Oral 2-hydroxyoleic acid inhibits reflex hypersensitivity and open-field-induced anxiety after spared nerve injury.
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.
Sensorimotor Function Group, SESCAM, Hospital Nacional de Parapléjicos, Toledo, Spain.
G
G
Avila-Martin
I
I
Galan-Arriero
A
A
Ferrer-Donato
X
X
Busquets
J
J
Gomez-Soriano
P V
PV
Escribá
J
J
Taylor
D000284:Administration, Oral; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009437:Neuralgia / Q000178:diet therapy* / Q000209:etiology / Q000503:physiopathology; D009829:Oleic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D017288:Pain Threshold / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000150:complications* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012021:Reflex, Abnormal / Q000187:drug effects*
C483229:2-hydroxyoleic acid; D009829:Oleic Acids