Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pain provoked by sexual intercourse in men is a well-recognized symptom that has received surprisingly little attention in the medical literature and has rarely been the subject of systematic study. Sexual pain disorders have generally been considered in the context of the sexual dysfunctions, and in men have received much less attention than in women. Reports of male sexual pain lack use of a uniform definition for the condition. Sexual pain, especially ejaculatory pain, is a common feature of chronic prostatitis/chronic pelvic pain syndrome (CPPS). However, a range of physical and medical causes for sexual pain in men has been reported, usually in the form of isolated clinical reports. Our understanding of the aetiology and pathogenesis of male sexual pain is very limited, and systematic evaluations of treatment approaches are lacking.
Int J STD AIDS 2006 Nov
PMID:The male sexual pain syndromes. 1706 72

Protein kinase B (PKB/Akt) is a member of the second-messenger regulated subfamily of protein kinases. It is implicated in signaling downstream of growth factors, insulin receptor tyrosine kinases and phosphoinositide 3-kinase (PI3K). Current studies indicate that nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and PI3K help mediate inflammatory hyperalgesia. However, little is known about the role of PKB/Akt in the nociceptive system. In this study, we investigated whether PKB/Akt in primary sensory neurons is activated after noxious stimulation and contributes to pain behavior induced in rats by capsaicin. We demonstrated that phospho-PKB/Akt (p-PKB/Akt) is increased in dorsal root ganglia (DRG) at 5 min after intradermal injection of capsaicin. p-PKB/Akt is distributed predominantly in small- and medium-sized DRG cells. After capsaicin injection, p-PKB/Akt (473) is colocalized with isotectin-B4 (IB4), tyrosine kinase A (TrkA), and calcitonin gene-related peptide (CGRP). Furthermore, most transient receptor potential vanilloid type 1 (TRPV1) positive DRG neurons double label for p-PKB/Akt. Behavioral experiments show that intradermal injection of a PI3K (upstream of PKB/Akt) inhibitor, wortmannin, dose-dependently inhibits the changes in exploratory behavior evoked by capsaicin injection. The PKB/Akt inhibitor, Akt inhibitor IV, has the same effect. The results suggest that the PKB/Akt signaling pathway in the periphery is activated by noxious stimulation and contributes to pain behavior.
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PMID:Activation of protein kinase B/Akt in the periphery contributes to pain behavior induced by capsaicin in rats. 1708 39

Mumps epididymo-orchitis has not been recorded as a cause of testicular symptoms without systemic features (including parotitis). The aim of the present study was to assess if we were missing cases in the genitourinary clinic during a previous outbreak of mumps in the community. During a prospective pilot study from November 2005 to February 2006, all patients presenting with symptoms or signs of epididymo-orchitis were studied. These patients were assessed for previous exposure to mumps virus or vaccine, and any current evidence of systemic illness. All patients included had a full sexual health screen (loop test, chlamydia polymerase chain reaction [PCR], gonorrhoea culture, HIV and Venereal Disease Research Laboratory [test]/Treponema pallidum particle agglutination assay), urinary tract infection excluded by urinalysis and mid-stream specimen of urine (MSSU) and mumps serology (Immunoglobulin M [IgM] and Immunoglobulin G [IgG]) performed. Twenty-three patients met inclusion criteria. Their ages ranged from 16 to 50 years, average 30.8 years. All had symptoms of these, 18 had testicular pain, eight swelling, (four had both pain and swelling) and three also had dysuria. On examination, 12 had tenderness, seven swelling, (two both tenderness and swelling) and six had no signs. Seventeen denied history of mumps, one patient had a record of vaccination and five described fever. None had parotid swelling. Three patients were chlamydia PCR positive, two had candida cultured, three had non-specific urethritis (>10 polymorphonuclear leucocyte/high powered field) and 13 had negative sexually transmitted infection screen (one known HIV-positive). Three had positive IgM mumps serology and two were IgG-positive. It is important to include mumps in the differential of epididymo-orchitis and to be aware of outbreaks in the community that may present with genital symptoms, as the management and partner notification will be different.
Int J STD AIDS 2007 May
PMID:Are we missing mumps epididymo-orchitis? 1752 97

Several lines of evidence indicate that phosphatidylinositol 3-kinase (PI3K) and PI3K-protein kinase B/Akt (PKB/Akt) signal pathway mediate the pain hypersensitivity induced by intradermal injection of capsaicin or nerve growth factor. However, the role of PI3K and PI3K-PKB/Akt signal pathway activation in neuropathic pain is still unclear. Using L5 spinal nerve ligation (L5 SNL) and immunohistochemistry, we found that the numbers of phospho-PKB/Akt-immunoreactive (p-PKB/Akt IR) positive neurons were significantly increased in ipsilateral L5 dorsal root ganglia (DRG) and adjacent L4 DRG started at 12 h after surgery and maintained to the 3rd day. Meanwhile, L5 SNL also induced an increased expression of p-PKB/Akt in ipsilateral L5 spinal dorsal horn. Double immunofluorescence staining showed that p-PKB/Akt expressed entirely in DRG neurons, especially in IB4-positive neurons. Intrathecal injection of PI3K inhibitor wortmannin or LY294002 and PKB/Akt inhibitor Akt inhibitor IV or (-)-Deguelin, started before L5 SNL, reduced the behavioral signs of neuropathic pain. Intraperitoneal injection of wortmannin or (-)-Deguelin as above also reduced the pain hypersensitivity. Post-treatment with wortmannin, started at the 1st day or the 3rd day after L5 SNL, decreased abnormal pain behaviors. Whereas the inhibitory effect of Akt inhibitor IV on established neuropathic pain was observed only in those rats that received the drug treatment started at the 1st day. Immunohistochemistry revealed that intrathecal injection of wortmannin significantly inhibited the activation of PKB/Akt in L5 DRG and L5 spinal cord. The data suggested that PI3K and PI3K-PKB/Akt signal pathway activation might contribute to the development of neuropathic pain.
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PMID:Activation of phosphatidylinositol 3-kinase and protein kinase B/Akt in dorsal root ganglia and spinal cord contributes to the neuropathic pain induced by spinal nerve ligation in rats. 1762 41

Endometriosis (EMS) is a chronic inflammatory disease of multifactorial etiology characterized by implantation and growth of endometrial glands and stroma outside the uterine cavity. EMS is a significant public health issue as it affects 15-20% of women in their reproductive age. Clinical symptoms may include pelvic pain, dysmenorrhea, dyspareunia, pelvic/abdominal masses, and infertility. Symptomatic treatments such as surgical resection and/or hormonal suppression of ovarian function and analgesics are not as effective as desired. Consequently, there is an enormous unmet need to develop effective medical therapy capable of preventing the occurrence and recurrence of EMS without undesirable side-effects. EMS-associated intra-abdominal bleeding episodes, local inflammation, adhesions, and i.p. immunologic dysfunction leads to pelvic nociception and pelvic pain. Increasing evidence supports the involvement of allergic-type inflammation in EMS. Invasion of mast cells, degranulation, and proliferation of interstitial component are observed in endometriotic lesions. Presence of activated and degranulating mast cells within the nerve structures can contribute to the development of pain and hyperalgesia by direct effects on primary nociceptive neurons. Therefore, treatments targeting endometrial mast cells may prove effective in preventing or alleviating EMS-associated symptoms. The Janus kinase 3 (JAK3) is abundantly expressed in mast cells and is required for the full expression of high-affinity IgE receptor-mediated mast cell inflammatory sequelae. JANEX-1/WHI-P131 is a rationally designed novel JAK3 inhibitor with potent anti-inflammatory activity in several cellular and in vivo animal models of inflammation, including mouse models of peritonitis, colitis, cellulitis, sunburn, and airway inflammation with favorable toxicity and pharmacokinetic profile. We hypothesize that JAK3 inhibitors, especially JANEX-1, may prove useful to prevent or alleviate the symptoms of EMS.
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PMID:Targeting mast cells in endometriosis with janus kinase 3 inhibitor, JANEX-1. 1763 Oct 2

This study examined pain and distress from needles in children undergoing blood sampling as a function of adult-child interaction and type of venous access (i.e., central external venous lines, internalized ports, or peripheral access via venipuncture). Participants were 55 pediatric oncology patients, aged 3-18 years, who were undergoing routine blood work. Pain ratings were obtained using the Faces Pain Scale-Revised (FPS-R) and conversation during the procedure was audio taped for coding using the Child-Adult Medical Procedure Interaction Scale-Revised (CAMPIS-R). Children's ratings of pain using the FPS-R were similar in the port (M=2.57/10, standard deviation [SD]=3.46) and peripheral (M=2.56/10, SD=3.24) groups, despite the fact that most children with internal ports were given a topical anesthetic. Similarly, there were no differences between port and peripheral groups in rates of child coping or distress, or parent and nurse observations of child pain. As would be expected, external line access was not associated with pain or distress, even among very young children, suggesting that they appropriately understood the pain rating scale. Results of the transcribed CAMPIS-R data indicate that the influences in adult-child interaction are bidirectional. Support was found for the well-established positive relationship between child distress and adult reassurance and empathy. Implications for intervention and selection of central venous access devices are discussed.
J Pain Symptom Manage 2008 Aug
PMID:Pain, distress, and adult-child interaction during venipuncture in pediatric oncology: an examination of three types of venous access. 1840 Apr 58

Peripheral nerve lesion leads to the production of interleukin 6 (IL-6)-related neuropoietic cytokines involved in nerve protection and regeneration. This family of cytokines mainly signal through the signal transducer and activator of transcription (STAT) pathway that is locally activated in injured nerves. IL-6 is also involved in pain that frequently arises from peripheral nerve lesion. We investigated the possible activation of this major IL-6 signaling system in the spinal cord after peripheral nerve injury and its role in neuropathic pain. Ligation of L5-L6 spinal nerves (SNL) evoked an accumulation of active, phosphorylated form of STAT3 in microglial cells of dorsal spinal cord mostly in projection areas of injured nerves. SNL resulted also in a massive induction of IL-6 mRNA expression in dorsal root ganglia and increased concentration of IL-6 in dorsal spinal cord. Intrathecal injection of anti-rat IL-6 antibodies prevented the SNL-induced accumulation of phospho-STAT3 in the spinal cord. STAT3 pathway blockade with Janus kinase 2 inhibitor AG490 attenuated both mechanical allodynia and thermal hyperalgesia in SNL rats. These data show that in response to SNL injury Janus kinase/STAT3 system is activated mainly through IL-6 signaling in spinal microglia and that this transduction pathway participates in development of pain associated with nerve alteration.
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PMID:JAK/STAT3 pathway is activated in spinal cord microglia after peripheral nerve injury and contributes to neuropathic pain development in rat. 1863 82

The purpose of this study was to improve the evaluation process of children with type I Osteogenesis Imperfecta (OI) by providing a quantitative comparison of gait and selected functional assessments to age-matched controls. A 14-camera Vicon Motion Analysis System was used for gait analysis along with selected functional assessments (Pediatric Outcomes Data Collection Instrument [PODCI], Functional Assessment Questionnaire [FAQ], Faces Pain Scale-Revised [FPS-R]) conducted on 10 subjects with type I OI and 22 age-matched healthy controls. The results of the OI group demonstrated abnormal gait parameters including increased double support, delayed foot off, reduced ankle range of motion and plantarflexion during third rocker, along with greater ankle power absorption during terminal stance and reduced ankle power generation during push off. The functional assessment scores of the OI group were similar to the control group for basic mobility and function, but were lower than their peers in the sports and physical function category. The evaluation of individuals with OI by means of gait analysis and selected functional assessments, along with an accurate biomechanical model of the lower extremities, is proposed to better understand and predict OI disability and improve quality of life.
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PMID:Gait characteristics and functional assessment of children with type I osteogenesis imperfecta. 1924 79

Despite wide usage of the Numerical Rating Scale (NRS) for self-report of pain intensity in clinical practice with children and adolescents, validation data are lacking. We present here three datasets from studies in which the NRS was used together with another self-report scale. Study A compared post-operative pain ratings on the NRS with scores on the Faces Pain Scale-Revised (FPS-R) in 69 children age 7-17 years who had undergone a variety of surgical procedures. Study B compared post-operative pain ratings on the NRS with scores on the Visual Analogue Scale (VAS) in 29 children age 9-17 years who had undergone pectus excavatum repair. Study C compared ratings of remembered immunization pain in 236 children who comprised an NRS group and a sex- and age-matched VAS group. Correlations of the NRS with the FPS-R and VAS were r=0.87 and 0.89 in Studies A and B, respectively. In Study C, the distributions of scores on the NRS and VAS were very similar except that scores closest to the no pain anchor were more likely to be selected on the VAS than the NRS. The NRS can be considered functionally equivalent to the VAS and FPS-R except for very mild pain (<1/10). We conclude that use of the NRS is tentatively supported for clinical practice with children of 8years and older, and we recommend further research on the lower age limit and on standardized age-appropriate anchors and instructions for this scale.
Pain 2009 Jun
PMID:Three new datasets supporting use of the Numerical Rating Scale (NRS-11) for children's self-reports of pain intensity. 1935 97

Cytokines are upregulated in a variety of inflammatory conditions and cytokine/receptor interactions can activate JAK-STAT signaling. Previous studies demonstrated upregulation of numerous cytokines in the urinary bladder following cyclophosphamide (CYP)-induced cystitis. The role of JAK-STAT signaling in urinary bladder inflammation and referred somatic sensitivity has not been addressed. The contribution of JAK-STAT signaling pathways in CYP-induced bladder hyperreflexia and referred somatic hypersensitivity was determined in CYP-treated rats using a JAK2 inhibitor, AG490. Acute (4 h; 150 mg/kg ip), intermediate (48 h; 150 mg/kg ip), or chronic (75 mg/kg ip, once every 3 days for 10 days) cystitis was induced in adult, female Wistar rats with CYP treatment. Phosphorylation status of STAT-3 was increased in urinary bladder after CYP-induced cystitis (4 h, 48 h, chronic). Blockade of JAK2 with AG490 (5-15 mg/kg ip or intravesical) significantly (P < or = 0.05) reduced bladder hyperreflexia and hind paw sensitivity in CYP-treated rats. These studies demonstrate a potential role for JAK-STAT signaling pathways in bladder hyperreflexia and referred pain induced by CYP-induced bladder inflammation.
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PMID:Involvement of JAK-STAT signaling/function after cyclophosphamide-induced bladder inflammation in female rats. 1962 77


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