THE EFFECT OF HELICID ON THERMAL HYPERALGESIA AND EXPRESSION OF P-CREB IN SPINAL CORD DORSAL HORN IN A RAT MODEL OF NEUROPATHIC PAIN

Objective:To observe the effect of helicid on thermal hyperalgesia and expression of P-CREB in the spinal cord dorsal horn in rat model of the chronic constriction injury of the sciatic nerve.Method: Thirty-two adult male Wistar rats weighing 180～220 g were randomly divided into four groups(n=8 each group): sham group(sham operation),CCI group(CCI model),H1 group(oral helicid 25 mg·kg-1·d-1×10d after CCI operation 10 days) and H2 group(oral helicid 50 mg·kg-1·d-1×10d after CCI operation 10 days).The PWL(paw withdrawal latency) of the hind paws was measured by hot plate test(55℃±0.5℃) before CCI 1 day and on the 1st,3rd,5th,7th,9th,11th,12th,13th,14th,15th,16th,17th,18th,19th and 20th day after surgery(CCI).After CCI operation 20 days,the L4,5 segment of the spinal cord were taken for determination the expression of phosphorylated-CREB-immunoreaction(pCREB-IR) using immuno-histochemistry.Results: The first part: On the 9th day after CCI surgery,the PWL of four groups was compared with its preoperative PWL by with-in group test: Sham group had no difference(P0.05),and CCI Group,Group H1 and Group H2 had significant difference(P 0.05).The PWL was decreased at least 30%.After CCI surgery nine days,CCI group,Group H1 and Group H2 were tested respectively by between-group test and all had no significance difference(P0.05),indicating that CCI model was success.After taken helicid 1-10 days by gavage,Group H1 and Group H2 were compared respectively with CCI group by between-group tests: Pain threshold of H1 and H2 group was increased significantly.H2 group had significance from the 3rd day(P0.05).H1 group had significant difference from the 5th day(P0.05).After pain threshold of the two groups increased to the peak on the 7th day,it had remained stable level until the 10th day and the level of pain threshold of Group H2 maintained a relatively higher than Group H1.The second part: Compared with sham group,the number of p-CREB-IR cells in the spinal cord dorsal horn in CCI group,H1 group and H2 group was significantly increased(P0.01).The number of Group H1 and Group H2 was lower than that in CCI group(P0.01),and Group H2 was lower than that in Group H1.Conclusions: Oral helicid can dose-dependently reduce thermal hyperalgesia of CCI rats and decrease the number of p-CREB-IR cells in the spinal cord dorsal horn.It indicated that the effects of helicid on expression of p-CREB in the dorsal horn neurons is one of the ways that helicid treat neuropathic pain.