Mol Pain
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Chemotherapy drugs such as oxaliplatin can increase nociceptive neuron excitability to result in neuropathic pain in orofacial and other regions in patients following chemotherapy. However, mechanisms underlying chemotherapy-induced increases of nociceptive neuron excitability are not fully understood. Kv4.3 channels are voltage-gated K+ channels mediating A-type K+ (IA) currents to control neuronal excitability. ⋯ The amplitudes of IA currents were significantly reduced in these nociceptive-like V2 TG neurons of oxaliplatin-treated group. Furthermore, we found that the excitability of nociceptive-like V2 TG neurons was significantly higher in the oxaliplatin-treated group than in the control group. These findings raise a possibility that down-regulation of Kv4.3 channels and IA currents in nociceptive V2 TG neurons is an underlying mechanism of oxaliplatin-induced orofacial neuropathic pain.
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Aims The main objective was to investigate the effects of the transient receptor potential cation channel subfamily V member 1 (TRPV1) on nerve regeneration following sciatic transection injury by functional blockage of TRPV1 using AMG-517, a specific blocker of TRPV1. Methods AMG-517 was injected into the area surrounding ipsilateral lumbar dorsal root ganglia 30 min after unilateral sciatic nerve transection. The number of sciatic axons and the expression of growth-associated protein-43 (GAP-43) and glial fibrillary acidic protein was examined using semithin sections, Western blot, and immunofluorescence analyses. ⋯ After sciatic nerve transection, expression of glial fibrillary acidic protein was decreased and GAP-43 was increased at the proximal stump. However, the expression of both glial fibrillary acidic protein and GAP-43 increased significantly in AMG-517-treated groups. Conclusions TRPV1 may be an important therapeutic target to promote peripheral nerve regeneration after injury.
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Objective Previous studies of neuropathic pain have suggested that the P2X4 purinoceptor (P2X4R) in spinal microglia is essential for maintaining allodynia following nerve injury. However, little is known about its role in inflammatory soup-induced trigeminal allodynia, which closely mimics chronic migraine status. Here, we determined the contributions of P2X4R and related signaling pathways in an inflammatory soup-induced trigeminal allodynia model. ⋯ Double immunostaining indicated that p38 and brain-derived neurotrophic factor were mainly expressed in microglial cells, whereas excitatory amino acid transporter 3 was primarily expressed in trigeminal nucleus caudalis neurons. Conclusions These data indicate that microglial P2X4R is involved in the regulation of excitatory amino acid transporter 3 via brain-derived neurotrophic factor-tyrosine receptor kinase B signaling following repeated inflammatory dural stimulation. Microglial P2X4R activation and microglia-neuron interactions in the trigeminal nucleus caudalis may play a role in the pathogenesis of migraine chronicity, and the modulation of P2X4R activation might be a potential therapeutic strategy.
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Aims Insular cortex is a brain region critical for processing of the sensation. Purinergic receptors are involved in the formation of chronic pain. The aim of the present study was to explore the role and mechanism of P2X3 receptors (P2X3Rs) in insular cortex in chronic visceral pain. ⋯ Incubation of P2X3Rs agonists α,β-mATP remarkably increased the frequency of spontaneous excitatory postsynaptic current and miniature excitatory postsynaptic current of the right hemisphere of insular cortex neurons of healthy control rats. Importantly, injection of A317491 significantly enhanced the colorectal distension threshold of neonatal maternal deprivation rats, while injection of α,β-mATP into right but not left insular cortex markedly decreased the colorectal distension threshold in healthy control rats. Conclusions Overall, our data provide integrated pharmacological, biochemical, and functional evidence demonstrating that P2X3Rs are physically and functionally interconnected at the presynaptic level to control synaptic activities in the right insular cortex, thus contributing to visceral pain of neonatal maternal deprivation rats.
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Background Diabetic neuropathy originating in distal lower extremities is associated with pain early in the disease course, overwhelming in the feet. However, the pathogenesis of diabetic neuropathy remains unclear. Macrophage migration inhibitory factor has been implicated in the onset of neuropathic pain and the development of diabetes. ⋯ Intriguingly, small interfering RNA-transfected knockdown of the migration inhibitory factor gene in methylglyoxal-treated skin keratinocytes increased expression of glyoxalase-I and intraepidermal nerve fibers in comparison with control small interfering RNA-transfected cells, which was decreased by induction of methylglyoxal. Conclusions Our findings suggest that migration inhibitory factor can aggravate diabetic neuropathy by suppressing glyoxalase-I and intraepidermal nerve fibers on the footpad skin lesions and provoke pain. Taken together, migration inhibitory factor might offer a pharmacological approach to alleviate pain syndromes in diabetic neuropathy.