Changes in Response Properties and Receptive Fields of Spinal Dorsal Horn Neurons in Rats after Surgical Incision in Hairy Skin

Background: Mechanical hyperalgesia and allodynia associated with chemical irritant application are mediated by spinal high-threshold (HT) as well as wide-dynamic-range neurons as a result of "central sensitization." Because the pathophysiology of pain is thought to differ depending on the type of injury and may vary between hairy and glabrous skin, the authors examined changes in properties of spinal dorsal horn neurons after surgical incisions in hairy skin of rats to obtain insights into the mechanisms of postoperative pain.

Methods: Withdrawal responses to punctate mechanical stimulation and gentle brushing were measured in awake rats in an area adjacent to the injured site (primary area) and in an area 2 cm from the injured site (secondary area) after 1-cm longitudinal incisions through the hairy skin, fascia, and muscle had been made in the hindquarters. In a separate study, responses of spinal wide-dynamic-range, HT, and low-threshold neurons to nonnoxious and noxious stimuli were recorded before and after similar incisions had been made in the centers of their receptive fields. Effects of spinal application of the [gamma]-aminobutyric acid A receptor antagonist bicuculline (15 [mu]g) on responses of HT neurons were then studied.

Results: Awake rats showed primary and secondary hyperalgesia to punctate mechanical stimulation 30 min after the incision and thereafter for 4 days and 1 day, respectively. Mechanical allodynia associated with brush stimulation was only seen in the primary area 30 min after the incision and thereafter for 1 day. The incision resulted in increases in activity of wide-dynamic-range neurons (receptive field sizes and responses to both innocuous and noxious stimuli). HT neurons did not respond to innocuous stimulation and showed very small increases or no changes in receptive field size and responses to noxious stimuli after the incision. However, the majority of HT neurons began to respond to innocuous stimuli after application of bicuculline (15 [mu]g/50 [mu]l) to the spinal cord.     

Rho mediates endocytosis of epidermal growth factor receptor through phosphorylation of endophilin A1 by Rho-kinase

After binding of epidermal growth factor (EGF), the EGF receptor is activated, internalized by endocytosis, and subsequently degraded in the lysosomal pathway. Endocytotic trafficking of the activated EGF receptor is essential for controlling EGF signaling. Upon ligand-induced activation of EGF receptors, Cbl (ubiquitin ligase) binds to the activated receptor and leads to translocation of the CIN85 (Cbl-interacting protein of 85 kDa)/endophilin complex in the vicinity of the activated EGF receptors. Endophilin is known as a key regulator of clathrin-mediated endocytosis, and the translocation of endophilin in the vicinity of active EGF receptor is thought to promote receptor internalization. The constitutively active mutant of small GTPase Rho inhibits EGF receptor endocytosis. In this study, we found that this inhibitory effect was canceled by the dominant negative form of Rho-associated kinase (Rho-kinase), which is an effector of Rho. To clarify the molecular mechanisms of endocytosis downstream of Rho/Rho-kinase signal, we searched for and identified endophilin A1 as a novel substrate of Rho-kinase. We identified the phosphorylation site of endophilin A1 at Thr-14 and made endophilin T14D (substitution of Thr-14 by Asp), which is expected to mimic the phosphorylation state of endophilin A1. Endophilin T14D inhibited EGF receptor internalization. Furthermore, phosphorylation of endophilin by Rho-kinase inhibited the binding to CIN85. Taken together, these results suggest that Rho-kinase phosphorylates endophilin downstream of Rho and regulates EGF receptor endocytosis through the inhibition of binding between endophilin and CIN85.     

Mechanisms underlying generation of cancer pain

As advances in cancer detection and treatment have increased the life expectancy of cancer patients, more attention to improving patient's quality of life (QOL) is needed. Among symptoms accompanying cancer, pain has strong impact on QOL. Most of cancer patients will experience moderate to severe pain and/or neuropathy during the course of their disease. Cancer pain can arise from different processes, either by direct tumor infiltration/involvement, or toxicity relating to chemotherapy used to treat cancer. The World Health Organization (WHO) has proposed a structured approach to drug selection for cancer pain, known as the "WHO analgesic ladder". However, several types of pain including bone cancer pain and chemotherapy-induced painful peripheral neuropathy are difficult to treat. The development of optimal analgesics for cancer pain has been hampered by the lack of understanding basic mechanisms that contribute to cancer pain. Recently, preclinical models of bone cancer pain and paclitaxel-induced painful peripheral neuropathy have been developed. These models have begun to provide insight into the mechanisms by which cancer pain is induced and how cancer pain-related sensory information is processed. In this paper, we review mechanism of cancer pain.     

Report on the international Primary Neurosurgical Life Support course in the eighth Asian Congress of Neurological Surgeons in Kuala Lumpur, Malaysia

On November 22, 2010, a simulation-based hands-on education course for medical staff in the neurosurgical fields was held in 8(th) Asian Congress of Neurological Surgeons (ACNS) in Kuala Lumpur, Malaysia. The present education course called Primary Neurosurgical Life Support (PNLS) course had been started by the Japan Society of Neurosurgical Emergency since 2008. This report summarizes the international version of PNLS course in 8(th) ACNS.     

Revision total hip arthroplasty due to pain from hypersensitivity to cobalt-chromium in total hip arthroplasty

We report a case with hypersensitivity to CoCr in total hip arthroplasty coupled with conventional polyethylene and CoCr femoral head. The patient complained of left hip pain and systemic fever, and computed tomography imaging revealed a periprosthetic cystic lesion, so we performed revision total hip arthroplasty using a titanium stem and ceramic head and highly crosslinked polyethylene. Hip pain and cystic lesion disappeared 3 years after revision surgery.     

A case of inflammatory myofibroblastic tumor of the urinary bladder

A 61 year-old man complaining of asymptomatic gross hematuria was admitted to our hospital in May 2005. Transurethral resection of bladder tumor (TUR-BT) was performed for a bladder tumor (urothelial carcinoma (UC), pTa, G2). The TUR-BT was performed again because cystoscopy revealed a nonpapillary bladder tumor on the posterior bladder wall in September 2007. The pathological findings showed a UC, pTa, G2 and an inflammatory myofibroblastic tumor (IMT), pT1. The TUR-BT was performed two more times for tumor recurrences. We considered a total cystectomy because of the possibility of a pathologically low grade sarcoma and the considerable enlargement of the tumor size for a month after the TUR-BT. Ultimately, a malignant sarcoma was not diagnosed from the pathological findings. We practiced conservative therapy with a steroid and the tumor was reduced.     

Determinants of pharmacodynamic trajectory of the therapeutic response to paroxetine in Japanese patients with panic disorder

Purpose  

The objective of this study was to evaluate genetic and pharmacokinetic factors to establish the pharmacotherapeutic effect of paroxetine (PAX) in patients with panic disorder (PD).