Inhibitory effect of repeated oral administration of chondroitin sulfate on the formalin-induced tactile allodynia in mice

[Speaker] Wataru Nemoto:1
[Co-author] Kotaro Yamada:2, Osamu Nakagawasai:1, Yoshiki Ogata:1, Hidetomo Sakurai:2, Koichi Tan-No:1
1:Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Japan, 2:Consumer Health Products Development, ZERIA Pharmaceutical Co., Ltd., Japan

Chondroitin sulfate (CS) is used for the treatment of osteoarthritis and joint pain. The anti-inflammatory and chondroprotective properties of CS and their mechanisms have been demonstrated. However, the effect of CS on pain transmission remains unclear. Therefore, to gain this issue, we examined the effect of CS on the formalin-induced biphasic nociceptive behavior and subsequent long-lasting tactile allodynia in mice. 20 μl of a 2% formalin solution (0.74% formaldehyde in saline) was injected in the right hindpaw under the skin of the plantar using a 26-gauge microsyringe. Immediately after the injection, nociceptive behavior consisting of licking or biting of the injected paw was recorded for periods of 5 min during the first (0-5 min) and second (10-30 min) nociceptive phases. Tactile allodynia induced by formalin was measured using von Frey filament test. Expression of phospho-p38 MAPK and c-Fos in the lumbar dorsal spinal cord were determined by Western blotting and immunohistochemistry, respectively. A single oral administration of CS (300 mg/kg) 30 min before a formalin injection into the hindpaw did not affect the nociceptive response during either first or second phases. On the other hand, a repeated oral administration of CS (300 mg/kg, b.i.d. for 20 days) significantly ameliorated the formalin induced-tactile allodynia from day 10 after formalin injection. In addition, the phosphorylation of spinal p38 MAPK and subsequent increase in c-Fos-immunoreactive dorsal lumbar neurons on day 14 after formalin injection were significantly attenuated by the repeated CS dosing. These findings suggest that repeated administration of CS attenuates formalin-induced persistent tactile allodynia through the inhibition of spinal p38 MAPK phosphorylation and subsequent up-regulation of c-Fos expression in the lumbar superficial dorsal horn neurons.
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