Analgesic effect of intrathecal SO3 on rats with chronic constriction injury and its regulation of intracellular calcium ion concentration of spinal dorsal root ganglion neurons
- VernacularTitle:鞘内注射?-芋螺毒素S03对大鼠慢性神经痛的镇痛作用及对DRG细胞内Ca~(2+)含量的影响
- Author:
Hong WANG
;
Xiaowei ZHOU
;
Hong ZHANG
;
Peitang HUANG
- Publication Type:Journal Article
- Keywords:
ω-conopeptide SO3;
chronic constriction injury(CCI);
dorsal root ganglion;
intracellular calium;
N-type calcium channel
- From:
Chinese Pharmacological Bulletin
1986;0(06):-
- CountryChina
- Language:Chinese
-
Abstract:
Aim To evaluate the effect of intrathecal administration of ?-conopeptide SO3,an neotype N-type calcium channel blocker,on pain related behaviors and changes in intracellular calcium ion concentration of the DRG neurons in a rat model of chronic constriction injury(CCI).Methods 40 male SD rats weighing 230~270 g were randomly divided into five groups of 8 animals each.Rats in the N group served as unoperated controls;in group C the rats were placed four loose ligatures around the right sciatic nerve;in group CN 20?l normal Saline was administered 14 days after operation;in group CS1 SO3 600 ng was administered the same time as group CN;in group CS7 SO3(30 ng?h~(-1)) was chronically administered for 7 days from the 7th day post-operation.Thermal hyperalgesia and mechanical allodynia were tested by measuring paw withdrawal latency(PWL) in response to thermal stimulation and by von-Frey filaments.The animals were decapitated on time.The DRGs(L_4-L_6) were homogenized into single cells and intracellular calcium ion concentration([Ca~(2+)]_i) was measured by flow cytometry.Results The CCI procedure leads to the development of spontaneous pain,heat hyperalgesia and tactile allodynia in the hind foot innervated by the injured nerve.Intrathecal of SO3 produced significant antinociceptive effects on both thermal hyperalgesia and mechanical allodynia.In CCI rats,significant increases were observed in [Ca~(2+)]_i on the contralateral side and ipsilateral side of DRGs on day 14 after operation.I.t NS did not show any difference in [Ca~(2+)]_i to those in group C.The treatment with i.t SO3 600 ng suppressed the increases in [Ca~(2+)]_i of bilateral side of DRGs.Chronically administration of SO3 suppressed the increases in [Ca~(2+)]_i of bilateral side of DRGs further.Conclusion Selective N-type VSCC blockers are potent and efficacious antinociceptive agents when they are administered by the spinal route,and they are effective in a rat model of neuropathic pain.The antinociceptive effect provided by intrathecal SO3 is associated with N-type calcium channel,which suppresses the increases in [Ca~(2+)]_i in the DRGs.
