This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Slide 1
Michel P. Rathbone Neurologist McMaster University
Slide 2
Definition Anatomy of pain Types of pain - neuropathic and
nocioceptive Chronic pain epidemiology Sensitization peripheral and
central Imaging Pain and mental status - cognition
Slide 3
Pain -An unpleasant sensory and emotional experience associated
with actual or potential tissue damage, or described in terms of
such damage International Association for the Study of Pain
Slide 4
There is a new realization that chronic pain is a disease of
the brain
Slide 5
Slide 6
Neuropathic Nociceptive However, in clinical practice, there is
usually the combination of these types of pain in a patient with
chronic pain
Slide 7
Pain initiated as a direct consequence of a lesion or disease
affecting the somatosensory system No physiological advantage
(warning) Causes suffering and distress Characteristics include
burning, paresthesias, painful cold, electric shocks, itchiness,
and can be associated with numbness Allodynia (painful response to
non painful stimuli) and/or hyperalgesia (increased response to
painful stimuli)
Slide 8
IASP Definitions: Peripheral Neuropathic and Central
Neuropathic Pain Neuropathic pain Pain initiated or caused by a
primary lesion or dysfunction in the nervous system Peripheral
neuropathic pain Pain initiated or caused by a primary lesion or
dysfunction in the peripheral nervous system Central neuropathic
pain Pain initiated or caused by a primary lesion or dysfunction in
the central nervous system
Slide 9
Spinal cord injury central neuropathic pain Cervical or lumbar
radiculopathies Brachial plexus injuries Peripheral nerve injuries
(median, ulnar, radial, peroneal nerves) Phantom Limb pain (after
amputation) Complex Regional Pain Syndrome (CRPS) Brain infarction
(especially in the thalamus and brainstem)/traumatic brain injury
Fibromyalgia (?)
Slide 10
An appropriate physiological response transmitted to a
conscious level Nociceptors activated in any body tissue Organism
warned of tissue damage Coordinated reflexes and behavioral
responses Low back pain is the most common complaint and can arise
from degenerative changes in the spine aggravated by changes in
gait and posture.
Slide 11
Low back pain Headaches Spasticity e.g. in brain and spinal
cord injured patients Whiplash injuries Fractured/sprained/strained
joint (ankle, shoulder, wrist) Arthritis Fibromyalgia (?)
Slide 12
It is estimated that about 15% to 29% of Canadians suffer from
chronic pain (Boulanger, 2007). About one million patients in
Canada have neuropathic pain (Moulin, 2002)
Slide 13
Slide 14
Definition: Increased responsiveness of nociceptive neurons to
their normal input, and/or recruitment of a response to normally
subthreshold inputs. Peripheral sensitization: Increased
responsiveness and reduced threshold of nociceptive neurons in the
periphery to the stimulation of their receptive fields. Central
sensitization: Increased responsiveness of nociceptive neurons in
the central nervous system to their normal or subthreshold afferent
input IASP, 2012
Slide 15
Thalamus HI S BKBK ILIL 3. Area of Primary Hyperalgesia 1.
Local trauma 2. Release of kinins from injury site Pain
Pathophysiology Peripheral Sensitization Leads to Central
Sensitization
Slide 16
Thalamus Gl u CGRPCGRP 4. Antidromic release of peptides from
axon collaterals => FLARE, WHEAL 5. Zone of secondary
hyperalgesia mediated by SP, Glu, CGRP SPSP Gl u CGRPCGRP
PERIPHERAL SENSITIZATION SPSP Pain Pathophysiology Peripheral
Sensitization Leads to Central Sensitization
Slide 17
Thalamus Gl u CGRPCGRP 6. Increased nociceptive input from the
periphery SPSP Gl u CGRPCGRP CENTRAL SENSITIZATION SPSP 7. Wind up
of dorsal horn neurons Pain Pathophysiology Peripheral
Sensitization Leads to Central Sensitization
Studies looking at mechanical stimuli for chronic whiplash and
central sensitization: Deep tissue stimulation: pressure algometry
Skin and nerve tissue stimulation: light touch, pinwheel,
vibration, Brachial Plexus Provocation test Thermal stimulation:
heat, cold Electrical stimuli: EMG, transcutaneal electrical
stimulation Local anesthetic use does not impact central
sensitization, but facet blocks help, suggesting nociceptive input
arise from the zygapophyseal joint. The coexistence of sensory
hypersensitivity and hypoaesthesia in chronic WAD indicates that
both central facilitatory and inhibitory processes are affected in
these patients (VanOsterwijck, 2013)
Slide 21
14 whiplash patients and 14 healthy controls were given painful
stimuli (single electrical stimulus intramuscular, repeated
electrical stimulation both intramuscular and transcutaneous, and
heat) and thresholds were measured at the neck and lower limb. All
patients in the whiplash group had significantly lower pain
threshold for all painful stimuli except for heat. The authors
found a hypersensitivity to peripheral stimulation in whiplash
patients. Hypersensitivity was seen after cutaneous and muscular
stimulation both at the neck and lower limb. Because
hypersensitivity was observed in healthy tissues, it resulted from
alterations in the central processing of sensory stimuli (central
hypersensitivity). Use of local anesthetic did not influence pain
thresholds or hypersensitivity at the neck and the lower limb sites
in response to single and repeated intramuscular and transcutaneous
electrical stimulation, and it did not influence neck pain
intensity. These results suggest generalized hypersensitivity was
not dependent on nociceptive input arising from the painful and
tender muscles. Central hypersensitivity was not dependent on a
nociceptive input arising from the painful and tender muscles.
Slide 22
Neuro-immunological involvement A cascade of events are
proposed following an injury within the central nervous system at
the cellular level. Cells (glia, neurons) become activated and
produce and release cytokines leading to further activation and
release of pain mediators. Glial or neuronal pro-inflammatory
cytokines can sensitize peripheral nociceptive fields and dorsal
root ganglia. Cytokines and growth factors have been associated in
the involvement of generating pathological pain states throughout
the nervous system especially proinflammatory cytokines like IL-1,
IL-6, and TNF, which are upregulated both at the local site of
injury and in the spinal cord in persistent pain. Immune activation
with cytokine production may indirectly induce pain mediators such
as glutamate, nitric oxide, and prostaglandins in the CNS, leading
to further spinal sensitization. Neuroinflammation occurs in which
immune cells migrate from the periphery to the CNS in association
with pain; leading to further changes in the CNS and potentially to
central sensitization. These infiltrating immune cells contribute
to neuronal activation and algesic mediator release, further
perpetuating the maintained excitability and sensitization in the
CNS which leads to behavioral sensitivity and pain. Winkelstein et
al, 2004)
Slide 23
Proposed relationship between mechanical injury (e.g.
musculoskeketal disorder) and nociceptive physiological responses.
Winkelstein et al, 2014)
Slide 24
Sava et al., 2009, Mol Pain
Slide 25
The central areas in the brain associated with central
sensitization include the thalamus, amygdala, insula cortex,
supplementary motor cortex, posterior parietal cortex, prefrontal
cortex, anterior cingulate cortex, periaquedutal gray, basal
ganglia, cerebellar cortex, and the primary and secondary sensory
cortex. (May, 2011)
Slide 26
Lee et al (2007) Brainstem activity contributed to the
maintenance of the CS state Activity in the somatosensory cortex
reflected the perceptual consequence of CS, that is an increase in
the intensity of pain experienced
Slide 27
Results of mixed-effects analysis of the average group response
for controls and patients in response to cold and punctuate
stimuli. Figure one is all areas affected by pain. Red primary
somatosensory cortex; Light blue secondary somatosensory cortex;
Dark blue anterior cingulate cortex; Green - insula
Slide 28
a. Patients vs. Controls b. High PainDETECT vs. Low
PainDETECT
Slide 29
Chronic pain has been associated with poorer performance in
various cognitive functions. Tamburin et al (2014) found patients
with chronic low back pain had poorer decision making performance
and cognitive flexibility skills compared to healthy controls.
Compared to controls, chronic pain patients took longer to complete
tests of sustained attention and mental flexibility (Oosterman et
al, 2012). Reduction in psychomotor speed (Sjogren, 2004)
Slide 30
Neurocognitive Test Performances In Chronic Pain Patients.
William Parkinson PhD, Yasir Rehman MD, Michel Rathbone MD, Mohit
Bhandari MD, Shucui Jiang PhD, Dinesh Kumbhare MD, Jonathan Adachi.
Background & Purpose: C Background & Purpose: Chronic pain
is likely to be associated with weaknesses, relative to control
groups, in at least some cognitive functions including processing
speed, attention, and possibly working memory, but differences
between studies obscure the size of effects. This study provided a
quantitative analysis of the magnitude of the association between
chronic pain and neurocognitive test performances. Methods:
Methods: Meta-analysis was performed using the Cochrane, PRISMA
guidelines. Conclusions: 1. Chronic pain was associated with Effect
Sizes of 1/3 to close to a full SD poorer performance. 2.
Correlates of chronic pain were non-specific, with relative
weaknesses in tests requiring speed, working memory, learning,
executive functions, and a range of attention abilities. 3. More
research is needed to test non-verbal abilities, executive
functions, and to control for estimated pre-morbid IQ.
Slide 31
Definition Types of pain - neuropathic and nocioceptive Chronic
pain epidemiology Sensitization peripheral and central Imaging Pain
and mental status cognition Research studies vs. Individuals
Slide 32
Most treatments for CS should target the brain (mainly
pharmacological) Pain neuroscience education and cognitive
behavioral therapy targeting cognitive and emotional sensitization.
Dry needling Transcranial magnetic stimulation Melatonin Cervical
radiofrequency neurotomy for cervical facet joint pain (whiplash
patients) Targeting metabolic factors low carbohydrate or ketogenic
diet to diminish hyperexcitability of the CNS. Manual therapy
(Sterling et al, 2010) Exercise therapy activates endogenous
analgesia, and has been shown to reduce fMRI changes (Micalos et
al, 2014)
Slide 33
As most chronic pain conditions involve central sensitization,
treatment strategies need to be able to desensitize the CNS. Most
conditions require a multimodal analgesic approach to include
pharmacotherapy, cognitive-information processing therapies, and
rehabilitation.
Slide 34
.. CBZ OXC TCA TPM LTG Lidocaine Na + Peripheral Sensitization
Spinal Cord TCA: Tricyclic antidepressant, SSRI: Selective
serotonin reuptake inhibitor, SNRI: Serotonin and norepinephrine
reuptake inhibitor, CBZ: Carbamazepine, OXC: Oxcarbazepine, TPM:
Topiramate, LTG: Lamotrigine; GBP: Gabapentin; LVT: Levetiracetam;
PREGAB: Pregabalin;. Adapted from Beydoun A., Backonja M.M;
Mechanistic stratification of antineuralgic agents. Journal of Pain
and Symptom Management, 2003:25:5S (p.S27) with permission from the
U.S. Cancer Pain Relief Committee Medication Ca ++ : GBP LVT OXC
LTG PREGAB NMDA : Ketamine Dextromethorphan Methadone Memantine
Central Sensitization Descending Inhibitory Pathways (NE/5HT,
opioid receptors) TCAs SSRIs SNRIs Alpha adrenergic agents Opioids
Tramadol