Objective To observe the distribution features of phosphorylated p 44/42 extracellular signal-regulated kinase(p-ERK) induced by affective pain in the anterior cingulate cortex (ACC) of the rat.Methods Twelve male SD rats were randomly divided into the control group (n=6) and spinal nerve ligation (SNL) group (n=6).The rats of the SNL group were exposed to unilateral L5 spinal nerve ligation (SNL) surgery.The behavior was examined by mechanical pain thresholds (MPTs) and the pain affect was measured using open-field test, elevated zero maze.The expressions of p-ERK in ACC (AP 3.2,2.7,2.2mm from Bregma) were detected with immunofluorescence test .Results In comparison with the control group , the unilateral mechanical pain threshold in the SNL group decreased significantly after operation . The operation also resulted in pronounced anxiety-like behavior .The p-ERK labelled cells in different levels of ACC ( AP 3.2,2.7,2.2mm from Bregma) of SNL rats were (11.89 ±2.57),(32 ±4.67 ) and (17.56 ±2.04 ), respectively, while the control group rats were (12.44 ±2.16),(10 ±0.87 ) and (10.11 ±1.36).These data indicated that compared with the control group, the expressions of p-ERK in ACC(AP 2.7,2.2mm from Bregma) increased significantly in the SNL group after operation(P<0.01), besides for the level of ACC(AP 3.2mm from Bregma) (P>0.05).Conclusion The results suggest that the neuropathic pain can result in anxiety-like behavior and increased expressions of p-ERK in ACC of the rat.This change may be closely related to the expressions of p-ERK in ACC(AP 2.7,2.2mm from Bregma), but not to the level of ACC(AP 3.2mm from Bregma).

Objective To explore the relationship between mechanical withdrawal threshold ( MWTs) and local cutaneous blood perfusion ( BP ) in rats with acute inflammation induced by carrageenan.Methods Twenty male Sprague-Dawley ( SD) rats were randomly divided into control and model groups.The acute inflammatory rat model was established by subcutaneously injecting with carrageenan into the left hindpaw.MWTs were measured by Dynamic Plantar Aesthesiometer 37450 before injection ( as base) of carrageenan and at 4 h, 24 h, 48 h, 72 h after carrageenan injection. The local cutaneous BP was detected by Pericam Perfusion Speckle Imager ( Pericam PSI) at the time after measuring of MWTs.The above two behaviors were compared and the relationship between them was analyzed.Results MWTs of the model group rats were decreased while BP significantly increased than that in the control group ( P<0.01 ) .The MWTs and BP in the model rats showed a negative correlation, especially the correlation index showed significant differences at 4 h and 72 h after carrageenan injection ( P<0.01) .Conclusions Carrageenan-induced acute inflammation in rats causes significant changes in mechanical pain threshold, which has a negative correlation with local cutaneous blood perfusion.

Objective To observe the clinical efficacy of electroacupuncture in treating severe functional constipation. Method Seventy patients with severe functional constipation were randomized into a treatment group (35 cases) and a control group (35 cases). The treatment group was intervened by deeply needling bilateral Tianshu (ST25) and Fujie (SP14) with electrical stimulation in addition to ordinary acupuncture at bilateral Shangjuxu (ST37);the control group was by superficially needling the areas beside bilateral Tianshu, Fujie and Shangjuxu with sham electroacupuncture. The two groups were both treated for successive 8 weeks and were followed up for another 3 months. The complete spontaneous bowel movements (CSBMs), Bristol stool form Scale (BSFS) and difficulty in bowel movements were observed every week. Result The two groups both showed significant improvements in average weekly CSBMs (P<0.05,P<0.01), and the CSBMs at the end of the treatment were better in the treatment group than in the control group (P<0.05); the two groups were both effective in improving BSFS and difficulty in bowel movements, without significant between-group differences(P>0.05). Conclusion Electroacupuncture can improve CSBMs in severe functional constipation, but it’s insignificantly different from sham acupuncture in improving stool form and defecation difficulty.

BACKGROUND: Bupivacaine is widely used to alleviate post-operation pain and cure acute and chronic pain caused by inflammation or cancer.Its analgesic time cannot meet the request that drug is released slowly to prolong the analgesic time in clinic.OBJECTIVE: To detect the alleviating effect of bupivacaine polylactic acid microspheres taking high molecular polymer-polylactic acid as vector in rabbits with high performance liquid chromatograph (HPLC) and traditional skin test method.DESIGN: A completely randomized controlled animal experimental study.SETTING: School of Pharmacy, Second Military Medical University of Chinese PLAMATERIALS: Sixteen New Zealand rabbits, weighing (2.58±0.17)kg were used in this experiment.INTERVENTIONS: The experiment was carried out at the Department of pharmaceutics, School of Pharmacy, Second Military Medical University of Chinese PLA between September and November 2002. ① Animal models were established according to traditional skin test method. ② Totally 16 New Zealand rabbits were randomly divided into 2 groups: Group A and Group B, with 8 in each one. 5 mg/kg bupivacaine parenteral solution was injected subcutaneously in Group A, 5 mg/kg bupivacaine polylactic acid microspheres were implanted between subcutaneous tissue and sarcolemma in Group B. We took 1.5 mL blood from ear border vein at 5, 10, 20, 30,45 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after administration of bupivacaine parenteral solution respectively in Group A and another 1.5 mL at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 3 6, 48 and 60 hours after admistration of bupivacaine microsphere powder for index detection. ③ HPLC method was used to detect the concentration and releasing effect of bupivacaine in blood serum.MAIN OUTCOME MEASURES: Concentration change of bupivacaine in blood serum and efficacy diameter of local anesthetic.RESULTS:All the 16 rabbits entered the stage of result analysis. ①Change of bupivacaine concentration: Plasma bupivacaine concentration in Group A reached the peaked quickly after subutaneous injection with the high concentration of 2.466 4 mg/L, then declined quickly. Plasma bupivacaine concentration in Group B was relative stable, reached a peak much slowly after subcutaneous implantation, with peak concentration of 0.778 1 mg/L, and the plasma bupivacaine concentration maintained a relative low level, the mean retention time was obviously prolonged (P ＜ 0.05).② Alleviating effect of bupivacaine: The analgesic time was significantly longer in the bupivacaine microsphere group than in the bupivacaine parenteral solution group (P ＜ 0.05).CONCLUSION:Bupivacaine polylactic acid microspheres have sustained release effects in rabbits.

OBJECTIVE: To observe the direct intervention effects of electroacupuncture (EA) and non-steroid anti-inflammatory drugs (NSAIDs) on pain memory, and to explore their effects on cAMP/PKA/cAMP pathway in anterior cingulate gyrus (ACC). METHODS: Fifty clean healthy male SD rats were randomly divided into a control group, a model group, an indomethacin group, an EA group and a sham EA group, 10 rats in each group. Except the control group, the pain memory model was established in the remaining four groups by twice injection of carrageenan at foot; 0.1 mL of 2%λ-carrageenan was subcutaneously injected at the left foot of rats; 14 days later, when the pain threshold of rats of each group returned to the basic level, the second injection was performed with the same procedure. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36) for 30 min; the rats in the indomethacin group was treated with indomethacin intragastric administration with the dose of 3 mg/kg; the rats in the sham EA group was treated with EA without electricity at the point 0.3 mm forward "Zusanli" (ST 36) with the depth of 2 mm for 30 min; the rats in the control group was not given any invention. All the above interventions were performed 5 h, 1 d, 2 d and 3 d after the second injection of 2% λ-carrageenan. The left-side paw withdrawal thresholds (PWT) were observed before the first injection, 4 h, 3 d, 5 d after the first injection, before the second injection and 4 h, 1 d, 2 d, 3 d after the second injection. Three days after the second injection, the number of positive cells of cAMP, p-PKA, p-CREB and the number of positive cells of protein co-expression in the right ACC brain area were detected by immunofluorescence, and the relative protein expression of p-PKA and p-CREB were detected by Western blot. RESULTS: Compared with the control group, the PWTs in the model group decreased significantly 4 h, 3 d and 5 d after the first injection and 1 d, 2 d and 3 d after the second injection (<0.05); compared with the control group, the positive expression of cAMP, p-PKA and p-CREB in the right ACC brain area in the model group increased significantly (<0.05), and the number of positive cells of the co-expression of cAMP/p-PKA and p-PKA/p-CREB also increased significantly (<0.05). Compared with the model group, indomethacin group and sham EA group, the PWTs in the EA group were increased significantly 1 d, 2 d and 3 d after the second injection (<0.05); compared with the model group, indomethacin group and sham EA group, the positive expression of p-PKA and p-CREB in the right ACC brain area in the EA group decreased significantly (<0.05), and the number of positive cells of co-expression of cAMP/p-PKA and p-PKA/p-CREB was decreased significantly (<0.05). Compared with the model group and sham EA group, the positive expression of cAMP in the right ACC brain area was decreased in the EA group (<0.05). CONCLUSION EA have a direct intervention effect on pain memory, which have significant advantage over NSAIDs in the treatment of chronic pain. The advantage effect of EA on pain memory may be related to the inhibition of cAMP/PKA/CREB pathway in ACC area.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Cyclic AMP ; metabolism ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Electroacupuncture ; Gyrus Cinguli ; metabolism ; Male ; Pain Threshold ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction