Articles: hyperalgesia.
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Opioids are the most effective analgesics for the treatment of moderate to severe pain. However, chronic opioid treatment can cause both hyperalgesia and analgesic tolerance, which limit their clinical efficacy. In this study, we determined the role of pre- and postsynaptic NMDA receptors (NMDARs) in controlling increased glutamatergic input in the spinal cord induced by chronic systemic morphine administration. ⋯ Furthermore, intrathecal injection of the NMDAR antagonist significantly attenuated the development of analgesic tolerance and the reduction in nociceptive thresholds induced by chronic morphine. Collectively, our findings indicate that chronic opioid treatment potentiates presynaptic, but impairs postsynaptic, NMDAR activity in the spinal cord. PKC-mediated increases in NMDAR activity at nociceptive primary afferent terminals in the spinal cord contribute critically to the development of opioid hyperalgesia and analgesic tolerance.
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Previous studies have demonstrated that fractalkine, a newly discovered chemokine, is implicated in spinal cord neuron-to-microglia activation signaling as well as mediation of neuropathic and inflammatory pain via its sole receptor CX3CR1, which is specifically expressed on microglia. However, whether it is involved in bone cancer pain (BCP) and the underlying mechanisms have not been elucidated. ⋯ Furthermore, we demonstrated that blockade of CX3CR1 suppressed the activation of microglia and the expression of p38 mitogen-activated protein kinase (MAPK) in the spinal cord in BCP rats. These results suggest a new mechanism of BCP, in which the microglia CX3CR1/p38 signaling cascade potentially plays an important role in facilitating pain processing in BCP rats.
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Caesalpinia pyramidalis Tul. (Fabaceae) is a plant found in the Northeast of Brazil that is popularly used to treat inflammation. Acute pancreatitis (AP) is an inflammatory disease for which abdominal pain is a relevant symptom. As there is no specific therapy for AP, we investigated the effect of the ethanol extract from the inner bark of C. pyramidalis (EECp) on the AP induced by common bile duct obstruction (CBDO) in rats. ⋯ Our results demonstrated that EECp decreases inflammation, lipoperoxidation and hyperalgesia in CBDO-induced AP, making it of interest in future approaches to treat this condition.