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Regulation Of Brain-derived Neurotrophic Factor And Its Precursor On The Pain

Posted on:2011-09-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:L Q YangFull Text:PDF
GTID:1114360305992982Subject:Anesthesia
Abstract/Summary:PDF Full Text Request
Objective:To explore the behavioral impact with different delivery modes for anti-BDNF, anti-proBDNF and anti-proBDNF compound of opioid, non-steroidal drugs on rats after the cutting of hind footMethods:1) Anti-BDNF, anti-proBDNF were injected with different delivery modes, cutting pain models were established, and then values of PWT were measured after cutting.2) Morphine and anti-proBDNF were injected Separately and compoundly in abdomen, cutting pain models were established, and PWT values were measured after cutting.3) Naloxone and anti-proBDNF were injected Separately and compoundly in abdomen, cutting pain models were established, and PWT values were measured after cutting.4)Flurbiprofen and anti-proBDNF were injected Separately and compoundly in abdomen, cutting pain models were established, and PWT values were measured after cutting.Results:1) PWT values increased with intrathecal injection of anti-BDNF and intraperitoneal injection of anti-proBDNF in rats after cutting.2) PWT value was higher of anti-proBDNF injection combined with morphine than that of anti-proBDNF and morphine injection Separately.3) PWT value was lower of anti-proBDNF injection combined with naloxone than that of anti-proBDNF injection after cutting. PWT value was lower of anti-proBDNF injection combined with high-dose naloxone than that combined with low-dose naloxone.4) PWT value was higher of anti-proBDNF injection combined with flurbiprofen than that of anti-proBDNF and flurbiprofen injection Separately.Conclusions:Intrathecal injection of anti-BDNF and intraperitoneal injection of anti-proBDNF can reduce the hyperalgesia caused by hind foot cutting of rats, their efficacy is dose-dependent and the best dose is 10mg/kg. Morphine and flurbiprofen can enhance anti-proBDNF s role of reducing hyperalgesia caused by hind foot cutting of rats. Naloxone can not flip anti-proBDNF s effect of reducing hyperalgesia caused by hind foot cutting of rats absolutely. ProBDNF s pharmacological effects can not be achieved through the combination with opioid receptor.Objective:To study the changes of BDNF, TrkB, proBDNF, Sortilin, P75NTR, BDNFmRNA in the spinal cord and dorsal root ganglia after the hind foot cut in rats.Methods:1) 48 rats were randomly divided into eight groups.Those are control group,0.5h, 1h,3h,6h,24h,72h group after cutting, cutting group after the intraperitoneal injection of anti-proBDNF. Immunohistochemistry tests were carried out after the extraction of spinal cord and the right dorsal root ganglia.2) 42 rats were randomly divided into seven groups.Those are control group,0.5h, 1h,3h,6h,24h, 72h group after cutting. Elisa, Western blot and RT-PCR experiments were carried out after the extraction of spinal cord and the right dorsal root ganglia.Results:1) The expression of BDNF, TrkB in the spinal cord increased and that of proBDNF, Sortilin, P75NTR had no significant change after hind foot cutting of rats. The expression of BDNF, TrkB, proBDNF, Sortilin and P75NTR increased in the dorsal root ganglia.2)The protein content of BDNF, TrkB in the spinal cord increased and that of proBDNF, Sortilin, P75NTR had no significant change after hind foot cutting of rats. The protein content of BDNF, TrkB, proBDNF, Sortilin and P75NTR increased in the dorsal root ganglia. The expression of BDNFmRNA had no significant changes in spinal cord while that increased in dorsal root ganglia after hind foot cutting of rats.Conclusions:BDNF and proBDNF play their biological effects through binding to their high-affinity receptors in the cutting pain. ProBDNF is transformated into mature BDNF before reaching the spinal cord and the latter promotes the incidence of hyperalgesia of cutting pain through transport to the spinal cord.Objective:To study the behavioral impact of BDNF, proBDNF on rats of inflammatory pain and neuropathic pain and the expression of them in both pain models.Methods:1) Inflammatory pain and neuropathic pain models were established after intraperitoneal injection and intrathecal injection of anti-BDNF, anti-proBDNF and PIS values, PWT values were measured after injections 2)The expression of BDNF and proBDNF was detected in the spinal cord and dorsal root ganglia with immunohistochemistry after the establishment of inflammatory pain and neuropathic pain models.Results:1) Intrathecal injection of anti-BDNF and intraperitoneal injection of anti-proBDNF could reduce PIS values of inflammatory pain rats in stationary phase and could also reduce PWT values of neuropathic pain rats.2)The expression of BDNF in the spinal cord and dorsal root ganglia increased in inflammatory pain model, while proBDNF s expression had no significant change in the spinal cord and increased in the dorsal root ganglia.The expression of BDNF in the spinal cord and dorsal root ganglia increased in neuropathic pain model, while proBDNF's expression had no significant change in the spinal cord and increased in the dorsal root ganglia.Conclusions:BDNF and its precursor are involved in the regulation of stationary phase in the formalin inflammatory pain and neurotrophic pain. In inflammatory pain proBDNF is transformated into mature BDNF before reaching the spinal cord and then BDNF promotes the incidence of pain through transport to the spinal cord and so does in neuropathic pain.
Keywords/Search Tags:Brain-derived neurotrophic factor, Precursor of brain-derived neurotrophic factor, cutting pain, inflammatory pain, neuropathic pain
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