Intrathecal ketorolac prevents, but does not reverse, the development of thermal hyperalgesia after heat sensitization in mice

S. R. Galoer, T. P. Malen, Frank Porreca

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Abstract

The present studies were designed to investigate the activity of the intrathecally (i.th.) injected cyclooxygenase inhibitor ketorolac on the development of thermal hyperalgesia evoked by thermal sensitization in mice. Thermal sensitization was induced by immersing the left hind paw of ether-anesthetized mice into a 50°C water bath for 1 min. Thermal hyperalgesia was determined by comparing baseline (presensitization) paw withdrawal latency to a focused radiant heat source to paw withdrawal latencies after treatment. Saline or ketorolac (100 nmol and 200 nmol) were injected J. th. either 15 min before or after thermal sensitization of the hindpaw. Hyperalgesia was determined 2, 4 and 6 hrs afterwards. Paw withdrawal latency of the saline control group was significantly reduced to 5.8 ±0.7 sec from a pretreatment mean of 8.8 ±1.1 sec. The pretreatment paw withdrawal latencies after 100 nmol and 200 nmol of i.th. ketorolac pretreatment were 6.8 ±1.1 sec and 8.0 ±1.4 sec, respectively and the post-treatment paw withdrawal latencies were 8.5 ±1.3 sec and 8.2 ±1.3 sec. In contrast, the i.th. administration of 100 nmol and 200 nmol of ketorolac after sensitization produced post-treatment paw withdrawal latencies of 3.8 ±0.8 sec and 6.2 ±0.6 sec, respectively. These data suggest that spinal prostanoids may be involved in the development of central sensitization, manifested as hyperalgesia, after a peripheral nociceptive insult. Additionally, these data also suggest that once the prostanoid-related mechanisms mediating this central sensitization are initiated, then it is difficult to reverse this process by i.th. applied non-steroidal antiinflammatory agents.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - 1996

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Ketorolac
Hyperalgesia
Hot Temperature
Central Nervous System Sensitization
Prostaglandins
Cyclooxygenase Inhibitors
Non-Steroidal Anti-Inflammatory Agents
Baths
Ether
Therapeutics
Control Groups
Water

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Intrathecal ketorolac prevents, but does not reverse, the development of thermal hyperalgesia after heat sensitization in mice",
abstract = "The present studies were designed to investigate the activity of the intrathecally (i.th.) injected cyclooxygenase inhibitor ketorolac on the development of thermal hyperalgesia evoked by thermal sensitization in mice. Thermal sensitization was induced by immersing the left hind paw of ether-anesthetized mice into a 50°C water bath for 1 min. Thermal hyperalgesia was determined by comparing baseline (presensitization) paw withdrawal latency to a focused radiant heat source to paw withdrawal latencies after treatment. Saline or ketorolac (100 nmol and 200 nmol) were injected J. th. either 15 min before or after thermal sensitization of the hindpaw. Hyperalgesia was determined 2, 4 and 6 hrs afterwards. Paw withdrawal latency of the saline control group was significantly reduced to 5.8 ±0.7 sec from a pretreatment mean of 8.8 ±1.1 sec. The pretreatment paw withdrawal latencies after 100 nmol and 200 nmol of i.th. ketorolac pretreatment were 6.8 ±1.1 sec and 8.0 ±1.4 sec, respectively and the post-treatment paw withdrawal latencies were 8.5 ±1.3 sec and 8.2 ±1.3 sec. In contrast, the i.th. administration of 100 nmol and 200 nmol of ketorolac after sensitization produced post-treatment paw withdrawal latencies of 3.8 ±0.8 sec and 6.2 ±0.6 sec, respectively. These data suggest that spinal prostanoids may be involved in the development of central sensitization, manifested as hyperalgesia, after a peripheral nociceptive insult. Additionally, these data also suggest that once the prostanoid-related mechanisms mediating this central sensitization are initiated, then it is difficult to reverse this process by i.th. applied non-steroidal antiinflammatory agents.",
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AU - Galoer, S. R.

AU - Malen, T. P.

AU - Porreca, Frank

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