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Persistent Postsurgical Pain:Risk Factors and Prevention
Division of Pain Medicine
Department of Anesthesiology
University Hospitals ofCleveland
Salim Hayek, MD,PhD
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Persistent Postsurgical Pain:
Risk Factors and Prevention
Salim M. Hayek, MD, PhD
Division of Pain Medicine
Department of AnesthesiologyUniversity Hospitals of Cleveland
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Conflicts of Interest
None Relevant
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Persistent Postoperative Pain
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Learning Objectives
Physiology & Pathophysiology of Pain
Nociceptive vs. Neuropathic Pain
Predictors of Chronic Postsurgical Pain
Targets for Prevention of PersistentPostsurgical Pain
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Postoperative Pain
Pain
Score
POD10 32 54 6 180
PPP
Persistent Postsurgical Pain (PPP) = Pain >
3-6 mo after surgery
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Kehlet H et al., Lancet. 2006 May 13;367:1618-25
PPP--Incidence
Compares in its scale to morbidity of other forms of neuropathicpain such as post-herpetic neuralgia and post-stroke pain (5-10%)
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PPPA significant problemEtiologiesOngoing Inflammation
Neuropathic Pain: surgicalinjury to peripheral nervesDrug seeking/psychogenic
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Immediate Post-op
Activation ofnociceptors
Inflammation~ injury to nerves
Around-the-Clock
Medication
Breakthrough Pain
Most patients respond well to opiates and COX inhibitors.If nerves are injured during surgery, a neuropathiccomponent of the pain might develop immediately and then
persist in the absence of any peripheral noxious stimulusor ongoing peripheral inflammation
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PAIN = 2 subtypes
Pain: nociceptive or neuropathicNociceptive: tissue insultnociceptor
activationNeuropathic: pathological lesion or
dysfunction of the nervous system
Neuropathic pain treatmentdiffers from that of nociceptivepain
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Kehlet H et al., Lancet. 2006 May 13;367:1618-25
Inflammatory PainThe phenomena, although evoked within a
matter of minutes, outlast the precipitatingtissue injury for several hours or days
However, they are generally reversible Inflammatory pain is the pain that, in the
absence of any peripheral nerve damage,drives acute postoperative pain until the
surgical wound has healedIf a focus of ongoing inflammation persists,
however, so will the pain
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Kehlet H et al., Lancet. 2006 May 13;367:1618-25
Neuropathic Pain
Occurs as a result of a primary lesionor dysfunction in the nervous system
Key feature: combination of sensoryloss with paradoxical hypersensitivity
spontaneous pain, dysesthesia,
hypersensitivity, including allodyniaand hyperalgesia and hyperpathia
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Jung BF et al., Pain 2003; 104: 1-13Rasmussen PV et al., Pain 2004; 110: 461-469
Surgical nerve injury PPP
Postsurgical chronic pain closely resemblesneuropathic pain in most patients
Major nerves trespass the surgical fieldof most of the surgical proceduresassociated with chronic pain, and damageto these nerves is probably a prerequisitefor the development of postsurgicalchronic pain
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Aasvang E & Kehlet H. Br J Anaesth 2005; 95: 69-76
Inflammatory vs. Neuropathic
In a subset of patients, a continuousinflammatory response, such as after
inguinal mesh hernia repair, can contributeto a maintained inflammatory pain
Differentiation of neuropathic from non-
neuropathic causes of postsurgical pain isessential
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Kehlet H et al., Lancet. 2006 May 13;367:1618-25
Inflammatory vs. Neuropathic
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Rogers ML, Eur J Cardiothorac Surg 2002; 21: 298-301Benedetti F, Thorac Cardiovasc Surg 1998; 115: 841-847
Neuropathic Pain following Surgery
Signs of neurological damage, in the formof hypoesthesiamastectomy
hernia repair
mandibular osteotomy
Use of a rib retractor blocks intercostalnerve conduction by 50100% (EMG)degree of nerve damage correlates with
intensity of chronic pain
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Kehlet H et al., Lancet. 2006 May 13;367:1618-25
Neuronal Plasticity & Pain
2 kinds of plasticity:Reversible changes in the software of the
system, operates during inflammatory pain
After nerve injury, the hardware itself isaltered
no simple continuum from acute to
chronic pain that correlates with theduration or intensity of peripheral injury
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Neuropathic Pain Changes
Up regulation of 2 subunit of Ca2+ ChNeuroimmune sequelae pain sensitivityDegeneration of nerve cut end/infl. cells
Release of TNF- signaling moleculesMicroglia are activated in the spinal cord
Interruption of nerve contact with target
small unmyelinated neurons death (excitotoxic)inhibitory interneurons death
even cortical changes in gray mater
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PPPEtiologies
Ongoing InflammationNeuropathic Pain: surgical
injury to peripheral nerves
Drug seeking/psychogenic
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Kehlet H et al., Lancet. 2006 May 13;367:1618-25
PPP--Risk Factors
Nerve Injury
Genetic Susceptibility
Preceding Pain
Psychosocial Factors
Age & Sex
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Mikkelsen T et al., Anesth Analg. 2004 Jul;99(1):146-51Jaaskelainen SK et al., Neurology. 2004 Jun 8;62(11):1951-7
Nerve Injury
Seems to be necessary--in most cases
Most patients with post-surgical
nerve damage no painSevere nerve damage after mandibular
osteotomy neuropathic pain only in 10%
Nerve damage alone: Not sufficientfor the development of PPP
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Genetic Susceptibility
Inconsistent pain response likely heritableGeneration of painExperience of painResponse to analgesics
Rats: Susceptibility to neuropathic painClinical evidence
High COMT activity TMJ painMelanocortin-1 receptor gene (associated with
red hair/fair skin) greater female specific -opioid analgesia
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Preceding PainCorrelates with development of PPPSevere pre-amputation pain phantom
limb pain1
Intensity of acute post-operative paincorrelates with PPP followingBreast surgery2
Thoracotomy3
Inguinal herniorrhaphy4
1. Nikolajsen L et al., Lancet. 1997 Nov 8;350(9088):1353-72. Tasmuth T et al., Pain. 1996 Dec;68(2-3):343-7
3. Katz J et al., Clin J Pain. 1996 Mar;12(1):50-54. Callesen T et al., Br J Surg. 1999 Dec;86(12):1528-31
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Kehlet H et al., Lancet. 2006 May 13;367:1618-25
Psychosocial Factors
Modulators of the pain responseExpectation of post-op painFear of post-operative pain
Pre-operative anxietyPast memoriesSocial environment
WorkLevels of physical activityCatastrophizing
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Poobalan AS et al., Clin J Pain. 2003 Jan-Feb;19(1):48-54Katz J et al., Pain. 2005 Dec 15;119(1-3):16-25
Age & Sex
Older patients undergoingherniorrhaphy have a lower
risk for developing PPP thanyoung patients
Women have morepostoperative pain than men
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Kehlet H et al., Lancet. 2006 May 13;367:1618-25
Prevention Strategies
Surgical TechniqueAvoid intraoperative nerve injury
Careful dissection inflammatory responses
Use minimally invasive techniques
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Grant AM et al., Br J Surg. 2004 Dec;91(12):1570-4Macrae WA, Br J Anaesth. 2001 Jul;87(1):88-98
Prevention StrategiesSurgical Technique
HerniorrhaphyLaparoscopic technique can risk of nerve
damageLight weight mesh ~less inflammation
MastectomyPreservation of intercostal brachial nerve could
decrease chronic painIncreased use of sentinel lymph node biopsy
might ALNDThoracic SurgeryThoracoscopic techniques >> rib retractorsIntracostal suture / muscle sparing
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SNRIAntidepressants
NMDA blockers
Neurogenic soup
blockers
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