21. Molecular marker of pain
ms sec min hour day week month year
AMPA
NMDA,
Sub-P, CGRP
Ca, NO, PKC
apoptosis ???
Neuronal Sprouting
dynorphin
NPY, galanin
c-fos
Kao & Sun, Chinese J Pain, 2003.
pErk
30. Mixed Type
Caused by a
combination of both
primary injury or
secondary effects
Clincal Pain
Nociceptive
Pain
Caused by activity in
neural pathways in
response to potentially
tissue-damaging stimuli
Neuropathic
Pain
Initiated or caused by
primary lesion or
dysfunction in the nervous
system
Postoperative
pain
Cancer pain
Osteoporosis
Arthritis
Back pain
Postherpetic
neuralgia
Neuropathic
spinal stenosis
Cancer pain
Myofascial pain
Central post-
stroke pain
Phantom pain
Trigeminal
neuralgia
Polyneuropathy (eg,diabetic,
chemotherapy)
75. 孫維仁
COX-2
NSAID on COX-1/2
COX-1
N-terminal
Carboxylic
group
of NSAID
forms
“salt bridge”
with
Arginine
at 120
C-terminal
containing
active sites
Arachidonic
Acid
NSAID
(flurbiprofen)
phenyl group
binds to
hydrophobic
channel
N-terminal
Carboxylic
group
of NSAID
forms
“salt
bridge”
with
Arginine
at 120
C-terminal
containing
active sites
Arachidonic
Acid
NSAID
(flurbiprofen)
phenyl group
binds to
hydrophobic
channel
Kurumbail et al. Nature. 1996; 384: 644-648
76. 孫維仁
Specific COX-2 Inhibitor
- “Side Pocket”
Hydrophilic
“side pocket”
N-terminal
C-terminal
containing
active sites
Arg 513,
Hist 90 – forms
hydrogen bonds with
oxygen in sulfonamide
side chain
Specific COX-2
inhibitor – phenyl
group binds to
hydrophobic channel
Arachidonic
Acid
Arg 120
Kurumbail et al. Nature 1996; 384: 644-648
78. Antidepressants in
Multiple mechanisms of action
RCTs and meta-analyses demonstrate benefit of
amitriptyline, nortriptyline, desipramine
Variable onset of analgesia
Independent of antidepressant activity
Improvements in insomnia, anxiety, depression
*Not approved by
FDA for this use.
79. Tricyclic Antidepressants
for Neuropathic Pain Disorders
Start at 10-25 mg at bedtime
increase every few days as tolerated to a target dose of 50 mg
if no effect at 2 wk, continue to increase
may need ≥150 mg
Can split dose to reduce side effects
Expect partial effect
use multiple agents
Consider preprescription cardiac evaluation