[Effects of blockade of 5-HT2A receptors in inflammatory site on complete Freund's adjuvant-induced chronic hyperalgesia and neuropeptide Y expression in the spinal dorsal horn in rats].

Abstract

5-hydroxytryptamine (5-HT) released in inflammatory tissues plays a pivotal role in pain hypersensitivity. However, it is not clear whether 5-HT2A receptors in the inflamed tissues mediate this effect. The present study investigated the contribution of 5-HT2A receptors in the periphery to chronic inflammatory pain. Complete Freund's adjuvant (CFA) was injected subcutaneously in the hindpaw of rats. The selective 5-HT2A receptor antagonist ketanserin was given in the inflamed site. Paw withdrawal latency responding to heat or mechanical stimuli was measured. Expression of neuropeptide Y (NPY) in the spinal dorsal horn and dorsal root ganglia (DRG) was assayed using immunohistochemistry technique. The results showed that ketanserin administered in the inflamed site inhibited thermal hyperalgesia in a dose-dependent manner (20, 40 and 80 µg) induced by the intraplantar injection of CFA. Ketanserin given once per day at a dose of 80 µg abolished heat hyperalgesia and also attenuated mechanical allodynia on the third day. CFA injection increased the expression of NPY in superficial laminae of the spinal cord, but not in the DRG. The local treatment of ketanserin completely inhibited CFA-induced increase in NPY expression in superficial laminae of the spinal cord. These results indicated that activation of 5-HT2A receptors in the inflamed tissues was involved in the pathogenesis of inflammatory pain and the blockade of 5-HT2A receptors in the periphery could relieve pain hypersensitivity and normalize the cellular disorder in the spinal dorsal horn associated with pathological pain. The present study suggests that the peripheral 5-HT2A receptors can be a promising target for pharmaceutical therapy to treat chronic inflammatory pain without central nervous system side effects.

• Authors: Bing-Qing Huang, Bing Wu, Yanguo Hong, Wei Hu
• Journal: Sheng li xue bao : [Acta physiologica Sinica] (Sheng Li Xue Bao) Vol. 67 Issue 5 Pg. 463-9 (Oct 25 2015) ISSN: 0371-0874 [Print] China
• PMID: 26490063 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuropeptide Y
• Receptor, Serotonin, 5-HT2A
• Serotonin 5-HT2 Receptor Antagonists
• Serotonin
• Freund's Adjuvant
• Ketanserin

Topics

• Animals
• Freund's Adjuvant (adverse effects)
• Ganglia, Spinal (metabolism)
• Hot Temperature
• Hyperalgesia (chemically induced, drug therapy)
• Inflammation (drug therapy)
• Ketanserin (pharmacology)
• Neuropeptide Y (metabolism)
• Pain (drug therapy)
• Pain Measurement
• Rats
• Receptor, Serotonin, 5-HT2A (metabolism)
• Serotonin
• Serotonin 5-HT2 Receptor Antagonists (pharmacology)
• Spinal Cord Dorsal Horn (metabolism)