Pain III: Adjuncts - McDougall 3

Question 1

Advantages of smoked cannabis

Answer 1

Pain relief, improved sleep, reduced anxiety

Question 2

Disadvantages of smoked cannabis

Answer 2

Not appropriate for al patients
Psychotropic effects
Smoking is not safest mode of administration

Question 3

Phytocannabinoids

Answer 3

Derived from cannabis plant

Question 4

Synthetocannabinoids

Answer 4

Man made

Can reduce nociception in arthritic joints locally

Question 5

Endocannabinoids

Answer 5

Present naturally in the body
Ie. Anandamide
May be an effective system to control arthritis pain naturally
Local inhibition of breakdown reduces nociception and inflammation

Question 6

Cannabinoid receptors

Answer 6

CB1, CB2

Question 7

CB1

Answer 7

Located on central and peripheral nerves

Agonist decreases signal in OA joint mechanosensitivity

Question 8

CB2

Answer 8

Associated with immunocytes

Question 9

Endocannabinoid synthesis

Answer 9

Phospholipids - phospholipase C _ archidonic acid- anandamide, 2AG, Noladin, NADA, Virodhamine

Question 10

Limitations of endocannabinoids

Answer 10

Only switched on when we need them

Enzymes are produced that chew then up pretty quickly

Question 11

FAAH inihibition

Answer 11

Fatty acid amide hydrolase

Increase bioavailability of Anandamide, reducing mechanosensitivity of joints

Question 12

AMT

Answer 12

Anandamide membrane transporter

Question 13

FAAH

Answer 13

Fatty acid amide hydrolase

Processes anandamide into ethanol amine and arachidonic acid

Question 14

NAPE

Answer 14

N-arichidonyl-phosphatidylehtanolamine

Hydrolyzed into anandamine

Question 15

Leukocyte rolling and inflammation

Answer 15

Endocannabinoids decrease rolling
Prevents leukocytes from entering tissue and releasing compounds to cause inflammation and sensitization of the peripheral nerve

Question 16

TRPs

Answer 16

Transient receptor potential channels

Molecular sensors of taste, temperature and pain

Question 17

TRPV1

Answer 17

Chilli receptor
Expressed on C-fibres and Adelta-fibres, in laminae I/II of spinal cord
Non-selective cation channel
Endogenous ligands: anandamide, endovanilloids
Exogenous ligands: capsaicin, resiniferatoxin

Question 18

Capsaicin

Answer 18

Hot component of chilli peppers
Acts on sensory nerves
Initial sensitization followed by prolonged desensitization

Question 19

Acute low concentration (TRPV1)

Answer 19

Sensitization, followed by Ca2+ dependent phosphorylation of ion channel causing desensitization

Question 20

Prolonged exposure/high concentration (TRPV1)

Answer 20

Destruction of C- and Adelta-fibres

Destruction recovers in adults but nerve loss is permanent in neonates

Question 21

Therapeutic potential of TRPV1

Answer 21

Topical capsaicin creams or patch for peripheral neuropathic pain
Found greater pain relied than oral medications
Adverse effects: skin irritation, burning oedema

Question 22

Therapeutic potential of TRPV1 antagonists

Answer 22

AMG517
Highly potent, selective, oral bioavailability
HOWEVER, systemic TRPV1 blockade, causing concentration dependent hyperthermia lasting days: blocked thermoregulatory centres in CNS

Question 23

TRPM8

Answer 23

Cool TRP
Melastatin TRP family
Non-selective cation channel
15% of small diameter sensory neurons
Expression increases in models of neuropathic pain
Exogenous ligands: menthol, icilin, spearmint