PAIN AND SHOULDER
Transcript of PAIN AND SHOULDER
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PAIN AND SHOULDER
OCTOBER 27, 2020 | 5:00–6:00 P.M. ET
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KOJI AOKI
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Effects of Shoulder Distraction on Canine Shoulder
Arthroscopy
Koji Aoki, Jun-Yan Sek, Fernando Freitas, Miriam Bates
Presenter: Koji Aoki, BVSc, MVS, DACVS-SA
University of Saskatchewan
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Disclosure
• No conflict of interest to this study
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Background
• Iatrogenic articular cartilage injury (IACI) associated with arthroscopy is common
• IACI in human literatures• 31% IACI in ankle arthroscopy
• J. Vega, 2016
• 77.6 % IACI in knee arthroscopy• J. Compton, 2020
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Background
• Use of joint distractor in Vet Med• Decrease IACI and increase procedural success rate
• Canine stifle and hip
• K. Kim, 2016, J, Kim 2019
P. BOTTCHER, 2009
Leipzig Distractor
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Background
• Use of joint distractor in Vet Med• Decrease IACI and increase procedural success rate
• Canine stifle and hip
• K. Kim, 2016, J, Kim 2019
• No study • Effect of shoulder joint distraction on arthroscopy
P. BOTTCHER, 2009
Leipzig Distractor
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Objective
• To evaluate the effect of shoulder distraction using a Leipzig distractor on
• IACI
• Surgery time
• Visibility and palpability of intra-articular structure
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Hypothesis
• Shoulder (Leipzig) distraction device would
• Decrease IACI
• Decrease surgery time
• Improve visibility and palpability of the intra-articular structures
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Outline
1. Ex vivo – cadaveric study
2. Clinical case series
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1. Cadaveric Study
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Material and Methods
• 30 shoulder joints • From 15 large breed canine cadavers
• Body weight 20.7 kg to 42.7 kg (mean 31.3 kg)
• Euthanized unrelated to this study
• Body in -20 °C and thawed to room temperature (22 °C)
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Material and Methods
• Non-distraction group (n = 15)• Standard lateral shoulder arthroscopy
• Camera port establishment• Distal to the acromion process• 18g needle• 10 ml of saline infusion • A 2.7mm arthroscope
• An egress port • 18g needle
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Material and Methods
• Non-distraction group (n = 15)• Standard lateral shoulder arthroscopy
• Camera port establishment• Distal to the acromion process• 18g needle• 10 ml of saline infusion • A 2.7mm arthroscope
• An egress port • 18g needle
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Material and Methods
• Non-distraction group (n = 15)• Standard lateral shoulder arthroscopy
• Instrument port • 18g spinal needle
• 2.7 mm blunt obturator
• 3.4-mm hook tipped probe
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Material and Methods
• Distraction group (n = 15)
• Leipzig distractor placement • Prior to establishing ports
• 2.4 mm positive threaded half pin
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B
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Material and Methods
• Distraction group (n = 15)
• Leipzig distractor placement • Prior to establishing ports
• Camera and egress ports• Same as non-distraction group
• No distraction performed
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Material and Methods
• Distraction group (n = 15)
• Joint distraction • Visualizing medial collateral ligament
• To prevent excessive distraction
Medial glenohumeral ligament
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Material and Methods
• Distraction group (n = 15)
• Joint distraction
• Instrument port • Same as non-distraction group
• 18g spinal needle
• 2.7 mm blunt obturator
• 3.4-mm hook tipped probe
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Material and Methods
• Joint space• Measured on captured digital arthroscopic images
• Using a 3.4-mm hook tipped probe at the middle of medial glenohumeral ligament
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Material and Methods
• Visibility and palpability of intra-articular structures • Using a 3.4-mm hook tipped probe
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Medial glenohumeral ligament
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Medial glenohumeral ligament Subscapularis
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Medial glenohumeral ligament Subscapularis Glenoid
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Medial glenohumeral ligament Subscapularis Glenoid Supraglenoid Tubercle
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Medial glenohumeral ligament Subscapularis Glenoid Supraglenoid Tubercle
Biceps
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Medial glenohumeral ligament Subscapularis Glenoid Supraglenoid Tubercle
Biceps Caudal Humeral head
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Medial glenohumeral ligament Subscapularis Glenoid Supraglenoid Tubercle
Biceps Caudal Humeral head Caudal synovial pouch
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Visibility Score
Score 1 The structure is not visible
Score 2 The structure is partially visible
Score 3 The entire structure is visible
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Visibility Score
Score 1 The structure is not visible
Score 2 The structure is partially visible
Score 3 The entire structure is visible
Palpability Score
Score 1 The structure is not palpable
Score 2 The structure is partially palpable OR the entire structure is palpable only with limited angle
Score 3 The entire structure is palpable without restriction in motion
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Material and Methods
• Procedural duration • From the beginning of the instrument port establishment
Needle time Probe Time Palpation Time
Total Surgery Time
Visualizing and palpating Intra-articular structures
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Material and Methods
• Assessment of IACI • Dissection and disarticulation
• Humeral head and glenoid stained with Indian black
• Measurement of IACI area and number
Humeral head Glenoid
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Material and Methods
• Dissection around pin holes• For unexpected bony lesions
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Statistics
• Paired t test for normally distributed data• Mean ± SD
• Wilcoxon signed-rank tests for not normally distributed data• Median (interquartile range, IQR)
• Shapiro-Wilk test for normality
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Results
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Joint space
Joint space (IQR) 4 mm ( 1 mm) 8 mm (1.5 mm)
P value P = 0.01
Non-distraction Distraction
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Outcome Non distraction Distraction P value
Needle time 55 (110) sec 38 (43) sec = 0.39
Probe time 215 ± 112 sec 159 ± 82 sec = 0.15
Needle time Probe Time Palpation Time
Total Surgery Time
Visualizing and palpating Intra-articular structures
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Outcome Non distraction Distraction P value
Needle time 55 (110) sec 38 (43) sec = 0.39
Probe time 215 ± 112 sec 159 ± 82 sec = 0.15
Palpation time 138 (87) 66 (38) = 0.03*
Total surgery time 335 ± 147 sec 242 ± 88 sec = 0.01*
Needle time Probe Time Palpation Time
Total Surgery Time
Visualizing and palpating Intra-articular structures
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IACI
Outcome Non distraction Distraction P value
IACI glenoid 3 (7.5) mm2 0 (2.3) mm2 = 0.10
IACI head 11.5 (11.8) mm2 0 (2.5) mm2 = 0.004*
IACI total number 3 (3.5) 1.5 (1) = 0.004*
IACI
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Visibility and Palpability
• No significant difference for visibility or palpability scores for the intra-articular structures
• Higher visibility score of the supraglenoid tubercle in distraction group (P = 0.015)
Supraglenoid Tubercle
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Results
• Leipzig distractor• 132 ± 46 seconds for placement
• No complications during the procedure
• After the procedure • No loosening of the pins
• No fracture around the pin holes
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2. Clinical Case Series
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Clinical Case Series
• Distracted shoulder arthroscopy in clinical cases • 9 shoulder joints with shoulder OCDs
• From 5 dogs
• Age• 8 month to 17 month year old
• Body Weight• 17 – 42 kg
• Recorded perioperative complications
• Minimal follow up of 6 weeks• At WCVM, rDVM, phone interview,
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Clinical Case Series
• Results• Joint space increased with distraction
• Distraction device interfered visibility of caudal pouch (n=1/9)
• No perioperative complications associated with shoulder distraction
• No complications with follow up • Median 8 weeks (6-8 weeks)
Before distraction After
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Discussion
• Distraction provided larger working joint space • Decreased IACI with distracted shoulders
• Decreased joint exploration (palpation) time
• No difference in visibility or palpability of structures• Besides supra-glenoid tubercle visibility
• Most of the structures were thoroughly visible and palpable • Without distraction
• Resulting in no significant difference between the groups
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Discussion
• No obvious complications associated with the distractor• In vivo and ex vivo
• One clinical case experienced interference between the distractor and arthroscope
• Leipzig distractor needs to be placed cranio-lateral position than lateral
• OCD lesions were easy to manage in clinical cases • On subjective assessment
• No need for limb manipulation
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Limitation
• Depth of the IACI not measured• Required histopathology
• Performed by a single ACVS surgeon
• Limb manipulation not performed in non-distraction group• Manipulation could improve the procedural speed
• Small sample size and no controls in the clinical case series
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Conclusion
• Distractor decreased the area and incidence of IACI and shortened the arthroscopic time
• No major complications observed
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Questions?
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ALEXANDRA KALAMARAS
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Development and Assessment of
Neuropathic Pain in Dogs after TPLO for
Cranial Cruciate Ligament Rupture
Alexandra Kalamaras, DVM, MS
ACVS 2020/2021 Webinar Series
The Ohio State University
Columbus, Ohio
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Disclosure
• I hereby certify that, to the best of my knowledge, no aspect of
my current personal or professional situation might reasonably
be expected to significantly affect my views on the subject on
which I am presenting
• Funding provided by The Ohio State Canine Grant
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Outline
Background
• Neuropathic Pain & Assessment
• Neuropathic Pain in Orthopedic Conditions1
Experimental Design2
Results3
Discussion
• Limitations4
Conclusions
• Clinical Relevance5
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Background
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Pain
• Definitions
• Pain: unpleasant sensory and emotional experience associated with actual or potential tissue damage
• Nociception: neural process of encoding noxious stimuli
• Analgesia: absence of pain in response to stimulus normally painful
• Hyperalgesia: abnormally increased sensitivity to a painful stimulus
• Allodynia: normally non-painful stimulus experienced as painful
• Hyperesthesia: non-noxious stimulus results in exaggerated and painful response
Tranquilli & Grimm 2015; Lorenz et al. 2011
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Pain
Wiese & Yaksh 2015
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Pain
• Nociceptive vs. Neuropathic
• Nociceptive → normal functioning somatosensory system
• Neuropathic → dysfunction somewhere along the pain pathway
• International Association for the Study of Pain (IASP)
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Neuropathic Pain
• Definition in people:
• Pain that arises as direct consequence of lesion or disease
affecting the somatosensory system (Treede et al. 2008)
• Effects 1 in 10 adults over 30 (Yawn et al. 2010)
• Healthcare costs ~ $100 billion per year
• Huge impact on quality of life (IASP 2014)
• IASP Global Year Against Neuropathic Pain
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Neuropathic Pain
• Underexplored in veterinary patients
• Somatosensory nervous system malfunction
• Peripheral Sensitization
• Central Sensitization
• Chronic neurologic or orthopedic injury
• Hallmarks → allodynia, hyperalgesia, and hyperesthesia
• LOWER threshold to detect a painful stimulus
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Neuropathic Pain
Sensory Threshold (ST)
Minimum amount of stimulus that can be detected or is considered painful
(Kerns et al. 2019)
Mechanical ST
Strength of mechanical stimulus → conscious behavioral response
(Moore et al. 2013, Kerns et al. 2019)
Thermal ST
Hot/cold thermal stimulus →conscious behavioral response
(Freire et al. 2016, Knazovicky et al. 2016, Knazovicky et al. 2017)
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Neuropathic Pain Assessment
• Von Frey Anesthesiometry (VFA)
• Quantitative evaluation of ST – evaluated in dogs
• Normal (Freire et al. 2016; Kerns et al. 2019)
• Neurologic disease (Moore et al. 2013; Song et al. 2016; Thoefner et al. 2019)
• Osteoarthritis (Freire et al. 2016; Knazovicky et al. 2016; Knozovicky et al. 2017)
Neuropathic Pain
Hyperesthesia & Hyperalgesia
Lower ST
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Electronic Von Frey Device
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Neuropathic Pain Assessment
• Moderate interobserver agreement (Kerns et al. 2019)
• Neurologic injury and/or disease• Higher ST - acute spinal cord injury (Moore et al. 2013)
• Differences in ST – normal vs. spinal cord injury (Song et al. 2016)
• No difference in ST – normal vs. syringomyelia (Thoefner et al. 2019)
• Osteoarthritis (OA) and degenerative joint disease (DJD)• No difference in ST - normal vs. DJD (Freire et al. 2016)
• Lower ST – osteoarthritis (Knazovicky et al. 2016)
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Objectives
1. Assess ST in dogs before and after TPLO surgery in order to
evaluate for the development of neuropathic pain
2. Identify differences (if any) in ST among three different peri-
operative analgesic protocols for TPLO surgery in dogs
• Intravenous opioids
• Lumbosacral epidural
• Peripheral nerve blockade
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Hypothesis
ST values 8 weeks postoperative would be lower in dogs
receiving only perioperative opioid administration, indicative of a
neuropathic pain state
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Experimental Design
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Study Design
• Approved by Institutional Animal Care and Use Committee
(IACUC) of The Ohio State University
• Prospective double-blinded clinical trial
• Client owned dogs with CCLR enrolled (n = 45)
• Between May 2018 and August 2019
• Procedure:
• Stifle arthroscopy
• TPLO
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Patient Selection
• Preoperative diagnostics:
• Orthopedic and neurologic exams
• Orthopedic radiographs
• Complete blood count
• Serum biochemistry
• Urinalysis
Arthurs 2011
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Patient Selection
Inclusion Criteria
• Diagnosed with CCLR
• Weight > 15 kg and < 60 kg
• Preoperative TPA 20º – 34º
• Temperament amenable to
handling and hospitalization
• Owner consent to 2 week and 8
week recheck visits at The OSU
Main Campus location
Exclusion Criteria
• Neurologic, systemic, or other
orthopedic disease
• Tramadol or steroids (30 days)
• Prior orthopedic surgery on
affected limb
• Conversion to arthrotomy
• Fibular fracture or implant failure
• Complication → revision surgery
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Treatment Groups
• Three treatment groups (random assignment)
• Group 1 (MLK): n = 15
• Intravenous infusion of morphine, lidocaine & ketamine
• Group 2 (EPID): n = 15
• Lumbosacral ropivacaine & morphine epidural
• Group 3 (SSNB): n = 15
• Saphenous & sciatic nerve blockade with ropivacaine
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Treatments
• Premedication:
• Acepromazine 0.05 mg/kg IM
• Morphine 0.2 mg/kg IM
• General anesthesia induction:
• Propofol 4 mg/kg IV to effect
• General anesthesia maintenance:
• Isoflurane in oxygen
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Treatments
• Group 1 (MLK)
• Morphine 0.1 mg/kg/hr IV CRI
• Lidocaine 3 mg/kg/hr IV CRI
• After initial 2 mg/kg IV bolus
• Ketamine 0.6 mg/kg/hr IV CRI
• Medications in IV fluids
• Fluid bags labeled with patient #:
• (ex) Study Pt. #1
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Treatments
• Group 2 (EPID)
• 1% ropivacaine 0.2 mg/kg
• Preservative-free morphine 0.09 mg/kg
• Lumbosacral epidural
• Every patient shaved for epidural
• Board-certified anesthesiologist
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Treatments
• Group 3 (SSNB)
• 1% ropivacaine 2 mg/kg (each site)
• Ultrasound-guided nerve blocks
using a nerve stimulator:
• Saphenous nerve
• Sciatic nerve
• Board-certified anesthesiologistPortela, Verdier, & Otero 2018
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Surgery
• Stifle arthroscopy
• Medial meniscal tear(s) → treated
arthroscopically
• Intact medial meniscus → left intact
• Routine TPLO surgery
• Performed by board-certified surgeon
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Von Frey Anesthesiometry
• Evaluations:
• Preoperative
• 1 day, 2 weeks, & 8 weeks
postoperative
• 5 measurements from each
hind paw
• Highest and lowest discarded
• Average of middle 3 values
Moore et al. 2013
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Temporospatial Gait Analysis
• Evaluations:
• Preoperative
• 1 day, 2 weeks, & 8 weeks
postoperative
• Tekscan™ Animal Walkway
System
• Data from 5 best trials
• Velocity ≥ 0.8 and ≤ 1.3 m/sec
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Statistics
• Demographic data
• ANOVA models
• Categorical data
• Mixed effect models testing treatment effect on primary outcomes
• Kenward-Roger adjustment to degrees of freedom
• Control type I error rates
• Continuous data
• T-tests (2 variables) or ANOVA (> 2 variables)
• Two-sided significance of p<0.05
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Results
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CharacteristicTreatment 1
(n = 15) (MLK)
Treatment 2
(n = 15) (EPID)
Treatment 3
(n = 15) (SSNB)P-value
Weight (kg)
(mean SD)37.28 9.57 34.25 8.09 30.12 8.89 0.0975
Age (years)
(mean SD)4.93 2.15 5.2 2.57 5.33 3.24 0.9180
Sex
Female Intact
Female Spay
Male Neutered
Male Intact
0
7
8
0
2
5
7
1
0
8
7
0
0.5121
Surgical Limb
Left
Right
9
6
8
7
9
60.9999
Completeness of Tear
Full
Partial
11
4
9
6
13
2
0.3156
Current Bilateral CCLR
Yes
No
4
11
3
12
4
110.9999
Meniscal Status
Intact
Torn
7
8
9
6
9
60.8039
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Results
• Sensory Threshold
• Lower for surgical limb
(p < 0.0001)
• No difference among
treatment groups250
300
350
400
450
500
550
Preop Postop 2 Weeks 8 Weeks
Sensory Threshold (Average)
Epidural + Other Epidural + Surgical
Saphenous Sciatic + Other Saphenous Sciatic + Surgical
MLK + Other MLK + Surgical
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Results
• No difference among treatment groups
• Anesthesia duration (p = 0.8140)
• Temporospatial gait analysis
• Surgery duration not affected by surgeon (p = 0.8350)
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Discussion
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Discussion
Hypothesis rejected:
• No difference in ST among treatment groups
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Discussion
• ST lower in surgical limb
• Expected finding
• No difference in ST among treatment groups
• Even when ST scaled to body weight
• Discussed by Moore et al. 2013
• OA associated with lower ST (Knazovicky et al. 2016)
• Current study did not evaluate severity of OA
• May have missed an essential variable with regards to ST
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Limitations
• Low number of patients
• Type I error
• ST Data
• 8 weeks may not be enough time for neuropathic pain development
• No assessment of osteoarthritis (radiographically)
• Variability between surgeons or anesthesiologists
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Conclusion
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Conclusion
• No significant change in sensory threshold over time
• Unable to show a difference in neuropathic pain state development
• Sensory threshold values consistently lower in surgical limb
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Acknowledgements
• Nina R. Kieves, DVM, DACVS-SA, DACVSMR, CCRT
• Sarah Moore, DVM, DACVIM (Neurology)
• Turi Aarnes, DVM, MS, DACVAA
• Carolina Ricco Pereira, DVM, MS, DACVAA
• Stephen C. Jones, MVB, MS, DACVS-SA
• James Howard, DVM, MS, DACVS-SA
• Juan Peng, MAS
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Thank You!
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References
• Aguado D, Benito J, Gomez de Segura IA (2011) Reduction of the minimum alveolar concentration of isoflurane in dogs using a constant rate of infusion of lidocaine-ketamine in combination with either morphine or fentanyl. Vet J 189, 63-66.
• Bartel AKG, Campoy L, Martin-Flores M et al. (2016) Comparison of bupivacaine and dexmedetomidine femoral and sciatic nerve blocks with bupivacaine and buprenorphine epidural injection for stifle arthroplasty in dogs. Vet AnesthAnalg 43, 435-443.
• Boscan P, Wennogle S (2016) Evaluating femoral-sciatic nerve blocks, epidural analgesia, and no use of regional analgesia in dogs undergoing tibia-plateau leveling-osteotomy. J Am Anim Hosp Assoc 52, 102-108.
• Campoy L, Martin-Flores M, Ludders JW et al. (2012) Comparison of bupivacaine femoral and sciatic nerve block versus bupivacaine and morphine epidural for stifle surgery in dogs. Vet Anaesth Analg 39, 91-98.
• Caniglia AM, Driessen B, Pureto DA et al. (2012) Intraoperative antinociception and postoperative analgesia following epidural anesthesia versus femoral and sciatic nerve blockade in dogs undergoing stifle joint surgery. J Am Vet Med Assoc 241, 1605-1612.
• Conzemius MG, Hill CM, Sammarco JL et al. (1997) Correlation between subjective and objective measures used to determine severity of postoperative pain in dogs. J Am Vet Med Assoc 210, 1619-1622.
• Drygas KA, McClure SR, Goring RL et al. (2011) Effect of cold compression therapy on postoperative pain, swelling, range of motion, and lameness after tibial plateau leveling osteotomy in dogs. J Am Vet Med Assoc 238, 1284-1291.
• Duerr FM, Martin KW, Rishniw M et al. (2014) Treatment of canine cranial cruciate ligament disease. Vet Comp OrthopTraumatol 27, 478-483.
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References
• Ebner LS, Lerche P, Bednarski RM et al. (2013) Effect of dexmedetomidine, morphine-lidocaine-ketamine, and dexmedetomidine-morphine-lidocaine-ketamine constant rate infusions on the minimum alveolar concentration of isoflurane and bispectral index in dogs. Am J Vet Res 74, 963-970.
• Gurney MA, Leece EA (2014) Analgesia for pelvic limb surgery. A review of peripheral nerve blocks and the extradural technique. Vet Anaesth Analg 41, 445-458.
• Hoelzler MB, Harvey RC, Lidbetter DA et al. (2005) Comparison of perioperative analgesic protocols of dogs undergoing tibial plateau leveling osteotomy. Vet Surg 34, 337-344.
• Hofmeister EH, Chandler MJ, Read MR (2010) Effects of acepromazine, hydromorphone, or acepromazine-hydromorphone combination on the degree of sedation in clinically normal dogs. J Am Vet Med Assoc 237, 1155-1159.
• Hofmeister EH, Egger CM (2005) Evaluation of diphenhydramine as a sedative for dogs. J Am Vet Med Assoc 226, 1092-1094.
• Holton LL, Scott EM, Nolan AM et al (1998) Comparison of three methods used for assessment of pain in dogs. J Am Vet Med Assoc 212, 61-66
• Jones RS (2001) Epidural analgesia in the dog and cat. Vet J 161, 123-131.
• Knazovicky D, Helgeson ES, Case B et al. (2016) Widespread somatosensory sensitivity in naturally occurring canine model of osteoarthritis. Pain 157, 1325-1332.
• KuKanich B, Wiese AJ (2015) Opioids. Chapter in Veterinary Anesthesia and Analgesia (5th edition)
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References
• Lewis KA, Bednarski RM, Aarnes TK et al. (2014) Postoperative comparison of four perioperative analgesia protocols in dogs undergoing stifle joint surgery. J Am Vet Med Assoc 244, 1041-1046.
• Lorenz M, Coates J, Kent M (2011) Pain. Chapter in Handbook of Veterinary Neurology (5th edition)
• McCally RE, Bukoski A, Branson KR et al. (2015) Comparison of short-term postoperative analgesia by epidural, femoral nerve block, or combination femoral and sciatic nerve block in dogs undergoing tibial plateau leveling osteotomy. Vet Surg 44, 983-987.
• Mich PM, Hellyer PW, Kogan L et al. (2010) Effects of a pilot training program on veterinary students’ pain knowledge, attitude, and assessment skills. J Vet Med Educ 37, 358-368.
• Muir III WW, Wiese AJ, March PA et al. (2003) Effects of morphine, lidocaine, ketamine, and morphine-lidocaine-ketamine drug combination on minimum alveolar concentration in dogs anesthetized with isoflurane. Am J Vet Res 64, 1155-1160.
• Murrell JC, Psatha EP, Scott EM et al. (2008) Application of a modified form of the Glasgow pain scale in a veterinary teaching centre in the Netherlands. Vet Rec 162, 403-408.
• Palomba N, Vettorato E, De Gennaro C et al. (2019) Peripheral nerve block versus systemic analgesia in dogs undergoing tibial plateau levelling osteotomy: Analgesic efficacy and pharmacoeconomics comparison. Vet AnaesthAnalg, 47, 119-128.
• Portela DA, Verdier N, Otero PE (2018) Regional anesthetic techniques for the pelvic limb and abdominal wall in small animals: A review of the literature and technique description. Vet J 238, 27-40.
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References
• Reid J, Nolan AM, Hughes JML et al. (2007) Development of the short-form Glasgow Composite Measure Pain Scale (CMPS-SF) and derivation of an analgesic intervention score. Anim Welf 16, 97-104.
• Smith LJ, Yu JKA, Bjorling ED et al. (2001) Effects of hydromorphone or oxymorphone, with or without acepromazine, on preanesthetic sedation, physiologic values, and histamine release in dogs. J Am Vet Med Assoc 218, 1101-1105.
• Tomas A, Bledsoe D, Wall S et al. (2015) Initial evaluation of a canine stifle arthrotomy post-operative pain model. Vet J 204, 293-298.
• Tranquilli WJ, Grimm KA (2015) Introduction: Use, definitions, history, concepts, classification, and considerations for anesthesia and analgesia. Veterinary Anesthesia and Analgesia (5th edition)
• Treede RD, Jensen TS, Campbell JN (2008) Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neuro 70, 1630-1635.
• Wagner MC, Hecker KG, Pang DSJ (2017) Sedation levels in dogs: a validation study. BMC Vet Res 13, 110.
• Wendlund TM, Martin KW, Duncan CG et al. (2016) Evaluation of pacing as an indicator of musculoskeletal pathology in dogs. J Vet Med Anim Health 8, 207–213.
• Wiese AJ, Yaksh TL (2015) Nociception and Pain Mechanisms. Chapter in Handbook of Veterinary Pain Management (3rd edition)
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ALEXANDRA KALAMARAS
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Effect of Analgesic Protocols on
Postoperative Pain in Dogs after TPLO
for Cranial Cruciate Ligament Rupture
Alexandra Kalamaras, DVM, MS
ACVS 2020/2021 Webinar Series
The Ohio State University
Columbus, Ohio
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Disclosure
• I hereby certify that, to the best of my knowledge, no aspect of
my current personal or professional situation might reasonably
be expected to significantly affect my views on the subject on
which I am presenting
• Funding provided by The Ohio State Canine Grant
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Outline
Background
• Pain Perception & Assessment
• TPLO Analgesia1
Experimental Design2
Results3
Discussion
• Limitations4
Conclusions
• Clinical Relevance5
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Background
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Pain Assessment
• Methods for assessment of post-operative pain
• Simple descriptive scales (SDS)
• Visual analog scale (VAS)
• Numerical rating scale (NRS)
• Multifactorial pain scales (MFPS)
• Behavior-based composite scales
• Colorado State University Canine Acute Pain Scale (CSU-CAPS) (Mich et al. 2010)
• Glasgow Composite Measure Pain Scale – short form (CMPS-SF) (Holton et al. 2001, Morton et al. 2005, Reid et al. 2007)
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Pain Assessment
• Methods for assessment of post-operative pain
• Simple descriptive scales (SDS)
• Visual analog scale (VAS)
• Numerical rating scale (NRS)
• Multifactorial pain scales (MFPS)
• Behavior-based composite scales
• Colorado State University Canine Acute Pain Scale (CSU-CAPS) (Mich et al. 2010)
• Glasgow Composite Measure Pain Scale – short form (CMPS-SF) (Holton et al. 2001, Morton et al. 2005, Reid et al. 2007)
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Pain Assessment
• Methods for assessment of post-operative pain
• Simple descriptive scales (SDS)
• Visual analog scale (VAS)
• Numerical rating scale (NRS)
• Multifactorial pain scales (MFPS)
• Behavior-based composite scales
• Colorado State University Canine Acute Pain Scale (CSU-CAPS) (Mich et al. 2010)
• Glasgow Composite Measure Pain Scale – short form (CMPS-SF) (Holton et al. 2001, Morton et al. 2005, Reid et al. 2007)
Conzemius et al. 1997
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Minimal
Mild
Mild to Moderate
Reassessanalgesic plan
Moderate
Reassessanalgesic plan
Moderate toSevere
May be rigid toavoid painful
movement
Reassessanalgesic plan
Pain Score Psychological & BehavioralExample Response to Palpation Body Tension
Comments
© 2006/PW Hellyer, SR Uhrig, NG Robinson
Colorado State University
Veterinary Medical Center
Canine Acute Pain Scale
Date
Time
Tender to palpation
Warm
Tense
Rescore when awake
Supported by an Unrestricted Educational Grant from Pfizer Animal Health
1
2
3
4
0Comfortable when resting
Happy, content
Not bothering wound or surgery site
Interested in or curious about surroundings
Content to slightly unsettled or restless
Distracted easily by surroundings
Looks uncomfortable when resting
May whimper or cry and may lick or rub
wound or surgery site when unattended
Droopy ears, worried facial expression
(arched eye brows, darting eyes)
Reluctant to respond when beckoned
Not eager to interact with people or surroundings
but will look around to see what is going on
Unsettled, crying, groaning, biting or
chewing wound when unattended
Guards or protects wound or surgery site by
altering weight distribution (i.e., limping,
shifting body position)
May be unwilling to move all or part of body
Constantly groaning or screaming when
unattended
May bite or chew at wound, but unlikely to
move
Potentially unresponsive to surroundings
Difficult to distract from pain
Cries at non-painful palpation
(may be experiencing allodynia,
wind-up, or fearful that pain
could be made worse)
May react aggressively to palpation
May be subtle (shifting eyes or
increased respiratory rate) if dog
is too painful to move or is stoic
May be dramatic, such as a
sharp cry, growl, bite or bite
threat, and/or pulling away
Reacts to palpation of wound,
surgery site, or other body part
by looking around, flinching, or
whimpering
Flinches, whimpers cries, or
guards/pulls away
Nontender to palpation of
wound or surgery site, or to
palpation elsewhere
Animal is sleeping, but can be aroused - Not evaluated for pain
Animal can’t be aroused, check vital signs, assess therapy
RIGHT LEFT
Pain Assessment
• Methods for assessment of post-operative pain
• Simple descriptive scales (SDS)
• Visual analog scale (VAS)
• Numerical rating scale (NRS)
• Multifactorial pain scales (MFPS)
• Behavior-based composite scales
• Colorado State University Canine Acute Pain Scale (CSU-CAPS) (Mich et al. 2010)
• Glasgow Composite Measure Pain Scale – short form (CMPS-SF) (Holton et al. 2001, Morton et al. 2005, Reid et al. 2007)
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Cranial Cruciate Ligament Rupture
• Spontaneous cranial cruciate
ligament (CCL) rupture
common in dogs
• Tibial plateau leveling
osteotomy (TPLO) → stabilize
stifle by altering tibial plateau
angle (TPA)
Evans & de Lahunta 2013
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TPLO Perioperative Analgesia
• No gold standard perioperative
analgesic protocol
• Commonly reported options:
• Intravenous opioids
• Lumbosacral epidural analgesia
• Peripheral nerve blockade
Guedes 2011
Portela, Verdier, & Otero 2018
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Perioperative Analgesia
• Peripheral nerve block vs. intravenous opioids• Peripheral nerve block superior (Palomba et al. 2019)
• Peripheral nerve block vs. epidural • Epidural – more rescue opioids, urine retention (Campoy et al. 2012)
• No difference (Caniglia et al. 2012; McCally et al. 2015; Bartel et al. 2016)
• Intravenous opioids vs. epidural• No difference (Lewis et al. 2014)
• Intravenous opioids vs. epidural vs. peripheral nerve block• No difference (Boscan & Wennogle 2016)
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Objectives
1. Evaluate efficacy of three different analgesic protocols for
TPLO surgery in dogs
2. Identify superior and/or inferior protocols, if any, for immediate
postoperative pain control
3. Assess sedation levels associated with three different
analgesic protocols for TPLO surgery in dogs
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Hypotheses
1. Lumbosacral epidural analgesia and saphenous/sciatic nerve
blockade would provide superior analgesia compared to
intravenous opioids (demonstrated by lower pain scores)
2. Intravenous opioids would cause more sedation than
lumbosacral epidural analgesia and saphenous/sciatic nerve
blockade (demonstrated by higher sedation scores)
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Experimental Design
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Study Design
• Approved by Institutional Animal Care and Use Committee
(IACUC) of The Ohio State University
• Prospective double-blinded clinical trial
• Client owned dogs with CCLR enrolled (n = 45)
• Between May 2018 and August 2019
• Procedure:
• Stifle arthroscopy
• TPLO
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Patient Selection
• Preoperative diagnostics:
• Orthopedic and neurologic exams
• Orthopedic radiographs
• Complete blood count
• Serum biochemistry
• Urinalysis
Arthurs 2011
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Patient Selection
Inclusion Criteria
• Diagnosed with CCLR
• Weight > 15 kg and < 60 kg
• Preoperative TPA 20º – 34º
• Temperament amenable to
handling and hospitalization
• Owner consent to 2 week and 8
week recheck visits at The OSU
Main Campus location
Exclusion Criteria
• Neurologic, systemic, or other
orthopedic disease
• Tramadol or steroids (30 days)
• Prior orthopedic surgery on
affected limb
• Conversion to arthrotomy
• Fibular fracture or implant failure
• Complication → revision surgery
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Treatment Groups
• Three treatment groups (random assignment)
• Group 1 (MLK): n = 15
• Intravenous infusion of morphine, lidocaine & ketamine
• Group 2 (EPID): n = 15
• Lumbosacral ropivacaine & morphine epidural
• Group 3 (SSNB): n = 15
• Saphenous & sciatic nerve blockade with ropivacaine
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Treatments
• Premedication:
• Acepromazine 0.05 mg/kg IM
• Morphine 0.2 mg/kg IM
• General anesthesia induction:
• Propofol 4 mg/kg IV to effect
• General anesthesia maintenance:
• Isoflurane in oxygen
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Treatments
• Group 1 (MLK)
• Morphine 0.1 mg/kg/hr IV CRI
• Lidocaine 3 mg/kg/hr IV CRI
• After initial 2 mg/kg IV bolus
• Ketamine 0.6 mg/kg/hr IV CRI
• Medications in IV fluids
• Fluid bags labeled with patient #:
• (ex) Study Pt. #1
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Treatments
• Group 2 (EPID)
• 1% ropivacaine 0.2 mg/kg
• Preservative-free morphine 0.09 mg/kg
• Lumbosacral epidural
• Every patient shaved for epidural
• Board-certified anesthesiologist
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Treatments
• Group 3 (SSNB)
• 1% ropivacaine 2 mg/kg (each site)
• Ultrasound-guided nerve blocks
using a nerve stimulator:
• Saphenous nerve
• Sciatic nerve
• Board-certified anesthesiologistPortela, Verdier, & Otero 2018
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Surgery
• Stifle arthroscopy
• Medial meniscal tear(s) → treated
arthroscopically
• Intact medial meniscus → left intact
• Routine TPLO surgery
• Performed by board-certified surgeon
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Postoperative Monitoring
24 Hours Postoperative
• 0 hour (AK or NRK)
• Extubation
• 2 hours (AK)
• 4 hours (AK)
• 8 hours (AK)
• 24 hours (AK)
Assessments
• Sedation score
• Pain scores
• CSU-CAPS
• CMPS-SF
• Pain scores only if
sedation score ≤ 10
Rescue analgesia if CMPS-SF > 5
(morphine 0.4 mg/kg IM)
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Postoperative Monitoring
• Sedation scores
• One of two observers (NK or AK)
Hofmeister, Chandler & Read 2010
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Pain Score
• Pain scores• CSU-CAPS
• CMPS-SF
• One observer (AK)
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Statistics
• Demographic data
• ANOVA models
• Categorical data
• Mixed effect models testing treatment effect on primary outcomes
• Kenward-Roger adjustment to degrees of freedom
• Control type I error rates
• Continuous data
• T-tests (2 variables) or ANOVA (> 2 variables)
• Two-sided significance of p<0.05
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Results
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CharacteristicTreatment 1
(n = 15) (MLK)
Treatment 2
(n = 15) (EPID)
Treatment 3
(n = 15) (SSNB)P-value
Weight (kg)
(mean SD)37.28 9.57 34.25 8.09 30.12 8.89 0.0975
Age (years)
(mean SD)4.93 2.15 5.2 2.57 5.33 3.24 0.9180
Sex
Female Intact
Female Spay
Male Neutered
Male Intact
0
7
8
0
2
5
7
1
0
8
7
0
0.5121
Surgical Limb
Left
Right
9
6
8
7
9
60.9999
Completeness of Tear
Full
Partial
11
4
9
6
13
2
0.3156
Current Bilateral CCLR
Yes
No
4
11
3
12
4
110.9999
Meniscal Status
Intact
Torn
7
8
9
6
9
60.8039
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Results
• Sedation scores:
• Higher for MLK compared to
EPID and SSNB (p=0.0098)
• All decreased to 0 by 24-hour
time point0
2
4
6
8
10
12
14
0 2 4 8 24
Sedation Score
Epidural Saphenous Sciatic MLK
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Results
• Pain scores:
• Lower for SSNB compared to
EPID and MLK
• CSU-CAPS (p = 0.0139)
• CMPS-SF (p = 0.0024)
• No rescue analgesia needed
0
0.2
0.4
0.6
0.8
1
2 4 8 24
CSU-CAPS Score
Epidural Saphenous Sciatic MLK
0
1
2
3
4
5
2 4 8 24
CMPS-SF Score
Epidural Saphenous Sciatic MLK
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Results
• No difference among groups for anesthesia duration
(p = 0.8140)
• Surgical procedure duration not affected by surgeon
(p = 0.8350)
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Discussion
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Discussion
• First hypothesis rejected:
• Lower pain scores for SSNB (CSU-CAPS & CMPS-SF)
• No difference between MLK and EPID
• Second hypothesis accepted:
• Higher sedation score for MLK
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Discussion
• SSNB → superior analgesia• Similar:
• Campoy et al. 2012
• Palomba et al. 2019
• Contradicting:
• Caniglia et al. 2012
• McCally et al. 2015
• Bartel et al. 2016
• Boscan & Wennogle 2016
• No rescue analgesia for any patient
• Adequate postoperative pain management for each group
Differences:
• Medications
• Dose
• Assessment
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Discussion
• MLK → higher sedation scores
• Similar: Campoy et al. 2012
• Contradicting: Lewis et al. 2014
• MLK decreases isoflurane minimum alveolar concentration
(MAC) (Muir et al. 2003; Aguado et al. 2011; Ebner et al. 2013 )
• Current study → did not measure end-tidal isoflurane
• MLK patients may have received isoflurane > MAC
• Consider alternative to MLK if patient discharge same day
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Discussion
• No difference in anesthesia time
• Similar:
• Campoy et al. 2012
• McCally et al. 2015
• Palomba et al. 2019
• Lewis et al. 2014
• Boscan & Wennogle 2016
• Anesthesia duration should not be a factor in deciding between
perioperative analgesic protocols
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Limitations
• Low number of patients
• Type I error
• Variability between surgeons or anesthesiologists
• Intraoperative monitoring parameters not evaluated
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Conclusion
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Conclusion
• All protocols provided adequate post-operative pain management
• Improved pain scores with SSNB
• SSNB and EPID did not prolong anesthesia duration
• Higher sedation scores with perioperative intravenous MLK
• Consider in situations when higher sedation contraindicated
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Acknowledgements
• Nina R. Kieves, DVM, DACVS-SA, DACVSMR, CCRT
• Sarah Moore, DVM, DACVIM (Neurology)
• Turi Aarnes, DVM, MS, DACVAA
• Carolina Ricco Pereira, DVM, MS, DACVAA
• Stephen C. Jones, MVB, MS, DACVS-SA
• James Howard, DVM, MS, DACVS-SA
• Juan Peng, MAS
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Thank You!
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References
• Aguado D, Benito J, Gomez de Segura IA (2011) Reduction of the minimum alveolar concentration of isoflurane in dogs using a constant rate of infusion of lidocaine-ketamine in combination with either morphine or fentanyl. Vet J 189, 63-66.
• Bartel AKG, Campoy L, Martin-Flores M et al. (2016) Comparison of bupivacaine and dexmedetomidine femoral and sciatic nerve blocks with bupivacaine and buprenorphine epidural injection for stifle arthroplasty in dogs. Vet AnesthAnalg 43, 435-443.
• Boscan P, Wennogle S (2016) Evaluating femoral-sciatic nerve blocks, epidural analgesia, and no use of regional analgesia in dogs undergoing tibia-plateau leveling-osteotomy. J Am Anim Hosp Assoc 52, 102-108.
• Campoy L, Martin-Flores M, Ludders JW et al. (2012) Comparison of bupivacaine femoral and sciatic nerve block versus bupivacaine and morphine epidural for stifle surgery in dogs. Vet Anaesth Analg 39, 91-98.
• Caniglia AM, Driessen B, Pureto DA et al. (2012) Intraoperative antinociception and postoperative analgesia following epidural anesthesia versus femoral and sciatic nerve blockade in dogs undergoing stifle joint surgery. J Am Vet Med Assoc 241, 1605-1612.
• Conzemius MG, Hill CM, Sammarco JL et al. (1997) Correlation between subjective and objective measures used to determine severity of postoperative pain in dogs. J Am Vet Med Assoc 210, 1619-1622.
• Drygas KA, McClure SR, Goring RL et al. (2011) Effect of cold compression therapy on postoperative pain, swelling, range of motion, and lameness after tibial plateau leveling osteotomy in dogs. J Am Vet Med Assoc 238, 1284-1291.
• Duerr FM, Martin KW, Rishniw M et al. (2014) Treatment of canine cranial cruciate ligament disease. Vet Comp OrthopTraumatol 27, 478-483.
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References
• Ebner LS, Lerche P, Bednarski RM et al. (2013) Effect of dexmedetomidine, morphine-lidocaine-ketamine, and dexmedetomidine-morphine-lidocaine-ketamine constant rate infusions on the minimum alveolar concentration of isoflurane and bispectral index in dogs. Am J Vet Res 74, 963-970.
• Gurney MA, Leece EA (2014) Analgesia for pelvic limb surgery. A review of peripheral nerve blocks and the extradural technique. Vet Anaesth Analg 41, 445-458.
• Hoelzler MB, Harvey RC, Lidbetter DA et al. (2005) Comparison of perioperative analgesic protocols of dogs undergoing tibial plateau leveling osteotomy. Vet Surg 34, 337-344.
• Hofmeister EH, Chandler MJ, Read MR (2010) Effects of acepromazine, hydromorphone, or acepromazine-hydromorphone combination on the degree of sedation in clinically normal dogs. J Am Vet Med Assoc 237, 1155-1159.
• Hofmeister EH, Egger CM (2005) Evaluation of diphenhydramine as a sedative for dogs. J Am Vet Med Assoc 226, 1092-1094.
• Holton LL, Scott EM, Nolan AM et al (1998) Comparison of three methods used for assessment of pain in dogs. J Am Vet Med Assoc 212, 61-66
• Jones RS (2001) Epidural analgesia in the dog and cat. Vet J 161, 123-131.
• Knazovicky D, Helgeson ES, Case B et al. (2016) Widespread somatosensory sensitivity in naturally occurring canine model of osteoarthritis. Pain 157, 1325-1332.
• KuKanich B, Wiese AJ (2015) Opioids. Chapter in Veterinary Anesthesia and Analgesia (5th edition)
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References
• Lewis KA, Bednarski RM, Aarnes TK et al. (2014) Postoperative comparison of four perioperative analgesia protocols in dogs undergoing stifle joint surgery. J Am Vet Med Assoc 244, 1041-1046.
• Lorenz M, Coates J, Kent M (2011) Pain. Chapter in Handbook of Veterinary Neurology (5th edition)
• McCally RE, Bukoski A, Branson KR et al. (2015) Comparison of short-term postoperative analgesia by epidural, femoral nerve block, or combination femoral and sciatic nerve block in dogs undergoing tibial plateau leveling osteotomy. Vet Surg 44, 983-987.
• Mich PM, Hellyer PW, Kogan L et al. (2010) Effects of a pilot training program on veterinary students’ pain knowledge, attitude, and assessment skills. J Vet Med Educ 37, 358-368.
• Muir III WW, Wiese AJ, March PA et al. (2003) Effects of morphine, lidocaine, ketamine, and morphine-lidocaine-ketamine drug combination on minimum alveolar concentration in dogs anesthetized with isoflurane. Am J Vet Res 64, 1155-1160.
• Murrell JC, Psatha EP, Scott EM et al. (2008) Application of a modified form of the Glasgow pain scale in a veterinary teaching centre in the Netherlands. Vet Rec 162, 403-408.
• Palomba N, Vettorato E, De Gennaro C et al. (2019) Peripheral nerve block versus systemic analgesia in dogs undergoing tibial plateau levelling osteotomy: Analgesic efficacy and pharmacoeconomics comparison. Vet AnaesthAnalg, 47, 119-128.
• Portela DA, Verdier N, Otero PE (2018) Regional anesthetic techniques for the pelvic limb and abdominal wall in small animals: A review of the literature and technique description. Vet J 238, 27-40.
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References
• Reid J, Nolan AM, Hughes JML et al. (2007) Development of the short-form Glasgow Composite Measure Pain Scale (CMPS-SF) and derivation of an analgesic intervention score. Anim Welf 16, 97-104.
• Smith LJ, Yu JKA, Bjorling ED et al. (2001) Effects of hydromorphone or oxymorphone, with or without acepromazine, on preanesthetic sedation, physiologic values, and histamine release in dogs. J Am Vet Med Assoc 218, 1101-1105.
• Tomas A, Bledsoe D, Wall S et al. (2015) Initial evaluation of a canine stifle arthrotomy post-operative pain model. Vet J 204, 293-298.
• Tranquilli WJ, Grimm KA (2015) Introduction: Use, definitions, history, concepts, classification, and considerations for anesthesia and analgesia. Veterinary Anesthesia and Analgesia (5th edition)
• Treede RD, Jensen TS, Campbell JN (2008) Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neuro 70, 1630-1635.
• Wagner MC, Hecker KG, Pang DSJ (2017) Sedation levels in dogs: a validation study. BMC Vet Res 13, 110.
• Wendlund TM, Martin KW, Duncan CG et al. (2016) Evaluation of pacing as an indicator of musculoskeletal pathology in dogs. J Vet Med Anim Health 8, 207–213.
• Wiese AJ, Yaksh TL (2015) Nociception and Pain Mechanisms. Chapter in Handbook of Veterinary Pain Management (3rd edition)
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SAM CHIU
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The Effect of Meloxicam on Conditioned
Pain Modulation in the Canine Model
Sam Chiu (2nd Year Resident)
Jon Hash, Rachel C. Meyers, B. Duncan X. Lascelles
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Conflicts of Interest
• I hereby certify that, to the best of my knowledge, no
aspect of my current legal, personal or professional
situation might reasonably be expected to affect my
views on the subject on which I am presenting, other than
the following:
– Boehringer Ingelheim provided funding for this study
– B. Duncan X. Lascelles is a BI consultant
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18 Million
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80%
20%
Response to most analgesics in patients with osteoarthritis
Clinically Unsuccessful
Osteoarthritis pain control
Schnitzer TJ et al Osteoarthritis Cartilage 2015
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Push towards Precision Medicine
Edwards RR et al Pain 2016
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Biomarker
Disease subtype
Demographics
Risk Profiles
Clinical Features
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Biomarker
Disease subtype
Demographics
Risk Profiles
Clinical Features
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Biomarker
Disease subtype
Demographics
Risk Profiles
Clinical Features
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Central Sensitization (CS)
Peripheral Sensitization (PS) EAS
Impairment
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Central Sensitization (CS)
Peripheral Sensitization (PS) EAS
Impairment
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Central Sensitization (CS)
Peripheral Sensitization (PS) EAS
Impairment
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Central Sensitization (CS)
Peripheral Sensitization (PS) EAS
Impairment
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EndogenousAnalgesic System
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EASImpairment
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Clinical Significance
• OA Dogs may have central/peripheral sensitization and EAS
impairment
Chiu KW et al Sci Rep 2020
Novick D et al Pain 2016
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Clinical Significance
• OA Dogs may have central/peripheral sensitization and EAS
impairment
• Surgical perspective: Canine total hip replacement patients do not
have central sensitization reversal till 12 months post-op
Tomas A et al Vet Surg 2014
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VAS
∆
Conditioned Pain Modulation (CPM) paradigm
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Endogenous analgesic system
Osteoarthritis
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Endogenous analgesic system
Increased
pain
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Process of Predicting Analgesic Efficacy
Phenotype Administer AnalgesicAnalyze Pain Alleviation
based on Phenotype
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Process of Predicting Analgesic Efficacy
Phenotype Administer AnalgesicAnalyze Pain Alleviation
based on Phenotype
Apply Algorithm to Predict Analgesic
Response
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Aim of study
• To evaluate the ability of an NSAID to reverse EPM
impairment in dogs with osteoarthritis
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MethodsPlacebo-controlled double-blinded cross-over clinical study
• Subjects: 45 OA dogs with evidence of chronic pain
• Inclusion criteria:
– >1 year old with >6 months history of chronic pain
– Showing signs of stifle or hip pain without evidence of other
systematic disease (e.g. neurological deficits)
– High pain score based on validated client questionnaires
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Methods: Timeline
Screening
Randomize Day 0
(Visit 1)
Day 28
(Visit 2)
Washout
Day 42
(Visit 3)
Day 70
(Visit 4)
Group A Placebo NSAID
Group B NSAID Placebo
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Methods: Timeline
Screening
Randomize Day 0
(Visit 1)
Day 28
(Visit 2)
Washout
Day 42
(Visit 3)
Day 70
(Visit 4)
Group A Placebo NSAID
Group B NSAID Placebo
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Methods: Timeline
Screening
Randomize Day 0
(Visit 1)
Day 28
(Visit 2)
Washout
Day 42
(Visit 3)
Day 70
(Visit 4)
Group A Placebo NSAID
Group B NSAID Placebo
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Step 1 Step 2 Step 3
Pre-conditioning Mech/Hot test
stimulus
Post-conditioning Mech/Hot test
stimulus
22N mechanical Conditioning
stimulus (2 minutes)
Conditioning stimulus continued
Methods: Conditioned Pain Modulation Testing
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Methods: Conditioned Pain Modulation Testing
Step 1 Step 2 Step 3
Pre-conditioning Mech/Hot test
stimulus
Post-conditioning Mech/Hot test
stimulus
22N mechanical Conditioning
stimulus (2 minutes)
Conditioning stimulus continued
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• Step 1: Apply test stimulus (5 trials)
Mechanical stimulusThermal stimulus
49˚C
Methods: Conditioned Pain Modulation Testing
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Mechanical Quantitative Sensory Testing
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Step 1 Step 2 Step 3
Pre-conditioning Mech/Hot test
stimulus
Post-conditioning Mech/Hot test
stimulus
22N mechanical Conditioning
stimulus (2 minutes)
Conditioning stimulus continued
Methods: Conditioned Pain Modulation Testing
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• Step 2: Conditioning stimulus for 2 minutes
– Noxious mechanical stimulus
– delivered using 2mm diameter probe pushed into the
antebrachium using a pneumatic device
Air
Methods: Conditioned Pain Modulation Testing
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Step 1 Step 2 Step 3
Pre-conditioning Mech/Hot test
stimulus
Post-conditioning Mech/Hot test
stimulus
22N mechanical Conditioning
stimulus (2 minutes)
Conditioning stimulus continued
OR +
Methods: Conditioned Pain Modulation Testing
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Step 1 Step 2 Step 3
Pre-conditioning Mech/Hot test
stimulus
Post-conditioning Mech/Hot test
stimulus∆ = Post-conditioning – Pre-conditioning threshold
Intact endogenous analgesic system: ↑ ∆Impaired endogenous analgesic system: ↓ ∆
Methods: Conditioned Pain Modulation Testing
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Outcome Measures:
• Response to Analgesia –
– Liverpool Osteoarthritis in Dogs (LOAD)
– Canine Brief Pain Inventory (CBPI)
• Patient Phenotyping – Conditioned Pain Modulation (CPM)
– 2 test stimulus – mechanical and hot thermal
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Methods: Statistical analysis
• Distribution of data was assessed by Shiro-Wilk test
• Parametric and non-parametric data was analyzed by the
t-test and Wilcoxon test respectively
• Logistic regression model was used to address effects of
covariates.
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RESULTS
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Results – Patient data
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Patient demographics
Overall (n=52)
Age in years at start 7.55 ± 2.8
Weight (kg) 31.4 ± 9.9
BCS 5.3 ± 1.0 Sex MN n=21;
M n=2;
FS n=28;
F n=1
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Patient demographics
Placebo-Meloxciam Sequence
(n=26)
Meloxciam-Placebo Sequence
(n=26)
P value
Age in years at start
8.1 ± 2.9; 8, (2 – 12) 7.0 ± 2.7; 7, (2 – 12) 0.160
Weight (kg) 31.5 ± 7.5; 29.5, (19.9 – 53) 31.2 ± 12.0; 29.9, (19 – 69.8) 0.900
BCS 5.2 ± 1.0; 5, (4 – 8) 5.4 ± 1.0; 5, (4 – 8) 0.580
Sex FS n=14/26;
MN n=12/26
MN n=9/26
M n=2/26
FS n=14/26
F n=1/26
0.330
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Results - CMI Summary Table
∆ Meloxicam - ∆Placebo P-value
Liverpool Osteoarthritis in Dogs (LOAD)
2.95 ± 7.84 0.019
Canine Brief Pain Inventory (CBPI)
PSS: 0.94 ± 2.51 <0.001
PIS: 0.61 ± 2.24 <0.001
Both LOAD and CBPI showed a significant pain improvement after meloxicam administration as compared to placebo administration
-
-
-
(i.e. improvement)
(i.e. improvement)
(i.e. improvement)
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Results - Conditioned Pain Modulation
(Blunt Mechanical) (g)
-9 ± 273
-1 ± 204
∆
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Results - Conditioned Pain Modulation
(Blunt Mechanical) (g)
-9 ± 273
-1 ± 204
∆
∆ ~0: No improvement in CPM
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Results - Conditioned Pain Modulation
(Blunt Mechanical) (g)
-9 ± 273
-1 ± 204
∆
∆ >>0: Improvement in CPM
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Results - Conditioned Pain Modulation
(Blunt Mechanical) (g) ∆
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Results - Conditioned Pain Modulation
(Blunt Mechanical) (g)
-9 ± 273 g
∆
-1 ± 204
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∆
P = 0.417
Results - Conditioned Pain Modulation
(Blunt Mechanical) (g)
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Results - Conditioned Pain Modulation
(Hot Thermal) (s) ∆
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Results - Conditioned Pain Modulation
(Hot Thermal) (s) ∆
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Results - Conditioned Pain Modulation
(Hot Thermal) (s) ∆
0.45 ± 3.37s 0.47 ± 3.08 s
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Results - Conditioned Pain Modulation
(Hot Thermal) (s) ∆
P = 0.460
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Discussion – CPM
• Both the mechanical and thermal
testing did NOT support reversal
the EPM malfunction using
meloxicam
• Our study is first to report the
effect of an NSAID on dEPM in
dogs.
• Results similar to humans, Arendt-
Nielsen et al. showed etoricoxib
did not have an effect on CPM.
Arendt-Nielsen L et al Pain 2016
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Discussion - Limitations
• Washout period was short – order effect
• Limited number of dogs – may not have addressed the
individual variation
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Discussion – Clinical significance
• Meloxicam administration was not able to reverse
dysfunctional endogenous pain modulation in dogs with
persistent spontaneous OA pain.
• Evaluation of drugs that may reverse dEPM is warranted
to manage canine OA pain appropriately.
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Thank you
• Boehringer Ingelheim Vetmedica
• B. Duncan X. Lascelles
• Jon Hash, Rachel Meyers, Andrea Thomson and
everyone at Comparative Pain and Education Center to
make it happen!
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PAIN AND SHOULDER
OCTOBER 27, 2020 | 5:00–6:00 P.M. ET
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