Effect of resveratrol on c‐fos expression of rat trigeminal spinal nucleus caudalis and C1 dorsal horn neurons following mustard oil‐induced acute inflammation

Abstract

The dietary constituent, resveratrol, was recently identified as a transient receptor potential ankyrin 1 (TRPA1) antagonist, voltage-dependent sodium ion (Na ) channel, and cyclooxygenase-2 (COX-2) inhibitor. The aim of the present study was to investigate whether pretreatment with resveratrol attenuates acute inflammation-induced sensitization of nociceptive processing in rat spinal trigeminal nucleus caudalis (SpVc) and upper cervical (C1) dorsal horn neurons, via c-fos immunoreactivity. Mustard oil (MO), a TRPA1 channel agonist, was injected into the whisker pads of rats to induce inflammation. Pretreatment with resveratrol significantly decreased the mean thickness of inflammation-induced edema in whisker pads compared with those of untreated, inflamed rats. Ipsilateral of both the superficial and deep laminae of SpVc and C1 dorsal horn, there were significantly more c-fos-immunoreactive SpVc/C1 neurons in inflamed rats compared with naïve rats, and resveratrol pretreatment significantly decreased that number relative to untreated, inflamed rats. These results suggest that systemic administration of resveratrol attenuates acute inflammation-induced augmented nociceptive processing of trigeminal SpVc and C1 neurons. These findings support resveratrol as a potential therapeutic agent for use in alternative, complementary medicine to attenuate, or even prevent, acute trigeminal inflammatory pain.

Effect of lutein on the acute inflammation‐induced c‐Fos expression of rat trigeminal spinal nucleus caudalis and C1 dorsal horn neurons

“…Our present findings also agree with a previous report showing that 6 h after pretreatment with the polyphenol, resveratrol, there is a significant decrease in the mean thickness of inflammation‐induced edema in the whisker pad, compared with untreated, inflamed rats, and also a significant decrease in the number of c‐Fos‐immunoreactive SpVc and C1 neurons in inflamed rats compared with naïve rats . We have also previously observed the following findings in a CFA‐induced chronic inflammatory pain model: (i) the mechanical threshold is significantly lower in inflamed rats than in uninjected naïve rats, and this low threshold returns to control levels by 3 d after administration of lutein; (ii) lutein administration causes the inflammation‐induced edema to return to control levels; and (iii) the increased mean number of COX‐2‐immunoreactive cells in the whisker pads of inflamed rats also returns to control levels after administration of lutein .…”

“…Lutein (MW = 568.9; Sigma‐Aldrich, St Louis, MO, USA) was dissolved in dimethyl sulfoxide, and the stock solution was stored at −20°C in small aliquots until use. In line with our previous study in which administration of resveratrol 6 h before injection with mustard oil decreased expression of c‐Fos in the SpVc and C1 spinal neurons, the intraperitoneal (i.p.) administration of lutein in the present study was performed 6 h before injection with mustard oil.…”

“…To evaluate the effect of lutein on the symptoms of peripheral inflammation, injection‐induced edema of the whisker pad region was evaluated, 2 h after injection of mustard oil, by measuring the thickness of the edematous area in all rats in each of the three group . For naïve rats, vehicle in the form of paraffin oil was injected into the left side of the facial skin .…”

“…The frozen coronal samples were cut into sections of 40 μ m thickness using a cryostat (NX50; ThermoFisher, Waltham, MA, USA). Every third section was processed for immunohistochemistry, as described in previous reports . The sections were immunolabeled with rabbit polyclonal c‐Fos antiserum diluted 1:250 (SC‐52; Santa Cruz Biotech, Dallas, TX, USA), and then subjected to an avidin/biotin complex (ABC) method (PK‐6100, ABC Elite kit; Vector Laboratories, Burlingame, CA, USA).…”

Suppression of hyperexcitability of trigeminal nociceptive neurons associated with inflammatory hyperalgesia following systemic administration of lutein via inhibition of cyclooxygenase-2 cascade signaling

“…Based on our results from the behavioral analysis for escape threshold, we conducted immunohistochemical and electrophysiological experiments on days 3. We evaluated the effects of lutein on the symptoms of peripheral inflammation using CFA-induced edema of the whisker pad region and measuring the thickness of edematous areas among the three groups, as described previously [ 21 ]. In some experiments, the CFA-induced inflammation was verified with Evan’s blue staining (50 mg/mL, 1 mL/kg, i.v.)…”