Korean J Pain.  2011 Dec;24(4):179-184. 10.3344/kjp.2011.24.4.179.

Roles of Serotonergic and Adrenergic Receptors in the Antinociception of Selective Cyclooxygenase-2 Inhibitor in the Rat Spinal Cord

• Jeong HJ
• Lee SH
• Cho SY
• Lee CS
• Jeong CW
• Yoon MH
• Kim WM

• KMID: 2074011
• DOI: http://doi.org/10.3344/kjp.2011.24.4.179

Abstract

BACKGROUND
The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level.
METHODS
DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, alpha1 adrenergic and alpha2 adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed.
RESULTS
Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test.
CONCLUSIONS
Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level.

Keyword

analgesia; COX-2 inhibitor; inflammatory pain; mechanism; spinal cord

MeSH Terms

Adrenergic Antagonists
Analgesia
Animals
Catheters
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Dihydroergocristine
Formaldehyde
Humans
Male
Neurotransmitter Agents
Prazosin
Prostaglandin-Endoperoxide Synthases
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic
Spinal Cord
Thiophenes
Yohimbine
Adrenergic Antagonists
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Dihydroergocristine
Formaldehyde
Neurotransmitter Agents
Prazosin
Prostaglandin-Endoperoxide Synthases
Receptors, Adrenergic
Thiophenes
Yohimbine

Figure

• 

  Fig. 1 Time course (A) and dose-response curves of intrathecal DUP-697 on flinching response 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 mean ± SEM of 7 rats. Compared with control, *P < 0.05, †P < 0.005, ‡P < 0.001.

• 

  Fig. 2 The effects of intrathecal dihydroergocristine (3 µg), prazosin (3 µg), and yohimbine (10 µg) on the antinociception of intrathecal DUP-697 (300 µg) during phase 1 (A) and phase 2 (B) in the formalin test. Dihydroergocristine, prazosin, and yohimbine were administered 10 min before the delivery of DUP-697, and the formalin test was done 10 min later. None of these antagonists affected the antinociception of DUP-697 during both phases of the formalin test. Data are presented as the percentage of control. Each bar represents mean ± SEM of 7 rats.

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