Neuroscience/Objectives/Lecture 17

From PhysioWiki

The spinal cord: Pain and temperature sensation

Diagram the major pathway by which information from the body about pain and temperature reaches consciousness.

Spinothalamic tract:

1. Nociceptive fibers (Aδ and C fibers) from DRG enter spinal cord, synapsing in laminae I, II, and V.
2. Second-order neurons immediately decussate in the anterior white commissure and ascend.
3. Second-order neurons move medially and dorsally in the pons, and laterally in the midbrain.
4. Second-order neurons synapse in the ventral posterolateral nucleus of the thalamus. (Note that second-order neurons may also synapse in the reticular formation or periaqueductal gray, but this objective specificaly addresses the pathway by which protopathic sensation reaches consciousness, which is specific to the spinothalamic tract.)
5. Third-order neurons travel through the internal capsule, synapsing in the sensory cortex.

Distinguish between nociceptive pain and neuropathic pain, giving examples of each.

Nociceptive pain

Involve bradykinin, serotonin (5HT), histamine, and prostaglandins, all of which excite pain receptors. Usually results from inflammation (e.g. arthritis, sprained ankle). Can be treated with NSAIDs and COX-2 inhibitors, both of which inhibit nociceptive input from damaged tissue; the latter inhibits prostaglanding synthesis.

Neuropathic pain

Results from direct injury to nerves in PNS or CNS. Often due to diabetes, chemotherapy, viral infection, alcoholism, stroke, trauma, aging, etc.

Both types can participate in the maintenance of chronic pain.

Identify central mechanisms for pain control and describe two ways in which the transmission of pain sensation can be modified at the level of the spinal cord.

Descending pathways for modulating pain.

Periaqueductal gray
The PAG makes excitatory connections on the nucleus raphe magnus, which sends inhibitory 5HTergic fibers to neurons in laminae I, II, and V.

Locus ceruleus
The LC synthesized norepinephrine, which stimulates the release of enkephalins from the spinal cord dorsal horn. Enkephalins inhibit C and Aδ fibers in the dorsal horn.

Nucleus raphe magnus
Sends inhibitory 5HTergic fibers to neurons in laminae I, II, and V, as discussed above.

Explain the possible anatomical basis of referred pain.

Both visceral and cutaneous nociceptors enter the spinal cord through the same pathway. Synaptic contacts between these two populations of cells within the spinal cord make for substantial cross-talk between nociceptive modalities, giving rise to referred pain.

Define referred pain, hyperalgesia, allodynia, and central sensitization, giving examples of these for chronic pain patients.

Referred pain

When visceral pain is perceived as a cutaneous sensation (e.g. angina felt in the left arm).

Hyperalgesia

Increased sensitivity to pain, a consequence of central sensitization.

Allodynia

Experience of a non-noxious stimulus as painful (e.g. pain with showering after sunburn).

Facilitation

Also called "central facilitation". A transient increase in synaptic strength. Mediated by increased action potential frequency and enhanced neurotransmitter release.

Central sensitization

Also called "wind-up". Possibly occurs via the loss of inhibitory neurons, resulting in dorsal horn neurons that are hypersensitive to pain (hyperalgesia), allodynia, and facilitation.

Describe a number of causes of chronic pain in patients.

Chronic pain could be caused by ectopic impulse generation, in which action potentials are generated spontaneously at sites of demyelination, possibly due to an increase in the number of sodium channels. The result is the generation of chronic pain without any noxious stimuli. Such pain may respond well to anticonvulssants such as carbamazepine, dilantin, and gabapentin, which dampen ectopic impulse generation.

The sprouting of axonal collaterals off of mechanoreceptors in the superficial dorsal horn may result in collaterals that are hypersensitive to norepinephrine and epinephrine. This may lead to reflex sympathetic dystrophy (RSD). Treatment with clonidine may be beneficial as it decreases the release of norepinephrine.

Loss of neurons in the dorsal horn due to ongoing activity in injured primary afferent fibers (i.e. excitotoxicity) may result in apoptosis of local GABAergic inhibitory interneurons.

Depletion of inhibitory 5HTergic neurons impairs the descending pathways of pain modification, potentially resulting in chronic pain. This can be treated with tricyclic antidepressants.

Describe a potential treatment for chronic pain.

Opiates such as morphine and fentanyl treat chronic pain by targeting neurons of descending pathways in the periaqueductal gray, rostral ventral medulla, raphe nucleus, and the dorsal horn of the spinal cord. These neurons inhibit the perception of pain (e.g. neurons of the raphe nucleus inhibit via 5HTergic synapses).