Our duty towards animals The Five Freedoms Evaluatción y ...cvpba.org/wp-content/uploads/2017/09/Evaluation-and-treatment-of... · OCULAR 92.1 0 0 5.6 0.5 0 0 0 0.9 0.9 0 0 98.6

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Evaluatción y tratamiento en

dolor crónico en perros y gatos

Sheilah Robertson Senior Medical Director

Lap of Love Veterinary Hospice

Our duty towards animalsThe Five Freedoms

1. Freedom from hunger and thirst

2. Freedom from discomfort

3. Freedom from pain, injury and disease

4. Freedom to express normal behavior

5. Freedom from fear and distress

IASP - New definition of pain

Pain is a distressing experience associated

with actual or potential tissue damage with

sensory, emotional, cognitive and social

components

International Association for the Study of Pain

CHRONIC PAIN

Pain without apparent biological value

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Chronic pain in dogsFrom Bell et al 2014 Vet Rec

MOST COMMON

CAUSE %

THREE MOST

COMMON %

OSTEOATHRITIS

NEOPLASIA

AURAL

DENTAL

SPINAL

BLADDER

PANCREAS

SKIN

POSTOPERATIVE

MYOFACIAL

NEUROLOGIC

OCULAR

92.1

0

0

5.6

0.5

0

0

0

0.9

0.9

0

0

98.6

21.4

51.6

59.1

33

1.9

6.5

13.5

4.7

5.6

0.5

3.7

Getting old or getting sore?

Osteoarthritis / DJD

100 cats, 4 age groups

0-5

5-10

10-15

15-20

92% had radiographic evidence of DJD

Lascelles et al Veterinary Surgery 2010

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Chronic Pain

Cancer related

Chronic Pain

Ear Disease

Chronic Pain

Oral / dental

My personal experience

HOBBES SCOTTY SANDY

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The “quantity” of pain Impact on the owner

Animals live “in the moment”

How do we know they hurt?

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WHAT TOOLS

DO WE HAVE FOR

CHRONIC PAIN?

Assessment

Owner Veterinarian

QuestionnairesPhysical exam /

diagnostics

Tools for assessing osteoarthritis - DOGS

Clinical Measurement Instruments

Helsinki Chronic Pain Index

Canine Brief Pain Inventory

Health Related Quality of Life

Liverpool Osteoarthritis in Dogs

LOAD - for dogs

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Initial evaluation of nighttime restlessness

in a naturally occurring canine model of

osteoarthritis pain

Knazovicky et al Peer J 2015

Sleep and Night Time Restlessness Evaluation Score

SNoRE

Sleep and Night time Restlessness Evaluation - SNoRE

Twitching

Dreaming

Shifting position

Vocalizing

Pacing

North Carolina State University CVM Website

1. Over the last 7 days, what has been your dog’s ability to sleep without moving or getting

up (restful sleep)?

Never moves Constant moving

1 2 3 4 5 6 7 8 9 10

2. Fill in the oval next to the one number that best describes your dog’s sleep over the last

7 days

Never twitches Constant twitching

1 2 3 4 5 6 7 8 9 10

6 questions Other questions

3. Dreaming

4. Shifting position

5. Vocalizing

6. Pacing

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Activity monitors Assessment - cats

In a clinic At home

Question for owners

Ability to jump up and down

Reaction to handling, petting, grooming

Interaction with owners

Playing with other pets

Playing with toys

Zamprogno et al AJVR 2010

Owner videos

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Jumping up and Down

Images courtesy of Dr. M Petty

Libby

Access to elevated places

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Jumping

Stairs

Images courtesy of Dr. M Petty

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Litter box Grooming

www.catvets

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Tools for assessing osteoarthritis - CATS

Feline Musculoskeletal Pain Index

Feline Musculoskeletal Pain Index

17 questions completed by owner

Distinguishes between normal and chronic pain cats

Ongoing evaluation and validation

Current tool (v10) available for clinical use:

https://cvm.ncsu.edu

Benito et al JVIM 2013

FMPI4 3 2 1 0

Loss of Muscle Mass

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Why should we use these tools?

More objective

Changes in pain over timeChanges can be subtle and gradual

Setting goals for treatment

Monitoring efficacy of treatment

Decision making

QUALITY OF LIFE

PHYSICAL

HEALTH

FEELINGS TELOS

www.newmetrica.com

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VETMETRICA HRQL

On-line web-based owner questionnaire

Owner know the dog best

They see behavioral cues

22 questions

< 5 minutes

ENERGY HAPPINESS

COMFORT CALMNESS

4 Domains of QOL

VETMETRICA HRQL

Valid, reliable, sensitive

Responsive to clinical change

Age matched normal data for comparison

NOT disease specific40% of items listed by owners involved mobility

60% were ‘inactive’ items

Benito et al 2012

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Prevalence of degenerative joint disease and chronic kidney disease

PAIN68.8%

Marino et al 2013

Acute on chronic pain

Management

PHARMACOLOGIC NON- PHARMACOLOGIC

INTEGRATIVE

Treatment challenges

Degenerative joint disease is not curable

Long-term commitment from owner and veterinary surgeon

Time, money, effort

Some things will work and some will not

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TRANSMISSION

CENTRAL OR

SECONDARY

SENSITIZATION

PRIMARY OR PERIPHERAL

SENSITIZATION

Guillot et al 2014

What are the barriers to treating chronic pain?

Bell et al 2014 Vet Rec 175(17):428-434

0

10

20

30

40

50

60

70

80 MAJOR MINOR INSIGNIFICANT

Goals of treatment

Ensure good quality of life

The patient’s best interests

Set clear goals

Involve the owner

Decrease inflammation

Slow disease progression

Promote repair of damaged tissue

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What are people using?

0

10

20

30

40

50

60

70

80

90ALWAYS OFTEN OCC

RARELY NEVER

Bell et al 2014 Vet Rec 175(17):428-434

TCA = amitriptyline AP = acupuncture HP = homeopathy PT = physical therapy

Treating OA-pain in dogs

Most efficacious therapies:

NSAIDs

Exercise

Dietary modulation

“joint diets”

Systemic Review of NSAID Induced Adverse Effects in Dogs

Research and clinical studies

64 studies qualified for review

Adverse effects in 55% of studies

Monteiro-Steagall et al (2013) JVIM 27:1011-1019

Systemic Review of NSAID Induced Adverse Effects in Dogs

Vomiting

Diarrhea

Anorexia

Randomized, placebo controlled, blinded studies

No difference between treated and control dogs

Monteiro-Steagall et al (2013) JVIM 27:1011-1019

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Long term use of NSAIDs and side effects

No evidence that long-term NSAID use increases incidence of side effects

At a standard approved doses

No correlation between adverse event rates and length of treatment

Innes et al (2010) Vet Rec 166: 226-230

Minimizing Toxicity: Appropriate Use

Selection of patients

Risk factors for GI, renal and hepatic side effects

Drug and dose selection

Dose on lean body weight

Dose titration

Minimizing Toxicity: Appropriate Use

Owner education

Discuss signs of toxicity

Dispense owner information sheets

Discuss drug interactions

Multimodal drug therapy

When NSAIDs not fully effective….

Theoretically a good idea but little evidence

Amantadine: 1 study

Tramadol: dog and cat studies

Gabapentin: No studies

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NSAID for 5 weeks

On day 21 amantadine* or placebo was added

On day 42 amantadine group were more active

Acts at the NMDA receptor*3-5 mg/kg/day PO

Tramadol

Synthetic opioid

Inhibits reuptake of norepinephrine and serotonin

Multiple metabolites

Species differences

O-desmethyl-tramadol (M1)

Weight Loss

Decreases stress on joints

Role of fat in inflammation

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Weight loss – calorie restriction

Body Weight

Pelvic circumference

Subjective assessment

Kinetic gait analysis

Significant improvement

6.1 – 8.8 % loss

Therapeutic Exercise

Exercise – under-water treadmillDietary Supplements

Long chain fatty acids

Fish oils EPA + DHA

Cats 50 mg/kg Dogs 100mg/kg

Green lipped mussel extract

Glucosamine / chrondroitin

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NSAIDs

Journal of Feline Medicine and Surgery 2010

www.catvets.com http://isfm.net NSAID in cats

NSAID½ Life

(hours)

Clearance

mechanism

Carprofen 20 G, O

Ketoprofen 1.5 G, T

Meloxicam 15 O

Piroxicam 12 O

Robenacoxib 1.1-1.7 O

G = Glucuronidation

O = Oxidation

T = Thioesterification

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Assessment domains

0

1

2

3

4

5

6

Baseline 28 days

OWNER VET

GROOMING

ACTIVITY

JUMPING

DEMEANOR

GL

OB

AL

SC

OR

E

53 cats

Bennett et al 2009

(Meloxicam)

Detection of Clinically Relevant Pain Relief

in Cats with Degenerative Joint Disease

Associated Pain

Prospective, double-masked, placebo-

controlled, stratified, randomized, clinical study

of meloxicam

Gruen et al 2014

Meloxicam

Chronic musculoskeletal disorders

Day 1: 0.5 mg/ml oral suspension @ 0.1 mg/kg

Day 2 onwards: 0.05 mg/kg once daily

Europe and many other countries (Australasia)

Long-term use of meloxicam and kidney disease

Two retrospective studies

Cats with DJD ± CKD

Treatment and control groups

Effects on renal function

Effect on longevity

Gowan et al 2011, 2012

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What was reported?

LESS progression of renal disease in cats treated with meloxicam

No decrease in lifespan of cats with stable CKD treated with meloxicam Treatment group: once daily x 28 days

40/95 with CKD

Serum creatinine > 1.6 mg/dl

USG < 1.030

Placebo group n = 99

King et al 2015

Robenacoxib (Onsior)

INJECTED

OR ORALBLOOD

INFLAMMED

TISSUE

Tmax = 30 mins

t½ = < 2 hours

Gone in ~3 hours

20-24 hours

Gabapentin

?Eliminated by the kidney

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Prospective, randomized, placebo controlled, blinded, cross over study

Peak Vertical Force

Night time motor activity

Response to mechanical temporal summation

Monteiro et al 2017

NON DRUG

THERAPIES

My cat – Calvin!

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Catapuncture! Grooming

Massage / Grooming Feline joint diets

Significant increase in activity in the test diet group

Positive changes in:

Playing

Interaction

Seeking seclusion

Sleeping

Lascelles BD et al 2010; J Vet Intern Med

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Making life easier Making life easier

Thermal environmentCats 29-38oC (85-100oF)

THE FUTURE

OF PAIN

MANAGEMENT

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Grapiprant

EP4 receptor antagonist Grapiprant

PHOSPHOLIPIDS

ARACHIDONIC ACID

PGH2

LEUKOTRIENES

PGD2 PGF2α PGE2 PGI2 TXA2

EP1 EP2 EP3

CORTICOSTEROIDS

NSAIDs

EP4

Nerve growth factor [NGF]

Mediates pain signaling and nerve growth

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Monoclonal antibodies

mAbs – biological therapy

PETization – rapid translation of therapeutic mAbs between species

Proprietary cDNA library data

100% species-specific

Recognized as “native”

www.nexvet.com/

Bringing biologic therapies to veterinary care through scientific excellence and transformative technology.

Designed for catsFrunevetmab (NV-02) is a mAb being developed as a monthly subcutaneous injectable for the control of pain associated with feline osteoarthritis

Me

an

ch

an

ge

in a

ctivity c

ou

nts

/min

A Feline–Specific Anti-nerve Growth factor Antibody

Improves Mobility in cats with degenerative Joint

Disease-Associated Pain: A Pilot Proof of Concept

Study Gruen at al 2016

Clinical use

Subcutaneous injection

Duration of action 4-6 weeks

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Anti-Nerve Growth Factor - Dogs

Decreased pain

Improved:

Mobility and function

QoL

One treatment = 4 weeks

Webster et al 2014 AJVR

Lascelles et al 2015 BMC

www.nexvet.com

Cannabinoids

Stimulate serotonin production

Decrease inflammation

Pain relief

Cannabinoids in dogs and cats

Dogs extremely sensitive to THC

Toxicities from Medical Marijuana are common

Legal issues??

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What do we know about Cannabinoids?

3 Compounds of interest

THC, CBD and CBN

2 receptors of interest

CB1 - CNS

CB2 - Peripheral

More research needed

Euthanasia as a treatment option

Ethical analysis

Welfare of the animal

Discussed sooner rather than later

Better a week too early than a day too late

Should not be looked at as a failure

Evaluatción y tratamiento en dolor crónico en

perros y gatos

QUESTIONS