Cyclooxygenase-2 inhibition potentiates morphine antinociception at the spinal level in a postoperative pain model.

Abstract:

BACKGROUND AND OBJECTIVES:After peripheral inflammatory stimuli, spinal cord cyclooyxgenase-2 (COX-2) mRNA and protein levels increase, whereas COX-1 is unchanged. In animal models of inflammatory pain, intrathecal COX-2 selective inhibitors suppress hyperalgesia. However, the role of spinal COX-2 inhibition in postoperative pain is not well elucidated. This study investigates whether a water-soluble COX-2 selective inhibitor, L-745337, can modify allodynic responses in a rat model of postoperative pain. METHODS:Allodynia was induced in the left plantar hindpaw by surgical incision. Animals then received intrathecal (0-80 micro g) or subcutaneous (0-30 mg/kg) L-745337 coadministered with intrathecal morphine (0-2 nmol). Reduction of mechanical allodynia (increased withdrawal threshold) was quantified with calibrated von Frey hairs. RESULTS:L-745337 alone, whether intrathecal or systemic, had no effect on withdrawal threshold. When intrathecal L-745337 at doses of 40 to 80 micro g was combined with a subthreshold dose (0.5 nmol) of morphine, withdrawal thresholds were increased in a dose-dependent manner. Adding 80 micro g L-745337 to 1 nmol morphine produced an antiallodynic effect greater than that of morphine at twice the dose. Subcutaneous L-745337, up to 30 mg/kg combined with intrathecal morphine resulted in the same antiallodynic response as morphine alone. CONCLUSION:These results suggest a spinal interaction of COX-2 inhibition with opiate analgesia may allow a reduction of postoperative pain with lower doses of opiate.

journal_name

Reg Anesth Pain Med

authors

Kroin JS,Buvanendran A,McCarthy RJ,Hemmati H,Tuman KJ

doi

10.1053/rapm.2002.35521

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

451-5

issue

5

eissn

1098-7339

issn

1532-8651

pii

S1098733902000135

journal_volume

27

pub_type

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