Articles: neuropathic-pain.
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Despite the suggestion of a neuropathic component to sickle cell disease (SCD) pain, there are minimal data on the systematic assessment of neuropathic pain in patients with SCD. Neuropathic pain is defined as pain primarily initiated by dysfunction of the peripheral or central nervous system. ⋯ Neuropathic pain exists in SCD. Valid screening tools can identify patients that would benefit from existing and future neuropathic pain therapies and could determine the impact of these therapies.
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Brain Behav. Immun. · Mar 2014
Up-regulation of interleukin-23 induces persistent allodynia via CX3CL1 and interleukin-18 signaling in the rat spinal cord after tetanic sciatic stimulation.
Tetanic stimulation of the sciatic nerve (TSS) induces sciatic nerve injury and long-lasting pain hypersensitivity in rats, and spinal glial activation and proinflammatory cytokines releases are involved. In the present study, we showed that spinal interleukin (IL)-23 and its receptor, IL-23R, are crucial for the development of mechanical allodynia after TSS. In the spinal dorsal horn, both IL-23 and IL-23R are expressed in astrocytes, and this expression is substantially increased after TSS. ⋯ Activation of CX3CR1 and IL-18R induced similar behavioral and biochemical changes to those observed after TSS. These results indicate that the interaction among CX3CL1, IL-18 and IL-23 signaling in the spinal cord plays a critical role in the development of allodynia. Thus, interrupting this chemokine-cytokine network might provide a novel therapeutic strategy for neuropathic pain.
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This study examined the role of the glial-neuronal G protein-coupled receptor kinase 2 (GRK2) pathway in the development of trigeminal neuropathic pain. Male Sprague Dawley rats, weighing 220 to 240 g, were anesthetized with ketamine (0.2 g/kg) and xylazine (0.02 g/kg). Under anesthesia, the left lower second molar was extracted, followed by the placement of a mini-dental implant to intentionally injure the inferior alveolar nerve. This injury produced mechanical allodynia along with the downregulation of neuronal GRK2 expression in the medullary dorsal horn. On the other hand, early intracisternal treatment with MDL28170, a calpain inhibitor, produced prolonged antiallodynic effects and blocked this downregulation of neuronal GRK2 expression. The intracisternal infusion of minocycline, a microglia inhibitor, and l-α-aminoadipic acid, an astrocytic specific inhibitor, also blocked the induced mechanical allodynia and downregulated neuronal GRK2 expression, respectively. Double immunofluorescence showed that the interleukin (IL)-1β and IL-1R signals colocalize with the astrocytes and neurons, respectively, in the medullary dorsal horn following an inferior alveolar nerve injury. In addition, the intracisternal infusion of an IL-1 receptor antagonist also produced antiallodynic effects and blocked the downregulation of neuronal GRK2 expression. These results suggest that the glial-neuronal GRK2 pathway is a potentially important new target for treating neuropathic pain. Moreover, the IL-1β expressed in astrocytes plays a significant role in modulating this pathway. ⋯ This study showed that the glial-neuronal GRK2 pathway participates in the development of trigeminal neuropathic pain in rats. These results suggest that the glial-neuronal GRK2 pathway is a potentially important new target for the treatment of neuropathic pain.
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To report our experience related to the use of spinal cord stimulation (SCS) for relief of chronic pancreatitis-related neuropathic visceral pain. ⋯ SCS appears to be an effective long-term treatment for neuropathic visceral pain related to chronic pancreatitis.
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Prostacyclin is an important mediator of peripheral pain sensation. Here, we investigated its potential participation in mediating neuropathic pain and found that prostacyclin receptor (IP) knockout mice exhibited markedly decreased pain behavior. Application of an IP antagonist to the injury site or selective IP deficiency in myeloid cells mimicked the antinociceptive effect observed in IP knockout mice. ⋯ Fittingly, the IL1-receptor antagonist anakinra (IL-1ra) decreased neuropathic pain behavior in wild-type mice but not in IP knockout mice. Finally, continuous, but not single administration, of the cyclooxygenase inhibitor meloxicam early after nerve injury decreased pain behavior and the number of resident macrophages. Thus, early synthesis of prostacyclin at the site of injury causes accumulation of IL1β-expressing macrophages as a key step in neuropathic pain after traumatic injury.