Thalamus Flashcards
Thalamus: Important Pain Pathways
- Neo-apinothalamic pathway (lateral sensory-discriminative_
- Paleo-spinothaamic pathway (medial affective-motivation)
Thalamus: Important Sensory/Pain Nuclei
- Ventral Posterior Lateral (fast, discretely localized pain - body)
- Ventral Posterior Medial (fast, discretely localized pain - face)
- Dorsal Medial, Centromedian, Parafascicular (slow, poorly localized pain in face & body)
Thalamus: Cortical Pain Matrix
- Lateral Pain System - primary & secondary somatosensory cortex
- Meidal Pain System - anterior cingulate, insula, amygdala, hypothalamus
Peripheral Pain Anatomy Function
Pain Sensors: free nerve endings
- Temp. via transient receptor potential channels (TRP) TRPV1 sensitive to >43 C & Capsaicin, TRPM8 sensitive to <25 C
- Mechanical
- Chemical
Pain Transduction: Adelta and C fibers
- Adelta fibers- thinly myelinated, transmit temp & mechanical pain, discrete location, fast, sharp pain
- C fibers: unmyelinated, transmit temp, mechanical, & chemical pain (polymodal), diffuse, slow pain
-the fiber bodies lie in the dorsal root ganglia & use glutamate, substance P, & calcitonin-gene related peptide (CGRP) as neurotransmitters. These transmitters may be released at both the central (dorsal horn) and peripheral (skin, other organs) terminals
Peripheral Pain Receptor Sensation
- stimulation of nociceptive receptors triggers release of several substances (H+ ion, 5-HT, ATP, bradykinin, prostaglandins) that activate free nerve endings to fire an action potential (AP) back to the spinal cord dorsal horn
- activation of the nociceptive receptors causes the local release of sub P and CGRP from the free nerve endings at the site of injury, Sub P and CGRP in turn cause release of histamine from mast cells & vasodilation of local blood vessels
- combo of local tissue injury with release of above substances and the release of sub P and CGRP from the free nerve endings sensitizes the free nerve ending receptors such that their threshold from activation is lowered
- inflammatory chemical milieu activates previous silent nociceptive receptors on free nerve endings to become active thereby increasing the temporal & spacial summation of APs traveling to the dorsal horn
Spinal Cord Pain Processing
- nociceptive specific neurons (SPNs): neurons in the laminae I & II of the dorsal horn that respond only to Adelta or C fiber APs & encode only pain
- Wide dynamic range neurons (WDRNs) - neurons in laminae V of the dorsal horn that respond to a variety of synaptic input encode pain & non-pain stimuli
- WDRNs fire AP is a graded fashion depending on stimulus intensity; the latter is proportinal to stimulus frequncy. thus the greater the C-fiber AP frequency, the greater the AP response in the WDRNs
- WDRNs are responsible for wind up
Wind Up
signal amplification
- repetitive APs from C-fibers triggers wind up by glutamate activation of WDRN AMPA receptors and CGRP activation of WDRN CGRP receptors. Activation of these receptors leads to EDRN depolarization & release of the Mg++ block of the NMDA channel
- the enhanced Ca++ influx through the NMDA channel causes insertion of more Na+ channels & blockade of K+ channels in the WDRNs
- Sub P activation of NK1 receptors contributes to the process by prolonging WDRN depolarization
- combo activation from these transmitters reduces the threshold of the WDRNs, inc. the insertion of more receptors in WDRNs, leading to a lowered threshold for firing APs
Wind Up (Central Sensitization)
- functional consequences is that relative brief C-fiber stimulation can lead to long lasting facilitation of the pain pathway stimulated
- partial explanation of why & how patients experience hyperalgesia and is partially an explanation for long lasting chronic pain
Modulation of Pain: Gate Control Mechanisms
-Abeta fibers activate dorsal column interneurons that inhibit WDR neurons thus blunting activation of the latter neurons response to Adelta and C-fiber activity
Modulation of Pain: Descending Pathways
- Cortex, amygdala, hypothalamus all impinge upon periaqueductal gray & reticular formation neurons that in turn send descending fibers to modulate lamina II neurons in the dorsal horn
- descending systems may either inhibit or facilitate pain
Modulation of Pain: Endogenous Opioid
-activation of opioid receptors block presynaptic voltage-gated Ca++ channel and/or the opening of postsynaptic K+ channels, thus hyperpolarizing the postsynaptic neuron and reducing APs
