Chemical anatomy of pain pathways 2.2 Flashcards
Q: What is the primary aim of Part 2 of the lecture on neurochemistry?
A: To describe identified circuits in the dorsal horn, explain how neurochemistry has been exploited to identify these circuits, and discuss the specificity of modality within these circuits.
Q: What methods were used to identify spinal circuits mediating mechanical pain?
A: Marking and ablating excitatory and inhibitory subpopulations of spinal neurons, followed by behavioral and electrophysiological analysis.
Q: Which specific populations of neurons were marked and ablated in Duan et al.’s study?
A: Three excitatory subpopulations and three inhibitory subpopulations of spinal neurons, specifically somatostatin-expressing excitatory neurons and dynorphin-expressing inhibitory neurons.
Q: What is the role of somatostatin-positive neurons in pain perception?
A: They are necessary to sense mechanical pain.
Q: What is the role of dynorphin-positive neurons in pain modulation?
A: They are necessary to gate (suppress) mechanical pain.
Q: In the Von Frey test, what indicated that somatostatin-positive neurons are critical for mechanical pain sensation?
A: Mice with ablated somatostatin-positive neurons showed a significantly increased threshold for mechanical stimulation compared to control mice.
Q: What happens when dynorphin-expressing neurons are ablated?
A: The animals exhibited mechanical allodynia, meaning they responded to usually subthreshold stimuli.
Q: How did Foster et al. contribute to understanding pain circuitry?
A: They identified a glycinergic gate for pain located deeper in the spinal cord, which is more heterogeneous than the dynorphin-expressing inhibitory neurons.
Q: What was the outcome of ablating glycinergic neurons in Foster et al.’s study?
A: Mice became hypersensitive to mechanical, thermal, and noxious cold stimuli.
Q: How do excitatory interneurons contribute to pain behavior?
A: They are necessary for the full expression of pain behavior and help bridge nociceptive afferents and projection neurons.
Q: What are the behavioral effects of losing excitatory interneurons according to Wang et al.?
A: There is a near complete absence of supraspinally integrated pain behaviors and elevated mechanical withdrawal thresholds.
Q: What is the difference between reflex responses and supraspinally integrated behaviors in pain perception?
A: Reflex responses are immediate reactions (like withdrawing a paw), while supraspinally integrated behaviors involve higher processing in the brain (like licking or jumping).
Q: What experimental evidence supports the idea of different circuits mediating different types of pain hypersensitivity?
A: Elevated mechanical withdrawal thresholds and loss of nerve injury-induced mechanical hypersensitivity, while maintaining reflex responses to noxious heat.
Q: Why is understanding spinal circuits important for clinical applications?
A: They represent potential therapeutic targets for managing mechanical pain, which poses significant challenges in clinical settings.
