European journal of pharmacology
-
Visceral pain, especially in the abdominal region, represents one of the most common types of pain. Its chronic form is usually very hard to treat by conventional analgesic agents and adjuvants. We investigated the antinociceptive effect of botulinum toxin type A (BTX-A) in male Wistar rats in two models of visceral pain: peritonitis induced by intraperitoneal injection of 1% acetic acid and colitis induced by intracolonic instillation of 0.1% capsaicin. ⋯ BTX-A significantly reduced the number of abdominal writhes in both models of visceral pain after intrathecal application in a dose of 2 U/kg. In the experimental colitis model, BTX-A (2 U/kg) reduced both referred mechanical allodynia and c-Fos expression in the dorsal horn of the spinal cord (S2/S3 segments). In contrast to intrathecal administration, BTX-A (2 U/kg) administered into the cisterna magna had no effect on pain suggesting that the primary site of its action is a spinal cord.
-
Depression is an inflammatory, commonly occurring and lethal psychiatric disorder having high lifetime prevalence. Preclinical and clinical studies suggest that activation of immuno-inflammatory and oxido-nitrosative stress pathways play major role in the pathophysiology of depression. Honokiol (HNK) is a biphenolic neolignan possessing multiple biological activities including antioxidant, anti-inflammatory, anxiolytic, antidepressant and neuroprotective. ⋯ Pretreatment with HNK also prevented the increase in plasma corticosterone (CORT) and decrease in hippocampal BDNF level in LPS challenged mice. In conclusion, current investigation suggested that HNK pretreatment provided protection against LPS-induced depressive like behavior which may be mediated by repression of pro-inflammatory cytokines as well as oxido-nitrosative stress in HC and PFC. Our results strongly speculated that HNK could be a therapeutic approach for the treatment of depression and other pathophysiological conditions which are closely associated with neuroinflammation and oxido-nitrosative stress.
-
NMDA receptors (NMDAR) are important in the development and maintenance of central sensitization. Our objective was to investigate the role of spinal neurons and NMDAR in the maintenance of chronic visceral pain. Neonatal rats were injected with acidic saline adjusted to pH 4.0 in the gastrocnemius muscle every other day for 12 days. ⋯ Neonatal noxious somatic stimulation results in chronic visceral hyperalgesia and sensitizes a specific subpopulation of CRD-sensitive spinal neurons. The sensitization of these SL-S spinal neurons is attenuated by the NMDAR antagonist. The results of this study suggest that spinal NMDARs play an important role in the development of hyperalgesia early in life.
-
Central post-stroke pain (CPSP), one of the complications of cerebral ischemia and neuropathic pain syndrome, is associated with specific somatosensory abnormalities. Although CPSP is a serious problem, detailed underlying mechanisms and standard treatments for CPSP are not well established. In this study, we assessed the role of GPR40, a long-chain fatty acid receptor, showing anti-nociceptive effects, in CPSP. ⋯ BCAO-induced mechanical hyperalgesia was significantly decreased by intracerebroventricular injection of docosahexaenoic acid or GW9508, a GPR40 agonist; furthermore, these effects were reversed by GW1100, a GPR40 antagonist. The expression levels of glial fibrillary acidic protein, an astrocytic marker, and some free fatty acids were significantly decreased 5h after BCAO, although no effects of BCAO were noted on hypothalamic GPR40 protein expression. Our data show that BCAO-induced mechanical hyperalgesia is possible to be regulated by astrocyte activation and stimulation of GPR40 signaling.
-
Diabetic nephropathy is one of the most common causes of end-stage kidney disease. Aldosterone and angiotensin II appear to play a crucial role in the pathogenesis of this disease. The present study aimed to investigate effects of the combination therapy with spironolactone and candesartan on diabetic nephropathy and elucidate the underlying mechanism(s) involved. ⋯ This was associated with improving the renal function parameters. The combined therapy exhibited more profound response compared to the monotherapy. In conclusion, our results demonstrate that the combined therapy of spironolactone and candesartan can confer an additive benefit over the use of either drug alone against STZ-induced diabetic nephropathy, presumably via attenuating the inflammatory responses and oxidative status markers.