Pain Physiology SLS

Pain Physiology in the
Chronic Pelvic Pain
Context
Juan Diego Villegas-Echeverri, MD, FACOG
Unidad de Laparoscopia Ginecológica Avanzada y Dolor Pélvico
ALGIA
Clínica Comfamiliar
Pereira, Colombia SA
jvillegas@comfamiliar.com
Pain Physiology in the Chronic Pelvic Pain
Context
Juan Diego Villegas-Echeverri, MD, FACOG
No relevant financial relationships in the past twelve months
by presenter or spouse/partner.
Presentation Outline
1.
2.
3.
4.
5.
6.
Definitions
Why bother? Scope of the problem
Types of pain
Pain pathways
The neuro pathologic response to pain
Conclusions
Presentation Outline
1.
2.
3.
4.
5.
6.
Definitions
Why bother? Scope of the problem
Types of pain
Pain pathways
The neuro pathologic response to pain
Conclusions
Pain
An
unpleasant
sensory
and
emotional experience associated
with actual or potential tissue
damage or described in terms of
such damage.
It is a complex collection of multiple,
learned perceptions that change
over time and that motivate
individuals
to
circumstance
appropriate self-protective action.
. IASP Task Force on Taxonomy. Pain Terms. A Current List with Definitions and Notes on Usage.
In: Classification of Chronic Pain. Part III. Merskey H, Bogduk N. IASP Press, Seattle, 1994.
. International association for the study of pain IASP. Annual meeting. Seattle, 2000
. Berkley KJ. Neuroscience, FSU. 2005
Chronic Pelvic Pain
•
•
•
•
Non-malignant
Non cyclic pain*
>3mo duration*
Localizes
–
–
–
–
Anatomic pelvis
Anterior abdominal wall at or below the umbilicus
Lumbosacral back
Buttocks
• Sufficient severity to cause functional disability or lead to
medical care.
• Related negative cognitive, behavioral and social
consequences.
. Howard F: ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists.
ACOG Number 51, March 2004
. Fall M, Baranowski AP, Fowler CJ et al. EAU guidelines on chronic pelvic pain. Eur Urol 2004;46:681–9.
A lack of physical findings does not negate
the significance of a patient’s pain.
Normal examination results do not preclude
the possibility of finding pelvic pathology.
It is more likely that patients are poorly
evaluated and not that the physical
examination is normal.
. Howard F: ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists.
ACOG Number 51, March 2004
Chronic Pelvic Pain Syndrome
•
•
•
•
CPP
Impaired usual function
Signs of depression
Pain out of proportion
to pathology
• Unresponsive to usual
therapy
• Altered family roles
. ACOG Patients educational pamphlet AP 129. Chronic pelvic pain. Washington DC 1989
. Issa W, Roumeguere Te, Bossche MV. Chronic pelvic pain syndrome. Rev Med Brux. 2013;34(1):29
Presentation Outline
1.
2.
3.
4.
5.
6.
Definitions
Why bother? Scope of the problem
Types of pain
Pain pathways
The neuro pathologic response to pain
Conclusions
•
•
•
•
20 - 30% of all ObGyn Office visits
15 - 20% of all ER ObGyn Visits
20 - 40% of all Gyn Laparoscopies
Up to 61% undiagnosed - untreated
• 41% never seek consultations
• 31% with symptom related anxiety
(compared with 7% without CPP)
• 50% had also urinary symptoms
and/or functional bowel disease
. Zondervan KT, Yudkin Pl et al. The community prevalence of chronic pelvic pain in women and associated illness behaviour. Brit J Gen Practice 2001;541
. Zondervan KT, Yudkin Pl et al. Chronic pelvic pain in the community. Symptoms, investigations and diagnoses. Am J Obstet Gynecol 2001;184:1149
• Up to 75% of Gyn medical
disability in the United States
• 80%
of
patient’s
are
unsatisfactorily managed
• Only
15%
of
physicians
surveyed said they “enjoyed”
caring for CPP patients
. Zondervan KT, Yudkin Pl et al. The community prevalence of chronic pelvic pain in women and associated illness behaviour. Brit J Gen Practice 2001;541
. Zondervan KT, Yudkin Pl et al. Chronic pelvic pain in the community. Symptoms, investigations and diagnoses. Am J Obstet Gynecol 2001;184:1149
. Pizzo PA, Clark NM. Alleviating suffering 101--pain relief in the United States. N Engl J Med 2012;366(3):197
Quality of Life
•
•
•
•
•
•
•
•
•
Inability to exercise
Difficulty sleeping
Lack of enjoyment of leisure
Inability to perform chores
Interference with socializing
Difficulty walking
Interference with sexuality
Difficulty concentrating
Inability to work
81%
79%
67%
65%
65%
59%
54%
49%
41%
. Mathias SD et al. Obstet Gynecol. 1996;87:321-327.
. Postgraduate course 5. Chronic Pelvic Pain. IPPS. 31st AAGL meeting.November 2002. Miami, Fla
. Yunker A, Sathe NA, Reynolds WS, Likis FE, Andrews J. Systematic review of therapies for noncyclic chronic pelvic
pain in women. Obstet Gynecol Surv 2012;67(7):417
Cost
• Medical cost
U$ 1.2 billion/year
• Productivity loss
U$ 15 billion/year
. Association of professors of gynecology and Obstetrics: monography January 2000
Presentation Outline
1.
2.
3.
4.
5.
6.
Definitions
Why bother? Scope of the problem
Types of pain
Pain pathways
The neuro pathologic response to pain
Conclusions
Pain Source
Nociceptive
Somatic Pain
Non nociceptive
Visceral Pain
Neuropathic Pain
Mixed Pain
Acute Pain
Chronic Pain
Pain Duration
. Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005
. Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45
Nociceptive pain
arises from the stimulation of specific pain receptors
. Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005
. Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45
Somatic Pain
– Caused by the activation of pain receptors
• Body surface
• Musculoskeletal tissues
– Usually aggravated by activity and relieved by rest
– Receptors respond to stimuli released from damaged
cells
•
•
•
•
•
Heat
Cold
Vibration
Stretch
Chemical
. Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005
. Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45
Visceral Pain
– Caused by damaged or injured internal
organs or abdominal muscles (spasm)
– Caused by the activation of pain
receptors in the chest, abdomen or
pelvic areas
– Vague and not well localized
– Usually described as pressure-like,
deep squeezing, dull or diffuse
– Referred pain
. Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005
..Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45
Non Nociceptive Pain
arises from within the peripheral and central nervous system
. Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005
. Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45
Neuropathic Pain
• Caused by injury or malfunction to the
spinal cord and peripheral nerves
• Typically a burning, tingling, shooting,
stinging, or "pins and needles"
sensation
• Also complain of a stabbing, piercing,
cutting, and drilling pain
• Usually occurs days, weeks or months
after the injury
• Tends to occur in waves of frequency
and intensity
• Is diffuse and occurs at the level or
below the level of injury
. Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005
. Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45
. Attal N. Neuropathic pain: mechanisms, therapeutic approach, and interpretation of clinical trials. Continuum (Minneap Minn) 2012 (1):161-75
Acute Pain
• Typically is produced by sudden injury
• Accompanied by physical signs
• Tends to resolve as the injury or disease does
. Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005
. Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45
. Inui K. Pain pathway. Brain Nerve. 2012 ;64(11):1215
Chronic Pain
•
•
•
•
3-6 mo duration
Persistent pain
In many cases no physical cause can be found
Is a disorder in itself rather than being the symptom of a
disease process
• Repeated pain from an acute injury changes the nervous
system responses
. Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005
. Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain 2012 ;13(10):936
. Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45
. Inui K. Pain pathway. Brain Nerve. 2012 ;64(11):1215
. Farmera MA, Baliki MN. A dynamic network perspective of chronic pain. Neuroscience Letters 2012; 520:197
Acute vs. Chronic Pain
• Acute Pain
Symptom of tissue damage
and an underlying disease
• Chronic Pain
Pain becomes a disease
«Some individuals who have acute pain can be caught in a
vicious cycle that leads to chronic pain and disability»
. Crombez G, Eccleston C, Van Damme et al. Fear-avoidance model of chronic pain: the next generation. Clin J Pain. 201228(6):475
. Quinlan J, Carter K. Acute pain management in patients with persistent pain. Curr Opin Support Palliat Care 2012; 6(2):188
Pain is a direct or indirect consequence of several
diseases. However patients with moderate to severe
pain are often under-treated in both developing and
developed countries(…)
It is important to recognize that pain is a problem in its
own right, not “just” an indicator of an underlying disease
or damage process, but one which extracts a great toll
on individuals and society. Alleviation of pain itself, as a
symptom, should be a therapeutic target. In order to
improve the quality of life, the objective should be to
avoid any unpleasant perception with an approach based
on the right communication between the care giver and
the patient
WHO Normative Guidelines on Pain Management.
Report of a Delphi Study to determine the need for guidelines and to identify the number and topics of guidelines that should be developed by WHO
Geneva, June 2007
Presentation Outline
1.
2.
3.
4.
5.
6.
Definitions
Why bother? Scope of the problem
Types of pain
Pain pathways
The neuro pathologic response to pain
Conclusions
Descartes “Tubules”
• 3 components
– First order neurone
• cell body in dorsal root ganglion
• Transmits pain from a peripheral
receptor
– Second-order neurone
• Dorsal horn of the spinal cord
• Axon crosses the midline
• Ascend in the spinothalamic tract
to the thalamus
– Third-order neurone
• Projects to the postcentral gyrus
(via the internal capsule)
• Generate periferical response
. Fornasari D. Pain mechanisms in patients with chronic pain.Clin Drug Investig 2012;32 Suppl 1:45
•
The progression of pain research has
been hindered by the dominating
view that pain is a purely nociceptive
phenomenon
•
Now we know is much more complex
(even more for the chronic pain)
–
Peripheral receptors
–
Neural pathways
–
Spinal Cord mechanisms & long tracts
–
Brainstem, thalamus, cortex & other
areas
–
Descending pathways
. Staud R. Peripheral pain mechanisms in chronic widespread pain. Best Pract Res Clin Rheumatol 2011;25(2):155
. Farmera MA, Baliki MN. A dynamic network perspective of chronic pain. Neuroscience Letters 2012; 520:197
A beta fibres
Local
interconnections
Initial connections
Ascending pathways
A delta fibres
Spinal cord
Gate Control
Neospinothalamic tract
Perception of Pain
In cerebral cortex
First pain
Second pain
(pain only nociceptors)
(polimodal nociceptors)
A delta fibres
Spino-reticulo-diencephalic pathway
C fibres
Peripheral receptors
Sensory and motor cortex areas
Premotor cortex
Pre Frontal cortex
Other parts of the parietal cortex
Cingulate cortex
Insula
Occipital cortex
Descending modulation
Brain regions involved in pain processing
Somatosensory Cortex
Prefrontal
Cortex
Insular Cortex
Thalamus
Anterior
Cingulate
Cortex
(ACC) / Locus
coeruleus
Anatomy of Pain Overlaps Anatomy of Emotion
. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005;9(4):463
Common areas of activation in pain studies
(PET and MRI )
•
Anterior Cingulate Cortex (ACC) / Locus coeruleus
– Cognitive functions and reasoning
•
•
•
•
Reward Anticipation
Decision Making
Empathy
Emotion
–
•
•
•
•
Integrates emotional stimuli with attentional
functions
Prefrontal cortex
– Perform and accomplish
– Working memory
– Decision making
– Planning and judgment
Insular Cortex
– Processes convergent information to produce
emotionally relevant context for sensory experience
Somatosensory Cortex
Thalamus (and Amygdala)
• Processing
• Memory of emotional reactions
. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005;9(4):463
Presentation Outline
1.
2.
3.
4.
5.
6.
Definitions
Why bother? Scope of the problem
Types of pain
Pain pathways
The neuro pathologic response to pain
Conclusions
• Pain mechanisms in patients with chronic
pain
– Altered Pain processing
– Cross – Talk
– Convergence and Hiperalgesia
• Visceral – somatic
• Visceral - visceral
– Dorsal horn neuroplasticity
– Centralization
– Neurogenic inflamation / Antidromic transmission
– Visceral “Silent” Afferents
.Fornasari D. Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012;32 Suppl 1:45
Altered Pain-Processing
Severe, unrelieved pain for more than 24 hr
Excessive and prolonged stimulation of N-methyl-Daspartate (NMDA) receptors
Plastic neuropathic change at dorsal horn receptor cell
Produces hyperexcitable neurons, allodynia and
hyperalgesia
. Doggweiler-Wiygul R. Chronic pelvic pain. World J Urol 2001;19:155
. Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain 2012;13(10):936
Repeat Stimulation of Nociceptive Neurons
Changes Nerve Fibers
Lowers Threshold
Peripheral Sensitization
Exaggerated Transmission Response
Recruits higher and Lower Neurons
Self-Sustaining Activation
. Doggweiler-Wiygul R. Chronic pelvic pain. World J Urol 2001;19:155
. Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain 2012;13(10):936
Spinal Windup
Neuronal plasticity
Barrage of painful stimuli to dorsal horn
Decrease threshold or loss of inhibition (allodynia)
Expansion of receptive fields
Permanent biochemical change
Exaggerated reflex output with end-organ dysfunction
Up regulation of sensory processing
. Puretić MB, Demarin V. Neuroplasticity mechanisms in the pathophysiology of chronic pain. Acta Clin Croat 2012;51(3):425
. Herrero JF, Laird JM, López-García JA. Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog Neurobiol. 2000 ;61(2):169
Zermann D et al. J Urol. 1999;160:102-105.
Cross-talk
The very strong electrical signals originated in
poorly isolated (or poorly myelinated) nerves
produce de novo electrical signals on
adjacent afferent nerve fibers that are not
involved in the painful stimuli
. Furuta A, Suzuki Y, Hayashi N, Egawa S, Yoshimura N. Transient receptor potential A1 receptor-mediated neural cross-talk and afferent sensitization induced by
oxidative stress: implication for the pathogenesis of interstitial cystitis/bladder pain syndrome. Int J Urol 2012;19(5):429
. Ren K, Dubner R. Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol. 2008;21(5):570
Visceral somatic convergence
• Only 2 to 7% of all afferent
fibers of each dorsal root
ganglion are visceral
• The interneurons in the dorsal
horn are greatly influenced by
somatic fibers
• So
– The somatic pain is referred
as visceral pain (specially in
the abdominal wall)
– The visceral pain is diffuse
and poorly located
• Visceral muscular reflex and
induced myalgia - PFTM
. Giamberardino MA, Berkley KJ, Affaitati G, et al. Influence of endometriosis on pain behaviors and muscle hyperalgesia induced by a ureteral calculosis in female rats.
Pain 2002;95:247-57.
. Staud R. Peripheral pain mechanisms in chronic widespread pain. Best Pract Res Clin Rheumatol 2011;25(2):155
Visceral-somatic hiperalgesia
Refered neurogenic
inflamation
– BPS/IC + vulvodinia
– IBS + abdominal
trigger points
. Staud R. Peripheral pain mechanisms in chronic widespread pain. Best Pract Res Clin Rheumatol 2011;25(2):155
. Brumovsky PR, Gebhart GF. Visceral organ cross-sensitization - an integrated perspective. Auton Neurosci 2010;153(1-2):106
Visceral - visceral hiperalgesia
– BPS/IC + IBS
– Endometriosis + BPS/IC
(”evil twins”)
– Hernias + PCS
. Chung MK, Chung RP, Gordon D. Interstitial cystitis and endometriosis in patients with chronic pelvic pain:
The "Evil Twins" syndrome. JSLS 2005;9(1):25.
. Furuta A, Suzuki Y, Hayashi N, Egawa S, Yoshimura N. Transient receptor potential A1 receptor-mediated neural cross-talk and afferent sensitization induced by oxidative stress:
implication for the pathogenesis of interstitial cystitis/bladder pain syndrome.
Int J Urol 2012;19(5):429
Dorsal horn neuroplasticity
• Nociceptive stimuli modulation in patients
with CPP (highly subjective)
– Primary hiperalgesia
• Afferent pathways remodeling - dorsal
horn
• Downstream influences from supraspinal
sites
– Secondary hiperalgesia and allodynia
• Hiperalgesia far from the original painful site
. Crosby ND, Weisshaar CL, Winkelstein BA.Spinal neuronal plasticity. Neurosci Lett 2013. doi:pii: S0304-3940(13)00224
. Wu J, Hu Q, Huang D, Chen X, Chen J. Effect of electrical stimulation of sciatic nerve on synaptic plasticity of spinal dorsal horn.
Brain Res 2012;1448:11-9
Central sensitization
•
Enhanced nociceptive synaptic transmission within the spinal cord following
persistent pain states
–
–
–
–
Dissociation of pain
Perception from a noxious stimulus or injury
Expansion of hyperalgesia beyond the site of injury
Extra-dermatomal hypersensitivity across other somatic and visceral structures
. Farmera MA, Baliki MN. A dynamic network perspective of chronic pain. Neuroscience Letters 2012; 520:197
•
•
•
•
•
•
Despite removal of original (primary pain generator) “insult” pain persists
(30-50%)
The dorsal horn is still hyper excitable with spontaneous activity.
Phantom limb
Spinal memory
Reorganization of somatosensory cortex
“ A chance to cut is NOT a chance to cure”
. Gustin SM, Peck CC, Cheney LB, Macey PM, Murray GM, Henderson LA. Pain and plasticity: is chronic pain always associated with somatosensory cortex activity and reorganization?
J Neurosci 2012;32(43):14874
. Garland EL. Pain processing in the human nervous system: a selective review of nociceptive and biobehavioral pathways. Prim Care 2012;39(3):561
. Saab CY. Pain-related changes in the brain: diagnostic and therapeutic potentials. Trends Neurosci 2012;35(10):629
Neuro-inflammation by
antidromic transmission
• Release of neuropeptides at the terminus of afferent
nerves
–
–
–
–
Substance P
CRGP
Neurokinin A
Neurokinin B
• Resulting in tissue reaction
– Reddening (vasodilation)
– Edema (plasma extravasation)
– Hyperalgesia
• Non neuropathic refered pain
– Dyspareunia and PCS
. Wesselmann U. Neurogenic inflammation and chronic pelvic pain. World J Urol 2001;19:180
. Hornick L, Slocumb JC. Treating chronic pelvic pain. Focus on pain triggers and neurogenic inflammation.
Adv Nurse Pract 2008;16(2):44
Visceral “Silent” Afferents
• Thinly or unmyelinated – easily damaged locally
• 30% to 80% visceral afferents are silent
• Silent afferents become active with prolonged
stimuli
• Silent afferents
sensitization
play
major
role
in
tissue
• Many more interneuronal synapses
. Keszthelyi D, Troost FJ, Simrén M, Ludidi S, Kruimel JW, Conchillo JM, Masclee AA. Revisiting concepts of visceral nociception in irritable bowel syndrome.
Eur J Pain 2012;16(10):1444
. Bueno L, Fioramonti J. Visceral perception: inflammatory and non-inflammatory mediators. Gut 2002;51 Suppl 1:i19
. Schott GD. Visceral afferents: their contribution to 'sympathetic dependent' pain. Brain 1994;117 ( Pt 2):397
Presentation Outline
1.
2.
3.
4.
5.
6.
Definitions
Why bother? Scope of the problem
Types of pain
Pain pathways
The neuro pathologic response to pain
Conclusion
In summary
• Pain itself can be the disease
• Sometimes the normal responses
to pain create new pain generators
– Look for the original insult – if still
present
– Treat all sources of pain and
dysfunction
– “Turn down the pain”
• Avoid inducing further wind-up in
patients with pre-existing upregulation
If you only have a hammer, it’s tempting to
treat everything as if it were a nail.
- Abraham Maslow
(1.908 – 1.970)