J Korean Med Sci.  2013 Feb;28(2):308-314. 10.3346/jkms.2013.28.2.308.

Intrathecal Gabapentin Increases Interleukin-10 Expression and Inhibits Pro-Inflammatory Cytokine in a Rat Model of Neuropathic Pain

• Lee BS
• Jun IG
• Kim SH
• Park JY

• KMID: 1429210
• DOI: http://doi.org/10.3346/jkms.2013.28.2.308

Abstract

We examined the possible anti-inflammatory mechanisms of gabapentin in the attenuation of neuropathic pain and the interaction between the anti-allodynic effects of gabapentin and interleukin-10 (IL-10) expression in a rat model of neuropathic pain. The anti-allodynic effect of intrathecal gabapentin was examined over a 7-day period. The anti-allodynic effects of IL-10 was measured, and the effects of anti-IL-10 antibody on the gabapentin were assessed. On day 7, the concentrations of pro-inflammatory cytokines and IL-10 were measured. Gabapentin produced an anti-allodynic effect over the 7-day period, reducing the expression of pro-inflammatory cytokines but increasing the expression of IL-10 (TNF-alpha, 316.0 +/- 69.7 pg/mL vs 88.8 +/- 24.4 pg/mL; IL-1beta, 1,212.9 +/- 104.5 vs 577.4 +/- 97.1 pg/mL; IL-6, 254.0 +/- 64.8 pg/mL vs 125.5 +/- 44.1 pg/mL; IL-10, 532.1 +/- 78.7 pg/mL vs 918.9 +/- 63.1 pg/mL). The suppressive effect of gabapentin on pro-inflammatory cytokine expression was partially blocked by the anti-IL-10 antibody. Expression of pro-inflammatory cytokines was significantly attenuated by daily injections of IL-10. The anti-allodynic effects of gabapentin may be caused by upregulation of IL-10 expression in the spinal cord, which leads to inhibition of the expression of pro-inflammatory cytokines in the spinal cords.

Keyword

Allodynia; Gabapentin; Interleukin-10; Intrathecal; Pro-inflammatory Cytokines

MeSH Terms

Amines/pharmacology/*therapeutic use
Analgesics/pharmacology/*therapeutic use
Animals
Antibodies/immunology/pharmacology
Behavior, Animal/drug effects
Cyclohexanecarboxylic Acids/pharmacology/*therapeutic use
Cytokines/*metabolism
Disease Models, Animal
Injections, Spinal
Interleukin-10/genetics/immunology/*metabolism
Male
Neuralgia/*drug therapy/metabolism/pathology
Rats
Rats, Sprague-Dawley
Recombinant Proteins/biosynthesis/genetics/pharmacology
Spinal Cord/metabolism
Up-Regulation
gamma-Aminobutyric Acid/pharmacology/*therapeutic use
Amines
Analgesics
Antibodies
Cyclohexanecarboxylic Acids
Cytokines
Recombinant Proteins
Interleukin-10
gamma-Aminobutyric Acid

Figure

• 

  Fig. 1 Time course of paw withdrawal thresholds after spinal nerve ligation and with or without daily intrathecal injections of gabapentin (30 µg) over a 7-day period (6 rats per group). All data points are expressed as the mean ± SEM. *P < 0.05 vs SNL group, †P < 0.05 vs Sham group.

• 

  Fig. 2 Intrathecally injected gabapentin reduces the expression of TNF-α (A), IL-1β (B), and IL-6 (C) but increases the expression of IL-10 (D) in the dorsal horn in SNL rats (6 rats per group). The anti-allodynic effect of gabapentin on the expression of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 are inhibited by daily injections of the anti-IL-10 antibody (10 µg). Protein expression of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 on day 7 are significantly attenuated by IL-10 (1 µg) daily injections compared with the SNL alone group. All data points are expressed as the mean ± SEM. *P < 0.05 vs sham group; †P < 0.05 vs SNL group; ‡P < 0.05 vs SNL + gabapentin group. SNL, spinal nerve ligation; Ab, antibody.

• 

  Fig. 3 Time course of paw withdrawal thresholds over the 7 day period of daily injections of various doses (0.1, 0.3, or 1 µg) of IL-10 in SNL rats (6 rats per group). A single large dose injection of IL-10 (7 µg) on day 7 does not produce an anti-allodynic effect. *P < 0.05 vs SNL group, †P < 0.05 vs sham group. SNL, spinal nerve ligation.

• 

  Fig. 4 Time course of paw withdrawal thresholds over the 7 day period of daily injections of anti-IL-10 antibody (10 µg) with intrathecally administered gabapentin (30 µg). *P < 0.05 vs SNL group, †P < 0.05 vs sham group. ‡P < 0.05 vs SNL + gabapentin group. SNL, spinal nerve ligation; Ab, antibody.

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