ABSTRACT
Background@#Inflammation is known to underlie the pathogenesis in neuropathic pain. This study investigated the anti-inflammatory and neuroprotective mechanisms involved in antinociceptive effects of co-administration of acetaminophen and L-carnosine in chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. @*Methods@#Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8) treated with normal saline/acetaminophen/acetaminophen + L-carnosine. CCI was used to induce neuropathic pain in rats. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests, respectively. Investigation of spinal proinflammatory cytokines and antioxidant system were carried out after twenty-one days of treatment. @*Results@#The results showed that the co-administration of acetaminophen and Lcarnosine significantly (P < 0.001) increased the paw withdrawal threshold to thermal and mechanical stimuli in ligated rats compared to the ligated naïve group.There was a significant (P < 0.001) decrease in the levels of nuclear factor kappa light chain enhancer B cell inhibitor, calcium ion, interleukin-1-beta, and tumour necrotic factor-alpha in the spinal cord of the group coadministered with acetaminophen and L-carnosine compared to the ligated control group. Co-administration with acetaminophen and L-carnosine increased the antioxidant enzymatic activities and reduced the lipid peroxidation in the spinal cord. @*Conclusions@#Co-administration of acetaminophen and L-carnosine has anti-inflammatory effects as a mechanism that mediate its antinociceptive effects in CCIinduced peripheral neuropathy in Wistar rat.
ABSTRACT
@# Multiple causes of neuropathic pain have been identified and its incidence is likely to increase owing to the ageing global population. Glycyrrhiza glabra (licorice) is a medicinal plant known to be a highly efficacious medicinal herb with several pharmacological effects. Few researchers have demonstrated anti-nociceptive activity of licorice acute pain. The aim of this study was to investigate the anti-nociceptive effect of prepared aqueous extract of Glycyrrhiza glabra root administration on chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain and some selected inflammatory biomarkers in adult male wistar rats. Seven groups of 5 rats per group were used. Groups 1 and 2 were controls. Administration started in groups 3, 4, and 5 three days after surgery and continued for 18 days. Group 3 received 10mg/kg of Imipramine. Groups 4 and 5 received 75mg/kg and 150mg/kg of licorice respectively. Groups 6 and 7 received 75mg/kg and 150mg/kg respectively for 10 days before surgery. Paw withdrawal thresholds were assessed using hot plate method on days 3, 7, 14, and 21. On day 21, plasma level of tumor necrotic factor (TNF-α) and C-reactive protein (CRP) were determined using appropriate ELISA kits. There was significant change in pain threshold in the extract treated ameliorative groups when compared with the control and the ameliorative reference drug. TNF- alpha and CRP concentrations were significantly reduced in groups 6 and 7, compared with groups 1, 2 and 3. In conclusion, anti-nociceptive activity of licorice and its effect on TNF-α, and CRP are dose dependent and administration before surgery was more effective.
ABSTRACT
Glucocorticoid receptors (GR) are ubiquitously expressed in metazoans. Different and contrasting phenotypes have been reported upon their activation. This study investigated the behavioral phenotypes characteristic of GR stimulation in male Wistar rats. Rats in each of the four groups of rats received one of the following treatments: distilled water (control) or one of three doses of dexamethasone (treatment) injected intraperitoneally for 7â¯days. The Rats were afterwards subjected to the Y maze, the elevated plus maze (EPM), the Morris water maze (MWM), and the novel object recognition (NOR) test. At the end of the study, the animals were anesthetized and neural activity from the prefrontal cortex recorded. Blood was collected via cardiac puncture to evaluate the levels of plasma insulin and glucose, and the prefrontal cortexes excised to determine the levels of insulin, markers of oxidative stress, and calcium in the homogenate. This study showed that treatment with dexamethasone significantly reduced the total and percentage alternation in the Y maze, but had no significant effect on object recognition in the NOR test, long-term and short-term spatial memory in the MWM, or anxiety-like behavior in the EPM. Plasma and brain insulin and calcium levels were elevated moderately following treatment with the lowest dose of dexamethasone. All doses of dexamethasone decreased brain superoxide dismutase and increased lactate dehydrogenase levels. No significant change in neural activity was observed. This study shows that activation of glucocorticoid receptors differentially affects different behavioral paradigms and provides evidence for a role for glucocorticoids in mediating insulin function in the brain.
