortex. Second order neurons can also convey information to the hypothalamus via the reticular formation.
Know the type of receptors that detect temperature information.
There are two types of temperature receptors on sensory endings: warm and cool receptors. Warm receptors function between 30 and 48 degrees C. These are usually associated with C fibers. Cool receptors function between 10 and 37 degrees C and there are significantly more cool receptors than warm. Cool receptors are associated with Aδ fibers.
Know how temperature receptors code their information.
Both warm and cool receptors alter their firing frequency of action potentials in response to changes in temperature. They are more sensitive to rate of change than absolute temperature.
Cool receptors increase the firing rate as the temperature decreases. They fire at a steady rate, then have a burst of rapid firing over the period the temperature is dropping before slowing again, but at a fast rate than the initial firing.
Warm receptors increase firing frequency as the temperature increases.
Know the types of manipulations that distinguish first pain from second pain.
First pain is a pricking pain, which is very local and well tolerated. This sensation is carried by Aδ fibers (slightly myelinated). Second pain is carried by the smaller, unmyelinated C fibers and is an aching/burning pain which is poorly localized and poorly tolerates.
Because Aδ fibers have smaller receptive fields than C fibers, pinprick sensation will always be better localized than the burning sensation of C fibers (large fields) leading to better spatial discrimination.
Know the stimuli that activate polymodal receptors.
Polymodal pain receptors have C fibers as their afferents. These sensory nerve endings have different receptors on different segments of the ending and also have different receptors on a single ending. These receptors respond to a variety of stimuli.
The vanilloid receptor 1 (VR1) is strongly activated by capsaicin, but also weakly responds to acid and temperature stimuli.
ASICs is a receptor that responds to acid. P2X responds to purines, such as ATP. Theoretically, there are also polymodal receptors that respond to mechanical stimulation, but Ribera did not give an example.
Know the identities of chemicals that act as pain activators and sensitizers.
Activators – depolarizes nerve ending to threshold → activation • Bradykinin • Potassium • Acid • Serotonin
Sensitizers – depolarizes, but not to threshold and makes it easier for activators to stimulate a potential • Prostaglandins • Substance P • ATP • Acetylcholine • Serotonin
Know the stimuli that activate the VR-1 receptor. Where is the VR-1 receptor located?
The VR1 receptor is strongly activated by capsaicin. Vanilloid moiety containing compounds activate it. It is also activated more weakly by acid and moderate heat (43 degrees C). This receptor is found on polymodal nociceptors.
Know what type of pain information is carried by C fiber afferents.
2nd pain is carried by C fibers, burning/aching poorly localized pain that is not well tolerated.
Know the location of the first synapse in the pain pathway.
Which neurotransmitters operate at this synapse?
The first synapse for the pain pathway occurs in the dorsal horn of the spinal column the substantia gelatinosa (Rexed’s lamina II). The major excitatory neurotransmitter released by primary nociceptive sensory neurons is Glutamate.
Know the differences between and the properties of AMPA and NMDA receptors at the dorsal horn synapse.
The 2nd order neurons in the dorsal horn have 2 different receptors for glutamate: AMPA and NMDA receptors. Both are ionotropic but have different mechanisms to allow flow of current.
AMPA receptors gives rise to a rapid synaptic response. Only require glutamate for opening channels
NMDA receptors require a simultaneous depolarization of the post-synaptic membrane in addition to glutamate binding before they are effectively activated. Slower excitatory potential. Prolonged release of glutamate at the dorsal horn synapse enables NMDA to more easily propagate an action potential → central sensitization
Know the basis for peripheral sensitization.
Sensitization of nociceptors is known as primary hyperalgesia because the mechanism causing increased sensitivity to pain occurs at the first site in the pathway.
In the presence of Prostaglandins, Substance P, APT, ACh and/or Serotonin, the threshold for activation of nociceptors decreases
Know the basis for central sensitization (e.g., at the dorsal horn synapse).
- Wind up: As C fibers are stimulated, post-synaptic AMPA receptors will be stimulated first as only glutamate is present. NMDA receptor is activated with prolonged glutamate and post-synaptic depolarization
- NMDA Receptor Phosphorylation: The NMDA receptor activation leads to increase in intracellular Ca2+. Phosphorylation of NMDA by PKC and tyrosince kinase inhibits Mg2+ binding the NMDA receptor, and NMDA is more easily opened. Now AMPA and NMDA are BOTH opened» sensitization!
- Substance P: is not removed from the synapse by re-uptake and will persist for long periods of time. This allows it to diffuse to many dorsal horn neurons, leading to broad central sensitization of the dorsal horn
