Anesth Pain Med.  2020 Jul;15(3):334-343. 10.17085/apm.20033.

Effect of two-week continuous epidural administration of 2% lidocaine on mechanical allodynia induced by spinal nerve ligation in rats

• Cheong Y
• Kim M
• Kim N
• Hwang B

• KMID: 2504896
• DOI: http://doi.org/10.17085/apm.20033

Abstract

Background
Lidocaine is an effective against certain types of neuropathic pain. This study aimed to investigate whether timing of initiating continuous epidural infusion of lidocaine affected the glial activation and development of neuropathic pain induced by L5/6 spinal nerve ligation (SNL) in rats.
Methods
Following L5/6 SNL, rats were epidurally infused 2% lidocaine (drug infusion initiated on days 1, and 7 post SNL model establishment) or saline (saline infusion initiated on day 1 post SNL model establishment) continuously for 14 days. Mechanical allodynia of the hind paw to von Frey filament stimuli was determined prior to surgery, postoperative day 3, and once weekly after SNL model establishment. At 7 days after the infusion of saline or lidocaine ended, spinal activation of proinflammatory cytokines and astrocytes was evaluated immunohistochemically, using antibodies to interleukin-6 (IL-6) and glial fibrillary acidic protein (GFAP).
Results
Continuous epidural administration of 2% lidocaine for 14 days increased the mechanical withdrawal threshold regardless of the difference in timing of initiating lidocaine administration. Epidurally infusing 2% lidocaine inhibited nerve ligation-induced IL-6 and GFAP activation. In the 2% lidocaine infusion group, rats maintained the increased mechanical withdrawal threshold even at 7 days after the discontinuation of 2% lidocaine infusion.
Conclusions
Continuous epidural administration of 2% lidocaine inhibited the development of SNL-induced mechanical allodynia and suppressed IL-6 and GFAP activation regardless of the difference in timing of initiating lidocaine administration.

Keyword

Anesthetics; Epidural; Glial fibrillary acidic protein; Hyperalgesia; Interleukin-6; Lidocaine; Neuralgia; Spinal nerves

Figure

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  Fig. 1. CONSORT diagram of the study design. SNL: spinal nerve ligation.

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  Fig. 2. Timeline of control group (A), no delay group (B), and 1-week delay group (C). Bar below the X-axis represents epidural infusion with lidocaine or saline for 14 days. SNL: spinal nerve ligation, IL: interleukin, GFAP: glial fibrillary acidic protein.

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  Fig. 3. Effect of continuous epidural infusion of 2% lidocaine for 14 days on SNL-induced mechanical allodynia, measured as paw withdrawal threshold to von Frey filament stimulus. Rats were randomly divided into four groups: sham (sham operation only without SNL), control (SNL, 2 ml/7 days, saline infusion started 1 day after SNL model establishment and administered for 14 days), no delay group (SNL, 2 ml/7 days, started 2% lidocaine infusion 1 day after SNL model establishment and administered for 14 days), and 1-week delay group (SNL, 2 ml/7 days, 2% lidocaine infusion started 7 days after SNL model establishment and administered for 14 days). Arrow indicates start point of lidocaine infusion. Values are presented as median (1Q, 3Q). SNL: spinal nerve ligation. *P < 0.05 vs. sham group. †P < 0.05 vs. control group (Mann–Whitney U test, n = 6–8 per group). ‡P < 0.05 vs. value just before lidocaine infusion (Wilcoxon signed-rank test, n = 6–8 per group).

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  Fig. 4. Photo-micrographic representation of hematoxylin and eosin-stained lumbar spinal nerve sections from sham (A), control group (B), no delay group (C), and 1-week delay group (D). Rats received infusion of saline or 2% lidocaine (10 μl/h) for 14 days. Original magnification × 400. Spinal sections displayed normal histological appearance. Based on microscopic examination, we found no gliosis, demyelination, fibrosis, inflammation, hemorrhage, or necrosis at the lumbar level in the spinal nerve.

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  Fig. 5. Effect of continuous epidural infusion of 2% lidocaine on the protein expressions of IL-6 (A) and GFAP (B) in a rat model of SNL-induced neuropathic pain. Rats were randomly divided into three groups: control (SNL, 2 ml/7 days, started saline infusion 1 day after SNL model establishment and administered for 14 days), no delay group (SNL, 2 ml/7 days, 2% lidocaine infusion started 1 day after SNL model establishment and administered for 14 days), and 1-week delay group (SNL, 2 ml/7 days, 2% lidocaine infusion started 7 days after SNL model establishment and administered for 14 days). Data are presented as mean ± SD. SNL: spinal nerve ligation, IL: interleukin, GFAP: glial fibrillary acidic protein. *P < 0.05 vs. control group.

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