Exam 5 Flashcards
How does pain information travel to the brain? What parts of the brain receive input?
Fast and pain pathways involve axons from lamina I and V that decussate to form anterolateral column of spinothalamic tract that projects up to posterior thalamus
Thalamus then projects to somatosensory cortex, posterior insula, and cingulate
What are the differences between slow and fast pain?
FAST PAIN pathway relays local, sharp, pricking sensory information via myelinated Adelta fibers from lamina I and V from dorsal horn
SLOW PAIN pathway relays dull, achy, burning sensations via unmyelinated C fibers from lamina I and II
What are the 3 reticular formation nuclei associated with pain sensation? Where do they project?
A5-7 - NE pathway projects to cortex/spinal cord for attention/arousal
Parabrachial (PB) - pathway to amygdala
Periaqueductal gray (PAG) - descending pathway controls sensitivity to pain
How do the somatosensory, cingulate and insular cortices, and PAG participate in the processing of pain?
Somatosensory (S1/S2) - receives somatosensory input from thalamus
Cingulate - integrates affective/emotional aspects of pain to determine behavioral patterns based on pain experience
Insula - integrates appetitive and aversive aspects of pain (empathy)
PAG - receives input from thalamus, PB, and amygdala to produces defense responses and supraspinal pain regulation
What are the defense responses produced by the PAG?
Fight/flight in response to pain/aversive stimuli regulated by cingulate, amygdala, hypothalamus, and PFC
Ventrolateral PAG deals with passive coping (hyporeactivity, quiescence) while lateral PAG deals with active coping (sympathetic activity)
Describe the descending control of pain: nuclei, paths, neurotransmitters, actions in the dorsal horn.
PAG receives input from amygdala and hypothalamus
Hypothalamus receives input from hippocampus and amygdala
Amygdala receives input from ACC, insula, PFC, hippocampus
PAG is central, projecting to A5-7 and raphe nucleus reticular formation
- raphe nuclus regulates pain via serotonin ON or OFF cells
- A5-7 inhibits pain via NE a2 receptors
What are opioid interneurons? Where are they found? What about TCAs?
Descending serotonin/NE pathways stimulate dorsal horn (and PAG) opioid interneurons which inhibit spinothalamic pain neurons by downregulating substance P
TCAs and other NE reuptake inhibitors enhance antinociceptive action of opioids by increasing NE
*opiate drugs are agonists of opioid NTs
How does a placebo work? What parts of the brain are involved?
Placebo anticipates reduction in pain by reinforcing descending control of pain ACC, insula, and dlPFC
What are the distinguishing characteristics of acute, inflammatory and neuropathic pain? What is the axon reflex?
ACUTE - nociceptive pain in response to noxious stimulus to alert to tissue injury
INFLAMMATORY - response to tissue injury/inflammation leads to increased sensitivity to pain that stops when inflammation clears
NEUROPATHIC - occurs in response to intense non-damaging pain or damage/dysfunction of CNS/PNS neurons that leads to unnecessary persistent pain transmission
Axon reflex refers to inflammatory response induced from the release of substance P from axons that transmit sensory info
What are the mechanisms of peripheral sensitization with inflammatory and neuropathic pain?
Inflammatory - hypersensitivity to inflammation leads to axon reflex and substance P release resulting in inflammatory cascade resulting in hypersensitivity to pain
Neuropathic - axon reflexes at site of injury causes sprouting of new axons to cause spontaneous pain
What are the mechanisms of central sensitization with inflammatory and neuropathic pain?
Inflammatory - with prolonged inflammatory pain, NMDA upregulates AMPA glutamate receptors in dorsal horn leading to hypersensitivity
Neuropathic - NMDA and PGE mechanisms lead to hypersensitivity along with allodynia (nociceptive sensation from adjacent, undamaged tissue)
What is the difference between hyperalgesia and allodynia?
Hyperalgesia is the term given for a general increase in sensitivity to pain
Allodynia involves the recruitment of sensation from adjacent, non-damaged tissues due to prolonged pain stimulus that causes substance P to restructure Abeta fibers to sprout into lamina II of dorsal horn causing C fibers to become more sensitive
What are the roles of the vmPFC and dlPFC in pain modulation? What happens to pain sensitivity with degeneration of the dlPFC?
vmPFC is associated with emotional, motivational, and hedonic quality of perceived pain involved mainly with chronic neuropathic pain
dlPFC is associated with emotional decision making along with localization of acute pain
mPFC and dlPFC mutually inhibit one another
*With chronic pain dlPFC degenerates and it becomes harder to cope with pain (downward spiral)
In migraine, what is cortical spreading depression?
With the onset of a migraine, cortical spreading depression leads to a sweep of cortical inhibition through visual, somatosensory, and motor cortices accompanied with a decrease in blood flow which leads to the perception of an ‘aura’ and visual scintillations.
What is the impact of pain afferents and dural blood vessels with a migraine? What is the peripheral sensitization in this case?
K, H, NO, AA, PGE from pia that accompany cortical spreading depression sensitizes trigeminal nerve
Release of peptides from axon leads local inflammation and aggravation of pain (peripheral sensitization)
What are the major characteristics of the sympathoadrenal stress response system in terms of: LC and its projections, impact on the PFC and peripheral structures?
Sympathoadrenal system generates short latency, initial stress response
Limbic structures project to BNST which regulates LC release of NE caudally via adrenal medulla and rostrally to feedback on limbic system (PFC, hippocampus, medulla)
What are the structures that form the HPA axis? What hormones do they release and where do those hormones act?
CRH and VP are released from PVN in response to stress
CRH travels down portal vessel to anterior pituitary to stimulate release of ACTH and Beta-endorphin (VP potentiates action of CRH)
ACTH triggers release of glucocorticoids (cortisol) from adrenal cortex
Where are CRH neurons located? What impact does changing their number or activity have on HPA activity?
PVN of hypothalamus releases CRH, as well as mPFC, hippocampus and amygdala
Increased CRH neurons increase stress response by leading to increased ACTH from anterior pituitary and cortisol from adrenals
What are the permissive actions of cortisol on metabolism and inflammation?
METABOLISM - initially low cortisol actions act via high affinity MRs to increase glucose levels via gluconeogenesis in liver, proteolysis in muscle, and lipolysis in adipose tissue
INFLAMMATION - initial, low levels of cortisol also permit inflammation and immunity
What are the suppressive actions of cortisol on metabolism and inflammation?
METABOLISM - longer duration stress leads to increased levels of cortisol which act via low affinity GRs causing high blood sugar, insulin resistance, protein loss/muscle wasting, and fat accumulation
INFLAMMATION - high levels of cortisol resolve inflammation and limits immune response by reducing histamine, and cytokine release , impairing necessary reactions to trauma/foreign substances
How does cortisol feedback impact CRH and ACTH release?
Cortisol provides negative feedback on HPA axis (PVN/pituitary) as well as hippocampus amygdala and PFC to maintain homeostatic levels of cortisol release and terminate initial stress response to psychogenic and physiological stress
- Persistent high levels of cortisol alter functions of limbic and HPA structures leading to increased set point and chronic states of stress
What is cortisol resistance and what impact does it have on cortisol release?
Cortisol resistance results from decreased GRs, causing decreased negative feedback, increased ACTH and cortisol production, leading to hypercortisolism (chronic pain, depression, anorexia)can result from high levels of cortisol d
What are the general functions of cortisol feedback in the hippocampus?
Cortisol feedbacks on hippocampus to regulate the course of stress response, acting on MRs to promote HPA axis or on GRs to turn down HPA axis
*Excess cortisol down regulates BDNF which causes decreased neuroplasticity
Compare the 3 phases brain stress responses and how MRs and GRs are involved.
STRESS phase - increased cortisol binds to MRs to maintain basal activity of HPA axis to enhace arousal, vigilance, alertness, and attention
RECOVERY/ADAPTATION phases - after 1-2hrs, cortisol decreases but still sufficient to act via GRs to form memories about stressful event and normalize brain to pre-stress levels
