Long Jingdong,Huang Hua,Yang Shulei,Zeng Junwei,Chen Yuanshou,Tian Hong,Liu Xiaohong.CB1 receptor in spinal dorsal horn are involved in analgesia of neuropathic pain by CP55940 in rats[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(20):2108-2112.
Long Jingdong,Huang Hua,Yang Shulei,Zeng Junwei,Chen Yuanshou,Tian Hong,Liu Xiaohong.CB1 receptor in spinal dorsal horn are involved in analgesia of neuropathic pain by CP55940 in rats[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(20):2108-2112.DOI:
CB1 receptor in spinal dorsal horn are involved in analgesia of neuropathic pain by CP55940 in rats
Objective To determine the role of cannabinoid receptor 1 (CB
1
R) in the analgesic effects of CP55940
a synthetic cannabinoid
in neuropathic rats with chronic constriction injury (CCI) of the sciatic nerve. Methods Fifty-six healthy male SD rats (8 weeks old) were divided into 7 groups: (1) sham group (n=8)
(2) CCI group (intrathecal injection of DMSO saline
n=8)
(3) AM251+CCI group (intrathecal injection of 10
-8
mol/L AM251
n=8)
(4) to (6) CP55940+CCI group (intrathecal injection of 0.01
0.05
and 0.20 mg/kg CP55940
respectively
n=8) and (7) AM251+CP55940+CCI group (intrathecal injection of 10
-8
mol/L AM251
followed by 0.05 mg/kg CP55940 in 10 min later
n=8). In the sham-operated rats
the sciatic nerve was visualized and left intact. SD rats in other 6 groups were intrathecally cathetered at 5 d before CCI operation. All rats were tested for heat hyperalgesia of the plantar surface of the hind paw in 1 d before surgery and 1
3
5
7
10 and 14 d after surgery. AM251
CP55940 and DMSO saline were intrathecally administered once a day for 14 consecutive days after CCI operation. The values of thermal withdrawal latency (TWL) were examined at 1 h after intrathecal injection. The expression of CB
1
R and protein kinase A (PKA) was detected by Western blotting. Results TWL in the CCI group was significantly lower than that in the sham group after operation (P0.05). Intrathecal administration of CP55940 (0.01
0.05 and 0.20 mg/kg) markedly suppressed the decrease of TWL in a dose-dependent manner after nerve injury (P0.05). Intrathecal administration of AM251 (CB
1
R antagonist
10
-8
mol/L) markedly suppressed the analgesic effect of CP55940 (0.05 mg/kg). Western blot assay showed that the expression of CB
1
R and PKA was markedly enhanced in the ipsilateral dorsal horn on days 7 (P0.05) and 14 (P0.05) after nerve injury. Intrathecal administrat
ion of CP55940 markedly suppressed the increased expression of PKA on days 7 (P0.05) and 14 (P0.05) after CCI. AM251 markedly suppressed the increased expression of CB
1
R on days 7 (P0. 05) and 14 (P0.05) after CCI. In addition
AM251 markedly suppressed the decrease of PKA expression after CP55940 administration on days 7 (P0.05) and 14 (P0.05). Conclusion Intrathecal administration of cannabinoid receptor agonist CP55940 provides postoperative analgesia effectively. CB
1
R activation and the following inhibition of PKA are involved in the analgesic effect of CP55940.