J Neuroinflamm
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It is known that histamine participates in pain modulation. However, the effect of central histamine on neuropathic pain is not fully understood. Here, we report a critical time window for the analgesic effect of central histamine in the partial sciatic nerve ligation model of neuropathic pain. ⋯ These results demonstrate that central histamine is analgesic within a critical time window in the PSL model of neuropathic pain via histamine H1 receptors. This effect may partly relate to the inhibition of microglial activation and IL-1β production in the spinal cord following nerve injury.
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Spinal cord injury (SCI) is a severe traumatic injury that often leads to paralysis. The neuroinflammation following SCI plays an important role during the secondary injury phase. C-C motif chemokine ligand 20 (CCL20) works like a magnet to attract inflammatory cells and subsequently regulate inflammation. However, the role and mechanisms of CCL20 in neuroinflammation following traumatic injury are poorly understood. ⋯ These results suggested that CCL20 aggravates neuroinflammation following SCI via regulation of Th17 cell recruitment and IL-17A level. Thus, CCL20-target therapy could be a promising clinical application for the treatment of SCI.
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Observational Study
Multivariate projection method to investigate inflammation associated with secondary insults and outcome after human traumatic brain injury: a pilot study.
Neuroinflammation has been proposed as a possible mechanism of brain damage after traumatic brain injury (TBI), but no consensus has been reached on the most relevant molecules. Furthermore, secondary insults occurring after TBI contribute to worsen neurological outcome in addition to the primary injury. We hypothesized that after TBI, a specific pattern of cytokines is related to secondary insults and outcome. ⋯ The multivariate projection method represents a valuable methodology to study neuroinflammation pattern occurring after secondary brain damage in severe TBI patients, overcoming multiple putative interactions between mediators and avoiding any subjective selection of relevant molecules.
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Spinal cord injury (SCI) causes loss of neurons and axons and results in motor and sensory function impairments. SCI elicits an inflammatory response and induces the infiltration of immune cells, predominantly macrophages, to the injured site. Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member (TNFRSF)-6B, is a pleiotropic immunomodulator capable of inducing macrophage differentiation into the M2 phenotype and enhancing angiogenesis. Because M2 macrophages are crucial for the recovery of impaired motor functions, we ask whether DcR3 is beneficial for the functional recovery of locomotion in Sprague-Dawley (SD) rats after SCI. ⋯ These results indicated that DcR3.Fc may promote the M2 macrophage infiltration and enhanced angiogenesis at the lesion site, thus preserving a greater amount of spinal cord tissues and enhancing functional recovery after SCI.
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Chronic neuropathic pain is a common symptom of multiple sclerosis (MS). MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) has been used as an animal model to investigate the mechanisms of pain in MS. Previous studies have implicated sensitization of spinal nociceptive networks in the pathogenesis of pain in EAE. However, the involvement of supraspinal sites of nociceptive integration, such as the primary somatosensory cortex (S1), has not been defined. We therefore examined functional, structural, and immunological alterations in S1 during the early stages of EAE, when pain behaviors first appear. We also assessed the effects of the antidepressant phenelzine (PLZ) on S1 alterations and nociceptive (mechanical) sensitivity in early EAE. PLZ has been shown to restore central nervous system (CNS) tissue concentrations of GABA and the monoamines (5-HT, NA) in EAE. We hypothesized that PLZ treatment would also normalize nociceptive sensitivity in EAE by restoring the balance of excitation and inhibition (E-I) in the CNS. ⋯ These findings implicate a pro-excitatory shift in the E-I balance of the somatosensory CNS, arising early in the pathogenesis EAE and leading to large-scale functional and structural plasticity in S1. They also suggest a novel antinociceptive effect of PLZ treatment.