Chronic intrathecal infusion of minocycline prevents the development of spinal-nerve ligation-induced pain in rats.
OBJECTIVE
Minocycline is a second-generation tetracycline with multiple biological effects, including inhibition of microglial activation. Recently, microglial activation has been implicated in the development of nerve injury-induced neuropathic pain. In this study, the authors examined the effects of continuous intrathecal minocycline on the development of neuropathic pain and microglial activation induced by L5/6 spinal-nerve ligation in rats.


METHODS
Under isoflurane anesthesia, male Sprague-Dawley rats (200-250 g) received right L5/6 spinal-nerve ligation and intrathecal catheters connected to an infusion pump. Intrathecal saline or minocycline (2 and 6 microg/h) was given continuously after surgery for 7 days (n = 8 per group). The rat right hind paw withdrawal threshold to von Frey filament stimuli and withdrawal latency to radiant heat were determined before surgery and on days 1 to 7 after surgery. Spinal microglial activation was evaluated with OX-42 immunoreactivity on day 7 after surgery.


RESULTS
Spinal-nerve ligation induced mechanical allodynia and thermal hyperalgesia on the affected hind paw of saline-treated rats. Intrathecal minocycline (2 and 6 microg/h) prevented the development of mechanical allodynia and thermal hyperalgesia induced by nerve ligation. It also inhibited nerve ligation-induced microglial activation, as evidenced by decreased OX-42 staining. No obvious histopathologic change was noted after intrathecal minocycline (6 microg/h) infusion.


CONCLUSIONS
In this study, the authors demonstrate the preventive effect of continuous intrathecal minocycline on the development of nociceptive behaviors induced by L5/6 spinal-nerve ligation in rats. Further studies are required to examine if continuous intrathecal minocycline could be used safely in the clinical setting.
Lin
Chia-Shiang
CS
Department of Anesthesiology, Mackay Memorial Hospital, Taipei, Taiwan.
Tsaur
Meei-Ling
ML
Chen
Chien-Chuan
CC
Wang
Tao-Yeuan
TY
Lin
Chih-Fu
CF
Lai
Yuen-Liang
YL
Hsu
Tien-Chi
TC
Pan
Yu-Yen
YY
Yang
Chen-Hsien
CH
Cheng
Jen-Kun
JK
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism / Q000517:prevention & control*; D007278:Injections, Spinal; D008026:Ligation; D008161:Lumbosacral Region; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D008911:Minocycline / Q000008:administration & dosage*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000378:metabolism / Q000517:prevention & control*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000601:surgery; D013997:Time Factors; D014110:Touch
D018712:Analgesics, Non-Narcotic; D009419:Nerve Tissue Proteins; D008911:Minocycline