The effect of a 5-HT2A receptor antagonist on pain-related behavior, endogenous 5-hydroxytryptamine production, and the expression 5-HT2A receptors in dorsal root ganglia in a rat lumbar disc herniation model.

Abstract

STUDY DESIGN:

Controlled, interventional, animal study.

OBJECTIVE:

To evaluate the effect of a 5-HT2A receptor antagonist on pain-related behavior, endogenous 5-hydroxytryptamine (5-HT) plasma levels, and expression of 5-HT2A receptors in dorsal root ganglia (DRGs) in a rat lumbar disc herniation model.

SUMMARY OF BACKGROUND DATA:

Application of nucleus pulposus on the nerve root induces immediate peripheral 5-HT production and the expression of 5-HT2A receptors in the adjacent DRG. However, the efficacy of a 5-HT2A receptor antagonist for pain relief in this situation and the mechanism remain unknown.

METHODS:

Autologous nucleus pulposus was applied to the left L5 nerve root of 91 adult female Sprague-Dawley rats. The selective 5-HT2A receptor antagonist sarpogrelate hydrochloride (SPG; 1 mg/kg or 10 mg/kg) or vehicle was administered orally once a day from 1 to 21 days postoperatively. Von Frey tests were used to test pain behavior before and after surgery. To assess the effect of SPG on endogenous 5-HT release surrounding the inflamed nerve root, we measured levels of 5-hydroxyindole acetic acid, a 5-HT metabolite, in plasma. Expression of 5-HT2A receptors in the left L5 DRG was examined with immunoblotting.

RESULTS:

The higher dose (10 mg/kg) of SPG significantly improved the mechanical withdrawal thresholds from 5 to 21 days after surgery compared with vehicle treatment. 5-hydroxyindole acetic acid in plasma was not significantly different among any groups at any time points. Both doses of SPG inhibited the expression of 5-HT2A receptors after surgery compared with vehicle treatment.

CONCLUSION:

A selective 5-HT2A receptor antagonist attenuated pain-related behavior and suppressed 5-HT2A receptor expression in the DRG, but did not affect peripheral 5-HT production. Selective 5-HT2A receptor antagonists may attenuate sciatica by blocking and downregulating 5-HT2A receptors in DRGs in lumbar disc herniation.

LEVEL OF EVIDENCE:

NA.

• Authors: Kinshi Kato, Miho Sekiguchi, Shin-ichi Kikuchi, Shin-ichi Konno
• Journal: Spine (Spine (Phila Pa 1976)) Vol. 40 Issue 6 Pg. 357-62 (Mar 15 2015) ISSN: 1528-1159 [Electronic] United States
• PMID: 25584948 (Publication Type: Journal Article)

Chemical References

• Receptor, Serotonin, 5-HT2A
• Serotonin 5-HT2 Receptor Antagonists
• Serotonin

Topics

• Animals
• Behavior, Animal (drug effects)
• Disease Models, Animal
• Female
• Ganglia, Spinal (drug effects, metabolism)
• Intervertebral Disc Displacement (drug therapy, metabolism, physiopathology)
• Pain Management (methods)
• Pain Measurement (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptor, Serotonin, 5-HT2A (analysis, biosynthesis)
• Serotonin (analysis, blood, metabolism)
• Serotonin 5-HT2 Receptor Antagonists (pharmacology)