dezocine and Disease-Models--Animal

MicroRNAs (miRNAs) play important roles in drug tolerance and regulating pain. The purpose of the present study is to explore the regulatory mechanism of miR-124-3p on dezocine tolerance against pain in a rat model. The expression of miR-124-3p and TRAF6 in spinal cord of rats was detected by quantitative reverse-transcription PCR. The paw withdrawal latency (PWL) and maximal potential efficiency % of rats were detected by PWL assay. The levels of IL-1β and TNF-α in spinal cord tissues of rats were measured by ELISA assay. The interaction between TRAF6 and miR-124-3p was predicted by TargetScan software (http://www.targetscan.org) and confirmed by the dual-luciferase reporter assay. The protein level of TRAF6 was determined by western blot. MiR-124-3p expression was highly downregulated in a dezocine-resistant model. MiR-124-3p overexpression could alleviate dezocine tolerance in rats. TRAF6 expression was significantly upregulated in a dezocine-resistant model. MiR-124-3p targeted TRAF6 and TRAF6 was negatively modulated by miR-124-3p. In addition, overexpression of TRAF6 could reverse the inhibitory effects of miR-124-3p on dezocine tolerance. Overexpression of miR-124-3p alleviates dezocine tolerance against pain via regulating TRAF6 in a rat model, providing a possible solution to address dezocine tolerance in clinical.

Topics: Analgesics; Animals; Bridged Bicyclo Compounds, Heterocyclic; Disease Models, Animal; Drug Tolerance; Gene Expression Regulation; Male; MicroRNAs; Pain; Rats; Rats, Sprague-Dawley; Tetrahydronaphthalenes; TNF Receptor-Associated Factor 6

To explore the analgesic effect of dizocine combined with ropivacaine on recurrent neuropathic pain in rat model of peripheral nerve compression. Rats were randomly divided into 5 groups: sham control group (S), peripheral nerve compression model group (M), dizocine group (D), ropivacaine group (R), and combined drug group (DR). Rat peripheral nerve compression model was constructed to observe the symptoms of the rats before and after surgery. Mechanical withdrawal threshold was measured on the 21st day after surgery. The electrophysiological changes of rat peripheral nerve were measured by biopotential recording system, including proximal latency, distal latency, and compound muscle action potential. The incubation period and nerve conduction velocity were further obtained. Histological changes were observed by HE staining and toluidine blue staining. Axon number and myelin damage grade were performed, and the ultrastructure was observed by transmission electron microscopy (TEM). The mechanical withdrawal threshold, nerve conduction velocity, and compound muscle action potential were effectively increased in combination group. However, the proximal latency, distal latency, and incubation period were significantly reduced. Furthermore, dizocine combined with ropivacaine can effectively reduce the degree of myelination. TEM shown that the DR group had the best therapeutic effect, and the histological appearance of the cross section was quite similar to that of the S group. Dizocine combined with ropivacaine has a significant analgesic effect in rat model of peripheral nerve compression.

Topics: Analgesics, Opioid; Anesthetics, Local; Animals; Bridged Bicyclo Compounds, Heterocyclic; Disease Models, Animal; Drug Therapy, Combination; Electrophysiological Phenomena; Male; Neuralgia; Pain Threshold; Peripheral Nerve Injuries; Rats; Rats, Wistar; Recurrence; Ropivacaine; Sciatic Nerve; Tetrahydronaphthalenes

The influence of sex in determining responses to opioid analgesics has been well established in rodents and monkeys in assays of short-lasting, phasic pain. The purpose of this investigation was to use a capsaicin model of tonic pain to evaluate sex differences in hyperalgesia and mu-opioid-induced antihyperalgesia in Fischer 344 (F344) rats. Capsaicin injected into the tail produced a dose-dependent thermal hyperalgesia in males and females, with the dose required to produce a comparable level of hyperalgesia being 3.0-fold higher in males than in females. These sex differences were modulated by gonadal hormones, inasmuch as gonadectomy increased the potency of capsaicin in males and decreased its potency in females. Morphine, buprenorphine, and dezocine administered by various routes [systemic (s.c.), local (in the tail), and central (i.c.v.)] generally produced marked antihyperalgesic effects in males and females. Although in most instances these opioids were equally potent and effective in males and females, selected doses of local and i.c.v. administered buprenorphine produced greater effects in females. When administered locally, the antihyperalgesic effects of morphine were mediated by peripheral opioid receptors in both males and females, since this effect was not reversed by i.c.v. naloxone methiodide. These data contrast with the finding that mu-opioids are more potent in male rodents in assays of phasic pain, thus suggesting that distinct mechanisms underlie male and female sensitivity to opioid antinociception in phasic and tonic pain models. These findings emphasize the need to test male and female rodents in tonic pain assays that may have greater relevance for human pain conditions.

Topics: Analgesics, Opioid; Analysis of Variance; Animals; Bridged Bicyclo Compounds, Heterocyclic; Buprenorphine; Capsaicin; Clinical Trials as Topic; Cycloparaffins; Disease Models, Animal; Female; Humans; Hyperalgesia; Male; Morphine; Pain Measurement; Rats; Rats, Inbred F344; Receptors, Opioid, mu; Tetrahydronaphthalenes