Download Pain in Spinal Cord Injury (SCI) and Traumatic Brain Injury (TBI)

Pain in Spinal Cord Injury
(SCI) and Traumatic Brain
Injury (TBI)
HOWARD T KATZ, MD
GULF STATES PHYSICAL MEDICINE AND
REHABILITATION
PAIN
Pain is “an unpleasant sensory and
emotional experience associated with
actual or potential tissue damage or
described in terms of such damage”
The International Association for the Study of PAin
Why do we feel pain?
•Pain warns organisms of injuries or the potential for
injury, alerting the organism to withdraw from the
painful stimulus.
•In higher species (such as humans) pain also stimulates
the areas of the brain responsible for anxiety and anger.
•Pain is an important concern in Spinal Cord Injury and
Traumatic Brain Injury.
ALL PAIN IS NOCICEPTIVE
Nociceptors
•Pain results from the activation of nociceptors, which
are peripheral neurons that respond to the stimuli we
perceive as painful.
•There are 2 types of nociceptors: C and Aδ (“Adelta”)
•Both carry signals to the dorsal root ganglion of the
spinal cord. They are also referred to as First Order
Pain Neurons.
“C” nociceptors
•Most common type of nociceptor in humans (around
70%)
•Small, unmyelinated nerve cells bundled together and
surrounded by Schwann cells
•Conduct signal at 0.4 to 1.4 m/s
•Respond to thermal, mechanical, or chemical noxious
stimuli
Aδ (A-delta) nociceptors
•Myelinated neurons
•Conduct signals at 5-30 m/s (much faster than the C
type)
•Respond primarily to heat and mechanical stimuli and
helps localize the pain
Interaction with Central Nervous System
All nociceptors terminate in the dorsal root ganglion of the spinal cord. There,
they activate one of four types of nocineurons:
•High threshold mechanical neurons excited by noxious cutaneous or visceral
stimuli. They release glutamate and other neuropeptides that activate dorsal
horn neurons
•Chemical nociceptors neurons are excited by chemical or thermal stimulation
•Thermal nociceptor neurons are also excited by chemical or thermal stimulation
•Polymodal nociceptors are exited by both noxious and non-noxious stimuli of
various types, and they respond incrementally as the intensity of the stimulation
increases
Neurospinothalmic Tract
After reaching the spinal cord, pain ascends
to the brain using on of four pathways. The
neurospinothalamic tract is the major and
fastest pathway . In this tract, signals cross
over the spinal cord, so an injury on the left
will travel up the spinal cord on the right, and
vice-versa.
Trigeminothalmic tract
Trigeminal fibers respond to noxious stimuli to the head,
fact, and intraoral cavity. These fibers entire the pons,
descend to the medulla and make synaptic connections
in the spinal trigeminal nucleus. The trigeminothalmic
tract provides immediate awareness of pain and its
location.
Paleopsinothalamic Pathway
This third pathway evolved earlier than the other two.
The pathway starts at multi-receptive C nociceptors and
signal is conveyed up both sides of the spinal cord to the
hypothalamus, basal ganglia, insular cortex, and the
sensory cortex. Also, this pathway stimulates cells in the
brain stem which activate the descending pain
suppression pathway.
Archispinothalamic Pathway
This is the oldest of the four pathways. Signals begin at C
fibers and ascend up the spinal cord on both sides,
activating the hypothalamus and limbic system.
Comparison of the four pathways
•Neurospinothalamic and Trigeminal are the fastest and cross the
midline, traveling on the opposite side of the stimuli
•Paleopsinothalamic and archispinothalamic pathways evolved earlier
than the others. They transmit pain signals more slowly and move up
both sides of the spinal canal
•All pathways end in the thalamus/hypothalamus
•The are also referred to as Second Order Pain Neurons
After pain signals reach the brain
•The thalamus sorts pain signals.
•Fast signals from the neospinothalmic tract are rerouted to the primary somatosenory cortex, the
secondary somatosensory cortext, the insula cortex, or
the anterior cingulate cortex
Primary somatosensory cortex
•Receives signals from both C and A-delta fibers
•Since A-delta fibers transmit signals much faster than C
fibers, they are the first to react to a painful stimulus and
localize it
•The ratio of A-delta fibers to slower C fibers provides
information on the intensity of the pain
•If painful stimulus is prolonged, then more C fibers are
activated, which provokes diffuse, aching pain
Secondary somatosensory cortex
•Activates only when a certain threshold of stimulation is
reached
•Above level of pain identification in the primary
somatosensory cortex and exhibits no dose response
•Though to be involved in learning, memory, and future
pain avoidance
Insula Cortex
•The relationship of the insula cortex to pain is still being
explored
•Study by Starr et al. suggests it is involved in defining
and regulating pain thresholds
•It also is believed to be involved in pain memory and
psychological reactions to pain
Anterior Cingulate Cortex
•Involved with the affective and emotional pain
•Pain is a subjective experience, and different people can
have very different pain reactions to the same stimulus
•Pain threshold can be decreased by anxiety and
depression
•The anterior cingulate cortex is integral to our subjective
experience of pain and treatment for pain
Amygdala
•The amygdala receives secondary activation signals the
insula cortex
•The amygdala influences our behavioral and emotional
responses to pain
•Recent research indicates neuroplasticity in the
amygdala, which may lead to development of new pain
management techniques
Prefrontal Cortex
•The prefrontal cortex receives secondary activation
signals from the anterior cingulate cortex
•The prefrontal cortex is central to controlled pain
modulation or an individual’s personal pain inhibition
mechanism
Basal Ganglia
•Sensory, motor, autonomic, cognitive, and emotional
components of pain are processed in the basil ganglia
•Signals arrive from the prefrontal, oribitofrontal, dorsolateral,
motor, premotor, sensorimotor and parietal corticies and
directly from the thalamus
•The basil ganglia also send back signals to the thalamus
•In studies, deep brain stimulation of the globus pallidus of the
basil ganglia resulted in 70% decrease in reported chronic
pain.
After signals reach the brain, con’t
•Signals traveling along the trigeminal and
paleospinothalmic pathways also reach the thalamus
•Signals can be routed from the thalamus to the basil
ganglia, prefrontal cortex, anterior cingulate cortex,
and the primary motor cortex
•Responsible for arousal and withdrawal, as well as
autonomic and affective responses to pain
Types of chronic pain
•Inflammatory pain results from direct insult to tissue
(whether through trauma, infection, or degenerative
processes).
•Neuropathic pain results from insult to the nervous system
itself (and may be either central or peripheral).
•A third type, nerve dysfunction pain, does not fit in either
category. Examples are migraines, fibromyalgia, and irritable
bowel syndrome.
•Both chronic inflammatory and chronic neuropathic pain are
common in TBI/SCI survivors.
Neuropathic Pain (con’t)
Neuropathic Pain is “a complex, chronic
pain state that usually is accompanied by
tissue injury. With neuropathic pain, the
nerve fibers themselves may be damaged,
dysfunctional or injured. These damaged
nerve fibers send incorrect signals to other
pain centers”. The American Chronic Pain Association
Neuropathic Pain (con’t)
•Neuropathic hyperalgesia can be both primary and
secondary
•Primary hyperalgesia occurs directly at the site of injury
•Secondary hyperalgesia involves undamaged nociceptive
fibers near the injury site and is thought to involve
central nervous system sensitization
•Secondary hyperalgesia responds only to mechanical
stimuli, not temperature stimuli
Neuropathic pain (con’t)
•In the 1990s, two studies provided
strong evidence that the central
nervous system was involved in
secondary hyperalgesia.
•Both studies used capsaicin, which
is responsible for the burning
sensation from chili peppers.
Neuropathic Pain (con’t)
•In a study by LeMotte et al., one arm was injected with
capsaicin. This caused intense burning pain and the
formation of three areas of hyperalgesia around the
infection site.
Tender to gentle stroking
Hyperalgesic to
normally painful
mechanic
stimulation (55
sq.cm)
(38 sq. cm.)
Hyperalgesic to heat (2 sq. cm)
Neuropathic Pain (con’t)
•In a study by Torebjörk et al, capsaicin was injected into
the top of the foot. The researchers directly electrically
stimulated the nearby superficial peroneal nerve,
producing a painful response at levels of stimulation that
would ordinarily be non-painful. Because the peroneal
nerve was stimulated directly, the study demonstrated
that neuropathic pain was a central nervous
phenomenon.
Neuropathic Pain (con’t)
•Centralized hypersensitivity to
mechnostimulation
•Both damaged and undamaged nociceptive
neurons demonstrate abnormal signal
generation
Neuropathic Pain (con’t)
In SCI:
•Changes in Na+ channel receptors reducing their
stimulation threshold
•Dormant astrocytes and microglial cells are activated
in the dorsal ganglia of the spinal cord
•Reorganization and remodeling of neural pathways
near the brain
Pain in SCI
•Chronic pain is extremely common in spinal cord injury
(SCI) survivors, affecting between 66% and 80% of
survivors.
•Pain in SCI can be extremely disabling and leads to poor
physical and mental health outcomes.
Musculoskeletal Pain in SCI
•Generally manifests as aching pain
•All bones and joints are at risk of damage in SCI
•Upper body pain is thought to result from overuse
•Nerve entrapment is also common
Visceral Pain in SCI
•Visceral pain is poorly localized pain in the abdomen or
around the pelvis
•Suvivors describe burning, cramping pain that varies in
intensity
•Visceral pain can occur in the absence of other
abdominal pathology
Neuropathic Pain in SCI
•Frequently described as burning, shooting, stabbing, or
tingling
•Most commonly occurs at or below the level of cord
injury, but also can occur above the level of injury
•Neuropathic pain is the most common type of chronic
pain in spinal cord injury and is very difficult to treat
PAIN in SCI
60+% complain of more than one type of pain
• 35% reported 2 types of pain
• 20% reported 3 types of pain
• 8% reported more than 3 types of pain
•70% neuropathic
•61% musculoskeletal
•35% spastic
•30% visceral
• 3% syringomyelia
NEUROPATHIC PAIN in SCI
•52% report pain below the level of injury
•38% report pain at the level of injury
• 5% report pain above the level of injury
•Mean pain intensity ranged between 50 and 60
Pain in SCI (con’t)
•There is no one agreed upon standard treatment for pain in SCI
•Clinicians often must try many different treatments to find an
effective ones for individual patients
•When treatment is found, it generally provides only incomplete
relief
•Depression and anxiety are common comorbidities
•Psychiatric treatment such as antidepressants and cognitive
behavioral therapy are often important parts of a treatment plan
for pain
Effectiveness of various pain
interventions
Effectiveness of various pharmacological treatments for
SCI pain as rated by survivors (Huetink et al)
Pharmacologic
agent
Effective to a large
extent
Somewhat
effective
Not effective
Opioids
54.5%
36.4%
9%
Benzodiazepines
52.9%
47.1%
0%
NSAIDS
50%
50%
0%
Anticonvulsants
46.9%
46.9%
6.3%
Antidepressants
38.5%
46.2%
15.4%
Cannabis/Alcohol
83.3%
16.7%
0%
Other Medications
38.5%
53.8%
7.7%
Effectiveness of various pain
interventions (con’t)
Effectiveness of various non-pharmacological treatments
for SCI pain as rated by survivors (Huetink et al)
Treatment
Effective to a large
extent
Somewhat effective
Not effective
Acupuncture
83.3%
16.7%
0%
Massage/relaxation
58.7%
38.7%
2.7%
Physiotherapy/exercise
68.8%
25%
6.3%
Psychological treatment
54.5%
27.3%
18.2%
Injections/neurosurgery
40%
30%
30%
TENS/Ultrasound
11.1%
55.6%
33.3%
Other
61.1%
27.8%
11.1%
Musculoskeletal Pain
• NSAIDs and physical therapy are first line treatments
• Prevent overuse of painful areas
• Opioids reasonable if other interventions are
ineffective
Painful muscle spasm
•Baclofen (muscle relaxant) is first line treatment
•Phenol or Botox injections may also be tried
Visceral pain
•Visceral pain has a delayed onset, and the etiology is
unclear
•The medical literature has little to say on effective
treatments for visceral pain
Nerve compression pain
•Both extremity and central nerves are at risk for
entrapment in SCI
•Treatment is similar to persons without a spinal cord
injury, including injections, massage, physical therapy,
and possible decompressive surgery.
Post-traumatic syringomyelia
•A cyst with cerebral spinal fluid (CSF) can develop in SCI
•Causes constant burning pain associated with allodynia
•Visible on MRI
•Because of severe complications, surgical treatment is
indicated
Treating neuropathic pain in SCI
•Neuropathic pain is clinically the most difficult to treat
•Pain is not necessarily severe, but frequently constant
and interferes with sleep, rehabilitation, and activities
•Even “successful” treatments may only result in 20% to
30% pain relief
Treating Neuropathic Pain
•GABA agonists
•Serotonin and norepinephrine reuptake inhibitors
(SNRIs)
•Glutamate receptor inhibitors
•NMDA receptor inhibitors
•Antidepressants/anticonvulsants
•All options can have adverse central nervous effects
Antidepressants: Amitriptyline
•Only tricyclic antidepressant that has been studied for
treatment of neuropathic pain following SCI in humans
•Adverse effects in 98% of patients (90% adverse effects for
plocebo)
•Studies conflicting about efficacy in SCI pain, but is reasonable
to try due to demonstrated effectiveness in similar conditions
•Side effects include dry mouth, constipation, nausea, bladder
retention, drowsiness, and fatigue
Antidepressants: SNRIs
• Venlafaxine and duloxetine, serotonin and
norepinephrine reuptake inhibitors (SRNIs), have
demonstrated effectiveness in diabetic neuropathy
• Venlafaxine can raise blood pressure
• Duloxetine is contraindicated if patient has hepatic
disease
Anticonvulsants:
+
Ca
antagonists
•Gabapentin and pregabalin can be effective in treating
neuropathic pain
•Reasonable first line treatments, although caution must
be exercised in the presence of renal disease
Anticonvulsants: Lamotrigine
•Na+ agonist, inhibits glutamate
•9 week trail showed significant pain reduction with no
significant difference in adverse effects compared to
placebo
•Due to risk of rare but life-threatening reactions, slow
upward titration is warranted
Opioids
•Demonstrated efficacy in reducing peripheral
neuropathic pain, but unclear role in central neuropathic
pain
•As needed opioid therapy for breakthrough pain is
reasonable
•Long-term opioid therapy may be considered if other
treatment options have been exhausted
Cannabinoids
•Some evidence of efficacy in central neuropathic pain in
multiple sclerosis
•Cannot be prescribed in Mississippi
Guidelines for pharmacologic treatment
of neuropathic pain
First line
Second line
Third line
Gabapentin
Pregabalin
Amitriptyline
Nortriptyline
Duloxetine
Venlafaxine
Lamotrigine
Tramadol
Opioids
Chronic pain in traumatic brain injury
(TBI)
•Difficult to assess pain in moderate to severe traumatic
brain injury due to emotional and cognitive deficits
•Though generally less severe, emotional and cognitive
deficits may impede diagnosis and treatment even in
mild traumatic brain injury
•Estimates of true prevalence vary widely (11% to 93%)
Chronic pain in TBI (con’t)
•Higher reported incidence of chronic pain in mild TBI
compared to severe TBI
•Difference may result from inability of severe TBI
survivors to communicate their pain to providers
•Most common pain complaint in TBI is headache, with
reported incidence between 44% and 64%
•TBI survivors with pre-existing headaches experience
worsening symptoms
Chronic pain in TBI (con’t)
•Complex regional pain syndrome (CRPS) is reported in a
minority of TBI survivors
•Neuropathic pain is believed to result from TBI, but
incidence is unknown
•Unlikely in SCI, neuropathic pain in TBI is believed to
result from direct insult to pain interpreting sections of
the brain
Chronic pain in TBI (con’t)
•Damage to mid-brain, brain stem, or cerebellum can
lead to spastic hypertonia
•Spasticity is more challenging to treat in TBI than in SCI
•Heterotopic ossification (HO), or bone formation within
soft tissue, affects 11% to 22% of TBI survivors
•HO common in hips, shoulders, and elbows
Treatment for headache in TBI
There are multiple types of headaches that TBI survivors may suffer
from, and treatment depends on the specific diagnosis.
Abortive treatments
Prophylactic treatments
Tension Headache
NSAIDs
Acetaminophen
TCAs (e.g. Amitriptyline)
Topiramate
Migraine
Acetaminophen Aspirin
Caffeine
Naproxen
Ibuprofen
Triptrans
Antiemetics
Dexamethazone
DHE
Midrin
SSRI
SNRI
Beta blockers
Verapamil
Amlodipine
Anticonvulsants
Cluster
SubQ or nasal triptans
Verapamil
Verapamil
Prednisone
Valproic acid
Topiramate
Treatment for complex regional pain
syndrome (CRPS) in TBI
•Difficult to treat
•Bisphosphonate compounds (Calcitonin, Clodronate,
Alendronate) have shown significant efficacy
•Steriod injections and topical analgesics Dimethyl
Sulfoxide (DMSO) and lidocaine may improve symptoms
Treatment of neuropathic pain and
spasticity in TBI
•The causes of neuropathic pain and spasticity in
different in TBI compared to SCI, but the treatment is
similar.
Treatment of heterotrophic ossification
(HO)
•
•
•
•
•
NSAIDS
COX-2 inhibitors
Physical therapy
Bisphosphonates (prophylaxis)
Radiation therapy
Opioids in chronic TBI and SCI pain
•Opium has been known as an analgesic for thousands of years
•Morphine and heroin, isolated in the 19th century, are
extremely potent analgesics, but the danger of dependence
and adverse effects is extremely high
•Other opioids are less potent but still carry significant risks of
abuse, dependence, and adverse effects
•Due to their efficacy and in spite of their risks, opioids remain
a treatment option in acute and chronic pain
Action of opioids
•Opioids bind to μ-opioid receptors throughout the central
nervous system.
•They act on components in the brain central to pain
processing (amygdala, thalamus, hypothalamus)
•Chronic exposure leads to more excitable neurons and
therefore can cause hyperalgesia
•Due to dopamine sensitivity, the frontal cerebral cortex (the
decision making center of the brain) is particularly prone to
alteration from opioids
Conclusion
Chronic pain is a common and complex clinical challenge
in both TBI and SCI survivors. Pain receives less attention
than motor deficits in SCI or cognitive and emotional
deficits in TBI, but the pain can be quite debilitating in its
own right. Treatment of pain is very important to the
rehabilitation and quality of life of TBI and SCI survivors.