Induction And Mechanism About Anxiety-like Behaviour Following Surgical Incision In The Rats

Part I Development of an Anxiety-Like Behavior in Incisional Pain in ratsObjective:The present study aimed to explore whether incision can cause anxiety-like behaviour and mechanical hypersensitivity in the rats and whether anxiety-like behaviour and mechanical hypersensitivity induced by incision can be reversed by analgesic drug morphine or anxiolytic drug gabapentin.Methods:A longitudinal incision was made in one plantar hind-paw of rats. Mechanical hypersensitivity was assessed by using nylon von frey filaments according to " up-down " algorithm. Anxiety-like behaviour was measured by elevated plus maze and open field test. Morphine was administered by intraperitoneal (i.p.) injection after surgical incision, or administration of gabapentin by i.p. injection before incision, the mechamical hypersensitivity and anxiety-like behavior were studies in the different time points.Results:1 The paw-withdrawal threshold (PWT) in the operated paw dramatically decreased from 1 hour,3 hours,6 hours, 1d after hindpaw surgical incision (P<0.01). At 3 days,5 days,7 days after surgery, the PWT was returned to basal level and was comparable to the pre-operation(P> 0.05).2 After hind-paw incision, the time spent in open arm in EPM tests was greatly reduced as compared with the pre-operation, suggesting that incision leads to anxiety-like behavior (P<0.01). Interestingly, the pain-related anxiety remained up to three and five postoperative days when the time spent in open arm in the experimental group. But in the 7 days, the anxiety-like behavior was no significantly different compared to pre-incision (P>0.05). Open-field test showed that the percentage of time spent in the inner square was significantly decreased at 1 hour,1 day, 3 days,5 days after surgery compared to pro-incision. However, there was no significant difference in the total travel distance (P>0.05).3. Large dose of morphine(10mg/kg) and gabapentin(300mg/kg) almost reversed incision-evoked mechanical hypersensitivity whereas small dose of morphine(2.5mg/kg) or gabapentin (30mg/kg) had only mild effect. Combined administration of small doses of morphine(2.5mg/kg) and gabapentin (30 mg/kg) synergistically reversed mechanical hypersensitivity after hind-paw incision.4.large dose of morphine (10mg/kg) and gabapentin (300mg/kg) dramatically attenuated anxiety-like behaviour induced by incision,while low dose of morphine or gabapentin had only marginal effect. Combined administration of small doses of morphine(2.5mg/kg) and gabapentin (30mg/kg) had not synergistic effect on incision-evoked anxiety-like behaviour.Conclusions:These results suggest that the anxiety-like behavior and mechanical hypersensitivity induced by acute incision may share the same mechanism, but the mechanism that maintains these phenomena may be different. So it may be a benefit aid in clinical to take anxiolytic measures to promote the restoring of patients.Part II Activation of ERK in ACC Contributes to the mechanical Hypersensitivity and Anxiety-like Behaviour Following Surgical Incision in the RatsObjective:To investigate the expression of ERK in ACC and inhibition of p-ERK with U0126 and PD98059 in the ACC to explore the role of p-ERK in the mechanical hypersensitivity and anxiety-like behaviour following surgical incision in the rats.Methods:A longitudinal incision was made in one plantar hind-paw of isoflurane-anesthetized rats. We measured the expression of p-ERK in ACC with immunohistochemistry techniques and western blot. Mechanical hypersensitivity was assessed by using nylon von frey filaments according to "up-down" algorithm. Anxiety-like behaviour was measured by elevated plus maze and open field test.Results:1. the number of P-ERK positive immunostaining cells in ACC was obviously increased 15min or 30 min after incision (P<0.01), but 1h after incision, the number of positive cells was the same as the control (P>0.05); however,6h after incision, the expression of P-ERK upregulated again and the number of P-ERK positive immunostaining cells was significant higher than the control (P<0.01), which sustain until 3d after incision. This result was consistent with the western blot.2. infusion of U0126 and PD98059 in the ACC 30 min before incision could increased the PWT 30min, 1h and 3h after incision, which was significant higher than the vihicle group (P<0.05); the results of open field test and elevated plus maze indicated that infusion of U0126 and PD98059 in the ACC 30 min before incision could obviously enhance the percentage of time spent in the open arm or in central segments compared to the vihicle group (P<0.01).3. infusion of U0126 in the ACC 6h after incision, 1h after the infusion the PWT showed no significant different compared to vehicle group. But the time spent in open arm in EPM tests (P<0.01) and percentage of time spent in the inner square (P<0.05) were greatly increased compared with vehicle group.Conclusions:The expression of p-ERK was upregulated in two phases in ACC following surgical incision in the rats, the first phase was connected with mechanical hypersensitivity and anxiety-like behaviour, while the second phase only had something to do in the sustaining of anxiety-like behaviour induced by surgical incision in the ratS。...