Role for cyclooxygenase 2 in the development and maintenance of neuropathic pain and spinal glial activation.
BACKGROUND
Lines of evidence have indicated that cyclooxygenase 2 plays a role in the pathophysiology of neuropathic pain. However, the site and mechanism of its action are still unclear. Spinal glia has also been reported to mediate pathologic pain states. The authors evaluated the effect of continuous intrathecal or systemic cyclooxygenase-2 inhibitor on the development and maintenance of neuropathic pain and glial activation in a spinal nerve ligation model of rats.


METHODS
Continuous intrathecal infusion of meloxicam (32 or 320 mug . kg . day) or saline was started immediately after L5-L6 spinal nerve ligation. Mechanical allodynia and thermal hyperalgesia were evaluated on days 4 and 7 postoperatively. Spinal astrocytic activation was evaluated with glial fibrially acidic protein immunoreactivity on day 7. In other groups of rats, continuous intrathecal meloxicam was started 7 days after spinal nerve ligation, and effects on established neuropathic pain and glial activation were evaluated. Last, effects of continuous systemic meloxicam (16 mg . kg . day) on existing neuropathic pain and glial activation were examined.


RESULTS
Intrathecal meloxicam prevented the development of mechanical allodynia and thermal hyperalgesia induced by spinal nerve ligation. It also inhibited spinal glial activation responses. In contrast, when started 7 days after the nerve ligation, intrathecal meloxicam did not reverse established neuropathic pain and glial activation. Systemic meloxicam started 7 days after ligation partially reversed neuropathic behaviors but not glial activation.


CONCLUSIONS
Spinal cyclooxygenase 2 mediates the development but not the maintenance of neuropathic pain and glial activation in rats. Peripheral cyclooxygenase 2 plays a part in the maintenance of neuropathic pain.
Takeda
Kenji
K
Tokyo University School of Medicine, Showa General Hospital, Kodaira, Tokyo.
Sawamura
Shigehito
S
Tamai
Hisayoshi
H
Sekiyama
Hiroshi
H
Hanaoka
Kazuo
K
D000818:Animals; D051546:Cyclooxygenase 2 / Q000502:physiology*; D008297:Male; D000077239:Meloxicam; D009457:Neuroglia / Q000502:physiology*; D010146:Pain / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000209:etiology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology*; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; D000077239:Meloxicam