Neuroscience
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Transcutaneous electric nerve stimulation (TENS) is widely used for the treatment of pain. TENS produces an opioid-mediated antinociception that utilizes the rostroventromedial medulla (RVM). Similarly, antinociception evoked from the periaqueductal grey (PAG) is opioid-mediated and includes a relay in the RVM. ⋯ In a separate group of animals, microinjection of CoCl(2) into the vlPAG temporarily reversed the decreased mechanical withdrawal threshold suggesting a role for the vlPAG in the facilitation of joint pain. No significant difference was observed for dlPAG. We hypothesize that the effects of TENS are mediated through the vlPAG that sends projections through the RVM to the spinal cord to produce an opioid-mediated analgesia.
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Extracellular signal-regulated kinases (ERK1 and ERK2) are phosphorylated in the nervous system after somatic or visceral stimulation or inflammation and play roles in central sensitization and pain hypersensitivity. ERK1/2 activation with cyclophosphamide (CYP)-induced cystitis has been demonstrated in urinary bladder and inhibitors of ERK1/2 phosphorylation reduce CYP-induced bladder hyperreflexia. In this study, we determined pERK1/2 expression and regulation in lumbosacral dorsal root ganglia (DRG) and spinal cord with CYP-induced cystitis (4 h, 48 h, chronic) using Western blotting and immunohistochemical techniques. ⋯ In contrast, pericellular pERK1/2-IR in DRG was not regulated by CYP-induced cystitis. A small percentage of bladder afferent cells in lumbosacral DRG expressed pERK1/2-IR in control rats; however, CYP-induced cystitis (48 h) significantly (P< or =0.01) increased the percentage of bladder afferent cells in the L6 and S1 DRG exhibiting pERK1/2-IR. These studies suggest that activation of the ERK pathway in lumbosacral DRG may play a role in neuroplasticity in micturition reflexes with CYP-induced cystitis.
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This study assessed the effect of the agonist 15d-PGJ(2) administered into the rat temporomandibular joint (TMJ) on nociceptive behavioral and the anti-inflammatory potential of this prostaglandin on TMJ. It was observed that 15-deoxy-(Delta12,14)-prostaglandin J(2) (15d-PGJ(2)) significantly reduced formalin-induced nociceptive behavior in a dose dependent manner, however injection of 15d-PGJ(2) into the contralateral TMJ failed to reduce such effects. This antinociceptive effect is dependent on peroxisome proliferator-activated receptors-gamma (PPAR-gamma) since pre-treatment with GW9662 (PPAR-gamma receptor antagonist) blocked the antinociceptive effect of 15d-PGJ(2) in the TMJ. ⋯ Taken together, these results demonstrate that 15d-PGJ(2) has a potential peripheral antinociceptive and anti-inflammatory effect in the TMJ via PPAR-gamma activation. The results also suggest that 15d-PGJ(2) induced-peripheral antinociceptive response in the TMJ is mediated by kappa/delta opioid receptors by the activation of the intracellular l-arginine/NO/cGMP/K(+)(ATP) channel pathway. The pharmacological properties of the peripheral administration of 15d-PGJ(2) highlight the potential use of this PPAR-gamma agonist on TMJ inflammatory pain conditions.
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Endocannabinoids have a variety of effects by acting through cannabinoid 1 (CB1) receptors located throughout the brain. However, since CB1 receptors are located presynaptically, and because the strength of downstream coupling varies with brain region, expression studies alone do not provide a firm basis for interpreting sites of action. ⋯ Areas of interest demonstrate a drug interaction when the CB1 receptor inverse agonist, rimonabant, is co-administered. This analysis highlights the corticostriatal-hypothalamic pathway, which is central to the motivational drive to eat.
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The purpose of this work is to study the effect of catalpol, an iridoid from Rehmannia glutinosa on neurodegenerative changes induced by beta-amyloid peptide Abeta(25-35) or Abeta(25-35)+ibotenic acid and the underlying mechanism. Results showed that catalpol significantly improved the memory deficits in the neurodegenerative mouse model produced by injection of Abeta(25-35)+ibotenic acid to the nucleus magnocellularis basalis, yet it is neither a cholinesterase inhibitor nor a muscarinic (M) receptor agonist. Instead, the choline acetyl transferase (ChAT) activity and the M receptor density in brain were significantly decreased in the model mice and catalpol could significantly elevate their levels. ⋯ When the action of BDNF was inhibited by k252a in the cultured neurons, the protective effect of catalpol was completely (neurite outgrowth length) or partially (ChAT positive neuron number and the M receptor density) abolished. Taken together, catalpol improves memory and protects the forebrain neurons from neurodegeneration through increasing BDNF expression. Whether catalpol could reverse the neurodegenerative changes already present before its application remains to be further studied.