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Original Research

Antinociceptive tolerance to NSAIDs in the agranular insular cortex is mediated by opioid mechanism

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Pages 1561-1568 | Published online: 06 Jul 2017

Figures & data

Figure 1 Serial coronal sections of the rat brain showing placement of microinjections in the AIC (black arrows).

Notes: The number below each section represents millimeters relative to bregma. Adapted from the Stereotaxic atlas in Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. Compact third edition. San Diego, CA: Academic Press; 1997. Copyright © 1997 by George Paxinos and Charles Watson.Citation18
Abbreviation: AIC, agranular insular cortex.
Figure 1 Serial coronal sections of the rat brain showing placement of microinjections in the AIC (black arrows).

Figure 2 Microinjections of NSAIDs into the AIC for 4 consecutive days.

Notes: (A) A progressive decrease in TF latency as compared to intact control group; (B) a progressive decrease in HP latency to intact control group. Statistical analysis was performed by repeated-measure ANOVA with post hoc Tukey–Kramer’s multiple comparisons test; n=6 per test group; **P<0.01, ***P<0.001.
Abbreviations: AIC, agranular insular cortex; ANOVA, analysis of variance; HP, hot plate; NSAIDs, nonsteroidal anti-inflammatory drugs; TF, tail-flick.
Figure 2 Microinjections of NSAIDs into the AIC for 4 consecutive days.

Figure 3 Pretreatment with naloxone (0.2 μg/0.5 μL) before microinjections of NSAIDs into the AIC.

Notes: (A, C and E) Naloxone prevents NSAID-induced antinociception in TF latency for diclofenac (A), ketorolac (C), and xefocam (E), respectively. (B, D and F) Naloxone prevents NSAID-induced antinociception in HP latency for diclofenac (B), ketorolac (D), and xefocam (F), respectively. Statistical analysis was performed by one-way ANOVA with post hoc Tukey–Kramer’s multiple comparisons test; n=6 per test group.
Abbreviations: AIC, agranular insular cortex; ANOVA, analysis of variance HP, hot plate; NSAIDs, nonsteroidal anti-inflammatory drugs; TF, tail-flick.
Figure 3 Pretreatment with naloxone (0.2 μg/0.5 μL) before microinjections of NSAIDs into the AIC.

Figure 4 Posttreatment with naloxone (0.2 μg/0.5 μL) after microinjections of NSAIDs into the AIC.

Notes: (A, C and E) Naloxone abolishes NSAID-induced antinociception in TF latency for diclofenac (A), ketorolac (C), and xefocam (D), respectively. (B, D and F) Naloxone abolishes NSAID-induced antinociception in HP latency for diclofenac (B), ketorolac (D), and xefocam (F), respectively. Each NSAID-injected group shows significant difference vs saline control and vs naloxone posttreated groups in both tests. Statistical analysis was performed by one-way ANOVA with post hoc Tukey–Kramer’s multiple comparisons test; n=6 per test group. ***P<0.001.
Abbreviations: AIC, agranular insular cortex; ANOVA, analysis of variance HP, hot plate; NSAIDs, nonsteroidal anti-inflammatory drugs; TF, tail-flick.
Figure 4 Posttreatment with naloxone (0.2 μg/0.5 μL) after microinjections of NSAIDs into the AIC.