Local administration of a synthetic cell-penetrating peptide antagonizing TrkA function suppresses inflammatory pain in rats.

Novel agents that inhibit nerve growth factor signaling are required for the treatment of inflammatory pain. The present study investigated the effect of local administration of inhibitory peptide of TrkA (IPTRK3), a synthetic cell-penetrating peptide that antagonizes TrkA function, in complete Freund's adjuvant (CFA)-induced hyperalgesia in rats. Three hours after subcutaneous injection of CFA into the plantar surface of the rat's left hind paw, 10 mM IPTRK3 was injected at the same site.

Upregulation of dorsal horn microglial cyclooxygenase-1 and neuronal cyclooxygenase-2 after thoracic deep muscle incisions in the rat.

Background: Plantar hindpaw incision produces hyperalgesia, transient upregulation of cyclooxygenase-2 (COX-2) and prolonged upregulation of cyclooxygenase-1 (COX-1) in rat lumbar spinal cord. Our hypothesis in this study was that a deep thoracic incision causes COX-1 and COX-2 upregulation in the dorsal horn coincident with pain-related behavior, and that specific cell types contribute to this increase in COX expression.

Methods: A left lateral thoracic skin incision was made in anesthetized rats, and superficial and deep muscles were incised.

Effect of synthetic cell-penetrating peptides on TrkA activity in PC12 cells.

As TrkA, a high-affinity receptor of nerve growth factor (NGF), is a potential target for relieving uncontrolled inflammatory pain, an effective inhibitor of TrkA has been required for pain management. To identify a specific inhibitor of TrkA activity, we designed cell-penetrating peptides combined with amino-acid sequences in the activation loop of TrkA to antagonize tyrosine kinase activity. To select a peptide inhibiting TrkA activity, we examined the effect of cell-penetrating peptides on tyrosine kinase activity of recombinant TrkA in vitro and studied their effects on NGF-stimulated neurite outgrowth and protein phosphorylation in PC12 cells.

Repeated exposures to hyperbaric air suppress neurite outgrowth in PC12 cells.

Hyperbaric exposure induces lesions of the CNS in scuba divers. Repeated exposures to hyperbaric air at 0.5 MPa for 30 min with short intervals suppressed NGF-stimulated neurite outgrowth, concomitant with a decrease in the protein expression of ERK in PC12 cells.

Local anesthetics suppress nerve growth factor-mediated neurite outgrowth by inhibition of tyrosine kinase activity of TrkA.

Local anesthetics (LAs) suppress sympathetic sprouting, which correlates with neuropathic pain. However, the precise mechanism of the suppression is unknown. Nerve growth factor (NGF) contributes to the sympathetic sprouting, and NGF signaling starts with NGF-stimulated autophosphorylation of TrkA, which is a high affinity receptor of NGF.

[Detection of deep vein thrombosis in preoperative patients using venous ultrasonography].

Background: Using Doppler ultrasonography (US), deep vein thrombosis (DVT) has been detected in the lower limbs of preoperative patients.

Methods: Of 1,087 patients scheduled for surgery from January to June 2002, US was performed in 85 patients with a history of thromboembolism, a presence of abnormality in the lower extremities, or prolonged bed rest.

Results: In five patients thrombi were detected by US, but not in patients with a history of thromboembolism.