Mol Pain
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Quercetin is a flavonoid that is widely found in fruits and vegetables. Quercetin inhibits cyclooxygenase-2 and modulates voltage-gated ion channels, however, its effect on nociceptive neuron-associated inflammatory hyperalgesia remains unknown. The present study investigated under in vivo conditions whether systemic administration of quercetin attenuates the inflammation-induced hyperexcitability of trigeminal spinal nucleus caudalis (SpVc) neurons associated with mechanical hyperalgesia and compared its effect to the non-steroidal anti-inflammatory drug, diclofenac. ⋯ In this study, the combination of three anesthetic agents did not result in any obvious "noxious pinch-evoked after discharges" in CFA inflamed day 2 rat as described previously in pentobarbital-anesthetized rats. Together, these results suggest that administration of quercetin attenuates inflammatory hyperalgesia associated with hyperexcitability of nociceptive SpVc WDR neurons via inhibition of the peripheral cyclooxygenase-2 signaling cascade and voltage-gated ion channels. These findings support the proposed potential of quercetin as a therapeutic agent in complementary alternative medicine strategies for preventing trigeminal inflammatory mechanical hyperalgesia.
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Projection neurons belonging to the anterolateral system (ALS) underlie the perception of pain, skin temperature and itch. Many ALS cells are located in laminae III-V of the dorsal horn and the adjacent lateral white matter. However, relatively little is known about the excitatory synaptic input to these deep ALS cells, and therefore about their engagement with the neuronal circuitry of the region. ⋯ Conversely, boutons with high levels of VGLUT2, which are likely to originate mainly from glutamatergic spinal neurons, account for only ∼5% of the excitatory synapses on antenna cells, but for a much larger proportion of the input to the non-antenna cells. VGLUT1 is expressed by myelinated low-threshold mechanoreceptors and corticospinal axons, and these innervate both antenna and non-antenna cells. However, the density of VGLUT1 input to the non-antenna cells is highly variable, consistent with the view that these neurons are functionally heterogeneous.
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Acupuncture is a complex treatment comprising multisensory stimulation, including visual and tactile sensations and experiences of body ownership. The purpose of this study was to investigate the role of these three components of acupuncture stimulation in acupuncture analgesia. 40 healthy volunteers participated in the study and received acupuncture treatment under three different conditions (real-hand, rubber-hand synchronous, and rubber-hand asynchronous). The tolerance for heat pain stimuli was measured before and after treatment. ⋯ Increased delta and decreased theta, alpha, beta, and gamma waves were observed after acupuncture treatment under all three conditions. Our findings clarified the role of cognitive components of acupuncture treatment in acupuncture analgesia through the rubber-hand illusion. This study is a first step toward separating various components of acupuncture analgesia, i.e. visual, tactile, and body ownership, and utilizing those components to maximize analgesic effects.
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Pain involves both sensory and affective dimensions. The amygdala is a key player in linking nociceptive stimuli to negative emotional behaviors or affective states. Relief of pain is rewarding and activates brain reward circuits. ⋯ Activation of the VTA-CeA neural pathway using optogenetic approaches relieved incisional pain. Administration of a D2 receptor agonist reversed the pain relief elicited by light-induced activation of the VTA-CeA pathway. These findings indicate that the VTA-CeA circuit is involved in pain relief in mice via dopamine receptor D2 in the CeA.
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Development of chronic pain has been attributed to dysfunctional GABA signaling in the spinal cord. Direct pharmacological interventions on GABA signaling are usually not very efficient and often accompanied by side effects due to the widespread distribution of GABA receptors in CNS. Transplantation of GABAergic neuronal cells may restore the inhibitory potential in the spinal cord. ⋯ We observed beneficial effects of the grafted cells in reducing hypersensitivity in all grafted animals, especially potent in the recombinant group. The level of pain-related cytokines was reduced in the grafted animals and correlation between these pain markers and actual behavior was indicated. This study demonstrated the feasibility of recombinant cell transplantation in the management of chronic pain.