Effects Of NSAIDs On Behavior And Fos Expression In Conscious Rat Model Of Vasculogenic Headache

Objective1、To verify the reliability and feasibility of the conscious model of vasculogenic headache induced by electrical stimulation of the superior sagittal sinus (SSS) in rats by treatment of two classical analgesic drugs, acetaminophen and ibuprofen.2、To observe distribution of Fos-immunoreactive neurons in trigeminal ganglia and trigeminal nucleus caudalis in conscious rats after electrical stimulation of the SSS, and to investigate the effects of acetaminophen and ibuprofen on Fos expression in trigeminal ganglia and trigeminal nucleus caudalis of rats after electrical stimulation of the SSS.Methods1、The study on the behavioral changes in rats:The42male SD rats were randomly divided into seven groups:control group, three groups with different doses of acetaminophen and three groups with different doses of ibuprofen. The changes of the behavior (the number of shakes, head-torsion and excessive grooming time) of each rat in response to electrical stimulation (parameter is a frequency of20Hz,3-5mA current and pulse width of0.25ms) of the SSS were observed.2、The study on Fos-immunoreactive neurons changes in rats:The male SD rats were randomly divided into three groups:control group (saline group, n=10), acetaminophen group (n=10) and ibuprofen group (n=10). The change of Fos expression of each rat was tested after electrical stimulation of the SSS.Results 1、The numbers of shakes and head-torsion in response to electrical stimulation in control group,20mg/kg acetaminophen group,40mg/kg acetaminophen group and80mg/kg acetaminophen group were10.17±2.86,6.33±1.7,4.33±1.21and4.5±1.52, respectively. There were significant differences between three groups of acetaminophen and control group (all P<0.05),20mg/kg acetaminophen group and40mg/kg acetaminophen group (P<0.05), but no significant difference between40mg/kg acetaminophen group and80mg/kg acetaminophen group (P>0.05). The numbers of shakes and head-torsion in response to electrical stimulation in control group,12.5mg/kg ibuprofen group,25mg/kg ibuprofen group and50mg/kg ibuprofen group were10.17±2.86,6.33±2.25,3.50±1.87and3.50±1.05, respectively. There were significant differences between three groups of ibuprofen and control group (all P<0.05),12.5mg/kg acetaminophen group and25mg/kg acetaminophen group (P<0.05), but no significant difference between25mg/kg acetaminophen group and50mg/kg acetaminophen group.2、The excessive grooming time in response to electrical stimulation in control group,20mg/kg acetaminophen group,40mg/kg acetaminophen group and80mg/kg acetaminophen group was28.68±7.67s,21.80±5.84s,14.65±2.57s and14.15±3.18s. There were significant differences between three groups of acetaminophen and control group (all P<0.05),20mg/kg acetaminophen group and40mg/kg acetaminophen group (P<0.05), but no significant difference between40mg/kg acetaminophen group and80mg/kg acetaminophen group. The excessive grooming time in response to electrical stimulation in control group,12.5mg/kg ibuprofen group,25mg/kg ibuprofen group and50mg/kg ibuprofen group was28.68±7.67s,20.57±5.04s,17.68±3.88s and14.88±3.72s. There were significant differences between three groups of ibuprofen and control group (all P<0.05),12.5mg/kg acetaminophen group and25mg/kg acetaminophen group (P<0.05), but no significant difference between25mg/kg acetaminophen group and50mg/kg acetaminophen group.3、After electrical stimulation, there was significant difference of Fos protein expression in bilateral trigeminal ganglia, spinal trigeminal nucleus caudalis between saline group and group of non-steroidal anti-inflammatory drugs, but no significant difference of Fos protein expression in bilateral trigeminal ganglia, spinal trigeminal nucleus caudalis between acetaminophen group and ibuprofen group.Conclusions1. It is feasible to set up a model of vasculogenic headache induced by electrical stimulation of the SSS, which could effectively simulate the onset of migraine process, and it means feasibility and high repeatability.2. Nociceptive behaviours including the number of shakes, head-torsion and excessive grooming can be inhibited by NSAIDs. Results showed that the behaviours reduced more effectively on moderate-dose group and high-dose group than low-dose group, allow for the drug side-effect, that moderate-dose was considered the recommended dose for animal model.3. The changes of Fos expression in bilateral trigeminal ganglia and spinal trigeminal nucleus caudalis after treatment of NSAIDs, suggested that such stuctures participated in the pain transmission and expression, and the pharmacology course of analgesics drugs.