Articles: neuralgia.
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Opioids are potent analgesic drugs, but their use has been limited due to their side effects. Antinociceptive effects of D2-like receptor agonists such as quinpirole have been shown at the spinal cord level; however, their efficacy is not as high as that of opioids. Dopaminergic agonists are long-prescribed and well-tolerated drugs that have been useful to treat clinically and experimentally painful conditions. ⋯ Coadministration of 1 nmol quinpirole and 30 pmol DAMGO completely reversed hyperalgesia in the CFA model, whereas 100 pmol DAMGO plus 1 nmol quinpirole reversed the allodynia in the SLL model. This work offers evidence about a synergistic antinociceptive effect between opioidergic and dopaminergic drugs. This combination may relieve painful conditions resistant to conventional treatments, and it may reduce the adverse effects of chronic opioid administration.
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Neuropathic orofacial pain conditions represent a challenge to diagnose and treat. Natural substances are promising therapeutic options for the control of pain.
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Neuroscience letters · Jun 2019
nNOS-PSD95 interactions activate the PKC-ε isoform leading to increased GluN1 phosphorylation and the development of neuropathic mechanical allodynia in mice.
It has been suggested that interactions of neuronal nitric oxide synthase (nNOS) with postsynaptic density 95 (PSD95) play important roles in the development of chronic neuropathic pain. Here we examine the possible role of nNOS-PSD95 interactions in central sensitization as represented by phosphorylation of the NMDA receptor GluN1 subunit (pGluN1) in mice with chronic constriction injury (CCI) of the sciatic nerve. Intrathecal administration of the nNOS-PSD95 interactions inhibitor, IC87201 on post-operative days 0-3 significantly reduced the CCI-induced increase in total NO levels in the lumbar spinal cord dorsal horn. ⋯ Administration of IC87201 significantly inhibited this translocation of PKC-ε, while the expression of PKC-α and -ξ in the cytosol and membrane fractions was unaffected by sciatic nerve injury or injection of IC87201. Furthermore, administration of the PKC-ε inhibitor, εV1-2 on post-operative days 0-3 attenuated the CCI-induced development of MA and pGluN1. Collectively these results demonstrate that spinal nNOS-PSD95 interactions play an important role in PKC-dependent GluN1 phosphorylation via activation of the PKC-ε isoform, and ultimately contributes to the development of MA in peripheral neuropathy.
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Cerebrovascular events, along with the early presentation of central pain, during pregnancy, are uncommon. We report a case of a parturient with intense central poststroke pain after an ischemic cerebrovascular incident at 15 weeks of gestation, attributed to cerebral venous thrombosis. After a multidisciplinary team consultation, she was scheduled for cesarean delivery at 35 weeks of gestation, under combined spinal-epidural anesthesia. Due to severe left-sided neurological deficits and ipsilateral intense neuropathic pain, the neuraxial technique was successfully performed using the paramedian approach.
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The present study aimed to investigate cerebral metabolic changes in a neuropathic pain model following deafferentation. A total of 24 Sprague-Dawley rats were included for modeling of right brachial plexus avulsion (BPA) through the posterior approach. As nerve injury would cause central sensitization and facilitate pain sensitivity in other parts of the body, thermal withdrawal latency (TWL) of the intact forepaw was assessed to investigate the level of pain perception following BPA-induced neuropathic pain. [Fluorine-18]-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET) was applied to the brain before and after brachial plexus avulsion to explore metabolic changes in neuropathic pain following deafferentation. ⋯ Conversely, SUVs in multiple brain regions decreased, including the contralateral somatosensory cortex, ipsilateral cingulate cortex, and ipsilateral temporal association cortex. The Pearson correlation analysis showed that the SUVs of the contralateral anterodorsal hippocampus and ipsilateral dorsolateral thalamus were negatively related to the TWL of the intact forepaw, whereas the SUVs in the contralateral somatosensory cortex and ipsilateral cingulate cortex were positively related to it (p < 0.05). These findings indicate that upregulation of metabolism in the anterodorsal hippocampus and dorsolateral thalamus and downregulation metabolism in the contralateral somatosensory cortex and ipsilateral cingulate cortex could be a unique pattern of metabolic changes for neuropathic pain following brachial plexus avulsion.