i: pain and analgesics

8/14/2019 I: Pain and Analgesics

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I: Pain and Analgesics

Pain an unpleasantsensory and emotionalexperience with actual or

potential tissue damage ordescribed in terms of suchdamage (InternationalAssociation for the Study of

Pain, 1979)

Analgesia absence ofpain


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Pain pathways

Specialized receptors = free nerve endings

Stimulation

Mechanical damage

Extreme temperature

Chemical irritation

Two types of neurons

A-delta: first pain, sharp

C: second pain, dull Four distinct processes

Transduction, transmission, modulation, perception


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Tissue damage

Release of chemical substances and enzymes (mediators)that alter the activity and sensitivity of sensory neurons

Prostaglandins, leukotriens: sensitization of receptors

Bradykinin and PGs: stimulate the neurons directly

Histamine: pain, itching

Result

increase in nociceptor activity

Hyperalgesia Neurogenic edema


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Dorsal horn

Wind-up

neurotransmittors causingenhanced excitability andsensitization of dorsal horncells

Persistent changes

Cause of allodynia (touchbecomes pain)

Prevented by pre-treatment

with e.g opioids


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Perception

Somatosensory cortex, cingulate cortex

Sensory discrimination

Emotional response

fear, anxiety and panic

subjective experience

Reticular formation

Increased arousal

Emotional response

Somatic and autonomic motor reflexes

Induction of biological and behavioural changes


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Perception cont.

Higher vertebrates Anatomical components for

perception of pain

From the last third ofembryonic development

Primitive vertebrates Fish, reptiles, amphibians

avoidance or escape behaviorpoorly developed cerebral

cortex


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Pharmacological treatment of

pain Periphery-along axons-CNS

Single treatment/polymodal

Continuosly/

intermittently1. Regional ane

2. NSAIDs

3. Opioids

4. NMDA-receptor agonists

5. Alpha-2-receptor agonists

6. Other agents


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1. Regional anesthesia

Lidocaine (lignocaine): Xylocain

Bupivacaine: Marcain

Tricaine: MS-222

Preoperatively and

postoperatively

Underuse in small species Na+channels


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Sensory, motor and sympathetic nerves

Duration

lipid solubility (bupivacaine > lidocaine)

Adrenaline (1: 200,000): cave appendices

Toxicity convulsions, hypotension, ventricular arrhythmia and myocardial depression

Application

Local infiltration, mucous membranes, eye, ear, around a nerve, intrapleurally,epidurally

1. Regional anesthesia cont.


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2. NSAIDs

Non-steroidal anti-inflammatory drugs

Reduce synthesis of PGs

Cox inhibitors (cyclooxygenase)

Diminish nociceptor activation

Block peripheral sensitization

Antipyretic

Anti-hyperalgesic

No sedation


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Salicylates (aspirin)

Ketoprofen: Romefen

Carprofen: Rimadyl PO, SC, IM

Gastrointestinal ulceration

and renal function disturbances,

embryotoxic, prolong bleeding

2. NSAIDs cont.


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3. Opioids

Spinal cord

Decreasing neurotransmitter release

Blocking postsynaptic receptors

Activating inhibitory pathways

Receptor subtypes

mu> delta> kappa

Supraspinal analgesia

Peripheral analgesia (prevent nociceptor sensitization)


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Morphine Fentanyl: Leptanal, Hypnorm

Sufentanil

Burprenorphine: Temgesic

Sedation

PO, SC, IM, IP

Side effects: respiratory depression, severe bradycardia, decreased gastric HCl secretion

Less from delta agonists

3. Opioids cont.


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4. NMDA-receptor antagonists

Spinal cord receptors

Repetitive c-fiber activation

Central hyperalgesia

Not effective against acute inflammatory pain

Effective against prolonged inflammatory pain

Neuropathic and cancer pain

Abolish the wind-up phenomenon

Work in synergy with opioids

Ketamine, tiletamine


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Xylaxine: Rompun

Medetomidine: Domitor

Receptors in the spinal cord and brain

Activated by descending noradrenergic pathways

Inhibit pre-synaptic calcium influx and neurotransmitter release

IM, SC, IP, IV

sedation, analgesia, muscle relaxation and anxiolysis

Side effects

Initial hypertension

Hypotension

Bradycardia

Decreased cardiac output

Depress insulin release

Diuresis

Hypothermia Specific antagonist atipamezole: Antisedan

5. Alpha-2-agonists


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6. Other agents Sedatives and tranquillizers

Diazepam, acepromazine, fluanisone

Relieve anxiety, decrease stress

Minimal respiratory and cardiovascular effects

Hypotension, hypothermia

GABA (enhancement), dopamine (blockade)

Antagonist (flumazenil)

SC, IM, IV

Tricyclic antidepressants

Amintryptilline


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II: Pain management

Prevention: preemptive approach

Recognition of pain

Choice of substance

Drug dose and duration


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Do animals experience pain?

No direct evidence

Subtle behavioural responses

Complex learning to avoid noxious stimuli

Self-administration of analgesics in chronic

pain conditions

Response to analgesics

Assessment central


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Why treat pain?

Legal and ethical reason

Beneficial for the animal

Beneficial for reserachRapid return to normal function

A higher survival rate

Counteract physiological changes Thoracic and abdominal pain affect ventilation

Reduction in food and water consumption


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Recognition of pain

Prey animals mask pain

Nocturnal species

Signs to look for

General appearance and condition Attitude, posture and movements

Interactions with cage mates

Reactions to manipulation

Food and water consumption

Production of faeces and urine

Species-typical signs of pain and distress

Procedure-specific signs


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Pain during anaesthesia No consciousness-no pain perception (acute

experiment)

Sensory nerve activity and sensitization stillpossible

Avoid unnecessary postoperative pain!

Recognition of pain during surgery

Spontanous movements

Movemenets in reaction to nociceptive stimulation

Respiration and puls frequency

Blood pressure

Withdrawal reflexes


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Postoperative pain

Peripheral sensitization

Central sensitization Amplification of pain

sensation

Surgery Inflammatory pain

Neuropathic pain

Prevention by preemptiveanalgesia


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Drug delivery

Oral delivery

Dosing

Consumption

Degradation

NSAIDs

Aspirin

carprofen

Opioids buprenorphine

Parenteral delivery

S/c, i/p, i/v, sublingual, rectal


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Drug Mouse Rat Guinea pig

morphine 2-5 mg/kg SC,

4 hourly

2-5 mg/kg SC

4 hourly

2-5 mg/kg SC

4 hourly

butorphanol 1-2 mg/kg SC

4 hourly

1-2mg/kg SC

4 hourly

2 mg/kg SC

buprenorphine 0.05-0.1 mg/kg SC 8-12

hourly

0.01-0.05 mg/kg SC or IV

0.1-0.25 mg/kg by mouth

8-12 hourly

0.05 mg/kg SC

8-12 hourly

carprofen 5 mg/kg SC or by mouth

24 hourly

5 mg/kg SC or by mouth

24 hourly

ketoprofen 5 mg/kg SC or by mouth

24 hourly

ibuprofen 30 mg/kg by mouth

24 hourly

15 mg/kg by mouth

24 hourly

lidocaine 4 mg/kg or 0.4 ml/kg of a 1% solution

bupivacaine 1-2 mg/kg or 0.4-0.8 ml/kg of a 0.25% solution

amitriptyline 1.2-5 mg/kg SC or IP

3-12 hourly

1-10 mg/kg SC or IP

3-12 hourly

imipramine 2.3 mg/kg SC or IP

12-24 hourly

10 mg/kg SC or IP

12-24 hourly


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Use of local anaesthetics

1. Topical, local infiltration,nerve block

Skin, eye, ear canal,epidurally, periost,

1. Reduction of anestheticneeds

2. Post-operative analgesia

3. Maximum dose for

lidocaine: 4mg/kg

bupivacaine: 2mg/kg


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Fish anaeshthesia MS-222 (tricaine)


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Use of NSAIDs

1. For mild-moderate pain

2. Acute and chronic pain

3. When opioids are contraindicated4. Preemptively before inhalation or injection

anaeshetsia: carprofen

5. In combination with local anaesthetics or opioidsfor severe postoperative pain

6. Not in pregnant animals


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Main use of opioids1. Preemptive analgesia and sedation

Before inhalation anesthesia

Before pentobarbital aneshtesia

Not before other injectables

1. Intraoperative pain relief (fentanyl)

With pentobarbital for acute experiments in pigs

Pig cardiac protocols

Rodent anesthesia

Hypnorm (fluanisone + fentanyl)

1. Postoperative pain relief

Buprenorphine (Temgesic) after Hypnorm orketamine combinations

Peak duration after 30min


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Management of postoperative

pain Preemptive analgesia

Good surgical technique

Sterile technique

Supportive therapy Soft food

Long drinking nipples

Soft bedding

Warm environment

Avoid social isolation


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Minor procedures

single dose of an opioid or NSAID sufficient (preoperatively when possible)

More invasive surgery

Continue treatment for up to 24-36h

After major surgery Continue analgesic administration for

36-72 hours

Combination therapy

Opioid

NSAID

Local analgesia

Management of postoperative

pain cont.


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Examples of analgesic treatment

Implantation of brain canula rat: Preemptive buprenorphine 0,05mg/kg

Isoflurane anestesia Local infiltration with bupivacaine

Ovarioectomy mouse

Ketamine/medetomidine ane Buprenorphine towards the end of theprocedure


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Arthrodesis lumbar spine rabbit

Preemptive carprofen

EMLA cream ear

Induction of aneasthesia with propofol Maintainance with isoflurane anesthesia

Local infiltration with bupivacaine

Buprenorphine before recovery

Feeding with baby food (carrot, apple)

Fluids i/v Continuation of bup for 24-48h and NSAID for 72 or more h

Examples of analgesic treatment

cont.


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i: pain and analgesics

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