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PAIN :PENCIL2: B+B2 LECTURE 7 - Coggle Diagram
PAIN
:PENCIL2:
B+B2 LECTURE 7
Introduction to pain
Pain as an acute warning signal is essential
Can tolerate pain for long term gain.
Pain is a complex multidimensional experience that is influenced by physiological and psychological factors.
Takes about 20ms for a signal to travel from pain receptors to the brain.
The subjective experience of pain makes it difficult to measure.
Can’t use a Likert scale for example, one person’s ‘3’ could be another person’s ‘5’.
Approximately 20% of Western World Adult populations have chronic pain that requires treatment.
A challenge for modern neuroscience is to identify biochemical, neuroanatomical or cognitive measures (Endophenotypes) of Pain.
Nociception
A nociceptor is a sensory neuron that responds to damaging or potentially damaging stimuli by sending ‘possible threat’ signals to the spinal cord and brain.
If the brain perceives the threat as credible, it creates the sensation of pain to direct attention to the body part, so the threat can be mitigated.
This process is called NOCICEPTION.
How and why we measure pain
Subjective - We can’t know how someone else feels (hence why we have to use fMRI)
There must be common factors because pain can be controlled (e.g. opioids, cognitive set, etc.)
Pain management has problems - Dosage / Addiction / Efficacy
Neuroimaging offers a way to map brain responses.
Brain responses can be correlated with behaviour.
The neural substrates of pain largely overlap with brain areas that are abnormal in mental illnesses such as depression and PTSD.
fMRI studies identify a Neural Pain Network
Dorsolateral Prefrontal Cortex (DLPFC)
Part of the fronto-parietal attention network implicated in studies of cognitive control.
Greater BOLD activity when controlling cognitive response
Part of Frontal-Striatal Network
DLPFC is HYPOACTIVE in Depression.
Orbitofrontal Cortex
Also called Ventromedial Prefrontal Cortex
OFC involved in decision making and future planning
Also task switching and evaluation
On the pathway between DLPFC and the Amygdala
Strongly implicated in many mental illnesses.
Cingulate Cortex / Gyrus
Part of Frontal-Striatal Network
Divided into cognitive (Dorsal) and emotional (Ventral) parts.
Involved in attention, reward, decision making and emotion.
Thalamus
The brains relay station for all sensory information (except olfaction)
Subcortical structure.
Many substructures, important visual areas include the pulvinar and the lateral geniculate nucleus (LGN)
Thalamus responds to bottom-up and top-down input.
Insula
Located in the lateral sulcus
Linked to body homeostasis, emotion processing and interoceptive awareness.
Anterior contains part of the gustatory cortex (taste)
Amygdala
Part of the limbic system
Emotion processing (of all kinds)
Increased activity (with Nucleus Accumbens) in response to dopamine
Component of the reward, motivation and learning networks.
Hippocampus
Part of the limbic system
Memory processing (of all kinds)
Let’s consider that emotion and memory are not separate, but linked.
Therefore amygdala and hippocampus are linked (both part of the limbic system)
Brain Networks
fMRI studies identify a Neural Pain Network
Many areas overlap with those in MDD
These areas also overlap with those in PTSD
The Pain Matrix
Subjects had heat applied to their hand outside of the fMRI scanner.
Algorithm used to calculate Pain Score from Pain Network
Reported pain correlated with predicted pain
Follow-up study also mapped social pain in the same network.
The long-term impact of Chronic Pain
Wager et al. (2013)
26 subjects with Chronic Back Pain (CBP) and age-matched control subjects.
VBM study of Gray Matter Volume
As you get older, you lose gray matter, atrophy.
CBP patients had reduced Gray matter in bilateral DLPFC and Right Thalamus
Being in chronic pain for one year is equivalent to 10-20 years of ageing
Equivalent to
1.3cm loss of gray matter for every year
of chronic pain
Correlational measure but demonstrates effects of long-term pain.
Anxiety and Pain
Subjects shown Square or Triangle
Triangle = Low Temp
Square = Low Temp (80%) or occasionally High Temp (20%)
Square = High Anxiety, training participants to be wary of the square.
BOLD contrast of square trials greater than trials shows Thalamus and Bilateral Hippocampus Activation
Anxiety increases sensation of Pain
Placebos
Bottom-Up and Top-Down
9 Subjects scanned with PET while heat applied to the hand
Opiates / Saline (Placebo) injected before heat was applied in separate scans
Analysis compared Opiates (Exp Cond) with Saline (Placebo) in the brain
Opiate effect more widespread
Placebo activated parts of the same network though
Cognition controlling physiological state.
Placebos are very real
Is it ethical? - Some patients remain untreated.
It can be good - people get better, shows the power of positivity, demonstrates that behavioural change is a real thing.
It can be bad - can mask if a treatment is effective (drugs, stimulation), might explain why little progress has been made with some drugs since the 1950s.
Placebos are becoming more effective
Could it be a publication bias? (e.g. severe cases excluded)
Greater awareness of the placebo effect?
Illness has changed over time? (Unlikely!)
Not really clear what causes this effect?
Placebos work even when you tell subjects it’s a placebo.
Neurochemistry of Placebos
Placebos reduce pain through release of endogenous opioids via expectations and conditioning mechanisms.
The respiratory centres may also be inhibited by endogenous opioids.
The Beta-adrenergic sympathetic system of the heart may also be inhibited during placebo analgesia.
Placebos can also act on 5-HT-dependent hormone secretion, on both the pituitary and adrenal glands, thereby mimicking the effect of the analgesic drug sumatriptan.
Integrated Cognitive and Neural Model of Placebo Effect
DLPFC controls context
Hippocampus informs context and memory
OFC predicts future events
Amygdala processes emotions that influence Behaviour
fMRI and the Placebo Effect
Wager et al. (2004)
Subjects received electric shocks on the hand
’Analgesic’ Cream applied to hand on 40% of trials
Control’ Cream applied to hand on 40% of trials
20% no cream applied
Placebo > Control shows DLPFC and OFC activity
Neuroimaging Endophenotypes
Neurochemical "tone"
Opioidergic and/or dopaminergic function: basal levels of excitatory and inhibitory neurotransmitters.
Descending modulatory system
Brainstem: 5-hydroxytryptaminergic and/or norepinephrinergic pathways.
Structural Integrity: Resilience
Cortical thickness: volumetric changes and integrity of white matter connections.
Psychological factors such as anxiety, depression, expectation or catastrophizing
Prefrontal-limbic-brainstem networks
Nociceptive input to N1
Dorsal posterior insula, S2 or operculum.
Brain dynamics
Oscillations and RSNs
Genes --> Pain experience, report and behaviour <-- Nociception-injury