Citronellol, a natural acyclic monoterpene, attenuates mechanical hyperalgesia response in mice: Evidence of the spinal cord lamina I inhibition

• Published in: Chemico-biological interactions Vol. 239; pp. 111 - 117
• Main Authors: Brito, Renan G., dos Santos, Priscila L., Quintans, Jullyana S.S., de Lucca Júnior, Waldecy, Araújo, Adriano A.S., Saravanan, Shanmugam, Menezes, Irwin R.A., Coutinho, Henrique D.M., Quintans-Júnior, Lucindo J.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 05-09-2015
• Subjects: Analgesics, Non-Narcotic - pharmacology; Animals; Citronellol; Dinoprostone - adverse effects; Edema - drug therapy; Fos; Hyperalgesia; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Male; Mice; Monoterpenes; Monoterpenes - pharmacology; Pain; Spinal Cord; Spinal Cord Dorsal Horn - drug effects; Tumor Necrosis Factor-alpha - adverse effects; PBS; PGE2; IL; CG; EP2; TNFR2; RVM; CNS; Fos; COX; TNFR1; Hyperalgesia; CT; BSA; Citronellol; Pain; TNF-α; Spinal Cord; NSAIDs; PAG; KC; Monoterpenes; DA
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2015.06.039

•We tested the anti-hyperalgesic and anti-edematogenic effects of citronellol (CT).•CT is able to reduce the mechanical hyperalgesia and paw edema.•CT reduced the Fos activation on spinal cord lamina I.•We are suggesting the possible involvement of descending pain-inhibitory mechanisms in the analgesic effect of CT.
We evaluated the anti-hyperalgesic effect of citronellol (CT) and investigated the spinal cord lamina I involvement in this effect. Male mice were pre-treated with CT (25, 50 and 100mg/kg, i.p.), indomethacin (10mg/kg, i.p.), dipyrone (60mg/kg, i.p.) or vehicle (saline+Tween 80 0.2%). Thirty minutes after the treatment, 20μL of carrageenan (CG; 300μg/paw), PGE2 (100ng/paw), dopamine (DA; 30μg/paw) or TNF-α (100pg/paw) were injected into the hind paw subplantar region and the mechanical threshold was evaluated with an electronic anesthesiometer. The CT effect on edema formation was evaluated after the right paw subplantar injection of CG (40μL; 1%) through the plethysmometer apparatus. To evaluate the CT action on the spinal cord, the animals were treated with CT (100mg/kg; i.p.) or vehicle (Saline+Tween 80 0.2%; i.p.) and, after 30min, 20μL of CG (300μg/paw; i.pl.) was injected. Ninety minutes after the treatment, the animals were perfused, the lumbar spinal cord collected, crioprotected, cut and submitted in an immunofluorescence protocol for Fos protein. CT administration produced a significantly reduction (p<0.05) in the mechanical hyperalgesia induced by CG, TNF-α, PGE2 and DA when compared with control group. The treatment with CT also significantly (p<0.05) decreased the paw edema. The immunofluorescence showed that the CT decrease significantly (p<0.05) the spinal cord lamina I activation. Thus, our results provide that CT attenuates the hyperalgesia, at least in part, through the spinal cord lamina I inhibition.