1、1Compensation of heroin dependent purine nucleotide pain threshold of ratsOf: Li Hongmei Li Kun, HE Hai Liu Jiankai Hong Min Abstract Objective To investigate the compensation of heroin dependent purine nucleotide pain threshold of rats. Methods 50 male Wistar rats were randomly divided into control
2、 group, group of heroin and heroin + AMP + GMP Group, heroin + AMP group, heroin + GMP group. the experiments 1,3,5,7 d detected by electronic tenderness rat tail pressure threshold, 2,4,6,8 d heat tail flick test for thermal hyperalgesia testing capacity in rats. Results control group on day 1 and
3、heroin heroin group compensation purine group pressure threshold has increased, but the difference was not significant (P 0.05); the first 3 days of heroin + purine groups from the pressure threshold was higher than the heroin group (P 0.05). the first 2 days of heroin group from the thermal tail-fl
4、ick latency (P 0.05); the first 4 days of heroin from the group of purine nucleotide + heat tail flick latency longer than heroin group (P 0.05 ). Conclusions of compensation can significantly increase purine nucleotide analgesic effect of heroin. 2Keywords: purine nucleotide; heroin; pain threshold
5、 Abstract Objective To investigate the effects of purine nucleotides compensation on pain threshold in heroin dependent rats. Methods 50 male Wistar rats were randomly divided into control (C), heroin (H), heroin plus purine nucleotides (Heroin + AMP + GMP, AMP and GMA were mixed in equimolar, HAG),
6、 heroin plus AMP (Heroin + AMP, HA) and heroin plus GMP groups (Heroin + GMP, HG). Rats tail pressure pain threshold was detected at 1, 3, 5 and 7 d by electric pressure pain instrument. Rat anti thermo pain ability was examined at 2, 4, 6, and 8 d by tail flick test. Results The pressure pain thres
7、hold on rats tail was increased in H and HAG groups from 1 d comparing to that of C group, but the difference was not significant (P 0.05); the threshold of HAG group was higher than that of H group from 3 d (P 0.05). The latency of tail flick was increased in H group from 2 d (P 0.05), and the late
8、ncy was higher in HAG group than that in H group from 6 day (P 0.05). Conclusions Purine nucletogides compensation can increase the analgesic effect of heroin in heroin dependent rats. Keywords: Purine nucleotides; Heroin; Pain threshold Purine nucleotide composition is divided into adenine 3nucleot
9、ides (AMP) and guanine nucleotide (GMP), phosphorylation in vivo to generate adenosine and guanosine. Exists between the cell purine nucleotides and purine nucleoside generated mainly through its receptor interaction effect (1). Some studies show that adenosine A1 receptor agonists as analgesics in
10、clinical applications (2), can significantly reduce neuropathic pain ( 3). Lao, etc. (4) also found that activation of adenosine A1 receptors to inhibit the pain response. adenosine receptor and opioid receptors in physiological and pathological conditions are closely linked (5). Heroin is typical o
11、f opioid receptor agonist, on the central nervous system can produce significant analgesia, sedation, can inhibit the patient due to tension, irritability, anxiety and other psychological factors and somatic hyperalgesia induced symptoms, but can cause physical dependence and psychological dependenc
12、e, withdrawal symptoms after the severe and intense craving for drugs. The preliminary laboratory study found that morphine, heroin and other opiates can cause excessive decomposition of the purine nucleotide (6 9), indicating that opioid dependence purine nucleotides in rat brain may lack, and the
13、purine nucleotides can enhance the pain threshold in morphine dependent rats 4(10). Therefore, this experiment in the previous study based on the results, focusing on heroin purine nucleotide analgesic effect. 1 Materials and methods 1.1 Materials and equipment male Wistar rats weighing (200 + -20)
14、g, Jilin University Medical Experimental Animal Center (Experimental Animal Production License No.: 2003 0001). Heroin (99% purity) provided by the Public Security Bureau of Jilin Province , When you use sterile triple-distilled water to dissolve. adenosine monophosphate (AMP), batch number: 0634 an
15、d a guanosine monophosphate (GMP), batch number: 0366 to Amersco products. YLS 3E electronic apparatus was purchased from Anhui tenderness Huaibei is China Bio Equipment Co., Ltd 1.2 Animal grouping and treatment of 50 rats were randomly divided into 5 groups of 10 each, general husbandry, to adapt
16、to the environment after 3 d experiment. Grouped as follows: the control group (C group): intraperitoneal injection twice daily and heroin the same volume of saline administered group. heroin group (H group): pre-production model at the laboratory to improve the methods, the establishment of rat mod
17、el of heroin 5dependence: 1 to 2 times daily morning and evening 7 days by intraperitoneal injection heroin, daily dose corresponding to 0.5,0.75,1.25,2.0,3.0,4.25,5.75 mg / kg, injected 1 day 8 5.75 mg / kg. heroin + AMP + GMP Group (HAG group): Heroin administration with the H group, and 2 times d
18、aily intraperitoneal dose of AMP + GMP, a dose of 7.5 mg / kg. heroin + AMP group (HA group): Heroin administration with the H group, and a daily dose of intraperitoneal injection of 2 7.5 mg / kg of AMP. heroin + GMP Group (HG group): Heroin administration with the H group, and 2 times daily intrap
19、eritoneal injection of GMP 7.5 mg / kg. 1.3 Compensation of heroin dependent purine nucleotide pain threshold of rats 1.3.1 tenderness tenderness experimental application YLS 3E electronic pain threshold of rats was measured. The rats were fixed into the tube, so that the role of animals in a comfor
20、table state of constant erection, with the flat head of the rat tail-pressing pressure When the animals crying in pain or struggle appears to display the pressure value that this animals pain threshold. experimental pain threshold measured before the start, the experiment began on day 1 pain thresho
21、ld measured every other day, in every morning 6to 3 h after the drug test for tenderness. 1.3.2 heat tail flick test on day 2 from the administration in the morning every other day starting 30 min after administration of the thermal tail flick test. The rats were placed in the vertical tail 52 hot w
22、ater, recorded from the rat tail into the water the time to throw in the water, as heat-sensitive evaluation of the latency in rats. 1.4 statistical analysis software used SPSS11.0, experimental data were analyzed to x +-s said, using t test. Links to free paper download 2 Results 2.1 The measuremen
23、t of tenderness experimental basis with the control group compared to the value of tenderness, to heroin and purine nucleotides on day 1 increased the pressure threshold occurred, but the difference was not significant (P 0.05). From day 3 onwards, given the period of heroin measured the pain thresh
24、old were higher (P 0.05), and with the number of times to be increased pressure threshold increased gradually. compensation for the three groups of purine nucleotides on day 3 of the pressure threshold than that of heroin to high drug group (P 0.05), with the increase in the number to be gradually i
25、ncreased 7pressure threshold. HAG, HA and HG pressure threshold between the two groups was no significant difference (P 0.05). Table 1. 2.2 The heat tail flick test of rats heat tail flick latency was no significant difference between 1 day (P 0.05), heroin group and compensation group of purine nuc
26、leotide in the administration of the first heat tail flick latency was significantly longer than 2 days the control group (P 0.05), HAG, HA and HG groups on day 2 in the administration of heat tail flick latency compared with the heroin group, the difference was not statistically significant (P 0.05
27、). However, the 4th day of administration, heat tail flick latency in rats significantly higher than that of heroin head (P 0.05), Table 2. Table 1, five groups of pressure threshold compared with rats on day 1 compared: 1) P 0.05; compared with the first 3 days: 2 ) P 0.05; compared with the first
28、5 days: 3) P 0.05; and heroin group: 4) P 0.05 Table 2, five groups of rats heat tail flick latency compared with the control group: 1) P 0.05; and heroin group: 2) P 0.05 3 Discussion Numerous studies show that the analgesic effect of 8opioids play one of the reasons is that it can promote the rele
29、ase of endogenous adenosine, morphine given under normal circumstances can lead to the release of adenosine, Cahill et al (11) receptor agonists can be observed induced adenosine release; Zhang et al (12) confirmed that the adenosine A1 receptor antagonist DPCPX to reduce the opioid analgesic effect
30、; Delander, etc. (13) found in the thermal pain test adenosine receptor antagonist theophylline can fight opium analgesic effect. Hwang et al (14) also found that intrathecal injection of morphine and adenosine receptor agonists in rat experimental allodynia produced positive synergy. opioid and ade
31、nosine shows a close relationship between. The study found that heroin and AMP and GMP (the composition of purine nucleotides) simultaneous administration can significantly improve the mechanical pain threshold in rats and thermal hyperalgesia, to extend the incubation period of pain reaction, indic
32、ating that AMP and GMP to enhance the town of heroin pain effect. The experimental results show that the heroin on purine nucleotides can enhance the analgesic effect of adult male rats. It is reasoned that heroin purine nucleotides may 9enhance the analgesic effect of aged rats, this area of great
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