[Tramadol inhibits c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats].
OBJECTIVE
To investigate effect of tramadol on c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats.


METHODS
The Brennan pain model was induced by incision on the planter surface of left hind paw in rats. Forty-eight rats were randomly divided into six groups: Sham group (Group C), control group (Group I,pretreatment with saline 5 ml), three tramadol pretreatment groups (Group T1, T10 and T20,pretreated with 1 mg/kg, 10 mg/kg and 20 mg/kg tramadol, respectively) and one tramadol treatment group (Group PT10, treated with tramadol 10 mg/kg immediately after operation). Pain behavior was assessed by withdrawal threshold to von Frey filament stimulation intensity, response latency of the hind paw to radiant thermal and a cumulative pain score 2 h after incision. Fos-positive neurons in spinal cord were identified by the immunohistochemical technique. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
WithdrawIal threshold to von Frey filament stimulation intensity and response latency of the hind paw to radiant thermal in Group I were significantly lower than those in Group C (P<0.01). Cumulative pain score in Group I was significantly higher than that in Group C (P<0.01). In Groups of T10 and T20, withdrawal threshold to von Frey filament stimulation intensity and response latency of the hind paw to radiant thermal were significantly higher than those in Group I (P<0.01), cumulative pain score was significantly lower than that in Group I in a dose-dependent manner (P<0.01), and were also those in Group PT10. The greatest density of Fos-positive neurons was located in lamine I-II in Group I. Serum IL-6 levels were significantly elevated in Group I. Pretreatment with tramadol showed a dose-depended inhibitory effect on c-fos expression and serum IL-6 production,but not in Group T1. Administration of tramadol postoperatively also suppressed the c-fos expression and serum IL-6 production as showed in PT10 but were weaker than those in Group T10.


CONCLUSIONS
Pretreatment with tramadol can produce dose-dependent inhibitory effect on c-fos expression in spinal cord dorsal horn and then suppress the inflammatory response to the trauma.
LIU
Yong-min
YM
Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China. sx169y@163.com
ZHU
Sheng-mei
SM
WANG
Kui-rong
KR
CHEN
Qing-lian
QL
ZHENG
Yue-ying
YY
D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014147:Tramadol / Q000494:pharmacology* / Q000627:therapeutic use
D000701:Analgesics, Opioid; D015850:Interleukin-6; D016760:Proto-Oncogene Proteins c-fos; D014147:Tramadol