Week 3: Neuropathic pain Flashcards
True or False: Neuropathic pain is a clinical description and not a diagnosis
TRUE
What is neuropathic pain
Pain caused by a lesion or disease of the somatosensory nervous system
What are the two key peripheral changes that occur in neuropathic pain
- Peripheral sensitisation mechanisms
- Ectopic impulse generation
What are the four key central (dorsal horn) changes that occur in neuropathic
- Increased glutamate levels
- Synaptic efficacy
- Axonal sprouting
- Disinhibition (+ apoptosis of interneurons)
What is ectopic impulse generation? (PERIPHERAL CHANGE)
Spontaneous firing of action potentials (ectopic discharge), resulting in pain in the absence of identifiable stimulus.
The action potential is generated within the nociceptive pathway and not in the peripheral terminal.
DETAILLED: In neuropathic pain, ectopic impulses manifest as the spontaneous firing of action potentials along the nociceptive pathway, leading to sensations of pain without any identifiable external stimulus. Unlike the normal physiological response where action potentials are generated at the peripheral terminals of sensory neurons in response to specific stimuli, in cases of neuropathic pain, the generation of action potentials occurs abnormally within the nociceptive pathway itself.
Where do ectopic impulses occur?
Thought to originate mainly in primary sensory afferents (1st order neurons).
Neuroma (Site of injury)
DRG (contains the cell body of sensory neurons)
How do ectopic impulses occur?
Spontaneous voltage gated sodium ion channels - can disrupt the normal balance of electrical charges across the cell membrane. This can result in the generation of ectopic action potentials.
What is dorsal horn axonal sprouting (CENTRAL CHANGE)
During the course of many of neuropathic diseases, axons can regenerate or sprout. The newly formed connections may lead to abnormal patterns of signalling within the spinal cord, including increased transmission of pain signals to higher brain regions *Own research
What is disinhibition & apoptosis of inhibitory neurons (CENTRAL CHANGE)
After nerve lesions, inhibitory interneurons (in between sensory & motor neurons) and descending modulatory control systems are dysfunctional - leads to disinhibition and further central sensitisation. Inhibitory interneurons normally control the activity of neurons and prevent them from becoming too active, when disinhibition occurs these interneurons become dysfunctional and more pain signals are sent than they should.
Nerve injury can induce a selective apoptosis or inhibitory GABAergic (release GABA) interneurons. Apoptosis is a process where cells are programmed to self-destruct. This can mean that specific types of inhibitory interneurons—cells that normally help control nerve activity—are targeted for self-destruction.
Note: With fewer inhibitory interneurons to control nerve activity, the nervous system becomes more sensitive or excitable. This means that nerve signals can become exaggerated or amplified, leading to increased sensitivity to stimuli and potentially causing pain even from mild sensations.
*Descending modulatory control system - These are pathways from the brain that send signals down to the spinal cord to help regulate pain. They can either increase (facilitate) or decrease (inhibit) the transmission of pain signals.
*Disinhibition - In the nervous system, there are mechanisms that act like brakes, controlling the activity of neurons and preventing them from becoming too active. When these brakes are removed neurons can become overly active, sending more signals than they should
True or False: Ectopic impulses are generated spontaneously at the incorrect location?
TRUE
One key aspect of ectopic impulses in neuropathic pain is that the action potentials are not necessarily initiated at the peripheral terminals of sensory neurons. Instead, they may arise at various locations along the nociceptive pathway, such as the cell bodies of sensory neurons in the dorsal root ganglia or even within the central nervous system, including the spinal cord or brain.
In terms of axonal sprouting what is happening with the a-delta fibres?
Afferent a-delta fibres (located in Laminae III & IV) sprout into Lamina II where they synapse with 2nd order neurons associated with danger messages (Triggered by a loss of nerve growth factor).
A-delta and C-fibres axonal sprouting?
A-delta and c-fibre afferents enter the spinal cord, they branch three to seven spinal cord segments. This branching allows pain signals to be transmitted to multiple levels of the spinal cord - amplifying the pain response.
The proprospinal interconnections (pathways in the spinal cord that carry pain messages over long distances) transmit nociceptive information more than eight spinal segments as well as across the midline to the contralateral dorsal horn
What contributes to increased efficacy of synapses
- Increased receptors
- Increased presynaptic release of glutamate
- Ca2 influx through NMDA receptor
