Surgical Incision Induces Pain-related Anxiety Through Amygdala Sensitization Which Is Inhibited By Morphine And Gabapentin

PART I : Anxiety-like behaviour in rats with incisional pain is reduced by morphine and gabapentinObjective: Anxiety has been described as an important comorbidity in the post-operative patients clinically. However, in animals the connection between the incisional pain and anxiety has hardly been investigated. Therefore, the present study is aimed to explore whether incision also causes anxiety-like behaviour in the rats and if anxiety induced by incision can be reversed by analgesic or anxiolytic drugs.Methods: Alongitudinal incision was made in one plantar hind-paw of isoflurane-anesthetized 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 the open field test. Morphine was administered by intraperitoneal (i.p.) injection after surgical incision, or administration of gabapentin by i.p. injection before incision.Results: In response to hind-paw incision, rats exhibited mechanical hypersensitivity and anxiety-like behavior. Large dose of morphine (10 mg/kg; i.p.) and gabapentin (300 mg/kg; i.p.) almost reversed incision-evoked mechanical hypersensitivity whereas small dose of morphine (2.5 mg/kg) or gabapentin (30 mg/kg) had only mild effect. Furthermore, large dose of morphine and gabapentin 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 (2.5 mg/kg; i.p.) and gabapentin (30 mg/kg; i.p.) synergistically reversed mechanical hypersensitivity but they had not synergistic effect on incision-evoked anxiety-like behaviour.Conclusions: These data suggest that surgical incision could induce anxiety-like behavior which could be prevented by the analgesic drug morphine and anxiolytic drug gabapentin.PART II :The effects of morphine and gabapentin administration on expression of p-CREB in amygdala of rats with incisional painObjective: Pain has a strong emotional component, and the amygdala plays a major role in emotional behaviours. The present study investigated the dynamic changes of phosphorylated cAMP response element (CRE)-binding protein (p-CREB) expression in both sides of the amygdala and observed the effects of morphine and gabapentin administration on expression of p-CREB in amygdala.Methods: In the hind-paw incision rat model, we measured the expressions of p-CREB in the central (CeA) and basolateral nuclei (BLA) in both sides of the amygdala using in immunohistochemistry techniques. In morphine and gabapentin group ,each rats was administrated by intraperitoneal (i.p.) with morphine (10 mg/kg) or gabapentin(300 mg/kg).Results: After incision, the expression of p-CREB was transiently upregulated in the central (CeA) and basolateral nuclei (BLA) in both sides of the amygdala. The upregulation of p-CREB in the amygdala was also inhibited by morphine and gabapentin.Conclusions: The present study shows that surgical incision induces an anxiety-like behavior through the amygdala sensitization and could be reversed by the analgesic drugs morphine and gabapentin. In addition, there may be distinct mechanisms to regulate the maintenance of anxiety-like behavior and pain hypersensitivity although they are induced by the same nociceptive signaling.