| Background and ObjectivePostoperative pain is acute pain occurs immediately after the surgery, its natureis nociceptive pain, usually lasts7d or less. Postoperative pain seriously affect thepatient’s pathological physiology, against the patient’s postoperative recovery.With more attention paid to the prevention and control of postoperative pain inrecent years, the research and treatment of postoperative pain has also made greatprogress. Local anesthetics, opioid, acetaminophen, nonsteroidal anti-inflammatorydrugs and a large number of COX2inhibitor analgesic drugs were applied to clinical,and have achieved some therapy. But in current, each analgesia method and analgesicdrug has its side effects and limitations, therefore understanding the molecularmechanism of postoperative pain, looking for new targets of postoperative paintreatment is still a hotspot of research in this field. In recent years, more and morepeople in the study of pain find that inflammatory factors involved in the mechanismof pain, plays an important role in the happening and development of the pain.Chemokines belongs to the chemotactic superfamily, is a collection of molecularweight at about10KDa protein secretion type single, named for the leukocytechemotaxis[2], and plays an important role in the regulation of inflammatory factors.Chemokines SDF-1(stromal cell-derived factor1) as a part of the CXC chemokines and its receptor CXCR4(CXC chemokine receptor4) belongs to CXCRG-protein-coupled receptors superfamily. Inflammatory factors play an important rolein pain, and SDF-1and its receptor CXCR4play an important role in regulatinginflammatory factors, but if SDF-1and its receptor CXCR4is involved in themechanism of pain is unclear. This study aims to through copy the postoperative painmodel by incision pain rats, application of CXCR4receptor antagonist AMD3100,observe the postoperative pain in rats to explore the SDF-1/CXCR4signalingpathways in the role of postoperative pain.Part1Effect of the chemokine SDF-1/CXCR4to incision pain inrats on central nervous systemMethodsFifty-five male SD rats (weight180-220g) were randomly divided into5groups: incision+intrathecal injection of saline; incision+intrathecal injection of5μg AMD3100; incision+intrathecal injection of10μg AMD3100; incision+intrathecal injection of20μg AMD3100; incision+immunohistochemical; All ratswere anesthetized with sevoflurane, and a left hind paw plantar incision wasperformed. Group Incision respectively in the preoperative and postoperative6h,1d,3d,7d perfusion and collected spinal cord, L4-5DRG under deep anesthesia, andthen applies immumohistochemical staining and observe the expression ofSDF-1/CXCR4by fluorescence microscope. In group Saline,5μg AMD3100,10μgAMD3100and20μg AMD3100respectively intrathecal injection of saline,5μgAMD3100,10μg AMD3100and20μg AMD310030min before incision and1-5day after incision. And observe the behavioral manifestation of pain behavioraltesting: paw withdrawal mechanical threshold, paw withdrawal thermal latency,cumulative pain score. The points of testing time are3days before incision operationto7days after incision. Results(1) Pain behavioral changes:Before operation, no significant differences in withdrawal threshold, withdrawallatency and cumulative pain score was found between groups. Compared topre-operation, decreases in withdrawal threshold and withdrawal latency wereobserved in group Saline,5μg AMD3100,10μg AMD3100and20μg AMD3100atevery point after surgery（P<0.01). Compared to group Saline, withdrawal thresholdand withdrawal latency of group5μg AMD3100,10μg AMD3100and20μgAMD3100were dose-dependently increased in1d to6d, the difference wasstatistically significant (P<0.05). And the cumulative pain score wasdose-dependently decreased in1d to6d, the difference was statistically significant(P<0.05)(2) Immunofluorescent:Compared with preoperative, the expression of SDF-1/CXCR4in spinal cordand DRG increased strongly after surgery, and the strongest expression is in day one.Part2Effect of the chemokine SDF-1/CXCR4to incision pain inrats on peripheral surgical siteMethodsThirty-five male SD rats (weight180-220g) were randomly divided into3groups: incision+subcutaneous injection of saline; incision+subcutaneous injectionof50μg AMD3100; incision+immunohistochemical. All rats were anesthetized withsevoflurane, and a left hind paw plantar incision was performed. Group Incisionrespectively in the preoperative and postoperative6h,1d,3d,7d perfusion andcollected skin around the incision (2×1cm) under deep anesthesia, and then appliesimmumohistochemical staining and observe the expression of SDF-1/CXCR4byfluorescence microscope. In group Peripheral Saline and50μg AMD3100respectively subcutaneous injection of saline,50μg AMD310030min beforeincision and1-5day after incision. And in group Peripheral Saline,50μg AMD3100 observe the behavioral manifestation of pain behavioral testing: paw withdrawalmechanical threshold, paw withdrawal thermal latency and cumulative pain score.The points of testing time are3days before incision to7days after incision.Results（1）Pain behavioral changes:Before operation, no significant differences in withdrawal threshold, withdrawallatency and cumulative pain score was found between groups. Compared topre-operation, decreases in withdrawal threshold and withdrawal latency wereobserved in group Peripheral Saline and50μg AMD3100after surgery(P<0.05). Andafter surgery, increases in cumulative pain score was observed in both groupcompared to pre-operation(P<0.05). Compared to group Peripheral Saline, thewithdrawal threshold was increased in2h to6d in group50μg AMD3100（P<0.05),withdrawal latency was increased in1d to6d in group50μg AMD3100（P<0.05),and the cumulative pain score was decreased in1d to6d in group50μg AMD3100（P<0.05).（2）Immunofluorescent:Compared with preoperative, the expression of SDF-1/CXCR4in skin increasedstrongly, and the strongest expression is6h.ConclusionThe upreglulation of SDF-1/CXCR4in spinal cord dorsal horn, DRG and skincontributed to the development and maintenance of incision pain in rats. |
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