Publications by authors named "Junichi Hachisuka"

27 Publications

  • Page 1 of 1

MrgprdCre lineage neurons mediate optogenetic allodynia through an emergent polysynaptic circuit.

Pain 2021 07;162(7):2120-2131

Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, United States.

Abstract: Most cutaneous C fibers, including both peptidergic and nonpeptidergic subtypes, are presumed to be nociceptors and respond to noxious input in a graded manner. However, mechanically sensitive, nonpeptidergic C fibers also respond to mechanical input in the innocuous range, so the degree to which they contribute to nociception remains unclear. To address this gap, we investigated the function of nonpeptidergic afferents using the MrgprdCre allele. In real-time place aversion studies, we found that low-frequency optogenetic activation of MrgrpdCre lineage neurons was not aversive in naive mice but became aversive after spared nerve injury (SNI). To address the underlying mechanisms of this allodynia, we recorded responses from lamina I spinoparabrachial (SPB) neurons using the semi-intact ex vivo preparation. After SNI, innocuous brushing of the skin gave rise to abnormal activity in lamina I SPB neurons, consisting of an increase in the proportion of recorded neurons that responded with excitatory postsynaptic potentials or action potentials. This increase was likely due, at least in part, to an increase in the proportion of lamina I SPB neurons that received input on optogenetic activation of MrgprdCre lineage neurons. Intriguingly, in SPB neurons, there was a significant increase in the excitatory postsynaptic current latency from MrgprdCre lineage input after SNI, consistent with the possibility that the greater activation post-SNI could be due to the recruitment of a new polysynaptic circuit. Together, our findings suggest that MrgprdCre lineage neurons can provide mechanical input to the dorsal horn that is nonnoxious before injury but becomes noxious afterwards because of the engagement of a previously silent polysynaptic circuit in the dorsal horn.
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http://dx.doi.org/10.1097/j.pain.0000000000002227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206522PMC
July 2021

Morphine acts on spinal dynorphin neurons to cause itch through disinhibition.

Sci Transl Med 2021 02;13(579)

Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Morphine-induced itch is a very common and debilitating side effect that occurs in laboring women who receive epidural analgesia and in patients who receive spinal morphine for relief of perioperative pain. Although antihistamines are still widely prescribed for the treatment of morphine-induced itch, their use is controversial because the cellular basis for morphine-induced itch remains unclear. Here, we used animal models and show that neuraxial morphine causes itch through neurons and not mast cells. In particular, we found that spinal dynorphin (Pdyn) neurons are both necessary and sufficient for morphine-induced itch in mice. Agonism of the kappa-opioid receptor alleviated morphine-induced itch in mice and nonhuman primates. Thus, our findings not only reveal that morphine causes itch through a mechanism of disinhibition but also challenge the long-standing use of antihistamines, thereby informing the treatment of millions worldwide.
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http://dx.doi.org/10.1126/scitranslmed.abc3774DOI Listing
February 2021

Parallel ascending spinal pathways for affective touch and pain.

Nature 2020 11 28;587(7833):258-263. Epub 2020 Oct 28.

Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA.

The anterolateral pathway consists of ascending spinal tracts that convey pain, temperature and touch information from the spinal cord to the brain. Projection neurons of the anterolateral pathway are attractive therapeutic targets for pain treatment because nociceptive signals emanating from the periphery are channelled through these spinal projection neurons en route to the brain. However, the organizational logic of the anterolateral pathway remains poorly understood. Here we show that two populations of projection neurons that express the structurally related G-protein-coupled receptors (GPCRs) TACR1 and GPR83 form parallel ascending circuit modules that cooperate to convey thermal, tactile and noxious cutaneous signals from the spinal cord to the lateral parabrachial nucleus of the pons. Within this nucleus, axons of spinoparabrachial (SPB) neurons that express Tacr1 or Gpr83 innervate distinct sets of subnuclei, and strong optogenetic stimulation of the axon terminals induces distinct escape behaviours and autonomic responses. Moreover, SPB neurons that  express Gpr83 are highly sensitive to cutaneous mechanical stimuli and receive strong synaptic inputs from both high- and low-threshold primary mechanosensory neurons. Notably, the valence associated with activation of SPB neurons that express Gpr83 can be either positive or negative, depending on stimulus intensity. These findings reveal anatomically, physiologically and functionally distinct subdivisions of the SPB tract that underlie affective aspects of touch and pain.
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http://dx.doi.org/10.1038/s41586-020-2860-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666110PMC
November 2020

Selective-cold output through a distinct subset of lamina I spinoparabrachial neurons.

Pain 2020 01;161(1):185-194

Department of Neurobiology and the Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, United States. Dr. Hachisuka is now with the Spinal Cord Group, Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Spinal projection neurons are a major pathway through which somatic stimuli are conveyed to the brain. However, the manner in which this information is coded is poorly understood. Here, we report the identification of a modality-selective spinoparabrachial (SPB) neuron subtype with unique properties. Specifically, we find that cold-selective SPB neurons are differentiated by selective afferent input, reduced sensitivity to substance P, distinct physiological properties, small soma size, and low basal drive. In addition, optogenetic experiments reveal that cold-selective SPB neurons do not receive input from Nos1 inhibitory interneurons and, compared with other SPB neurons, show significantly smaller inhibitory postsynaptic currents upon activation of Pdyn inhibitory interneurons. Together, these data suggest that cold output from the spinal cord to the parabrachial nucleus is mediated by a specific cell type with distinct properties.
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http://dx.doi.org/10.1097/j.pain.0000000000001710DOI Listing
January 2020

Conversion of Sox2-dependent Merkel cell carcinoma to a differentiated neuron-like phenotype by T antigen inhibition.

Proc Natl Acad Sci U S A 2019 10 16;116(40):20104-20114. Epub 2019 Sep 16.

Cancer Virology Program, Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA 15213;

Viral cancers show oncogene addiction to viral oncoproteins, which are required for survival and proliferation of the dedifferentiated cancer cell. Human Merkel cell carcinomas (MCCs) that harbor a clonally integrated Merkel cell polyomavirus (MCV) genome have low mutation burden and require viral T antigen expression for tumor growth. Here, we showed that MCV MCC cells cocultured with keratinocytes undergo neuron-like differentiation with neurite outgrowth, secretory vesicle accumulation, and the generation of sodium-dependent action potentials, hallmarks of a neuronal cell lineage. Cocultured keratinocytes are essential for induction of the neuronal phenotype. Keratinocyte-conditioned medium was insufficient to induce this phenotype. Single-cell RNA sequencing revealed that T antigen knockdown inhibited cell cycle gene expression and reduced expression of key Merkel cell lineage/MCC marker genes, including , , , and Of these, T antigen knockdown directly inhibited Sox2 and Atoh1 expression. MCV large T up-regulated Sox2 through its retinoblastoma protein-inhibition domain, which in turn activated Atoh1 expression. The knockdown of Sox2 in MCV MCCs mimicked T antigen knockdown by inducing MCC cell growth arrest and neuron-like differentiation. These results show Sox2-dependent conversion of an undifferentiated, aggressive cancer cell to a differentiated neuron-like phenotype and suggest that the ontology of MCC arises from a neuronal cell precursor.
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http://dx.doi.org/10.1073/pnas.1907154116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778204PMC
October 2019

Kappa Opioid Receptor Distribution and Function in Primary Afferents.

Neuron 2018 09;99(6):1274-1288.e6

Department of Neurobiology and the Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address:

Primary afferents are known to be inhibited by kappa opioid receptor (KOR) signaling. However, the specific types of somatosensory neurons that express KOR remain unclear. Here, using a newly developed KOR-cre knockin allele, viral tracing, single-cell RT-PCR, and ex vivo recordings, we show that KOR is expressed in several populations of primary afferents: a subset of peptidergic sensory neurons, as well as low-threshold mechanoreceptors that form lanceolate or circumferential endings around hair follicles. We find that KOR acts centrally to inhibit excitatory neurotransmission from KOR-cre afferents in laminae I and III, and this effect is likely due to KOR-mediated inhibition of Ca influx, which we observed in sensory neurons from both mouse and human. In the periphery, KOR signaling inhibits neurogenic inflammation and nociceptor sensitization by inflammatory mediators. Finally, peripherally restricted KOR agonists selectively reduce pain and itch behaviors, as well as mechanical hypersensitivity associated with a surgical incision. These experiments provide a rationale for the use of peripherally restricted KOR agonists for therapeutic treatment.
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http://dx.doi.org/10.1016/j.neuron.2018.08.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300132PMC
September 2018

Small RNAs, but Sizable Itch: TRPA1 Activation by an Extracellular MicroRNA.

Neuron 2018 08;99(3):421-422

Department of Neurobiology and the Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address:

Chronic itch is a major symptom of cutaneous T cell lymphoma (CTCL). In this issue of Neuron, Han and colleagues (2018) provide evidence that one of the itch mediators in CTCL is an extracellular miRNA that directly activates TRPA1 on sensory neurons.
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http://dx.doi.org/10.1016/j.neuron.2018.07.040DOI Listing
August 2018

Wind-up in lamina I spinoparabrachial neurons: a role for reverberatory circuits.

Pain 2018 Aug;159(8):1484-1493

Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, United States.

Wind-up is a frequency-dependent increase in the response of spinal cord neurons, which is believed to underlie temporal summation of nociceptive input. However, whether spinoparabrachial neurons, which likely contribute to the affective component of pain, undergo wind-up was unknown. Here, we addressed this question and investigated the underlying neural circuit. We show that one-fifth of lamina I spinoparabrachial neurons undergo wind-up, and provide evidence that wind-up in these cells is mediated in part by a network of spinal excitatory interneurons that show reverberating activity. These findings provide insight into a polysynaptic circuit of sensory augmentation that may contribute to the wind-up of pain's unpleasantness.
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http://dx.doi.org/10.1097/j.pain.0000000000001229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053328PMC
August 2018

Itch and neuropathic itch.

Pain 2018 03;159(3):603-609

Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA.

Neuropathic itch is a pathological condition that is due to damage within the nervous system. This type of itch can be severe and unrelenting, which has a very negative impact on quality of life. Neuropathic itch is more common than generally appreciated because most types of neuropathic pain have a neuropathic itch counterpart. Unfortunately, much like neuropathic pain, there is a lack of effective treatments for neuropathic itch. Here, we consider the neural basis of itch and then describe how injuries within these neural circuits can lead to neuropathic itch in both animal models and human disease states.
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http://dx.doi.org/10.1097/j.pain.0000000000001141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106783PMC
March 2018

Semi-intact ex vivo approach to investigate spinal somatosensory circuits.

Elife 2016 12 19;5. Epub 2016 Dec 19.

Department of Neurobiology, University of Pittsburgh, Pittsburgh, United States.

The somatosensory input that gives rise to the perceptions of pain, itch, cold and heat are initially integrated in the superficial dorsal horn of the spinal cord. Here, we describe a new approach to investigate these neural circuits in mouse. This semi-intact somatosensory preparation enables recording from spinal output neurons, while precisely controlling somatosensory input, and simultaneously manipulating specific populations of spinal interneurons. Our findings suggest that spinal interneurons show distinct temporal and spatial tuning properties. We also show that modality selectivity - mechanical, heat and cold - can be assessed in both retrogradely labeled spinoparabrachial projection neurons and genetically labeled spinal interneurons. Finally, we demonstrate that interneuron connectivity can be determined via optogenetic activation of specific interneuron subtypes. This new approach may facilitate key conceptual advances in our understanding of the spinal somatosensory circuits in health and disease.
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http://dx.doi.org/10.7554/eLife.22866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214752PMC
December 2016

Insight into B5-I spinal interneurons and their role in the inhibition of itch and pain.

Pain 2016 Mar;157(3):544-545

Department of Neurobiology Pittsburgh Center for Pain Research, University of Pittsburgh Medical Scientist Training Program, University of Pittsburgh Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1097/j.pain.0000000000000474DOI Listing
March 2016

Keratinocytes can modulate and directly initiate nociceptive responses.

Elife 2015 Sep 2;4. Epub 2015 Sep 2.

Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States.

How thermal, mechanical and chemical stimuli applied to the skin are transduced into signals transmitted by peripheral neurons to the CNS is an area of intense study. Several studies indicate that transduction mechanisms are intrinsic to cutaneous neurons and that epidermal keratinocytes only modulate this transduction. Using mice expressing channelrhodopsin (ChR2) in keratinocytes we show that blue light activation of the epidermis alone can produce action potentials (APs) in multiple types of cutaneous sensory neurons including SA1, A-HTMR, CM, CH, CMC, CMH and CMHC fiber types. In loss of function studies, yellow light stimulation of keratinocytes that express halorhodopsin reduced AP generation in response to naturalistic stimuli. These findings support the idea that intrinsic sensory transduction mechanisms in epidermal keratinocytes can directly elicit AP firing in nociceptive as well as tactile sensory afferents and suggest a significantly expanded role for the epidermis in sensory processing.
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http://dx.doi.org/10.7554/eLife.09674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576133PMC
September 2015

STAT3-dependent reactive astrogliosis in the spinal dorsal horn underlies chronic itch.

Nat Med 2015 Aug 20;21(8):927-31. Epub 2015 Jul 20.

1] Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. [2] Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

Chronic itch is an intractable symptom of inflammatory skin diseases, such as atopic and contact dermatitis. Recent studies have revealed neuronal pathways selective for itch, but the mechanisms by which itch turns into a pathological chronic state are poorly understood. Using mouse models of atopic and contact dermatitis, we demonstrate a long-term reactive state of astrocytes in the dorsal horn of the spinal segments that corresponds to lesioned, itchy skin. We found that reactive astrogliosis depended on the activation of signal transducer and activator of transcription 3 (STAT3). Conditional disruption of astrocytic STAT3 suppressed chronic itch, and pharmacological inhibition of spinal STAT3 ameliorated the fully developed chronic itch. Mice with atopic dermatitis exhibited an increase in scratching elicited by intrathecal administration of the itch-inducer gastrin-releasing peptide (GRP), and this enhancement was normalized by suppressing STAT3-mediated reactive astrogliosis. Moreover, we identified lipocalin-2 (LCN2) as an astrocytic STAT3-dependent upregulated factor that was crucial for chronic itch, and we demonstrated that intrathecal administration of LCN2 to normal mice increased spinal GRP-evoked scratching. Our findings indicate that STAT3-dependent reactive astrocytes act as critical amplifiers of itching through a mechanism involving the enhancement of spinal itch signals by LCN2, thereby providing a previously unrecognized target for treating chronic itch.
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http://dx.doi.org/10.1038/nm.3912DOI Listing
August 2015

Antioxidant Opuntia ficus-indica Extract Activates AHR-NRF2 Signaling and Upregulates Filaggrin and Loricrin Expression in Human Keratinocytes.

J Med Food 2015 Oct 18;18(10):1143-9. Epub 2015 May 18.

1 Division of Skin Surface Sensing, Kyushu University , Fukuoka, Japan .

Unlabelled: Opuntia ficus-indica (OFI) is a cactus species widely used as an anti-inflammatory, antilipidemic, and hypoglycemic agent. It has been shown that OFI extract (OFIE) inhibits oxidative stress in animal models of diabetes and hepatic disease; however, its antioxidant mechanism remains largely unknown. In this study, we demonstrated that OFIE exhibited potent antioxidant activity through the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and the downstream antioxidant enzyme

Nad(p)h: quinone oxidoreductase 1 (NQO1), which inhibited the generation of reactive oxygen species in keratinocytes challenged with tumor necrosis factor α or benzo[α]pyrene. The antioxidant capacity of OFIE was canceled in NRF2 knockdown keratinocytes. OFIE exerted this NRF2-NQO1 upregulation through activation of the aryl hydrocarbon receptor (AHR). Moreover, the ligation of AHR by OFIE upregulated the expression of epidermal barrier proteins: filaggrin and loricrin. OFIE also prevented TH2 cytokine-mediated downregulation of filaggrin and loricrin expression in an AHR-dependent manner because it was canceled in AHR knockdown keratinocytes. Antioxidant OFIE is a potent activator of AHR-NRF2-NQO1 signaling and may be beneficial in treating barrier-disrupted skin disorders.
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http://dx.doi.org/10.1089/jmf.2014.3396DOI Listing
October 2015

Understanding the switch from pain-to-itch in dermatitis.

Neurosci Lett 2014 Sep 4;579:188-9. Epub 2014 Jun 4.

Department of Neurobiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA; Pittsburgh Center for Pain Research, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA; Department of Anesthesiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Electronic address:

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http://dx.doi.org/10.1016/j.neulet.2014.05.018DOI Listing
September 2014

Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord.

Neuron 2014 May 10;82(3):573-86. Epub 2014 Apr 10.

Department of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; Department of Anesthesiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Electronic address:

Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5(-/-) mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch.
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http://dx.doi.org/10.1016/j.neuron.2014.02.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022838PMC
May 2014

Aberrant expression of S100A6 and matrix metalloproteinase 9, but not S100A2, S100A4, and S100A7, is associated with epidermal carcinogenesis.

J Dermatol Sci 2013 Dec 8;72(3):311-9. Epub 2013 Aug 8.

Department of Dermatology, Kyushu University, Fukuoka, Japan; Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: S100 proteins belong to a family of calcium-binding proteins that regulate cell proliferation and differentiation. Despite our growing knowledge about the biology of S100 proteins in some human cancers, little is known about the expression of S100 family members in epidermal tumors and their clinical significance.

Objective: To determine the expression of S100A2, S100A4, S100A6, S100A7, as well as matrix metalloproteinases 9 (MMP9) in a spectrum of epidermal tumors with benign and malignant characteristics.

Methods: Immunohistological staining was performed for S100A2, S100A4, S100A6, S100A7, and MMP9 in 101 cases of various types of epidermal tumors, viz., squamous cell carcinoma (SCC), Bowen's disease (BD), actinic keratosis (AK), basal cell carcinoma (BCC), keratoacanthoma (KA), and seborrheic keratosis (SK). Thirteen specimens of normal skin (NS) served as control.

Results: S100A2, S100A6, and S100A7 positive immunostaining was variably observed in different epidermal tumors. S100A4 staining was not observed in any epidermal tumors, but was clearly visible in dendritic cells. MMP9 immunostaining was positive only in 22/26 (84.62%) of SCC and 2/15 (13.33%) of BD cases. Expression of S100A2, S100A6, and S100A7 was increased in tumor cells compared to NS. However, only S100A6 expression was significantly associated with malignant transformation of epidermal tumors. Moreover, S100A6 expression was correlated with MMP9 expression in metastatic SCC.

Conclusions: Epidermal tumors show increased expression of S100A2 and S100A7 proteins. S100A4 may be a useful and distinct marker for epidermal dendritic cells. Expression of S100A6 and MMP9 in combination is associated with the development of SCC.
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http://dx.doi.org/10.1016/j.jdermsci.2013.07.005DOI Listing
December 2013

Combination cryosurgery with hyperthermia in the management of skin metastasis from breast cancer: A case report.

Int J Surg Case Rep 2012 10;3(2):68-9. Epub 2011 Nov 10.

Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Introduction: Skin metastases may impair the quality of life due to physical appearance, odour, and bleeding.

Presentation Of Case: A 70-year-old woman presented with two enlarging nodules (measuring 12 cm and 3 cm in diameter) consistent with metastatic breast cancer in the left subclavicular area. The larger tumour did not respond to initial cryosurgery. Therefore we added hyperthermia using a disposable body warmer. In addition, the cryosurgery technique was modified to freeze deeper tissue. The entire tumour was covered with dry cotton, to which liquid nitrogen was applied. Twenty weeks later, the tumour became nearly flat and the patient noted improved activity in her daily life.

Discussion: Combination treatment with sufficient freezing is important for controlling the tumour, while hyperthermia may accelerate the antitumor effects of cryosurgery.

Conclusion: [corrected] This treatment provides an alternative for unresectable breast cancer skin metastases resistant to chemotherapy and radiotherapy.
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http://dx.doi.org/10.1016/j.ijscr.2011.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267272PMC
October 2012

Successful treatment of epidermal growth factor receptor inhibitor-induced periungual inflammation with adapalene.

Case Rep Dermatol 2011 May 30;3(2):130-6. Epub 2011 Jun 30.

Karatsu Red Cross Hospital, Karatsu, School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Epidermal growth factor receptor (EGFR) inhibitors are increasingly used for cancer treatment, but commonly carry dermatologic side effects. Periungual inflammation is a particularly painful condition that additionally worsens quality of life. In this paper, we report 3 cases of successful treatment of periungual inflammation induced by 3 different EGFR inhibitors (gefitinib, erlotinib, and cetuximab) with topically applied adapalene.
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http://dx.doi.org/10.1159/000329914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130494PMC
May 2011

Are lifetime prevalence of impetigo, molluscum and herpes infection really increased in children having atopic dermatitis?

J Dermatol Sci 2010 Dec 23;60(3):173-8. Epub 2010 Oct 23.

Department of Dermatology, Kyushu University, Higashiku, Fukuoka, Japan.

Background: Cutaneous infections such as impetigo contagiosum (IC), molluscum contagiosum (MC) and herpes virus infection (HI) appear to be associated with atopic dermatitis (AD), but there are no reports of concrete epidemiological evidence.

Objective: We evaluated the association of childhood AD with these infections by conducting a population-based cross-sectional study.

Methods: Enrolled in this study were 1117 children aged 0-6 years old attending nursery schools in Ishigaki City, Okinawa Prefecture, Japan. Physical examination was performed by dermatologists, and a questionnaire was completed on each child's history of allergic diseases including AD, asthma, allergic rhinitis and egg allergy, and that of skin infections including IC, MC and HI, as well as familial history of AD.

Results: In 913 children (AD; 132), a history of IC, MC or HI was observed in 45.1%, 19.7%, and 2.5%, respectively. Multiple logistic regression analysis revealed that the odds of having a history of IC were 1.8 times higher in AD children than in non-AD children. Meanwhile, a history of MC was significantly correlated to the male gender, but not to a personal history of AD. As for HI, we found no correlated factors in this study.

Conclusions: The lifetime prevalence of IC was indeed higher in young children with a history of AD.
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http://dx.doi.org/10.1016/j.jdermsci.2010.09.003DOI Listing
December 2010

Responsiveness of C neurons in rat dorsal root ganglion to 5-hydroxytryptamine-induced pruritic stimuli in vivo.

J Neurophysiol 2010 Jul 19;104(1):271-9. Epub 2010 May 19.

Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.

Itching is a common symptom in dermatologic diseases and causes restless scratching of the skin, which aggravates the condition. The mechanism of the itch sensation, however, is enigmatic. The present study included behavioral tests and electrophysiological recordings from rat dorsal root ganglion (DRG) neurons in vivo to analyze the response to pruritic stimuli induced by topical application of 5-hydroxytryptamine (5-HT) to the skin. Topically applied 5-HT to the rostral back evoked scratching, whereas application of the vehicle did not. Following subcutaneous injection of the opioid receptor antagonist naloxone, the number of scratches decreased, suggesting that the scratching was preferentially mediated by itch but not pain sensation. To elucidate the firing properties of DRG neurons in response to topically applied 5-HT, intracellular recordings were made from DRG neurons in vivo. None of the Abeta and Adelta neurons responded to 5-HT; in contrast, 25 of 91 C neurons (27%) exhibited repetitive firing in response to 5-HT, which could be classified into two firing patterns: one was a transient type, characterized by low firing frequency that decreased within 5 min; the other was a long-lasting type, having high firing frequency that continued increasing after 5 min. The time course of the firing pattern of long-lasting C neurons was comparable to the scratching behavior. Intriguingly, the long-lasting-type neurons had a significantly smaller fast afterhyperpolarization than that of the 5-HT-insensitive neurons. These observations suggest that the long-lasting-firing C neurons in rat DRG sensitive to 5-HT are responsible for conveying pruritic information to the spinal cord.
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http://dx.doi.org/10.1152/jn.00938.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904207PMC
July 2010

Severity of disease, rather than xerosis, correlates with pruritus in patients with atopic dermatitis.

Int J Dermatol 2009 Apr;48(4):374-8

Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Atopic dermatitis (AD) is a chronic, relapsing skin disease characterized by xerosis and pruritus. As pruritus is an unpleasant sensation and the associated scratching aggravates the skin eruption considerably, it is important to control this symptom when treating AD. Dry skin is generally considered to be a potential cause of pruritus in xerotic skin diseases, but a clear correlation between pruritus and atopic xerosis has not been demonstrated. Aim To examine the contribution of atopic xerosis to the development of pruritus in AD.

Methods: Twenty-two patients with AD (12 males and 10 females; mean age, 27.5 years) were examined. Xerosis and the severity of disease were evaluated using the Objective Severity Assessment of Atopic Dermatitis (OSAAD) and the SCORing Atopic Dermatitis (SCORAD) index, respectively. A modified SCORAD index was calculated by removing the symptoms potentially associated with pruritus (intensity of itching and insomnia) from the standard SCORAD index. Pruritus was evaluated using both a visual analog scale and the Verbal Itch Score.

Results: The severity of AD (modified SCORAD index) correlated better than atopic xerosis (OSAAD score) with both pruritus scores, possibly indicating that the use of appropriate anti-inflammatory agents may be helpful in controlling pruritus as well as skin eruption in AD.

Conclusion: Our data suggest that the severity of disease (or skin inflammation) provides a greater contribution than xerosis to the development of pruritus in AD.
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http://dx.doi.org/10.1111/j.1365-4632.2009.03906.xDOI Listing
April 2009

A case of Carney complex.

Int J Dermatol 2006 Dec;45(12):1406-7

Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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http://dx.doi.org/10.1111/j.1365-4632.2006.02889.xDOI Listing
December 2006