Download Somatosensory and Pain

Somatosensory and Pain
Saygin, AP
Somatosensation
Is complex…
Touch, Pressure, Vibration
Temperature, Pain
Proprioception (sense of movement, position, force)
Sensory Axons
Faster vs. Slower
Pain pathways (rat model)
Both ascending and
descending
The spinoparabrachial pathway
(blue line) originates from
superficial dorsal horn of spinal
cord and projects to affective
areas of the brain. The
spinothalamic pathway (red line)
originates from the deep dorsal
horn and projects to areas of the
cortex concerned with sensory
discrimination and affect.
Hip = Hippocampus
PAG = Periaqueductal gray
PB = Parabrachial area
RVM = Rostroventral medial
medulla
VMH = Ventral medial nucleus of
hypothalamus
Somatosensory cortex
Insula
Anterior cingulate cortex (ACC)
Sensory and affective (pain is
unpleasant)
Neuropathy
(Peripheral) neuropathy: Damage to nerves due to injury or illness
Weakness, autonomic changes, and sensory changes
Twitches, loss of fine motor control
Loss of sensation, pain, pins and needles and other paresthesias
Impaired balance, posture
Mononeuropathy: Usually injury, compression.
Mononeuritis multiplex: loss of function of individual peripheral
nerves. Diabetes, infections (e.g. lyme disease, HIV), amyloidosis,
immune diseases like rheumatoid arthtritis and SLE
Polyneuropathy: Cells in different parts of the body are affected,
without regardless of nerve through which they pass. Distal
axonopathy, demyelinating diseases, diabetes.
Autonomic neuropathy: e.g., cardio, urinary, GI systems
Diabetic neuropathy
Neuropathy is the most common
complication in diabetes
Can affect all peripheral nerves:
pain, motor, sensory and
autonomic
Nerves are supplied by small blood
vessels
Diabetes leads to microvascular
injuries to the vessels. Can start
with vasoconstriction and lead to
neuronal ischemia.
Usually longer nerves affected first
– starts at the toes.
Pain
Of pain, you could wish only one thing: that it should
stop. Nothing in the world was so bad as physical pain.
In the face of pain, there are no heroes, no heroes, he
thought over and over as he writhed on the floor,
clutching uselessly at this disabled left arm. (George
Orwell, 1984)
Pain and Brain
Where is the pain?
Is the pain “all in your head”?
Pain arises from neural processing
at multiple levels…
Pain inhibition can also be high
level
-Endorphins
-Hypnosis, placebo
Nociceptive pain
Pain has a cause. Something external is making you
hurt and it will stop.
That’s “good pain”.
An unpleasant, subjective, sensory and emotional
experience which is associated with actual or potential
tissue damage…
Neuropathic pain
Neuropathic pain: BAD PAIN…
Nerves can generate pain by firing abnormally and this
pain sometimes doesn't go away.
Neuropathic pain
Neuropathic pain: BAD PAIN…
Nerves can generate pain by firing abnormally and this
pain sometimes doesn't go away.
Phantom pain is a kind of neuropathic pain which has
attracted a lot of attention - but many other millions
of people are affected by neuropathic pain who don’t
have phantom limbs.
See Flor et al. 2007 Nature Reviews Neuroscience 7,
873-881 for review of phantom pain
Phantom Limbs
Feels like limb is still there
Might move or be paralyzed
Pain is common
How do you treat a nonexistent limb’s pain?
Prior Treatment
Surgery, Further amputation
More modern: Treatments for neuropathic pain in general
Pain disorders when the limb is still present
Neuropathic pain
– First talked about during
the civil war by Mitchell causalgia
– Gunshot wound pain
never ending in some
soldiers
Pain disorders when the limb is still present
Causalgia is now called Complex Regional Pain Syndrome
(also Reflex Sympathetic Dystrophy)
Focal pain in limb (usually hands or feet) - can spread.
Usually after trauma, injury, surgery but can happen with no cause
“will just not heal and stop hurting”
Pain is usually sharp, burning. Can have sweating, bruising,
swelling.
Reduced tolerance for pain (hyperalgesia). Touch sensation will
usually turn to pain (allodynia). Sort of like when you have a
sunburn.
Causes of neuropathic pain
Peripheral nerve injury
– Nerve compression, trauma, amputation, diabetes,…
Dorsal root ganglia in the spinal cord
– Compression, inflammation
Spinal cord, brainstem, thalamus, cortex
– Infarction, tumors, trauma
How is neuropathic pain treated?
NSAIDs, Opioid painkillers
However, neuropathic pain usually only partially responds to
opioid painkillers
Some success with anticonvulsant (epilepsy) and
antidepressant medication. Guesses why?
Nerve blocks and ablations
Surgery usually doesn’t work. Amputation usually doesn’t
work.
Capsaicin at periphery
THC
Severe cases - Morphine pumps. Spinal cord stimulators,
cortical stimulators.
Why do some people develop chronic
neuropathic pain?
Noone knows right now… Genetic factors, immune
factors, neurotoxins are all probably factors
But here are some things we know about
neuropathic pain:
The nervous system is very adaptive…
Not always a good thing
Changes in the nervous system due to
long-term pain
Peripheral sensitization
Spinal mechanisms, LTP
Higher-up changes in CNS
(Central sensitization or centralization)
Peripheral Sensitization
Prolonged pain stimulus changes the sensitivity
of peripheral neurons - literally making them fire
at lower thresholds.
Spinal changes
Axonal sprouting in spinal cord
For example, normally C-fibers and A-delta fibers
connect to different laminae - after peripheral nerve
injury, axons will grow into each others’ layers.
Perhaps explains why normally non-painful mechanical
stimulation or touch sensation becomes painful in
patients (allodynia)
These people were initially thought to have
“psychogenic pain” - but in animal models we now
understand pain mechanisms better
Spinal neurons also increase
sensitivity
The mechanism was not very clear until now.
Pain neurotransmission in spinal cord is complex
- many neurotransmitter types, temporal
summation…
LTP in the spinal cord
Anyone remember Long term potentiation (LTP)
from your memory classes?
LTP in the spinal cord
Anyone remember Long term potentiation (LTP)
from your memory classes?
High frequency stimulation of a synapse  An
enduring facilitation of synaptic transmission
Important for learning and memory
LTP in the spinal cord
Evidence of pain stimulus causing LTP in spinal dorsal
root ganglia
One implication is also - in prolonged pain, this stimulus
may sometimes act as input which can sensitize the
spinal neurons and make them “learn”
Of course we don’t want neurons to learn pain but
understanding mechanisms is important
Central Sensitization
“Centralization”
Primary and secondary somatosensory, insular, anterior
cingulate, and prefrontal cortices (S1, S2, IC, ACC, PFC)
and thalamus.
MEG study found shrinkage of the extension of the
cortical hand representation for the CRPS affected side
correlated with pain intensity (Maihofner et al 2003).
Differences in affective pain-related areas such as the
anterior cingulate (Hsieh et al., 1995)
Research is being done on activating the pain inhibitory
pathway (esp. periacqueductal gray) in pain conditions
Cognitive/Affective component of chronic pain
Depression
Depression and Pain
Readings
Required:
http://juniorprof.wordpress.com/2009/05/25/whatcauses-chronic-pain-or-how-does-pain-become-chronic/
http://juniorprof.wordpress.com/2008/07/05/what-ishyperalgesia-what-is-allodynia/
Optional: Apkarian et al. for more on brain and pain, and
Sandkuhler on central sensitization and LTP