Pain - Indiana Osteopathic Association

Report
Central Sensitization: Clinical
Implications for Chronic Head and Neck
Pain
Arthur S. Roberts DDS, MD, MSc
Indiana Craniofacial Center, PC
Indiana University School of Dentistry
Oral Medicine
University of Edinburgh
College of Medicine and Veterinary Medicine
Pain Management
DISCLOSURES
• Innovative Health Solutions
• American Academy of Pain Management
WHY IS THIS IMPORTANT?
Prototype
•
•
•
•
•
•
•
35-55 y/o female
Extensive PMH
Multiple prior providers
Polypharmacy
Often hypervigilant
Either non-communicative or circumstantial
May be none of the above!!!
Chronic Pain Is Not Acute Pain
•
•
•
•
Pathologic not protective
Multidimensional (Biopsychosocial)
Entangled via neuromatrix
Pan-Systemic
Chronic pain implies an altered
neuromatrix
• “The neuromatrix, which is genetically determined
and modified by sensory experience, is the primary
mechanism that generates the neural pattern that
produces pain. Its output pattern is determined by
multiple influences, of which the somatic sensory
input is only a part, that converge on the
neuromatrix.” Melzack 2001
* Emphasis added
Neuromatrix Is A Process
Central Sensitization
• “Sensory-afferent signals overwhelm the
body's ability to filter them” [1,2]
– neuro-immune dysfunction,
– neuro-endodrine dysfunction
– NMDA (N-methyl-D-aspartate) dysregulation
– Sympatho-afferent coupling
– Altered serotonin and norepinephrine production
and utilization
Melzach, Woolf 2001
Common CS symptoms
•Depression
•Anxiety
•Sleep fragmentation
•Allodynia
•Hyperalgesia
•Fatigue
[1,3-5]
Two Etiological Pathways
• Chronification of nociceptive pain
– Neuroplastic changes
– Peripheral sensitization
– Central sensitization
• Chronic stress
–
–
–
–
–
Elevated levels of chronic stress
Anxiety
Sleep fragmentation
Decreased pain thresholds
Dysautonomia
Etiology of CSS
Genetic predisposition
Environmental
 Trauma
 Physical
 Psychological
 Infectious
 Lyme disease
 Chronic EBV
 Parasites
 Toxins
 Heavy metal
 Biotoxins
 Medications
 Sleep disturbances
 Sleep apnea
 Circadian
rhythm
disorders
 Metabolic
 Thyroid
disease
 Autoimmune
 Celiac disease
Dysregulation of the hypothalamic pituitary adrenal axis
Damage to hippocampal neurons
and reduced neurogenesis
• Disruption of the
normal circadian
cycle
• Reduced basal
cortisol levels
Kaplan 2013
Bimodality
Pain
Depression
Depression and
chronic pain share
common
neurophysiology and
neurobiology. They are
mutually reinforcing
neuropathologic
processes.
Kaplan 2013
Common genetic vulnerabilities
Common neurobiology




Neuroanatomy
Neuroendocrinology
Neuroimmunology
Neurotransmitters
From CS to CSS
Microglial Activation
Microglia Activation
Ischemia
Hypoxia
Neurodegenerative
Diseases
Infections
Medication
Trauma
Toxins
Kaplan 2013
Central Sensitization Syndrome
CSS = Chronic Pain + Neuropsychiatric Condition
 Neuroinflammatory
 Neurodysregulatory
 Neurodegenerative
Kaplan 2013
MDD
6.6% per
year = 21 M
people
16.7% over
a lifetime =
51 M people
50%
to
65%
Chronic
Pain
15% =
47 M
people
♀>♂ 2:1 ratio
1,2,3,4,5,7,9,11
When depression and chronic pain
occur together, treatment success is
dramatically lower and cost is
dramatically higher than when these
conditions occur separately.
Central Sensitization Syndromes (CSS)
Adapted from Wallace and Clauw [2]
MPS
TTH
MGN
MCS
IBS
PLMD
FMS
CSS
PD
RLS
DPSN
CFS
PTSD
TMD
BMS
AO
Tension-type HA
Migraine
Limb Movement Disorder
Fibromyalgia
Restless Leg Syndrome
Chronic Fatigue Syndrome
TMD
Atypical Odontalgia
Burning Mouth Syndrome
Post Traumatic Stress Disorder
Depression
Primary Dysmenorrhea
Irritable Bowel Syndrome
Multiple Chemical Sensitivities
Myofascial Pain Syndrome
Characteristic sequelae central
sensitization
• Vagal dysregulation [7, 18, 20]
• Sympatho-afferent coupling of sensitized trigeminal
complex [6,21-25]
• Decreased medullary descending inhibition
[8,11,12,15-17,23,26-32]
• Hypoactivity of the hypothalamic-pituitary-adrenal axis
– Autonomic nervous system alterations
• Increased sympathetic tone
• Low vagal tone
[5,12,14,20,21,23-25,33-38]
Vagal dysregulation
• Reduces endorphin release
• Alters serotonin production and utilization
– Altered accommodation of minimally painful
events
– Contributes to depression
[7, 18, 20]
Sympatho-afferent coupling
• Sensitized trigeminal complex
• Lowered parasympathetic drive
• Increased sympathetic drive
– Altered norepinephrine levels
– Dysfunctional sleep
– Anxiety
[6,21-25]
Decreased medullary descending inhibition
• Increases effect of peripheral nociceptive
input
– Lowered pain thresholds
– Hyperalgesia,
– Allodynia
– Greater impact of peripheral sensitization
[8,11,12,15-17,23,26-32]
Hypoactivity of the hypothalamic-pituitaryadrenal axis
• autonomic nervous system alterations
• increased sympathetic tone
• low vagal tone
• Immune abnormalities
• Fatigue
• Malaise
[5,12,14,20,21,23-25,33-38]
Indicators for central sensitization.
•
•
•
•
•
•
•
depression
anxiety
hyperalgesia
allodynia
stress related pain exacerbation
fatigue
poor sleep
Therapeutic Problems
• Polypharmacy
• different prescribing specialists
• iatrogenic contribution
– failing to differentiate chronic from acute pain
• Symptomatic - Acute symptoms of CSS disorders
need to be addressed
• Syndromic - Essential to treat the pathways in
chronic pain disease
[2,5,7,8,13-15,17,19,20,32]
Two approaches to CSS therapy
• Symptomatic approach: Address the effects of
CS after it has occurred
• Syndromic approach: Interrupt the CS
• Optimal outcomes often depend on doing
both.
– Pharmacological
– Non-pharmacological
[1,4,6,8,13,14, 40-44]
. Pharmacological Approaches
• Treating the effects
– Acetaminophen
– Serotonin (SSRI) and norepinephrine (SNRI) reuptake
inhibitors and tricyclic antidepressants (TCA)
– Opioids and Tramadol
• Drugs that may treat the central sensitization itself:
– N-methyl-D-aspartate (NMDA) receptor blockers
• Namenda, Ketamine, Memantine
– Calcium channel alpha(2) ligands
• Gabapentin, Lyrica
Non-pharmacological Approaches (NPT)
• Each element of neuromatrix is potential
therapeutic target
• Two broad operative groups:
– Reducing CS itself
– Responding to the effects of CS
Repetitive Transcranial Magnetic
Stimulation (rTMS)
• Safe and non-invasive
• Stimulation of the motor cortex and prefrontal cortex
• Limited application
–
–
–
–
–
–
–
–
Short duration of effects
Significant equipment costs
Greater efficacy in centrally, rather than peripherally, originated pain
Reverses intra-cortical motor dysfunction
Alters sensory-discriminative function
Restores of descending inhibition
Improves cognitive function [56,57]
Some investigators argue that the analgesic effects are independent of
descending inhibitory control and are influenced by other elements of
the neuromatrix [58]
Manual Therapy
• Improves function
• Improves descending inhibition
•
•
•
•
Widespread analgesia.
Short duration
Limited assistance in desensitizing the neuromatrix
Addresses functional rehabilitation
[4,13,60-64]
Virtual Reality
• Limited evidence
• Distraction in the hyper-vigilant patient
• Potential benefit in patients with movement
associated nociceptive etiology
• Not in widespread use
[13,65]
Improving Stress Tolerance and Neuro
feedback Training
• Stress
–
–
–
–
–
Etiologic and exacerbating factor for CS
Endogenous (chronic pain)
Exogenous (psychosocial changes)
Irritable, hyper-excitable chronic pain patient
Related to sympatho-afferent coupling in the hypothalamic-pituitaryadrenal axis of the neuromatrix.
– neuro-immune changes from upregulated pronociceptive immune
mediators in primary afferent nociceptors
• Reduction of stress levels improves:
• Pain threshold
• Maladaptive behavior
• Autonomic balance
[12,14,17,35,36,66-68]
Transcutaneous Electrical Nerve
Stimulation
• Activates poly-segmental inhibitory feedback
• Significant effect with focal, segmental chronic
pain
• Results in widespread pain are equivocal
[13,40, 69-73]
Percutaneous Electroneural Stimulation
(PENS)
•
Percutaneous stimulation of peripheral branches of multiple cranial and
cervical nerves
• Trigeminal, Vagus, Occipital
– Discreet
– Stimulates afferents
•
•
•
•
•
•
improved autonomic regulation
Improves centrally mediated pain
Improves sensory - discriminatory functions
serotonin/norepinephrine production and utilization
endorphin production
analgesia and mood improvement appears to follow a ‘learning
curve’[59]
• cost-effective, non-invasive, low co-morbidity option
[1,2,5, 6,8-10,12-15,20-23,25-28,42-44,53, 55]
Once initiated central sensitization can
engender additional presentations
•
•
•
•
Increased frequency and intensity of pain
Increased endogenous stress levels
Increased sympatho-afferent coupling
Autonomic dysfunction
–
–
–
–
–
anxiety
poor sleep
difficulty coping
lowered pain thresholds
increased risk of developing additional presentations of CS
• Persistent microglial inflammation
[2,74]
Removal Of The Initiating Stimulus Will Not
Insure Favorable Outcomes
•Continuing stimulus for the development
and/or maintenance of CS
– Extended disease course
– Additional CS presentations (syndromes)
– Devolves to dealing with the effects of the CS
rather than control or eradication of the CS
[2,3,74]
Stress Induced CS
• No biological axis may exist in the early stages
– Maladaptive behavior
• Engender biological issues
• Contribute to maintenance and exacerbation of CS
– PTSD
– Depression
– HPA induced changes
– Microglial activation
Conclusions
•
•
•
•
Potentially progressive
Devastating
Multimodal disease
Worldwide economic and social burden
Effective intervention
• Fundamental differences in acute and chronic
pain
• Effects on and by the neuromatrix
• biopsychosocial health of the individual
patient
• Integrate a comprehensive multidisciplinary
therapeutic plan
CSS Prognosis
Guarded
The comorbidity of neuropsychiatric
disease (depression, GAD, PTSD) and
chronic pain are common.
When depression and chronic pain
occur together, treatment success is
dramatically lower and cost is
dramatically higher than when these
conditions occur separately.
THANK YOU

similar documents