Pain Management in Orthopedic Surgery

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OTA Core Curriculum
June 2021
Joseph Borrelli, Jr., MD, MBA
Professor
Department of Orthopedic Surgery and Sports
Medicine
Morsani College of Medicine
University of South Florida, Tampa, FL
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Review 
pain
 pathways within the human body
Review means by which 
pain
 transmission is mitigated
Review variety of different classes of pain medications and
their mechanism of action
Review benefits and rationale for multi-modal pain relief
in orthopedic surgery
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Definition:
Unpleasant sensory and emotional experience associated with,
or resembling that associated with, actual or potential tissue
damage
   
International Association for the Study of Pain
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Difficult to define!!
Pain is a unique subjective experience of an
individual
Physiological protective system
Essential to warn, detect, and minimize contact with
damaging stimuli
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Dimensions of pain:
Sensory/discriminative
Intensity
Perception of sensory input
Quality, quantity and geographic area
Affective/motivational
Unpleasantness
Emotional/behavioral aspects of the pain experience
Cognitive/evaluative
Thoughts
How much pain an individual feels can depend upon past experiences
Modulation by central and peripheral nervous system can dampen or
augment pain perception
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Pain Threshold 
 the point at which any stimulus is felt as
pain
Similar pain threshold among healthy people
Remains the same in the same person over time
Adults have a higher pain threshold than children b/w 15-18 y/o
Aging increases the pain threshold and may be due to changes in
the skin thickness or the presence of peripheral neuropathies
Perceptual dominance 
 the increase in the pain threshold
at one point (part of the body) due to severe pain in another
point (part of body)
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Pain Tolerance 
 the intensity of pain that an individual will
tolerate before any visible responses
Varies amongst people and in the same person over time
Affected by cultural background, physical and mental health, expectations and
role behaviors
Tolerance is decreased with repeated pain, anger, fatigue, fear and sleep
deprivation
Tolerance is increased by drugs, alcohol consumption, distraction, hypnosis and
strong beliefs or faith
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Pain Classification
Nociceptive pain
Sensing of noxious stimuli
Protective role requiring immediate attention and responses
Inflammatory pain
Important to promote healing and protection of injured tissues.
Increases sensory sensitivity through pain hypersensitivity and tenderness.
Caused by activation of the immune system that causes inflammation after tissue injury
or infection
Pathological pain
Maladaptive response - results from abnormal functioning of the nervous system
Amplified sensory signals in the central nervous system
Fibromyalgia, irritable bowel syndrome, tension-type headache, temporomandibular joint disease
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Pain Classification
Acute pain
Caused by noxious stimuli and is mediated by nociception
Early onset and serves to prevent tissue damage
Chronic pain
Pain continuing beyond 3 months, or after healing is complete
May arise as a consequence of tissue damage or inflammation or have no
identified cause
Complex condition embracing physical, social and psychological factors
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4 major processes for pain to be perceived
1. Transduction – tissue damaging stimuli activate nociceptor
(pain receptor) nerve endings
2. Transmission – relay function carrying the impulse to the brain
regions
3. Modulation – neural process to reduce activity of the
transmission system
4. Perception – subjective awareness of the sensory signals
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Types of tissue damage perceived as stimuli
Thermal
Mechanical
Chemical
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Tissue injury releases potassium, serotonin, histamine, prostaglandins, substance P and
bradykinin from damaged vessels
These activate the sensory afferent nociceptor fibers which release prostaglandins which
sensitizes nociceptors and leads to primary hyperalgesia
Orthodromic transmission in sensitized afferents result in the release of substance P (sP)
in and around the site of injury. Substance P is responsible for further release of
bradykinin.
Substance P also stimulates release of histamine from mast cells and serotonin from
platelets, which in turn activates additional nociceptors and exacerbates the
inflammatory response.
Reflexes mediated by sympathetic efferents may sensitize nociceptors directly through
secretions of norepinephrine (NE), indirectly through further release of bradykinin and
prostaglandin, or by localized vasoconstriction.
Fields HL: Pain. New York: McGraw-Hill, 1987, p 36.
General Pain Pathway - Transmission
Nociceptors are the first order sensory pain fibers synapsing with the
secondary nerve fibers at the Dorsal Root ganglion
First order neuron has cell body in dorsal root ganglion and long axon to
periphery and short one to spinal column
A second order fibers transmit the impulse through the anterolateral
quadrant of the spinal cord to the brain stem, thalamus and somatosensory
cortex
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The dorsal horn is divided into discrete laminae based upon the
tendency of different types of afferent fibers to synapse at specific
laminae or depths.
Descending input from higher centers (higher spinal cord, midbrain,
and cerebral cortex) can modulate this transmission
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Pain Transmission
The 
delta fibers and C fibers 
 innervate both skin and internal organs,
including the periosteum, joints, viscera and muscles
Terminate as free peripheral nerve endings = nociceptors
Delta fibers are myelinated, typically transmit more quickly and give
sensation of immediate pain and are well localized
C fibers are unmyelinated, have a slower conduction velocity and could
be termed polymodal because a single C fiber may respond to a variety
of noxious stimuli and mediate the perception of “after pain”
These nociceptive afferent fibers synapse at the spinal cord dorsal horn,
where processing and modulation take place before further
transmission
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Sensitization
 – repeated stimuli threshold for afferent
nociceptors decrease  leading to lower pain threshold
Hyperactivity
 – Sympathetic Nervous System
Muscle contraction 
– a result of nociceptor activity as
primitive withdrawal effect
Self- sustaining Painful processes – Livingston “Vicious Circle
– painful processes set in motion secondary processes not
associated with tissue damage that cause a spread of the
nociceptive input leading to chronic pain
Neuropathic pain 
– pain from nerve damage e.g. causalgia
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Can occur by stimulation produced analgesia –
electrical stimulation from various brain regions can
block pain (midbrain to medulla)
Analgesia –
Endogenous opioid peptides in brain stem will suppress
pain (endorphins)
Exogenous opioids also act here
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Natural occurring OPIOID RECEPTORS
Mu 
 morphine receptors
Houde/Wallenstein 1956, Lasagna/Beecher 1954
Delta 
 based upon enkephalins
proposed by Kosterlitz (Lord et al. 1977)
Kappa 
 pharmacology of ketocyclazocine
Martin et al . 1976
Cannabinoid receptors in brain and spinal cord
Each of these receptors are G
1
 protein coupled receptors and
their activation leads to a reduction in neurotransmitter release
through inhibition of AC/cAMP  and cell hyperpolarization
reducing cell excitability
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Exogenous OPIOIDS
Morphine and its many derivative
Cannabinoids – modulates neurotransmiter release
Endogenous Opioid peptides
µ - opioids 
B-endorphins
Dynorphins
Enkephalins
Opioids regulate pain at spinal cord, brain stem, and cerebral cortex by
reducing neuro transmitter from first order neurons
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Natural Opioids 
 those derived from the poppy plant;
Parent compound = OPIUM
Morphine, codeine, thebaine
Semi-Synthetic and Synthetic Opioids
Create an altered chemical structure to have morphine like
analgesia with potential far greater potency but with decreased
the number and degree of untoward side effects
Respiratory depression, constipation, drowsiness, etc
 
Two types of non endogenous opioids
Synthetic Opioids 
 synthesized completely in the lab with a
natural opioid substrate;
Fentanyl, tramadol
 
 
 
 
 
 
 
 
 
 
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Semi-Synthetic Opioids 
 synthesized using chemical methods with
natural opiate 
as a substrate;
Heroin and hydromorphone (dilaudid)
Hydrocodone from codeine
Oxycodone from thebaine
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Hagedorn JC, Danilevich M, Gary JL. JAAOS, 2019;27:e831-e837.
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G protein-coupled receptors with opioids as ligands in brain
and spinal cord and peripheral neurons
Mu opioid receptors induce relaxation, trust and strong
analgesia
Kappa suppress mu-opioid effect while deltoid induce
impulsivity
The up and down regulation of the 3 receptors may account
for psychiatric disorder fluctuations
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Mu (µ)  - supraspinal and spinal analgesia; sedation; inhibition of
respiration; slowed GI transit; modulation of hormones and
neurotransmitter release; euphoria
Delta (𝛿) – supraspinal and spinal analgesia; modulation of
hormone and neuro transmitter release
Kappa (κ) - supraspinal and spinal psychomimetic effects; slowed
GI transit; dysphoria
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Naloxone (Narcan) 
 antagonist of MOR, KOR, and DOR
Competitor inhibitor of opioids, reverses opioids by
blocking MOR and preventing the euphoria associated
with opioids
Pure MOR antagonist
Buprenorphine 
 partial agonist, activates the opioid
receptors to a lesser degree than morphine, outcompetes
morphine for the MOR receptor causes decreased overall
opioid stimulus leading to a lower peak effect
NSAIDs 
 Block formation 
of thromoboxane 
and 
prostaglandins
 by
blocking Cox-1 and Cox-2 enzymes (cyclooxygenase-1)
By doing so 
NSAIDs mitigate surgical and traumatic pain by directly
blocking pain transmission and reducing local inflammation and
additional tissue damage –decreases the nociceptive stimulus
Celecoxib 
 only selective COX-2 inhibitor
Increased risk of thrombosis, stroke and heart attack
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Acetaminophen
Acts on COX-2 enzyme centrally with little anti-
inflammatory effect
May block COX-3 found in CNS
Activates the serotonergic pathways potentiating
pain modulation
Affects endogenous cannabinoid and vanilloid
system through AM404 to 
decrease pain
transmission
 and 
decrease body temperature
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(
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Narcotic
Codeine
 
Hydrocodone
   
Hydromorphone (Dilaudid)
Morphine
Oxycodone
Tramadol
Fentanyl transdermal 
(mcg/hr)
  
  
  
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0.15
  
1
  
4
  
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0.1
  
2.4
 
Gabapentinoids (gabapentin/pregabalin)
Analog of neurotransmitter (GABA)
Affects a voltage-gated calcium channel that reduces
neurotransmitter release and decreases post-synaptic
excitability and therefore decrease neuropathic pain
Predominant effect in the dorsal horn of spinal cord
Not capable of being sole modality for acute surgical pain
Controversial use to decrease pain in acute postoperative
setting
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Pain has many dimensions and so no single drug or technique is
sufficient to provide complete/near complete pain relief without side
effects
Therefore, drugs and techniques should be used in combination to
maximize the beneficial effects of combination therapy while minimizing
the side effects of an individual approach.
Multimodal analgesia is a combination of two or more analgesics with a
different mode of action, designed to improve analgesia and decrease
side effects through reduction in analgesic dose, particularly opioids.
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>80% 
of patients who undergo surgical procedures experience acute
postoperative pain,
~ 75% 
of those with postoperative pain report the severity as either
moderate, severe or extreme!
<50% 
of the patients who undergo surgery report adequate
postoperative pain relief,
Inadequately controlled pain negatively affects 
quality-of-life, function
and 
functional recovery,
 the 
risk of postsurgical complications
 and the
risks of persistent po
stsurgical pain,
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The 
American Pain Society (APS), 
with input from the
American Society of Anesthesiologists (ASA)
,
commissioned a guideline on management of
postoperative pain to promote evidence based, effective,
and safe postoperative pain management in adults
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The panel recommends that clinicians offer multi-modal analgesia, or the use of
a variety of analgesic medications and techniques combined with non-
pharmacological interventions for the treatment of postoperative pain in
children and adults, (strong recommendation, high quality evidence)
Multi-modal analgesia, defined as the use of a variety of analgesic medication
techniques that 
target different mechanisms of action 
in the peripheral and/or
central nervous system have an additive or synergistic effect and are more
effective pain relief compared with single drug interventions
Clinicians might offer local anesthetic base regional analgesic techniques,
systemic opioids and other analgesics
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If get opioid prescription within 7 days of surgery had 44% chance of
on long term opioids over those with no prescription
If started taking NSAIDs within 7 days of surgery were 4 times more
likely to become long term NSAID  users compared to those with
prescription
Alam A,  Arch intern Med 2012; 172(5): 425 - 430
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Selection of multi-modal therapies is a challenge because for each
surgical procedure, many potential multi-modal therapy combinations
are possible
When using multimodal analgesia, clinicians should be aware of the
different side effect profile for each analgesic medication or technique
used, and provide appropriate monitoring to identify and manage
adverse events,
Examples of Recommended multi-modal therapies:
Chou R, Gordon DB, de Leon-Casasola OA, et al. Guidelines on the Management of Postoperative Pain. The
Journal of Pain, Vol. 17, No. 2 (February) 2016: pp 131-157.
Multi – Modal for Common Orthopaedic Surgical Procedures
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From 11 randomized and quasi randomized trials with 1062 patients
showed the fascia iliaca compartment block was superior to opioids
for preoperative analgesia for hip fracture patients
High block success rate with few adverse effects
Faster the block is administered from the time of presentation the
less opioids consumed
Femoral nerve and Adductor canal nerve blocks are effective in knee
surgery
Adductor canal block will spare the quadriceps
J Pain Research 2017.10 2833-41
British Journal of Anaesthesia, 120 (6): 1368-1380 (2018) doi: 10.1016/j.bja.2017.12.042
JBJS 2020,00:1-7
Anesthesia, 2014; 120: 540 - 550
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Upper Extremity Block Coverage:  Complications
Systemic
Phrenic Nerve
Nerve Injury
Pneumothorax
Vascular puncture
Horner syndrome
Brachial plexus neuritis
CRPS
Bronchospasm (hiccups)
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Local Wound Infiltration (LIA) 
 infiltration of a large volume
dilute solution of a long-acting local anesthetic agent at the end
of surgery
Local analgesics blocks the ion-gated Na channels on the A-delta
and C-type nerves and therefore block nociceptive nerve
endings to produce analgesia
Pain relief usually lasts longer than the duration of the local
anesthetic and the anti-inflammatory effect of the local
anesthetic could be contributing factor for this prolonged effect,
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Infiltration carried out at the 
conclusion of surgery 
is more
effective than 
pre-incisional local wound infiltration
Local anesthetics possess antimicrobial properties and do not
influence wound healing,
Drugs commonly used for LIA - Lidocaine 0.5%, bupivacaine
0.25%, levobupivacaine, 0.25%, ropivacaine 0.2%
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15 member panel – expertise in  orthopedic
surgery and/or management
Literature review and panel review
Recommendations for acute pain for
musculoskeletal injury
Approved by the OTA October 16, 2018
Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019
Cognitive and Emotional Strategies
Discussion with patient of expected course and patient
experience
Pain greater than expected or depression, anxiety PTSD,
poor coping refer to psychosocial interventions
Anxiety reducing strategies to increase self efficacy like
aromatherapy, music therapy or cognitive behavior therapy
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Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019
Nociception and Pain
Nociception – physiology of actual or potential tissue damage
Pain – unpleasant thoughts emotions and behavior that
accompany nociception
Pain catastrophizing – ineffective coping strategy
No association between pain intensity and degree of
nociception
Pain intensity variation accounted for by psychological aspects
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Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019
Psychosocial Interventions
Improve overall mental health and decrease
depression, anxiety and PTSD
Cognitive behavior therapy, self management
interventions and training, peer support and online
social networking
Difficult for many to access
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Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019
Physical Strategies
TENS – adjunct, based on Gate Theory of pain, use
strong sub painful frequencies
Cryotherapy for acute and post op pain, variable
results, beware of nerve palsies
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Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019
Opioids Safety and Effectiveness
Use the lowest effective dose for shortest period
of time
No benzodiazepines with opioids
Avoid long acting opioids in acute pain
Prescribe precisely – no ranges of dose or time
Combine with NSAIDs make more effective
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Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019
Combination Pharmaceutical Strategies
Multimodal Analgesia
Recommended over monomodal opioid therapy
Periarticular local or regional anesthetic injections as
adjunct
NSAID effective for musculoskeletal pain with no clinical
evidence that fracture healing is effected
Tailored to patients injuries and comorbidities
Short term corticosteroids may be beneficial
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Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019
Patients on long term opioids
Recommends multimodal analgesia
Consultation with Acute Pain Service when patient on
medication assisted therapy (e.g. methadone)
Opioid tolerant patient must be identified early and
pain controlled (review section in reference below)
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Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019
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Opportunities exist to further improve pain management, with
increased 
effectiveness, longevity and safety
Nature and extent of surgery, anesthetic medications used,
routes of administration and anesthetic techniques are
important factors 
which determine the intensity of the post-op
pain
Therefore, to assure adequate control of postoperative pain
these factors should be taken into account when establishing
surgical pain treatment protocols
C
o
n
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l
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Multimodal Pain Management Regimens 
are strongly encouraged,
particularly following ORTHOPEDIC SURGERY, in order to maximize
effectiveness and safety, decrease complications and long term
addiction,
All patients should receive:
When possible, regional anesthesia +/- general
Round the clock regimen of NSAIDs, COXIBs, and/or acetaminophen,
Short term opioids or synthetic analgesics (Tramadol)
Adjuvants
Alpha-2 adrenergic agonist (clonidine, dexmedetomidine)
Gabapentin-type drugs (gabapentin, pregabalin)
Glucocorticoids (dexamethasone)
Local Infiltration Analgesia (LIA) 
 local wound infiltration
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https://www.ncbi.nlm.nih.gov/books/NBK219252/
Int J Mol Sci
. 2018 Aug; 19(8): 2164.
https://anesthesiaexperts.com/uncategorized/basic-review-pain-
pathways-analgesia/
International Association for the Study of Pain. IASP Terminology.
Available from: 
https://www.iasp-
pain.org/Education/Content.aspx?ItemNumber=1698
.
Woolf CJ. 
What is this thing called pain?.
 
The Journal of clinical
investigation
. 2010 Nov 1;120(11):3742-4.
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Pain management in orthopedic surgery involves reviewing pain pathways, mitigating pain transmission, understanding pain medications, and implementing multi-modal pain relief strategies. Pain is a complex and subjective experience with sensory, affective, emotional, and cognitive dimensions. Factors such as pain threshold and perceptual dominance play a role in pain perception and management.

  • Pain Management
  • Orthopedic Surgery
  • Pain Pathways
  • Pain Relief Strategies
  • Pain Perception

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  1. Narcotics and Pain Management Narcotics and Pain Management OTA Core Curriculum June 2021 Joseph Borrelli, Jr., MD, MBA Professor Department of Orthopedic Surgery and Sports Medicine Morsani College of Medicine University of South Florida, Tampa, FL Core Curriculum V5

  2. Objectives Objectives Review pain pathways within the human body Review means by which pain transmission is mitigated Review variety of different classes of pain medications and their mechanism of action Review benefits and rationale for multi-modal pain relief in orthopedic surgery Core Curriculum V5

  3. Introduction: Pain Introduction: Pain Definition: Unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage International Association for the Study of Pain Core Curriculum V5

  4. Introduction: Pain Introduction: Pain Difficult to define!! Pain is a unique subjective experience of an individual Physiological protective system Essential to warn, detect, and minimize contact with damaging stimuli Core Curriculum V5

  5. Introduction: Pain Introduction: Pain Dimensions of pain: Sensory/discriminative Intensity Perception of sensory input Quality, quantity and geographic area Affective/motivational Unpleasantness Emotional/behavioral aspects of the pain experience Cognitive/evaluative Thoughts How much pain an individual feels can depend upon past experiences Modulation by central and peripheral nervous system can dampen or augment pain perception Core Curriculum V5

  6. Introduction: Pain Introduction: Pain Pain Threshold the point at which any stimulus is felt as pain Similar pain threshold among healthy people Remains the same in the same person over time Adults have a higher pain threshold than children b/w 15-18 y/o Aging increases the pain threshold and may be due to changes in the skin thickness or the presence of peripheral neuropathies Perceptual dominance the increase in the pain threshold at one point (part of the body) due to severe pain in another point (part of body) Core Curriculum V5

  7. Introduction: Pain Introduction: Pain Pain Tolerance the intensity of pain that an individual will tolerate before any visible responses Varies amongst people and in the same person over time Affected by cultural background, physical and mental health, expectations and role behaviors Tolerance is decreased with repeated pain, anger, fatigue, fear and sleep deprivation Tolerance is increased by drugs, alcohol consumption, distraction, hypnosis and strong beliefs or faith Core Curriculum V5

  8. Introduction: Pain Introduction: Pain Pain Classification Nociceptive pain Sensing of noxious stimuli Protective role requiring immediate attention and responses Inflammatory pain Important to promote healing and protection of injured tissues. Increases sensory sensitivity through pain hypersensitivity and tenderness. Caused by activation of the immune system that causes inflammation after tissue injury or infection Pathological pain Maladaptive response - results from abnormal functioning of the nervous system Amplified sensory signals in the central nervous system Fibromyalgia, irritable bowel syndrome, tension-type headache, temporomandibular joint disease Core Curriculum V5

  9. Introduction: Pain Introduction: Pain Pain Classification Acute pain Caused by noxious stimuli and is mediated by nociception Early onset and serves to prevent tissue damage Chronic pain Pain continuing beyond 3 months, or after healing is complete May arise as a consequence of tissue damage or inflammation or have no identified cause Complex condition embracing physical, social and psychological factors Core Curriculum V5

  10. General Pain Pathway General Pain Pathway 4 major processes for pain to be perceived 1. Transduction tissue damaging stimuli activate nociceptor (pain receptor) nerve endings 2. Transmission relay function carrying the impulse to the brain regions 3. Modulation neural process to reduce activity of the transmission system 4. Perception subjective awareness of the sensory signals Core Curriculum V5

  11. General Pain Pathway General Pain Pathway Types of tissue damage perceived as stimuli Thermal Mechanical Chemical Core Curriculum V5

  12. General Pain Pathway General Pain Pathway - - Transduction Transduction Tissue injury releases potassium, serotonin, histamine, prostaglandins, substance P and bradykinin from damaged vessels These activate the sensory afferent nociceptor fibers which release prostaglandins which sensitizes nociceptors and leads to primary hyperalgesia Orthodromic transmission in sensitized afferents result in the release of substance P (sP) in and around the site of injury. Substance P is responsible for further release of bradykinin. Substance P also stimulates release of histamine from mast cells and serotonin from platelets, which in turn activates additional nociceptors and exacerbates the inflammatory response. Reflexes mediated by sympathetic efferents may sensitize nociceptors directly through secretions of norepinephrine (NE), indirectly through further release of bradykinin and prostaglandin, or by localized vasoconstriction. Fields HL: Pain. New York: McGraw-Hill, 1987, p 36. Core Curriculum V5

  13. General Pain Pathway - Transmission Nociceptors are the first order sensory pain fibers synapsing with the secondary nerve fibers at the Dorsal Root ganglion First order neuron has cell body in dorsal root ganglion and long axon to periphery and short one to spinal column A second order fibers transmit the impulse through the anterolateral quadrant of the spinal cord to the brain stem, thalamus and somatosensory cortex Core Curriculum V5

  14. General Pain Pathway General Pain Pathway - - Transmission Transmission The dorsal horn is divided into discrete laminae based upon the tendency of different types of afferent fibers to synapse at specific laminae or depths. Descending input from higher centers (higher spinal cord, midbrain, and cerebral cortex) can modulate this transmission Core Curriculum V5

  15. General Pain Pathway General Pain Pathway - - Transmission Transmission Pain Transmission The delta fibers and C fibers innervate both skin and internal organs, including the periosteum, joints, viscera and muscles Terminate as free peripheral nerve endings = nociceptors Delta fibers are myelinated, typically transmit more quickly and give sensation of immediate pain and are well localized C fibers are unmyelinated, have a slower conduction velocity and could be termed polymodal because a single C fiber may respond to a variety of noxious stimuli and mediate the perception of after pain These nociceptive afferent fibers synapse at the spinal cord dorsal horn, where processing and modulation take place before further transmission Core Curriculum V5

  16. Processes that Enhance Pain Processes that Enhance Pain Sensitization repeated stimuli threshold for afferent nociceptors decrease leading to lower pain threshold Hyperactivity Sympathetic Nervous System Muscle contraction a result of nociceptor activity as primitive withdrawal effect Self- sustaining Painful processes Livingston Vicious Circle painful processes set in motion secondary processes not associated with tissue damage that cause a spread of the nociceptive input leading to chronic pain Neuropathic pain pain from nerve damage e.g. causalgia Core Curriculum V5

  17. General Pain Pathway General Pain Pathway - - Modulation Modulation Can occur by stimulation produced analgesia electrical stimulation from various brain regions can block pain (midbrain to medulla) Analgesia Endogenous opioid peptides in brain stem will suppress pain (endorphins) Exogenous opioids also act here Core Curriculum V5

  18. General Pain Pathway General Pain Pathway - - Modulation Modulation Natural occurring OPIOID RECEPTORS Mu morphine receptors Houde/Wallenstein 1956, Lasagna/Beecher 1954 Delta based upon enkephalins proposed by Kosterlitz (Lord et al. 1977) Kappa pharmacology of ketocyclazocine Martin et al . 1976 Cannabinoid receptors in brain and spinal cord Each of these receptors are G1 protein coupled receptors and their activation leads to a reduction in neurotransmitter release through inhibition of AC/cAMP and cell hyperpolarization reducing cell excitability Core Curriculum V5

  19. Pain Mitigation Pain Mitigation Exogenous OPIOIDS Morphine and its many derivative Cannabinoids modulates neurotransmiter release Endogenous Opioid peptides - opioids B-endorphins Dynorphins Enkephalins Morphine C17H19NO3 Opioids regulate pain at spinal cord, brain stem, and cerebral cortex by reducing neuro transmitter from first order neurons Core Curriculum V5

  20. Pain Mitigation: Analgesic Classes: Pain Mitigation: Analgesic Classes: Non Non- -endogenous Opioids endogenous Opioids Two types of non endogenous opioids Natural Opioids those derived from the poppy plant; Parent compound = OPIUM Morphine, codeine, thebaine Semi-Synthetic and Synthetic Opioids Create an altered chemical structure to have morphine like analgesia with potential far greater potency but with decreased the number and degree of untoward side effects Respiratory depression, constipation, drowsiness, etc Core Curriculum V5

  21. Pain Mitigation: Analgesic Classes: Pain Mitigation: Analgesic Classes: Non Non- -endogenous Opioids endogenous Opioids Semi-Synthetic Opioids synthesized using chemical methods with natural opiate as a substrate; Heroin and hydromorphone (dilaudid) Hydrocodone from codeine Oxycodone from thebaine Synthetic Opioids synthesized completely in the lab with a natural opioid substrate; Fentanyl, tramadol Core Curriculum V5

  22. Pain Mitigation: Analgesic Classes: Pain Mitigation: Analgesic Classes: Non Non- -endogenous Opioids endogenous Opioids Opioid Type Characteristics Morphine natural Analgesic, metabolically active, neuroexcitable, metabolites can cause seizures Codeine Natural Metabolized by liver to morphine, 7% Caucasians cannot do this, no effect Hydrocodone Semisynthetic Metabolized to hydromorphone Oxycodone Semisynthetic Metabolized to oxymorphone, may effect potency of fluoxetine, atorvastatin, erythromycin Hydromorphone Semisynthetic Metabolically active. neuroexcitatory Fentanyl Synthetic Metabolized by liver, , may effect potency of fluoxetine, atorvastatin, erythromycin Tramadol Synthetic Metabolized to O-desmethyltramadol(M1), inhibits serotonin and norepinephrine reuptake to cause analgesia Hagedorn JC, Danilevich M, Gary JL. JAAOS, 2019;27:e831-e837. Core Curriculum V5

  23. Opioid Receptors Opioid Receptors G protein-coupled receptors with opioids as ligands in brain and spinal cord and peripheral neurons Mu opioid receptors induce relaxation, trust and strong analgesia Kappa suppress mu-opioid effect while deltoid induce impulsivity The up and down regulation of the 3 receptors may account for psychiatric disorder fluctuations Core Curriculum V5

  24. Opioid Receptors: Physiological Effects Opioid Receptors: Physiological Effects Mu ( ) - supraspinal and spinal analgesia; sedation; inhibition of respiration; slowed GI transit; modulation of hormones and neurotransmitter release; euphoria Delta (?) supraspinal and spinal analgesia; modulation of hormone and neuro transmitter release Kappa ( ) - supraspinal and spinal psychomimetic effects; slowed GI transit; dysphoria Core Curriculum V5

  25. Opioid Antagonist and Partial Agonists Opioid Antagonist and Partial Agonists Naloxone (Narcan) antagonist of MOR, KOR, and DOR Competitor inhibitor of opioids, reverses opioids by blocking MOR and preventing the euphoria associated with opioids Pure MOR antagonist Buprenorphine partial agonist, activates the opioid receptors to a lesser degree than morphine, outcompetes morphine for the MOR receptor causes decreased overall opioid stimulus leading to a lower peak effect Core Curriculum V5

  26. Pain Mitigation: Analgesic Classes: Pain Mitigation: Analgesic Classes: Non Non Opioids Medications Opioids Medications NSAIDs Block formation of thromoboxane and prostaglandins by blocking Cox-1 and Cox-2 enzymes (cyclooxygenase-1) By doing so NSAIDs mitigate surgical and traumatic pain by directly blocking pain transmission and reducing local inflammation and additional tissue damage decreases the nociceptive stimulus Celecoxib only selective COX-2 inhibitor Increased risk of thrombosis, stroke and heart attack Core Curriculum V5

  27. Pain Mitigation: Analgesic Classes: Pain Mitigation: Analgesic Classes: Non Non Opioids Medications Opioids Medications Acetaminophen Acts on COX-2 enzyme centrally with little anti- inflammatory effect May block COX-3 found in CNS Activates the serotonergic pathways potentiating pain modulation Affects endogenous cannabinoid and vanilloid system through AM404 to decrease pain transmission and decrease body temperature Core Curriculum V5

  28. Oral Morphine Equivalents (OME) Oral Morphine Equivalents (OME) Narcotic Codeine Hydrocodone Hydromorphone (Dilaudid) Morphine Oxycodone Tramadol Fentanyl transdermal (mcg/hr) OME 0.15 1 4 1 1.5 0.1 2.4 Core Curriculum V5

  29. Pain Mitigation: Analgesic Classes: Pain Mitigation: Analgesic Classes: Non Non- -endogenous Opioids endogenous Opioids Gabapentinoids (gabapentin/pregabalin) Analog of neurotransmitter (GABA) Affects a voltage-gated calcium channel that reduces neurotransmitter release and decreases post-synaptic excitability and therefore decrease neuropathic pain Predominant effect in the dorsal horn of spinal cord Not capable of being sole modality for acute surgical pain Controversial use to decrease pain in acute postoperative setting Core Curriculum V5

  30. Multi Multi- -Modal Pain Relief Modal Pain Relief Pain has many dimensions and so no single drug or technique is sufficient to provide complete/near complete pain relief without side effects Therefore, drugs and techniques should be used in combination to maximize the beneficial effects of combination therapy while minimizing the side effects of an individual approach. Multimodal analgesia is a combination of two or more analgesics with a different mode of action, designed to improve analgesia and decrease side effects through reduction in analgesic dose, particularly opioids. Core Curriculum V5

  31. American Pain Society Multi American Pain Society Multi- -Modal Pain Relief Modal Pain Relief >80% of patients who undergo surgical procedures experience acute postoperative pain, ~ 75% of those with postoperative pain report the severity as either moderate, severe or extreme! <50% of the patients who undergo surgery report adequate postoperative pain relief, Inadequately controlled pain negatively affects quality-of-life, function and functional recovery, the risk of postsurgical complications and the risks of persistent postsurgical pain, Core Curriculum V5

  32. American Pain Society Multi American Pain Society Multi- -Modal Pain Relief Modal Pain Relief The American Pain Society (APS), with input from the American Society of Anesthesiologists (ASA), commissioned a guideline on management of postoperative pain to promote evidence based, effective, and safe postoperative pain management in adults Core Curriculum V5

  33. American Pain Society Multi American Pain Society Multi- -Modal Pain Relief Modal Pain Relief The panel recommends that clinicians offer multi-modal analgesia, or the use of a variety of analgesic medications and techniques combined with non- pharmacological interventions for the treatment of postoperative pain in children and adults, (strong recommendation, high quality evidence) Multi-modal analgesia, defined as the use of a variety of analgesic medication techniques that target different mechanisms of action in the peripheral and/or central nervous system have an additive or synergistic effect and are more effective pain relief compared with single drug interventions Clinicians might offer local anesthetic base regional analgesic techniques, systemic opioids and other analgesics Core Curriculum V5

  34. Long term analgesic use after low risk surgery Long term analgesic use after low risk surgery If get opioid prescription within 7 days of surgery had 44% chance of on long term opioids over those with no prescription If started taking NSAIDs within 7 days of surgery were 4 times more likely to become long term NSAID users compared to those with prescription Alam A, Arch intern Med 2012; 172(5): 425 - 430 Core Curriculum V5

  35. American Pain Society Multi American Pain Society Multi- -Modal Pain Relief Modal Pain Relief Selection of multi-modal therapies is a challenge because for each surgical procedure, many potential multi-modal therapy combinations are possible When using multimodal analgesia, clinicians should be aware of the different side effect profile for each analgesic medication or technique used, and provide appropriate monitoring to identify and manage adverse events, Examples of Recommended multi-modal therapies: Chou R, Gordon DB, de Leon-Casasola OA, et al. Guidelines on the Management of Postoperative Pain. The Journal of Pain, Vol. 17, No. 2 (February) 2016: pp 131-157. Core Curriculum V5

  36. Multi Modal for Common Orthopaedic Surgical Procedures Type of Surgery Systemic Pharmacologic Local, Intraarticular Regional Neuraxial Anesthetic Nonpharmacologic Total hip Opioids, NSAIDs and or acetaminophen, gabapentin, pregabalin, i.v. ketamine Intra articular local and/or opioid Site specific with local Epidural with local with/or with opioid or intrathecal opioid Cognitive modalities, TENS Total Knee Opioids, NSAIDs and or acetaminophen, gabapentin, pregabalin, i.v. ketamine Intra articular local and/or opioid Site specific with local Epidural with local with/or with opioid or intrathecal opioid Cognitive modalities, TENS Spinal Fusion Opioids, NSAIDs and or acetaminophen, gabapentin, pregabalin, i.v. ketamine Intra articular local and/or opioid Epidural with local with/or with opioid or intrathecal opioid Cognitive modalities, TENS Core Curriculum V5

  37. Regional Anesthetic Techniques Regional Anesthetic Techniques From 11 randomized and quasi randomized trials with 1062 patients showed the fascia iliaca compartment block was superior to opioids for preoperative analgesia for hip fracture patients High block success rate with few adverse effects Faster the block is administered from the time of presentation the less opioids consumed Femoral nerve and Adductor canal nerve blocks are effective in knee surgery Adductor canal block will spare the quadriceps JBJS 2020,00:1-7 Anesthesia, 2014; 120: 540 - 550 J Pain Research 2017.10 2833-41 British Journal of Anaesthesia, 120 (6): 1368-1380 (2018) doi: 10.1016/j.bja.2017.12.042 Core Curriculum V5

  38. Regional Anesthetic Techniques Regional Anesthetic Techniques Upper Extremity Block Coverage: Complications Systemic Phrenic Nerve Nerve Injury Pneumothorax Vascular puncture Horner syndrome Brachial plexus neuritis CRPS Bronchospasm (hiccups) Core Curriculum V5

  39. Locoregional Analgesia for Post Locoregional Analgesia for Post- -op Pain op Pain Local Wound Infiltration (LIA) infiltration of a large volume dilute solution of a long-acting local anesthetic agent at the end of surgery Local analgesics blocks the ion-gated Na channels on the A-delta and C-type nerves and therefore block nociceptive nerve endings to produce analgesia Pain relief usually lasts longer than the duration of the local anesthetic and the anti-inflammatory effect of the local anesthetic could be contributing factor for this prolonged effect, Core Curriculum V5

  40. Locoregional Analgesia for Post Locoregional Analgesia for Post- -op Pain op Pain Infiltration carried out at the conclusion of surgery is more effective than pre-incisional local wound infiltration Local anesthetics possess antimicrobial properties and do not influence wound healing, Drugs commonly used for LIA - Lidocaine 0.5%, bupivacaine 0.25%, levobupivacaine, 0.25%, ropivacaine 0.2% Core Curriculum V5

  41. Best Practice for Acute Pain Management Best Practice for Acute Pain Management 15 member panel expertise in orthopedic surgery and/or management Literature review and panel review Recommendations for acute pain for musculoskeletal injury Approved by the OTA October 16, 2018 Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019 Core Curriculum V5

  42. Best Practice for Acute Pain Management Best Practice for Acute Pain Management Cognitive and Emotional Strategies Discussion with patient of expected course and patient experience Pain greater than expected or depression, anxiety PTSD, poor coping refer to psychosocial interventions Anxiety reducing strategies to increase self efficacy like aromatherapy, music therapy or cognitive behavior therapy Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019 Core Curriculum V5

  43. Best Practice for Acute Pain Management Best Practice for Acute Pain Management Nociception and Pain Nociception physiology of actual or potential tissue damage Pain unpleasant thoughts emotions and behavior that accompany nociception Pain catastrophizing ineffective coping strategy No association between pain intensity and degree of nociception Pain intensity variation accounted for by psychological aspects Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019 Core Curriculum V5

  44. Best Practice for Acute Pain Management Best Practice for Acute Pain Management Psychosocial Interventions Improve overall mental health and decrease depression, anxiety and PTSD Cognitive behavior therapy, self management interventions and training, peer support and online social networking Difficult for many to access Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019 Core Curriculum V5

  45. Best Practice for Acute Pain Management Best Practice for Acute Pain Management Physical Strategies TENS adjunct, based on Gate Theory of pain, use strong sub painful frequencies Cryotherapy for acute and post op pain, variable results, beware of nerve palsies Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019 Core Curriculum V5

  46. Best Practice for Acute Pain Management Best Practice for Acute Pain Management Opioids Safety and Effectiveness Use the lowest effective dose for shortest period of time No benzodiazepines with opioids Avoid long acting opioids in acute pain Prescribe precisely no ranges of dose or time Combine with NSAIDs make more effective Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019 Core Curriculum V5

  47. Best Practice for Acute Pain Management Best Practice for Acute Pain Management Combination Pharmaceutical Strategies Multimodal Analgesia Recommended over monomodal opioid therapy Periarticular local or regional anesthetic injections as adjunct NSAID effective for musculoskeletal pain with no clinical evidence that fracture healing is effected Tailored to patients injuries and comorbidities Short term corticosteroids may be beneficial Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019 Core Curriculum V5

  48. Best Practice for Acute Pain Management Best Practice for Acute Pain Management Patients on long term opioids Recommends multimodal analgesia Consultation with Acute Pain Service when patient on medication assisted therapy (e.g. methadone) Opioid tolerant patient must be identified early and pain controlled (review section in reference below) Hsu J. Mir Hassan, Wally Megan et al, J Orthop Trauma Volume 33, Number 5, May 2019 Core Curriculum V5

  49. Conclusions Conclusions Opportunities exist to further improve pain management, with increased effectiveness, longevity and safety Nature and extent of surgery, anesthetic medications used, routes of administration and anesthetic techniques are important factors which determine the intensity of the post-op pain Therefore, to assure adequate control of postoperative pain these factors should be taken into account when establishing surgical pain treatment protocols Core Curriculum V5

  50. Conclusions Conclusions Multimodal Pain Management Regimens are strongly encouraged, particularly following ORTHOPEDIC SURGERY, in order to maximize effectiveness and safety, decrease complications and long term addiction, All patients should receive: When possible, regional anesthesia +/- general Round the clock regimen of NSAIDs, COXIBs, and/or acetaminophen, Short term opioids or synthetic analgesics (Tramadol) Adjuvants Alpha-2 adrenergic agonist (clonidine, dexmedetomidine) Gabapentin-type drugs (gabapentin, pregabalin) Glucocorticoids (dexamethasone) Local Infiltration Analgesia (LIA) local wound infiltration Core Curriculum V5

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