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, 6+11 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