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Intrathecal Lamotrigine Attenuates Antinociceptive Morphine Tolerance and Suppresses Spinal Glial Cell Activation in Morphine-Tolerant Rats
Journal of Korean Medical Science ; : 300-307, 2013.
Article in English | WPRIM | ID: wpr-25343
ABSTRACT
Glial cells play a critical role in morphine tolerance, resulting from repeated administration of morphine. Both the development and the expression of tolerance are suppressed by the analgesic lamotrigine. This study investigated the relationship between the ability of lamotrigine to maintain the antinociceptive effect of morphine during tolerance development and glial cell activation in the spinal cord. In a rat model, morphine (15 microg) was intrathecally injected once daily for 7 days to induce morphine tolerance. Lamotrigine (200 microg) was co-administered with morphine either for 7 days or the first or last 3 days of this 7 day period. Thermal nociception was measured. OX-42 and GFAP immunoreactivity, indicating spinal microglial and astrocytic activation were evaluated on day 8. Tolerance developed after 7 days of intrathecal morphine administration; however, this was completely blocked and reversed by co-administration of lamotrigine. When lamotrigine was coinjected with morphine on days 5-7, the morphine effect was partially restored. Glial cell activation increased with the development of morphine tolerance but was clearly inhibited in the presence of lamotrigine. These results suggest that, in association with the suppression of spinal glial cell activity, intrathecally coadministered lamotrigine attenuates antinociceptive tolerance to morphine.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Spinal Cord / Triazines / Immunohistochemistry / Neuroglia / Astrocytes / Rats, Sprague-Dawley / Microglia / CD11b Antigen / Drug Tolerance / Analgesics Limits: Animals Language: English Journal: Journal of Korean Medical Science Year: 2013 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Spinal Cord / Triazines / Immunohistochemistry / Neuroglia / Astrocytes / Rats, Sprague-Dawley / Microglia / CD11b Antigen / Drug Tolerance / Analgesics Limits: Animals Language: English Journal: Journal of Korean Medical Science Year: 2013 Type: Article