Mol Pain
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Spinal nociceptive transmission receives biphasic modulation from supraspinal structures. Recent studies demonstrate that the anterior cingulate cortex facilitates spinal excitatory synaptic transmission and nociceptive reflex. However, whether the top-down descending facilitation can cause long-term synaptic changes in spinal cord remains unclear. ⋯ Spinal application of N-methyl-D-aspartate (NMDA) receptor antagonist D-AP5 abolished this enhancement, suggesting that the activation of the NMDA receptor is required. Furthermore, spinal application of methysergide, a serotonin receptor antagonist, also blocked the anterior cingulate cortex-induced spinal long-term potentiation. Our results suggest that the anterior cingulate cortex stimulation can produce heterosynaptic form of long-term potentiation at the spinal cord dorsal horn, and this novel form of long-term potentiation may contribute to top-down long-term facilitation in chronic pain conditions.
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Extracellular regulated protein kinase (ERK) pathway activation in astrocytes and neurons has been reported to be critical for neuropathic pain development after chronic constriction injury. TGN-020 was found to be the most potent aquaporin 4 inhibitor among the agents studied. ⋯ Additionally, TGN-020 suppressed ERK phosphorylation in astrocytes and neurons after injury. The findings suggested that the analgesic effects of TGN-020 in neuropathic pain were mediated mainly by the downregulation of chronic constriction injury-induced astrocytic activation and inflammation, which is via the inhibition of ERK pathway in the spinal dorsal horn and dorsal root ganglion.
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Our previous study reported the translocator protein to play a critical role in neuropathic pain and the possible mechanisms in the spinal cord. However, its mechanism in the peripheral nervous system is poorly understood. This study was undertaken to explore the distribution of translocator protein in the dorsal root ganglion and the possible mechanisms in peripheral nervous system in a rat model of spared nerve injury. ⋯ Our results suggested Ro5-4864 could alleviate neuropathic pain and attenuate p-ERK and brain-derived neurotrophic factor activation in dorsal root ganglion. Furthermore, Ro5-4864 stimulated the expression of myelin regeneration proteins which may also be an important factor against neuropathic pain development. Translocator protein may present a novel target for the treatment of neuropathic pain both in the central and peripheral nervous systems.
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Diabetic peripheral neuropathy is a major debilitating late complication of diabetes, which significantly reduces the quality of life in patients. Diabetic peripheral neuropathy is associated with a wide spectrum of sensory abnormalities, where in loss of sensation or hypoalgesia to applied external stimuli is paradoxically accompanied by debilitating tonic spontaneous pain. In numerous studies on animal models of diabetic peripheral neuropathy, behavioural measurements have been largely confined to analysis of evoked withdrawal to mechanical and thermal stimuli applied to dermatomes, whereas spontaneous, on-going pain has not been widely studied. ⋯ Neither early hypersensitivity nor late hypoalgesia were associated with markers of cellular stress in the dorsal root ganglia. Whereas significant neutrophil infiltration was observed in the dorsal root ganglia over both early and late stages post-Streptozotocin, T-cell infiltration in the dorsal root ganglia was prominent at late stages post-Streptozotocin. Thus, longitudinal analyses reveal that similar to patients with chronic diabetic peripheral neuropathy, mice show tonic pain despite sensory loss after several months in the Streptozotocin model, which is accompanied by neuroimmune interactions in the dorsal root ganglia.
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Jung Ye-Ha, Kim H, Jeon SY, Kwon JM, Lee D, Choi Soo-Hee and Kang Do-Hyung. Aberrant interactions of peripheral measures and neurometabolites with lipids in complex regional pain syndrome using magnetic resonance spectroscopy: A pilot study. ⋯ The authors regret this error. Lip09-dependent right thalamus and Lip13a-dependent left thalamus may be important to elucidate abnormal interactions between lipids in the central thalamus and peripheral measures in CRPS patients, suggestive of unique mechanisms underlying lipidassociated pathophysiology in CRPS, These findings may be used to develop personalized therapies according to the dominant side of the thalamus (right versus left) and the presence and interactions of specific metabolites.