Oral 2-hydroxyoleic acid inhibits reflex hypersensitivity and open-field-induced anxiety after spared nerve injury.

Abstract

BACKGROUND:

Recently, fatty acids have been shown to modulate sensory function in animal models of neuropathic pain. In this study, the antinociceptive effect of 2-hydroxyoleic acid (2-OHOA) was assessed following spared nerve injury (SNI) with reflex and cerebrally mediated behavioural responses.

METHODS:

Initial antinociceptive behavioural screening of daily administration of 2-OHOA (400 mg/kg, p.o.) was assessed in Wistar rats by measuring hindlimb reflex hypersensitivity to von Frey and thermal plate stimulation up to 7 days after SNI, while its modulatory effect on lumbar spinal dorsal horn microglia reactivity was assessed with OX-42 immunohistochemistry. In vitro the effect of 2-OHOA (120 μM) on cyclooxygenase protein expression (COX-2/COX-1 ratio) in lipopolysaccharide-activated macrophage cells was tested with Western blot analysis. Finally, the effects of 2-OHOA treatment on the place escape aversion paradigm (PEAP) and the open-field-induced anxiety test were tested at 21 days following nerve injury compared with vehicle-treated sham and pregabalin-SNI (30 mg/kg, p.o.) control groups.

RESULTS:

Oral 2-OHOA significantly reduced ipsilateral mechanical and thermal hypersensitivity up to 7 days after SNI. Additionally 2-OHOA decreased the COX-2/COX-1 ratio in lipopolysaccharide-activated macrophage cells and OX-42 expression within the ipsilateral lumbar spinal dorsal horn 7 days after SNI. 2-OHOA significantly restored inner-zone exploration in the open-field test compared with the vehicle-treated sham group at 21 days after SNI.

CONCLUSIONS:

Oral administration of the modified omega 9 fatty acid, 2-OHOA, mediates antinociception and prevents open-field-induced anxiety in the SNI model in Wistar rats, which is mediated by an inhibition of spinal dorsal horn microglia activation.

• Authors: G Avila-Martin, I Galan-Arriero, A Ferrer-Donato, X Busquets, J Gomez-Soriano, P V Escribá, J Taylor
• Journal: European journal of pain (London, England) (Eur J Pain) Vol. 19 Issue 1 Pg. 111-22 (Jan 2015) ISSN: 1532-2149 [Electronic] England
• PMID: 24824524 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 European Pain Federation - EFIC®

Chemical References

• 2-hydroxyoleic acid
• Oleic Acids

Topics

• Administration, Oral
• Animals
• Anxiety (drug therapy, etiology, physiopathology)
• Hyperalgesia (drug therapy, etiology, metabolism, physiopathology)
• Male
• Microglia (drug effects, metabolism)
• Neuralgia (diet therapy, etiology, physiopathology)
• Oleic Acids (administration & dosage, therapeutic use)
• Pain Threshold (drug effects)
• Peripheral Nerve Injuries (complications, physiopathology)
• Rats
• Rats, Wistar
• Reflex, Abnormal (drug effects)