Korean J Pain.  2010 Dec;23(4):236-241. 10.3344/kjp.2010.23.4.236.

Roles of Opioid Receptor Subtype in the Spinal Antinociception of Selective Cyclooxygenase 2 Inhibitor

• Choi CH
• Kim WM
• Lee HG
• Jeong CW
• Kim CM
• Lee SH
• Yoon MH

• KMID: 1454706
• DOI: http://doi.org/10.3344/kjp.2010.23.4.236

Abstract

BACKGROUND
Selective inhibitors of cyclooxygenase (COX)-2 are commonly used analgesics in various pain conditions. Although their actions are largely thought to be mediated by the blockade of prostaglandin (PG) biosynthesis, evidences suggesting endogenous opioid peptide link in spinal antinociception of COX inhibitor have been reported. We investigated the roles of opioid receptor subtypes in the spinal antinociception of selective COX-2 inhibitor.
METHODS
To examine the antinociception of a selective COX-2 inhibitor, DUP-697 was delivered through an intrathecal catheter, 10 minutes before the formalin test in male Sprague-Dawley rats. Then, the effect of intrathecal pretreatment with CTOP, naltrindole and GNTI, which are micro, delta and kappa opioid receptor antagonist, respectively, on the analgesia induced by DUP-697 was assessed.
RESULTS
Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. Naltrindole and GNTI attenuated the antinociceptive effect of intrathecal DUP-697 during both phases of the formalin test. CTOP reversed the antinociception of DUP-697 during phase 2, but not during phase 1.
CONCLUSIONS
Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. The delta and kappa opioid receptors are involved in the activity of COX-2 inhibitor on the facilitated state as well as acute pain at the spinal level, whereas the micro opioid receptor is related only to facilitated pain.

Keyword

antinociception; cyclooxygenase; intrathecal; opioid receptor subtype

MeSH Terms

Acute Pain
Aluminum Hydroxide
Analgesia
Analgesics
Animals
Carbonates
Catheters
Cyclooxygenase 2
Formaldehyde
Humans
Male
Naltrexone
Opioid Peptides
Pain Measurement
Prostaglandin-Endoperoxide Synthases
Rats
Rats, Sprague-Dawley
Receptors, Opioid
Receptors, Opioid, kappa
Somatostatin
Thiophenes
Aluminum Hydroxide
Analgesics
Carbonates
Cyclooxygenase 2
Formaldehyde
Naltrexone
Opioid Peptides
Prostaglandin-Endoperoxide Synthases
Receptors, Opioid
Receptors, Opioid, kappa
Somatostatin
Thiophenes

Figure

• 

  Fig. 1 Time course (A) and dose-response curves of intrathecal DUP-697 on flinching during phase 1 (B) and phase 2 (C) in the formalin test. DUP-697 was administered 10 min before the formalin injection. Data are presented as the number of flinches or the percentage of control. Each line represents means ± S.E.M. of 5-8 rats. Compared with control, *P < 0.05, †P < 0.005, ‡P < 0.001.

• 

  Fig. 2 The effects of intrathecal CTOP (15 µg), naltrindole (10 µg) and GNTI (50 µg) on the antinociception by intrathecal DUP-697 (300 µg) during phase 1 (A) and phase 2 (B) in the formalin test. CTOP, naltrindole and GNTI were administered 10min before the delivery of DUP-697, and then the formalin test was done 10 min later. Both of naltrindole and GNTI reversed the effect of DUP-697 during phase 1 and phase 2 in the formalin test. CTOP antagonized the antinociception of DUP-697 during phase 2, but not during phase 1. Data are presented as the percentage of control. Each bar represents means ± S.E.M. of 5-8 rats. Compared with DUP-697, *P < 0.05.

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