Pain & analgesics /certified fixed orthodontic courses by Indian dental academy

INDIAN DENTAL ACADEMY
Leader in continuing dental education
www.indiandentalacademy.com


I: Pain and Analgesics
• Pain
”an unpleasant sensory and
emotional experience with
actual or potential tissue
damage or described in terms
of such damage”
(International Association for
the Study of Pain, 1979)
• Analgesia
absence of pain


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

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

Dorsal horn
• Wind-up
– neurotransmittors causing
enhanced excitability and
sensitization of dorsal horn
cells
– Persistent changes
– Cause of allodynia (”touch
becomes pain”)
– Prevented by pre-treatment
with e.g opioids


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

Perception cont.
• Higher vertebrates
– Anatomical components for
perception of pain
– From the last third of
embryonic development

• Primitive vertebrates
– Fish, reptiles, amphibians
– avoidance or escape
behavior
– poorly developed cerebral
cortex

Pharmacological treatment of
pain
•
•
•

Periphery-along axons-CNS
Single treatment/polymodal
Continuosly/
intermittently
1.
2.
3.
4.
5.
6.

Regional ane
NSAIDs
Opioids
NMDA-receptor agonists
Alpha-2-receptor agonists
Other agents

1. Regional anesthesia
•
•
•
•

Lidocaine (lignocaine): Xylocain®
Bupivacaine: Marcain ®
Tricaine: MS-222®
Preoperatively and
postoperatively
• Underuse in small species
• Na+channels


1. Regional anesthesia cont.
•
•

Sensory, motor and sympathetic nerves
Duration
–
–

•

Toxicity
–

•

lipid solubility (bupivacaine > lidocaine)
Adrenaline (1: 200,000): cave appendices
convulsions, hypotension, ventricular
arrhythmia and myocardial depression

Application
–

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

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

2. NSAIDs cont.
•
•
•
•
•

Salicylates (aspirin)
Ketoprofen: Romefen®
Carprofen: Rimadyl ®
PO, SC, IM
Gastrointestinal ulceration
and renal function disturbances,
embryotoxic, prolong bleeding


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)

3. Opioids cont.
–
–
–
–
–
–
–

Morphine
Fentanyl: Leptanal®, Hypnorm®
Sufentanil
Burprenorphine: Temgesic®
Sedation
PO, SC, IM, IP
Side effects:
•
•

respiratory depression, severe
bradycardia, decreased gastric
Less from delta agonists


HCl secretion

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

5. Alpha-2-agonists
–
–
–
–
–
–
–
–

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®

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

II: Pain management
•
•
•
•

Prevention: preemptive approach
Recognition of pain
Choice of substance
Drug dose and duration


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

Why treat pain?
• Legal and ethical reason
• Beneficial for the animal
• Beneficial for reserach
– Rapid return to normal function
– A higher survival rate
– Counteract physiological changes
• Thoracic and abdominal pain affect ventilation
• Reduction in food and water consumption

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

Pain during anaesthesia
• No consciousness-no pain
perception (acute experiment)
• Sensory nerve activity and
sensitization still possible
• Avoid unnecessary
postoperative pain!
• Recognition of pain during
surgery
– Spontanous movements
– Movemenets in reaction to
nociceptive stimulation
– Respiration and puls frequency
– Blood pressure
– Withdrawal reflexeswww.indiandentalacademy.com

Postoperative pain
• Peripheral sensitization
• Central sensitization
– Amplification of pain
sensation

• Surgery
– Inflammatory pain
– Neuropathic pain

• Prevention by preemptive
analgesia

Drug delivery
• Oral delivery
–
–
–
–

Dosing
Consumption
Degradation
NSAIDs
• Aspirin
• carprofen

– Opioids
• buprenorphine

• Parenteral delivery
– S/c, i/p, i/v, sublingual, rectal

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

24 hourly

ketoprofen

ibuprofen

24 hourly
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


Use of local anaesthetics
1.

Topical, local
infiltration, nerve
block
•

1.

Skin, eye, ear canal,
epidurally, periost,

Reduction of
anesthetic needs
Post-operative
analgesia
Maximum dose for

2.
3.
•
•

lidocaine: 4mg/kg
bupivacaine: 2mg/kg

Fish anaeshthesia
• MS-222 (tricaine)


Use of NSAIDs
1.
2.
3.
4.

For mild-moderate pain
Acute and chronic pain
When opioids are contraindicated
Preemptively before inhalation or
injection anaeshetsia: carprofen
5. In combination with local anaesthetics or
opioids for severe postoperative pain
6. Not in pregnant animals

Main use of opioids
1.

Preemptive analgesia and sedation
–
–
–

1.

Before inhalation anesthesia
Before pentobarbital aneshtesia
Not before other injectables

Intraoperative pain relief (fentanyl)
–
–
–

With pentobarbital for acute
experiments in pigs
Pig cardiac protocols
Rodent anesthesia
–

1.

Hypnorm® (fluanisone + fentanyl)

Postoperative pain relief
–
–

Buprenorphine (Temgesic®) after
Hypnorm or ketamine combinations
Peak duration after 30min


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

Management of postoperative
pain cont.
•

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 analgesiawww.indiandentalacademy.com

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 the
procedure

Examples of analgesic treatment
cont.
• 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

Thank you
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