Acute and neuropathic orofacial antinociceptive effect of eucalyptol

Abstract

Terpenes have a wide range of pharmacological properties, including antinociceptive action. The anti-inflammatory and antinociceptive effects of eucalyptol are well established. The purpose of this study was to evaluate the antinociceptive effect of eucalyptol on acute and neuropathic orofacial pain in rodent models. Acute orofacial and corneal nociception was induced with formalin, capsaicin, glutamate and hypertonic saline in mice. In another series, animals were pretreated with capsazepine or ruthenium red to evaluate the involvement of TRPV1 receptors in the effect of eucalyptol. In a separate experiment, perinasal tissue levels of IL-1β, TNF-α and IFN-γ were measured. Rats were pretreated with eucalyptol before induction of temporomandibular joint pain with formalin or mustard oil. In another experiment, rats were submitted to infraorbital nerve transection (IONX) to induce chronic pain, followed by induction of mechanical hypersensitivity using Von Frey hairs. Locomotor performance was evaluated with the open-field test, and molecular docking was conducted on the TRPV1 channel. Pretreatment with eucalyptol significantly reduced formalin-induced nociceptive behaviors in all mouse strains, but response was more homogenous in the Swiss strain. Eucalyptol produced antinociceptive effects in all tests. The effect was sensitive to capsazepine but not to ruthenium red. Moreover, eucalyptol significantly reduced IFN-γ levels. Matching the results of the experiment in vivo, the docking study indicated an interaction between eucalyptol and TRPV1. No locomotor activity changes were observed. Our study shows that eucalyptol may be a clinically relevant aid in the treatment of orofacial pain, possibly by acting as a TRPV1 channel antagonist.

Eucalyptol alleviates inflammation and pain responses in a mouse model of gout arthritis

“…Eucalyptol has been shown to exert obvious anti‐inflammatory effects in several inflammatory conditions, including asthma, colitis, cigarette smoke‐induced acute lung inflammation, and influenza virus‐induced infection (Juergens, Stober, Schmidt‐Schilling, Kleuver, & Vetter, ; Kennedy‐Feitosa et al, ; Li et al, ; Santos et al, ). Eucalyptol also possesses analgesic effects in several pain conditions, including neuropathic orofacial pain and pain elicited by application of TRPA1 channel IL‐6, agonists to human skin (Melo Junior et al, ; Takaishi et al, ). Our recent work contributed to these efforts by identifying that eucalyptol produces anti‐inflammatory effects on LPS‐induced pulmonary inflammation and exerts analgesic effects on CFA‐induced mouse model of inflammatory pain as well as acetic acid‐induced visceral pain via interactions with the TRPM8 channel (Caceres et al, ; Liu et al, ).…”

Bioactive Natural Compounds and Antioxidant Activity of Essential Oils from Spice Plants: New Findings and Potential Applications

“…Eucalyptol (1,8-cineole) is the most frequent major constituent of R. officinalis EO, and it has well-established anti-inflammatory and antinociceptive activities [ 185 , 186 ]. Studies have demonstrated that its anti-inflammatory activity occurs by suppression of lipopolysaccharide-induced proinflammatory cytokine production through the action of TNF-α, IL-6, NF-κB, and IL-1β, and reduction of oxidative stress through radical scavenging activity and regulation of signaling pathways [ 187 ].…”

The potent anti-inflammatory effect of Guilu Erxian Glue extracts remedy joint pain and ameliorate the progression of osteoarthritis in mice

“…In the joint, the tissues containing nociceptors include primarily the joint capsule, ligaments, synovium, bone, and the outer edge of the menisci (in the knee) [ 10 – 12 ]. Inflammation lowers the threshold for nociception; while cytokines are being assessed as possible candidates for biochemical markers, inflammation is increasingly being considered as an important part of the pathophysiology of OA [ 13 – 15 ]. According to the American College of Rheumatology 2000 guidelines, patients with OA of the knee, a condition characterized by cartilage degradation, are often treated with steroids, non-steroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 selective NSAIDs (e.g., celecoxib), which relieve pain and inflammation but are not capable of restoring tissues once OA has initiated [ 16 , 17 ].…”