Download Updates Neuropathic Pain

Neuropathic & Muscle Pain:
Rational Polypharmacy
Anticonvulsants,
Antidepressants, Muscle
Relaxers
Steven Stanos, DO
Center for Pain Management
Rehabilitation Institute of Chicago
IASP
NEUROPATHIC PAIN:
“initiated or caused by a
primary lesion or dysfunction
in the nervous system”
“Nociceptive” vs. “Non-Nociceptive”
Beydoun A, Backonja. J Pain Symp Management 2003.
Cutaneous Sensation
C-fiber
• Small diameter
• Slow conducting
• Unmyelinated
Caterina, Cur Op in Neurobiology (9), 1999.
A-δ
• Medium diameter
• Fast conducting
• Lightly myelinated
• Polymodal
Primary Afferent C & Aβ Fibers
Sensation Mediated
Fibre Threshold Principal
Receptors
Class For
Transmitters Engaged Physiological
Activation
SP/NKA
NK
Noxious
C
High
(pain)
CGRP
CGRP
EAA
NMDA
AMPA
mGlu
Aβ
Low
EAA
Millan, Progress in Neurobiology, 1999.
AMPA
Innocuous
(no pain)
Pathological
Highly noxious
(hyperalgesia)
Cold Allodynia
(pain)
Mechanical
allodynia
Neuropathic Pain: A PARADOX
Cutting a telephone wire

Spontaneous
Paresthesias
Dysesthesias
Pain
 Movement evoked pain
 Tenderness with
denervation
Peculiar symptoms
Paroxysmal
Electric shock-like
Tingling
Shooting
Burning
Neuropathic Pain
MECHANISMS
•
•
•
•
•
Ectopic activity in sensitized C-nociceptors
Regenerating nerve sprouts
Recruitment of silent nociceptors
Spontaneous/evoked activity in DRGs
Neuronal “hyperexitability”
Molecular Changes
•
•
•
•
Sodium channel accumulation
Glutamate receptor activity
Reduction of GABA-ergic inhibition
Penetration of calcium into cells
Jensen T. European J Pain 2002; (6) A.
Peripheral Sensitization
SKIN
Plasma Extravasation
Vasodilation
Macrophage
Mast
Cell
TNF-α
IL-6
LIF
Tissue
Damage
Pressure ?
Heat
5-HT3 Histamine PGE2
VR1
H+
5-HT3 H1
Bradykinin
EP
H+
IL1ß NGF ATP
B1/B2
IL1-R TrkA P2X ASIC
Ca2+
(PKC)
PKA
PKC
TTXr
(SNS/SNS2)
TTXs
Gene
Regulation
TTXr
Sub P
Adapted from Woolf CJ, et al. Science. 2000;288:1765-1768.
Peripheral
Nerve
Terminal
Central Mechanisms/ Wind Up
Hansson PT, Fields HL, Hill RG, Marchettini P eds, Neuropathic Pain: Pathophysiology and Treatment,
International Association for the Study of Pain Press, Seattle, 2001
Central Sensitization
Voltage sensitive:
Ligand gated:
N & P/Q channels
Α2δ subunit
L channel
NMDA / glutamate
Type
C
fibers
GLU
SP
Voltagegated
Ca2+ channel
GLU
SP
AMPA
Na+
Ca2+
K
NMDA
Ca2+
+
Type
C
fibers
Ca2+
Ca2
+
NOsynthase
NO
Immediate-early
genes
(C-fos, C-jun)
IP3
ACPD
GL
U
SP
Adapted with permission from Ollat H, Cesaro P. Pharmacology of neuropathic pain. Clin Neuropharmacol.
1995; 18:391-404.
Mendell, NEJM 348;13,2003
SODIUM CHANNELS
• Tetrodotoxin-sensitive
• Tetrodotoxin-resistant
Future:
cloning human DRG
GABA
Glutamate
Excitatory
GABA
Inhibitory
GABA
Modulate receptor
(-)GABA transaminase
(-) reuptake
Enhance GABA
1st Generation
Barbiturates
Benzodiazipines
Valproate
2nd Generation
Tiababine (Gabitril)
Topiramate (Topamax)
Vigabitrin (Sabril)
Zonisamide (Zonegran)
*Gabapentin (Neurontin)
*Pregabalin (Lyrica)
NSAIDs
Tricyclic
Antidepressants
Antiepileptics
Topical Analgesics
Tricyclic Antidepressants
• Central blockade of monoamine uptake
• Enhancement of descending inhibition
• Adrenergic blockade on sprouts, NMDA
antagonistic effects, opioid modification, and
sodium channel blockade
• Constant vs. Paroxysmal pain
• Nortriptyline = Amitriptyline
(McQuay, Pain, 1996)
Tricyclic Antidepressants: Adverse
Effects
• Commonly reported
AEs (generally
anticholinergic):
–
–
–
–
–
–
–
–
–
blurred vision
cognitive changes
constipation
dry mouth
orthostatic
hypotension
sedation
sexual dysfunction
tachycardia
urinary retention
AEs = adverse effects.
Fewest
AEs
• Desipramine
• Nortriptyline
• Imipramine
• Doxepin
• Amitriptyline
Most
AEs
Neuropathy
PHN
Central Pain
All types
3.0
2.3
1.7
TCA all types
2.4
2.3
1.7
TCA serot / norad
2.0
2.4
1.7
SSRI
6.7
ND
ND
Antidepressants
Ion Channel Blockers
Mexilitine
10.0
Phenytoin
2.1
Carbamazepine
3.3
Gabapentin
3.7
3.2
NMDA Antagonist
Dextromethorphan
1.9
Oxycodone
Capsaicin
2.5
5.9
Sindrup, Jenson Pain 83, 1999
5.3
Tricyclic Antidepressants: Positive
Controlled Trials
Study
Painful DPN
Max
Max
N
Weeks
29
108
12
14
Pain relief
Pain relief
26
6
Max
Amitriptyline (25-150, PBO)
Desipramine (12.5-150, PBO),
Amitriptyline (12.5-150, PBO)
Desipramine (50 or 200, PBO),
Clomipramine (50 or 75, PBO)
Desipramine (12.5-250, PBO)
20
12
Neuropathy
symptoms
Pain relief
PHN
Watson
Max
Graff-Radford
Kishore-Kumar
Raja
Amitriptyline (12.5, PBO)
Amitriptyline (12.5-150, PBO)
Amitriptyline (12.5-200, PBO)
Desipramine (12.5-250, PBO)
Nortriptyline (10-160, PBO)
24
58
49
26
76
8
12
8
12
24
Sindrup
Agent (mg/d)
Primary End Point
Pain relief
Pain relief
Pain intensity
Pain relief
Pain intensity, relief;
cognitive function
Max et al. Neurology. 1987;37:589
1987;37:589--596;
596; Max et al. N Engl J Med. 1992;326:1250
1992;326:1250--1256;
1256; Sindrup et al. Br J Clin
Pharmacol.
Pharmacol. 1990;30:683
1990;30:683--691;
691; Max et al. Pain. 1991;45:3
1991;45:3--9; Watson et al. Neurology. 1982;32:671
1982;32:671--673;
673; Max
et al. Neurology. 1988;38:1427
;16:188--192;
1988;38:1427--1432;
1432; GraffGraff-Radford et al. Clin J Pain. 2000
2000;16:188
192; KishoreKishore-Kumar et al.
Clin Pharmacol Ther. 1990;47:305
1990;47:305--312;
312; Raja et al. Neurology. 2002;59:1015
2002;59:1015--1021.
1021.
Antidepressants
Class of
Medicatio Medication
n
Action
Tricyclic
Amitripyline
Nortriptyline
Serotonergic, noradrenergic, anticholinergic, Na+
channel blocker,
antihistaminic
Noradrenergic,
anti-cholinergic, Na+
channel blocker,
antihistaminic
Tricyclic
Desipramine
SSRI
Escitalopram
Citalopram
Sertraline
Serotonergic
SNRI
Vanlefaxine
Duloxetine*
Atypical
Mirtazepine
Site of
Action
Therapeutic
Effects
Side Effects
Brain
Descending
pathways
peripheral
nerve
Brain
Descending
pathways
peripheral
nerve
Brain
Descending
pathways
Antidepressant
Drowsiness, Dry
Analgesic (neuropathic mouth, constipation,
pain at low dose)
arrythmia, urinary
retention, weight
gain
Antidepressant
Drowsiness, agitation
Analgesic (neuropathic
pain at low dose)
Antidepressant
sexual dysfunction,
perspiration
Serotonergic
Noradrenergic
Brain
Descending
pathways
Antidepressant
Analgesic
sexual dysfunction,
perspiration,
drowsiness
Serotonergic
Antihistaminic
Brain
Descending
pathways
Antidepressant
Drowsiness, weight
gain
*FDA indicated for diabetic peripheral neuropathy.
Physician's Desk Reference. Montvale, NJ: Thomson PDR; 2005
Pharmacologic Profile of
Antidepressants
Type of Action
Receptor Type
TCAs
Amitriptyline
Clomipramine
Imipramine
Desipramine
Maprotiline*
Nortriptyline
SNRIs
SSRIs
Duloxetine
Venlafaxine
Citalopram
Fluoxetine
Paroxetine
(±)?
Ion channel
blockade
Sodium channel
Calcium channel
+
+
+
+
(±)
?
?
?
Monoamine
transporter
blockade
5-HT
Norepinephrine
Dopamine
+
+
–
(±)
+
+
–
+
–
–
–
–
–
–
–
–
–
–
+
–
α-Adrenergic
+
+
H1-Histaminergic
+
+
Receptor
Muscarinicblockade
cholinergic
+
+
+
+
*Tetracyclic antidepressant. NMDA
+=present; (+)=weak; –=not present; ?=unknown; 5-HT=serotonin.
Sindrup S, Jensen T. Hansson P, Fields H, Hill R, Marchettini P, eds. Neuropathic Pain: Pathophysiology
and Treatment Progress in Pain Research and Management. Seattle, Wash: IASP Press;2001:169-183.
1st generation anticonvulsants
• Phenytoin
Diabetic Neuropathy:
NNT: 2.1
• Carbamazepine
(300 – 1000 mg/day)
Trigeminal Neuralgia:
NNT: 2.6 NNH:
3.4
Diabetic Neuropathy:
• Valproic acid:
3.3
FDA-Approved Treatments for
Neuropathic Pain
• Carbamazepine
– Trigeminal neuralgia
• Duloxetine
– Peripheral diabetic neuropathy
• Gabapentin
– Postherpetic neuralgia
• Lidocaine Patch 5%
– Postherpetic neuralgia
• Pregabalin
– Peripheral diabetic neuropathy
– Postherpetic neuralgia
AED action
Medication
Action
Side Effects
Interaction
Gabapenitin
Pregabalin
Ca++ Channel
modifiers
Short term memory loss,
Opioids
weight gain, confusion
Topirimate
Ca++, Na++ chan,
fatigue, wt loss, nrw
GABA-ar, CA in, free angle glaucoma, renal
radical scavenger
stones
BCPs, First gen AEDs
Tiagabine
GABA Reuptake
inhibitor
First gen AEDs
Lamotrigine
Anti TB drugs, First
Ca++, Na+ chan, Dec Dizzy, somn, nausea,
gen AEDs,
NMDA Ca, GABA-ar
ataxia, Stevens Johnson
oxcarbazepine
Oxcarbazepine
Na+ chan, K+ efflux
Levetiracitam
Blocks inhibitors of Somnolence, dizzy,
GABA-ar (Zinc, beta agitation, headache,
carboline)
aggression
Dyspepsia, drowsiness,
confusion, seizure
Hyponatremia, nausea,
BCPs, cyclosporine
HA, dizzy, hepatotoxicity
Physician's Desk Reference. Montvale, NJ: Thomson PDR; 2005
None
Topiramate (Topamax)
25, 100, 200mg
1. Modulation of voltage-gated Na channels
2. Potentiate GABA inhibition
3. Block Glutamate neurotransmission
4. Modulate Ca channels
5. Inhibition of carbonic anhydrase
side effect. perioral paresthesias
Side effects: diarrhea, anorexia, somnelance, asthenia,
weight loss, confusion
6. Renal stones: 2-4 times greater risk
7. Oligohydrosis, metabolic acidosis warning
Chong, Clin J Pain (19),2003.
Topiramate (Topamax)
(Edwards, 1998) DN, N=8, 258mg/day, VAS 8.7 vs. 4.5
(Zvarau,2000) TN/MS, N=6,200-300mg/day, 4=complete
(Haugh,2000) TN, N=8, avg. 175mg/day
(Potter, 2000) NPP, N=14, weekly titration 25mg,
First Pain Relief = 214 mg/day
Last visit dose = 271 mg/day, VAS 8.8 vs. 3.1
(Pappagallo, 1998) refractory chronic pain
Pain reduction correlated with allodynia
(Rosenthal,2003) DN, N= 323, titrated to 400mg/day
VAS: pre 68.0, post 46.2 (54.0)
>50% in VAS: 36%
Chong, Clin J Pain (19),2003.
Lamotrigine (Lamictal)
25, 100, 150, 200mg
•
•
•
•
•
Blocks voltage-sensitive sodium channels
Inhibits pre-synaptic glutamate release
Lack of drug interactions
No serum monitoring
Rash
Lamotragine (Lamictal)
Zabrzewska
Pain 73
(1997)
N = 14
DBPC
Refractory
TN
Superior to
placebo
11/13
400 mg
Eisenberg
2000
N = 59
NP
6.4 to 4.1
Eisenberg
Eur J Pain
7 (2003)
N = 14
Sciatica
VAS
7.9 to 4.1
50%
completed
25-400
mg/day
400 mg
Simpson
Neurology
60 (2003)
N= 227
RDBPC
HIVassociated
DSP/ ATN
Effective in
patients on
neurotoxic
ART
400 mg
Oxcarbazepine (Trileptal)
150, 300, 600mg
• Keto analog of
Carbamazepine (Tegretol)
• Active metabolite (MHD)
• Voltage-dependent sodium
channels
• N-type calcium channel effect
• Potentiate dopamine, inhibit
glutamate
• TGN: 900-2100 mg/day
• APS 2004: 700-800 mg/day
Ambrosio et al, Neurochemical Res 27, 2002.
Tiagabine
Selective GABA Reuptake Inhibitor (SGRI)
2, 4, 12, 16mg
Tiagabine(Gabitril)
Jenson
2002
N = 10
NP
refractory to
gabapentin
80% good to 12 mg/day
excellent
Kanard
2000
N = 17
Painful
Sensory
Neuropathy
50%
4 to 16 mg/
discontinued day
Taylor FB
J Clin Psych
2003
N=7
PTSD
6/7
Improved
4 – 12 mg/
day
Kirby
APS
2004
N = 14
Diabetic
Neuropathy
Decreased
pain,
improved
sleep
16 mg/day
Zonisamide: Mechanisms of Action
• Reduces repetitive neuronal firing via blockade
of Na+ channels1
• Reduces voltage-dependent T-type Ca+2
channels2, facilitates dopaminergic and
serotonergic neurotransmission1
• Weakly inhibits carbonic anhydrase2
• Blocks K+ evoked glutamate release3
•
Long half life: 63 – 69 hours
• Sulfonamide derivative
1Schauf.
2Suzuki,
Brain Res. 1987;413:185-188.
et al. Epilepsy Res. 1992;12:21-27.
Levetiracetam (Keppra)
• Atypical GABAergic & glycine effects
• (-) zinc & beta carbolines, enhancing
choride ion influx at GABA-A receptor
• No hepatic metabolism, low protein
binding
• Rapid dosage titration
• Case reports of rectal use (1000 BID)
Dunteman APS, 2004
Levetiracetam (Keppra)
Cochran
APS,2003
NP
N = 15
Rowbotham Neoplastic N = 10
AAN,2003
NP
Price
Clin J Pain,
20(1), 2004
Periph
3 cases
Neuropathy
Kaplan
APS, 2004
57% Radic
26% HA
17% DN
N = 53
65% very
effective
1000 2000mg
33%
responders
500 –
3000mg
500 –
1500mg
BID
92% good to 750 –
excellent
1500mg
Anxiety
Pregabalin Binds to the 2- Subunit
of Voltage-Gated Ca2+ Channels in the Central
Nervous System
Pregabalin
Presynaptic
α2-
subunit
Ca2+
channel
Neurotransmitters
Presynaptic
α2-
subunit
Ca2+
channel
Neurotransmitters
Postsynaptic
Postsynaptic
Schematic representation of pregabalin’s proposed mechanism of action
• Pregabalin selectively binds to 2- subunit of calcium channels
•
•
•
•
Modulates calcium influx in hyperexcited neurons
Reduces neurotransmitter release
Pharmacologic effect requires binding at this site
The clinical significance of these observations in humans is currently unknown
Taylor. CNS Drug Rev. 2004;10:1832004;10:183-188.
Pregabalin Is Not a Calcium
Channel Blocker
Ion channel
Ion channel
PREGABALIN
α2
α2
EXTRACELLULAR
EXTRACELLULAR
CCB

α1
Ca2+
influx
blocked
α1
β
δ
Cell membrane
INTRACELLULAR
• Ca2+ channel blockers (CCBs) bind to 1 subunit
•
•
of L-type calcium channels and directly block the
pore
CCBs prevent movement of Ca2+
CCBs work in the peripheral vascular smooth
muscle and relax arteries to reduce systemic
blood pressure

α1
α1
β
Ca2+
influx
attenuated
δ
Cell membrane
INTRACELLULAR
• Pregabalin binds to the 2- subunit and
modulates the influx of Ca2+ into the cell in
hyperexcited neurons
– Pregabalin works at brain and spinal cord
synapses that have Ca2+ channels, but
does not alter vascular or cardiac function
Pregabalin modulates Ca2+ channels (does not block)
Triggle.
Triggle. Cleve Clin J Med.
Med. 1992;59:6171992;59:617-627; Taylor. CNS Drug Rev. 2004;10:1832004;10:183-188;
Data on file. Pfizer Inc, New York, NY.
Pregabalin: Predictable Response
Versus Gabapentin
Linear PK Profile
High Bioavailability
18
Steady State Cmax (μg/mL)
16
Pregabalin
Gabapentin
14
900 mg, 60%
12
μ
10
All doses
8
90%
1200 mg, 47%
2400 mg, 34%
3600 mg, 33%
6
4
Pregabalin
Gabapentin
2
1800 mg
Recommended
dose
0
0
600 1200 1800 2400 3000 3600 4200 4800
Dose (mg/d)
Lyrica® (pregabalin) Capsules CV [package insert]. New York, NY: Pfizer Inc; 2005;
2005; Neurontin® (gabapentin)
[package insert]. New York, NY: Pfizer Inc; 2004; Wesche,
Wesche, Bockbrader.
Bockbrader. Presented at: 24th Annual Scientific
Meeting of the American Pain Society; 2005.
Mechansims, Mechanisms
AED
Na+
Channel
Blockade
Pregabalin
Gabapentin
Lamotrigine
Ca2+
Channel
Blockade
Glutamate
Antagonism
GABA
Potentiation
Carbonic
Anhydrase
Inhibition
X
X*
X
Topiramate
X
Tiagabine
OxcarbazepineX
Zonisamide
X
Levetiracetam
X
X
X
X
X
X
X
X
X
X
X
X
mechanism unknown
*Mechanism not clearly established.
White HS. In: Pellock JM, Dodson WE, Bourgeois BFD, eds. Pediatric Epilepsy: Diagnosis and Therapy. 2nd ed. New
York, NY: Demos Medical Publishing Inc; 2001:301-316.
•
•
•
•
Muscle Relaxers: Patterns of
Use
85% took for back pain1
Average length of use: 2.1 years1
44.5% took longer than 1 year1
No difference in use patterns in those
patients with ambulatory impairment or
lung disease1
• Benzodiazepine and muscle relaxer use
associated with fractures in elderly2
1. Dillon C, et al. Spine 2004;8:892-96.
2. Coutinho E, et al. BMC Geriatrics 2008;9:21.
Muscle Relaxants
Muscle Relaxers
Name
Generic
Staring dose
Effective dose
Cyclobenzaprine
Flexeril
5mg TID
10-20mg TID
Orphenadrine
Norflex
100 mg BID
100 mg TID
Carisoprodol
Soma
350 mg TID
350 mg QID
Metaxalone
Skelaxin
400 mg TID
800 mg TID
Methocarbomal
Robaxin
500 mg QID
750 mg QID
Balcofen
Lioresol
5mg TID
10-20 mg TID
Cyclobenzaprine (Flexeril) (5mg, 10mg)
• FDA approved 1977 (10mg)
• Animal studies1: via serotonin receptors at spinal
level to block alpha-mononeuronal excitation
• “muscle spasm” dose: 5mg TID
• 2 studies for acute pain 2:
Result: 7 day treatment, by day 3, 78%-83% relief,
average 2 days earlier (30% reduction in time to
relief)
1. Honda M, et al. Eur J Pharmacol. 2003;458:91-99.
2. Borenstein DG, Korn S. Clin Ther. 2003;25:1056-73.
Cyclobenzaprine: Meta-analysis
• Treated patients 5x as likely to report
symptom improvement by day 14 vs.
placebo1
• Effect is greatest in first 4 days
• NNT: 2.7
• Effects size: 0.5
• Myofascial Pain2: (2 studies)
– Insufficient evidence
1. Browning R, et al. Arch Intern Med. 2001;161:1613-20
2. Leite et al. Cochrane Database 2009;3:CD006830.
Cyclobenzaprine HCl ER
(Amrix)
Amrix (Cephalon): 15mg or 30mg Q day
Tmax: 8.1 hrs,
T1/2: 34 hrs
Results:
15 mg and 30mg effective in treating muscle
spasm associated with painful MSK
conditions after 4 days
1. Malanga G, et al. Cur Med Res Opinioin 2009;251179-96.
2. Cyclobenzaprine ER/ Amrix package insert (Cephalon), 2009
Metaxalone
• FDA approved 19641
• “adjuvant therapy to
rest, PT, and other
measures for the
relief of discomforts ”
• 400mg to 800 mg TID
or QID
• 69.6% vs. 17.4%
marked or moderate
improvement
• Onset of action: 1 hr
• Peak levels: 2 hr
• Tmax: 4.3 h (fat
meal); 3.3 h (fasting)
• Duration: 4-6 h
1. Fathie K. Curr Ther Res Clin Exp. 1964;6:677-83.
Carisoprodol (Soma)
• FDA approved in 1959
• Human evidence of muscle relaxation limited, animal
models possible block of descending reticular formation
in spinal cord1
• Dose: 350mg QID
• Soma vs. Butabarbital2:at 4 days, greater overall relief
• Metabolite: meprobamate (Schedule IV)
• SOMA scheduled in individual states
• 14 of 20: list of abused mood-altering substances2
1. Physicians’ Desk Ref, 58th ed, PDR, 2004.
2. Hindle TH, California Med. 1972;117:7-11.
3. Prescription Drug Addiction:
http://www.addicusbooks.com/news_release_RxAddiction.htm
Abuse Potential: Soma
• n = 40, use of Soma for > 3 months, with/without history
of substance abuse
• Results: (with Hx substance abuse):
– 40% used in larger amounts than prescribed
– 30% used for an effect other than prescribed
– 10% used to augment effect of another med
– 20% attempted to obtain extra Soma prescription
– 10% used others, or obtained illegally
• All patients with Hx abuse: 65% used Soma in >1 of the
above
Reeves RR, et al. J Addict Dis. 1999;18:51-56.
Muscle Relaxants in Acute LBP
Bernstein et al, Spine 2004;29:1346-131.
• Good: APAP NSAIDs, muscle relaxers (acute),
TCAs (chronic)
• Fair: tramadol, benzos, gabapentin (radiculopathy)
• 36 trials in 4 systematic reviews
• Duration of trials 2 weeks or less
• Acute LBP: muscle relaxants superior 2-4 days
• Mixed results for cyclobenzaprine
Chou R, Huffman L. Ann Intern Med. 2007;147:505-14.
Tizanidine
• Peak serum levels:1-5 hrs
• ½ life: 4-8 hrs
• Side effects: dry mouth, somnolence,
hypotension, bradycardia
• Renal impairment: clearance 50%
• Max dose 36 mg/day
• Muscle spasm1:tizanidine vs. diazepam (7D)
Greater lateral flexion
• Myofascial Pain2: titrated to 12 mg, improved
pain, sleep, pressure thresholds
1. Fryda-Kaurimsky Z. J Int Med Res. 1981:9:501-5.
2. Malange G, et al Pain Phys 2002;5:422-32.
57
Topical Agents for Myofascial
Pain
• Lidocaine Patch 5%
• Diclofenac Patch 1.3%
Lidocaine Patch vs. lidocaine injection
Methods: lidocaine patch BID, placebo patch BID,
TrP injection 1 mL 0.5% bupicacaine
Outcomes: VAS, pain attacks, pain-related
function, pressure and pain thresholds
Results:
Affaitati G, et al. Clin Ther 2009;31:705-720.
Lidocaine Patch vs. bupivicaine injection
Affaitati G, et al. Clin Ther 2009;31:705-720.
Diclofenac Patch
• Study: MPS upper trapezius
• Diclofenac 60mg patch TID vs, Menthol
patch
• Outcomes: VAS, cervical ROM, pain
threshold, PGIC, neck disability index
• Results:
– Day 4: 27% reduction in VAS vs. 21%
– Day 8: 51% reduction in VAS vs. 25%
Hsieh L, et al J Pain Symptom Manage 2009, in press.