Original Article
Changes in expression of cyclooxygenase-2 in the spinal dorsal horn after intrathecal p38MAPK inhibitor SB203580 on neuropathic pain in rats
Abstract
Objective: To investigate the changes of cyclooxygenase-2 (COX-2) expression in the spinal cord dorsal horn after intrathecal a specific p38MAPK inhibitor—SB203580 on neuropathic pain in rats induced by chronic constrictive injury (CCI) to the sciatic nerve.
Methods: Twenty-four male SD rats after intrathecal catheter placement were randomly divided into 4 groups: a sham group with sham surgery, the neuropathic pain model of a NS group, a DMSO group and an SB group were established by CCI to sciatic nerve. NS or DMSO or SB203580 was injected IT NS or 2% DMSO or SB203580 twice a day for 5 consecutive days starting at 6th day when the model of CCI was established. Mechanical stimuli were measured before the surgery and on 1st, 3rd, 5th, 7th, 9th, and 11th day after the surgery. Then all rats were sacrificed and the lumbar segment of spinal cord was removed to determine the COX-2 expression in the dorsal horn by immunocytochemistry.
Results: Day 1 to 11 after the surgery, the threshold to mechanical on the surgery side was significantly lower in the NS group and the DMSO group than in the sham group. Day 7 to 11 after the surgery, the threshold to mechanical on the surgery side was significantly lower in the SB group than in the NS group and the DMSO group. The expression of spinal COX-2 was higher in the NS group and the DMSO group than in the sham group, but lower in the SB group than in NS group and the DMSO group.
Conclusions: Intrathecal administration of SB203580 has significant analgesic effect in the CCI rat model. Expression of COX-2 is significantly reduced when p38MAPK is inhibited by intrathecal SB203580, and p38MAPK stimulation is essential for COX-2 expression.
Methods: Twenty-four male SD rats after intrathecal catheter placement were randomly divided into 4 groups: a sham group with sham surgery, the neuropathic pain model of a NS group, a DMSO group and an SB group were established by CCI to sciatic nerve. NS or DMSO or SB203580 was injected IT NS or 2% DMSO or SB203580 twice a day for 5 consecutive days starting at 6th day when the model of CCI was established. Mechanical stimuli were measured before the surgery and on 1st, 3rd, 5th, 7th, 9th, and 11th day after the surgery. Then all rats were sacrificed and the lumbar segment of spinal cord was removed to determine the COX-2 expression in the dorsal horn by immunocytochemistry.
Results: Day 1 to 11 after the surgery, the threshold to mechanical on the surgery side was significantly lower in the NS group and the DMSO group than in the sham group. Day 7 to 11 after the surgery, the threshold to mechanical on the surgery side was significantly lower in the SB group than in the NS group and the DMSO group. The expression of spinal COX-2 was higher in the NS group and the DMSO group than in the sham group, but lower in the SB group than in NS group and the DMSO group.
Conclusions: Intrathecal administration of SB203580 has significant analgesic effect in the CCI rat model. Expression of COX-2 is significantly reduced when p38MAPK is inhibited by intrathecal SB203580, and p38MAPK stimulation is essential for COX-2 expression.
