Search

Objective. The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI). Methods. Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg) were administrated intragastrically at early phase of postoperation (before pain appearance) and later phase of postoperation (after pain appearance), respectively. The concentrations of TNF-α, IL-1β, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment. Results. TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-α and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1β increase. Conclusion. This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase.

Treating bone cancer pain continues to be a clinical challenge and underlying mechanisms of bone cancer pain remain elusive. Here, we reported that sonic hedgehog signaling plays a critical role in the development of bone cancer pain. Tibia bone cavity tumor cell implantation produces bone cancer-related mechanical allodynia, thermal hyperalgesia, and spontaneous and movement-evoked pain behaviors. Production and persistence of these pain behaviors are well correlated with tumor cell implantation-induced up-regulation and activation of sonic hedgehog signaling in primary sensory neurons and spinal cord. Spinal administration of sonic hedgehog signaling inhibitor cyclopamine prevents and reverses the induction and persistence of bone cancer pain without affecting normal pain sensitivity. Inhibiting sonic hedgehog signaling activation with cyclopamine, in vivo or in vitro, greatly suppresses tumor cell implantation-induced increase of intracellular Ca2+ and hyperexcitability of the sensory neurons and also the activation of GluN2B receptor and the subsequent Ca2+-dependent signals CaMKII and CREB in dorsal root ganglion and the spinal cord. These findings show a critical mechanism underlying the pathogenesis of bone cancer pain and suggest that targeting sonic hedgehog signaling may be an effective approach for treating bone cancer pain. [ABSTRACT FROM AUTHOR]

Background and Objectives: Lidocaine has been reported to attenuate the inflammatory response in addition to its anesthetic activity, but the mechanisms are poorly understood. The objective of this study is to determine if lidocaine prior to endotoxemia diminishes pulmonary dysfunction by blocking the NF-κB activation. Methods: Rats were assigned to: (1) control (0.9% sodium chloride); (2) lipopolysaccharides (LPS); (3) LPS + lidocaine 1 mg/kg; (4) LPS + lidocaine 2 mg/kg, and (5) LPS + lidocaine 4 mg/kg. The LPS and LPS + lidocaine 4 mg/kg groups were subjected to 1-, 3-, 6- and 12-hour time points. To investigate the activation of NF-κB, the expression of NF-κB in the nuclear and IκBα in the cytosol extracts were analyzed by Western blot. The concentration of TNF-α and IL-6 in serum was detected by ELISA. The pathologic changes of the lung were observed using HE staining. Results: After i.p. injection of LPS, the expression of NF-κB in the nuclear extracts was significantly increased and IκBα in the cytosol extracts was markedly decreased. The concentration of TNF-α and IL-6 in serum was increased. Pathological examination showed that the normal structure of the lung was destroyed badly. However, lidocaine reversed the above results. Conclusion: Lidocaine attenuates LPS-induced lung injury via mechanisms involving inhibiting NF-κB activation and cytokine release, which implies that lidocaine may be a potential anti-inflammatory agent in endotoxemia. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]