Anti-hypernociceptive and anti-oxidative effects of locally treated dobutamine in diabetic rats.

BACKGROUND: Oxidative stress as a significant factor in the development of diabetes induced neuropathic pain as well as the potential for prevention of this complication. Therefore, we hypothesized that locally administrated dobutamine, a beta-adrenoreceptor agonist, or esmolol, a beta-adrenoreceptor antagonist, can modulate the oxidative stress and ameliorate the diabetes induced neuropathic pain. METHODS: Effects of locally (intraplantar) treated two pharmaceutical preparations used in clinical applications, dobutamine or esmolol, were investigated by measuring thermal latencies, mechanical thresholds and several oxidative stress parameters in streptozotocin (STZ) induced diabetic rats. RESULTS: Diabetes induced hyperalgesia and allodynia more effectively relieved by dobutamine than esmolol. Anti-hypersensitive action of dobutamine continued through the experiment. Diabetes induced oxidative damage in the paw tissues since STZ rats showed significant increased malondialdehyde (MDA), nitric oxide (NO) and decreased superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) in the paw. Dobutamine, but not esmolol, restored the tissue oxidative and nitrossive stress parameters to those observed in the non-diabetic rats. CONCLUSIONS: Findings suggest that diabetes-induced oxidative stress may be partially responsible for the development of diabetic neural complications. Amelioration of oxidative stress by locally treated dobutamine can be beneficial in diabetes induced neuropathic pain.

Anti-inflammatory and Anti-nociceptive Actions of Systemically or Locally Treated Adipose-Derived Mesenchymal Stem Cells in Experimental Inflammatory Model.

Cell-based therapies using mesenchymal stem cells provide hopeful results. Therefore, in this present study, possible anti-inflammatory and anti-nociceptive actions of locally or systemically treated adipose-derived mesenchymal stem cells (ADMSCs) investigated in experimental inflammation model. ADMSCs were isolated from a male Wistar rat under anesthesia, and then they were cultured and expanded for transplantation in all the experimental animals. Effects of intraperitoneal or intraplantar ADMSC treatments on the hallmarks of the inflammatory nociception, such as hyperalgesia, allodynia, edema, and several biochemical parameters were investigated using a well-established carrageenan (CG)-induced hindpaw inflammation model in male rats. Both local and systemic ADMSC treatment increased the latencies, thresholds, and the development of edema in a time-dependent manner. In addition, administration of ADMSC suppressed the increased level of interleukin (IL)-1ß, IL-6, and nitric oxide (NO), but further enhanced that of IL-10. Locally treated ADMSC at inflammatory sites effectively suppressed the CG-induced inflammatory responses when compared to the intraperitoneal route of administration. Findings suggest that therapeutic potential of ADMSC can change depending on its route of administration. Local ADMSC treatments may suppress the development of inflammatory-nociception and edema by decreasing the production of pro-inflammatory cytokines and NO level and increasing the anti-inflammatory cytokine production at inflammatory sites.

Modulating actions of NMDA receptors on pronociceptive effects of locally injected remifentanil in diabetic rats.

BACKGROUND: In this study, we investigated the effects of locally (intraplantar) applied remifentanil, a µ opioid receptor agonist, to the paws and tested whether locally N-methyl d-aspartate (NMDA) receptors agonist or antagonist can modify remifentanil-induced effects in diabetic rats. METHODS: Effects of locally (intraplantar) remifentanil, NMDA and MK801 or their combinations were investigated by measuring the latencies, thresholds and two biochemical parameters (malondialdehyde (MDA) and nitric oxide (NO)), in streptozotocin induced diabetic rats. RESULTS: Diabetic rats exhibited hyperalgesia and allodynia and remifentanil treatment aggravated the hyperalgesia and allodynia. The hyperalgesic and allodynic effects of remifentanil decreased in diabetic rats as compared to healthy rats. MK801 suppressed the hyperalgesic and allodynic actions of remifentanil in diabetic rats. However, hyperalgesic and allodynic actions of NMDA increased in diabetic rats. In contrast to age matched group, the combination of NMDA and remifentanil did not produce synergistic actions in diabetic rats. The levels of MDA and NO in the paw tissues of the diabetic rats significantly increased. MK801 significantly decreased NO levels, but not MDA, in diabetic rats. CONCLUSIONS: The hyperalgesic and allodynic actions of locally treated remifentanil may decrease in diabetic conditions. Increases in NMDA receptors activation, reactive oxygen species production and NO release may modify the sensitivity to remifentanil in diabetes induced neuropathic pain states.

Preventive and therapeutic effects of a beta adrenoreceptor agonist, dobutamine, in carrageenan-induced inflammatory nociception in rats.

We hypothesized that locally administrated ß-adrenoreceptor agonist can modulate the inflammatory nociceptive parameters in carrageenan (CG)-induced peripheral inflammatory pain. This study was therefore aimed to assess the preventive and therapeutic effects of a ß-agonist, dobutamine, by investigating its pretreatment and posttreatment actions on the inflammation-induced hypersensitivities (thermal hyperalgesia, mechanical allodynia) to cutaneous stimulation, edema, and several biochemical oxidant and anti-oxidant parameters in a rat model of CG-induced hind paw inflammation. Effects of dobutamine were compared with those of esmolol, a ß-adrenoreceptor antagonist. CG injection to healthy rats lowered the thermal latencies (from 10.1 ± 0.2 to 4.9 ± 0.1 s) and mechanical thresholds (from 32.9 ± 0.5 to 18.9 ± 1.3 g) and caused the hyperalgesia and allodynia. In CG-induced inflamed paws, while intraplantar esmolol treatment (1 mg) produced significant decreases in latencies (4.1 ± 0.1 s) and thresholds (15.2 ± 2.4 g), dobutamine (1 mg) increased the latencies (11.3 ± 0.5 s) and thresholds (26.3 ± 2.8 g). In contrast to esmolol, dobutamine increased the superoxide dismutase level and decreased the myeloperoxidase, malondialdehyde, and nitric oxide levels in CG-induced inflamed paws. The present results can reveal that ß-adrenoreceptors may play a role in inflammatory nociceptive processes, and locally treated ß-adrenoreceptor agonists such as dobutamine can be a preferable, appropriate choice for the management of inflammatory nociception due to their preventive and therapeutic effects on CG-induced peripheral inflammatory nociception.