Perioperative Nerve Blockade: Clues from the Bench
Table 1
Effect of block on animal nerve injury models. Single means one application, local means on the injury site, and pre-emptive: yes: before the injury. SNL: spinal nerve ligation, CCI: chronic constriction injury, SNI: spared nerve injury, Seltzer: partial sciatic nerve ligation, d: day(s), dpi: day(s) postinjury, iv: intravenous, it: intrathecal, ip: intraperitoneal, ttt: treatment, DRG: dorsal root ganglion, SC: spinal cord, RTX: resiniferatoxin, and TTX: tetrodotoxin.
Author
Year
Drug
Duration
Route
Preemptive
Model
Time of effect
Effect
Behavioral changes
I. Kissin
1999
N-b-tetracaine
single
saphenous
yes
saphenous transection
7 dpi
Prevention early pressure hyperalgesia, caused hyperalgesia alone at 10 d
Lidocaine
Single
saphenous
yes
saphenous transection
1 dpi
Prevention early pressure hyperalgesia
Y. W. Yoon
1996
Bupivacaine
Single
dorsal root L4/5 5 dpi
no
SNL L5/6
5 dpi
L5: reduction of mechanical + cold allodynia and ongoing pain; L4: reduction of mechanical + cold allodynia
Z. Seltzer
1991
Marcaine
Single
sciatic/ saphenous
yes
sciatic/ saphenous transection
Autotomy is delayed and its magnitude decreased
P. M. Dougherty
1991
Lidocaine
Single
sciatic
yes
CCI
3 and 10 dpi
Reduction in duration and magnitude of thermal hyperalgesia
Lidocaine
Single
sciatic
yes
Seltzer
3 and 10 dpi
No effect
S. Abdi
2000
Lido/bupivacaine
Single
local before or 4 dpi
yes/no
SNL L5/L6
1 d after ttt
Reduction of mechanical allodynia, no long-term effect
J. M. Zhang
2000
Lidocaine
During 1 or 8 d
DRG following injury
no
DRG compression
1–28 dpi
Reduction of mechanical allodynia and hyperalgesia ipsilaterally with partial effect contralaterally
L. Luo
1995
Lido/tocainide
Single
it
yes
sciatic section
42 d after ttt
No effect on autotomy
S. R. Chaplan
1995
Lidocaine
Single
iv, it, local, 28 dpi
no
L5/L6 ligation
21 d after ttt
Reduction of mechanical allodynia only if plasma concentration was high enough, no long-term effect of local and it
J. Mao
1992
Bupivacaine
Single
sciatic, 3 dpi
no
CCI
1 d after ttt
Reduction of thermal hyperalgesia
J. M. Gonzalez-Darder
1985
Mepivacaine
Single
local
yes
sciatic section
7–70 dpi
Reduction and delay of autotomy
M. L. Sotgiu
1995
Lidocaine
Single
sciatic, iv or iv
yes
CCI
21 dpi
Reduction in paw licking during 2-3 weeks, then no difference
I. Bileviciute-Ljungar
1999
Lidocaine
Repeat
sciatic contra, dpi
no
CCI
36 dpi
Reduction of thermal hyperalgesia 3-4 d, small effect on pressure stimulation, reduction of autotomy 36 d
T. Yamamoto
1993
Bupivacaine
Single
sciatic
yes
CCI
till 14 dpi
Delaying of thermal hyperalgesia until day 14
Bupivacaine
Single
sciatic 15 min post
no
CCI
7 dpi
No effect on thermal hyperalgesia
M. R. Suter
2003
Bupvacaine
Long term
sciatic/spheres
yes
SNI
4 weeks
No effect on mechanical allodynia, thermal hyperalgesia, cold allodynia
Y. S. Lyu
2000
TTX
Single
DRG
no
Chung L5 ligation
2 h after ttt
Reduction of mechanical allodynia, no long-term effect
S. R. Chaplan
2003
ZD7288
Single
ip, 7 dpi
no
SNL L5/6
1 day after ttt
Reduction in mechanical allodynia for 2 h, no effect at 24 h
L. M. Batista
2009
Lidocaine
Single
sciatic
yes
CCI, nylon
over 28 days
Reduction of scratching, thermal hyperalgesia (noxious and non-noxious)
I. Sukhotinsky
2004
Lidocaine
Single
DRG L4 or L5
no
SNL
280 min
Reduction allodynia from 2 to 280 min after ttt, more effective on L5 than on intact L4
S. Eschenfelder
2000
Lidocaine
Single
dorsal root L5 before section
yes
SNL L5
57 dpi
No difference for mechanical hyperalgesia
Biochemical or electrophysiological changes
J. M. Zhang
2004
Lidocaine
7 d
ip, pump
no
SNL
7 and 14 dpi
Reduction in tyrosine hydroxylase staining
Lidocaine
14 d
sciatic, pump
yes
sciatic transection
14 dpi
Reduction in tyrosine hydroxylase staining
C. T. Lin
2009
Lidocaine
Single
median nerve
yes
median nerve transection
28 dpi
Dose dependent reduction of injury discharge pre and post electrical stimulation and of NPY and c-fos in cuneate nucleus
I. Omana-Zapata
1997
TTX
Single
intravenoous
no
sciatic transection
4–10 days
Dose dependent reduction of ectopic activity
I. Bileviciute-Ljungar
2001
Lidocaine
Single
contralateral subcutaneous
no
CCI
14 dpi
WDR L4/5 neuron ipsilateral: spontaneous hyperactivity reduced for 60 min
L. A. Colvin
2001
Amethocain
Single
dorsal roots L2–6
no
CCI
10–14 dpi
No effect on neuropeptide Y release in spinal cord (measurement period of 2 h)
J. Scholz
2005
Bupivacaine
7 d
sciatic, spheres
yes
SNI
7 dpi
Delay in apoptosis of inhibitory interneurons in the dorsal horn of spinal cord
Y. R. Wen
2007
Bupvacaine
3 d
sciatic, spheres
yes
SNI
3 dpi
Inhibition of p38MAPK activation in microglia in the spinal cord dorsal horn
W. Xie
2009
Bupivacaine/TTX
Long term
sciatic/DRG pump 7d
no
SNI/SNL
1–10 dpi
TTX: inhibition of NGF increase (DRG, d3) OX-42 (SC, d3) and GFAP (SC, d10); both: inhibition of glial activation (DRG, d1–10)
S. I. Chi
1993
Local anesthetic
sciatic or systemic
no
sciatic transection
2 and 14 dpi
Reduction in c-fos immunoreactivity in dorsal horn of spinal cord
S. I. Chi
1993
Lidocaine
sciatic or systemic
yes
sciatic transection
2 dpi
Reduction in c-fos immunoreactivity in dorsal horn of spinal cord
M. R. Suter
2009
Bupivacaine/RTX
2 d
sciatic, spheres
yes
SNI
2 dpi
Bupi: inhibition of microglia proliferation and p38MAPK activation in dorsal horn of spinal cord; RTX: no effect
Mixed outcomes
L. Liang
2010
TTX
Repeat
sciatic, daily
yes
electrical stimulation
up to 35 dpi
Reduction of mechanical allodynia, GFAP-staining on DRG
B. A. Rooney
2007
Lidocaine
Single
dorsal root
yes
bilateral dorsal root L4/5 section
up to 13 days
No increase in excitatory amino acid 10 min post injury, reduction in mechanical allodynia
W. Xie
2005
Bupivacaine
Long term
sciatic, after lesion
no
CCI and SNI
up to 70 d (CCI), 150 d (SNI)
Reduction in mechanical and heat pain for 60 d (CCI + SNI), suppression of hyperactivity at 20–28 dpi in A and C fibers
W. Xie
2005
TTX
Long term
sciatic, TTX (pump 3 or 7 d) just after lesion or 10 d later
no
CCI and SNI
up to 70 d (CCI), 150 d (SNI)
Reduction in mechanical and heat pain for 60 d (CCI + SNI), TTX 10 d effective only during infusion, suppression of hyperactivity at 20–28 dpi in A and C fibers
R. W. Colburn
1997
Bupivacaine
Repeat
spinal nerve before cut + before closure
yes
spinal nerve cryoneurolysis
10 dpi
Reduction of microglial, but only minimal on astrocytic response, no effect on mechanical allodynia
S. Lee
2007
Lidocaine
Single
spinal nerve, it
yes
SNL L5/6
1–4 dpi
Delay in mechanical allodynia by 1–4 d
C. Sato
2008
Ropivacaine
Repeat
epidural, daily 7–17 dpi
no
CCI
since 11 dpi
Relief of thermal hyperalgesia, small reduction of mechanical allodynia, NGF increase in DRG with ropivacaine
W. Xie
2007
TTX
7 d
sciatic, pump
yes
sciatic transection
35–49 dpi
Reduction of hyperexcitability of large and medium cells and sympathetic sprouting. No change in C fiber through TTX