Andersen, Hjalte Holm

Randers, Amalie

Simoni, Amalie H.

Jerwiarz, Anne

Melholt, Camilla

Pedersen, Jacob B.

Hilborg, Sigurd D.

Elberling, Jesper

Arendt-Nielsen, Lars

    Aalborg UniversitetStimulus-response evaluation of the antipruritic effect of homotopic, monophasic coldand TRP-agonist counter-stimulation on histamine-induced itch in healthy volunteersAndersen, Hjalte Holm; Randers, Amalie; Simoni, Amalie H.; Jerwiarz, Anne; Melholt,Camilla; Pedersen, Jacob B.; Hilborg, Sigurd D.; Elberling, Jesper; Arendt-Nielsen, LarsPublished in: Acta Dermato-VenereologicaDOI (link to publication from Publisher):10.2340/00015555-2211Publication date:2015Document VersionPublisher's PDF, also known as Version of recordLink to publication from Aalborg UniversityCitation for published version (APA):Andersen, H. H., Randers, A., Simoni, A. H., Jerwiarz, A., Melholt, C., Pedersen, J. B., ... Arendt-Nielsen, L.(2015). Stimulus-response evaluation of the antipruritic effect of homotopic, monophasic cold and TRP-agonistcounter-stimulation on histamine-induced itch in healthy volunteers.  Acta Dermato-Venereologica, 95(7), 902,No. PP3. DOI: 10.2340/00015555-2211General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright ownersand it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.            ? Users may download and print one copy of any publication from the public portal for the purpose of private study or research.            ? You may not further distribute the material or use it for any profit-making activity or commercial gain            ? You may freely distribute the URL identifying the publication in the public portal ?Take down policyIf you believe that this document breaches copyright please contact us at vbn@aub.aau.dk providing details, and we will remove access tothe work immediately and investigate your claim.Downloaded from vbn.aau.dk on: April 30, 2017902 8th World Congress on Itch (WCI) – September 27–29, 2015, Nara, JapanActa Derm Venereol 95POSTER ABSTRACTS (PP1–PP35)BASIC RESEARCH TRACK –  ANIMAL MODELPP1ITCH-RELATED BITING BEHAVIOR AND NEURONAL RESPONSIVENESS INDUCED BY INTRADERMAL INJECTION OF PRURITOGENS IN HAIRLESS MICEYuhki Ueda1, Kei Hashimoto1, Takamichi Kitano1, Kido Hi-roko1, Tatsumi Matsumoto1, Ritsuko Ishii1, Keiji Imoto2, Hide-masa Furue21Maruho Co., Ltd., Kyoto R&D Center, Kyoto, 2Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, JapanHairless mice (HR-1) are useful to investigate the effects of topical drugs for various dermatological diseases such as atopic dermatitis and herpes simplex virus infection accompanied by itch and pain. We aimed to clarify the characteristics of itch-related behavioral and neuronal responses to pruritogens in HR-1 mice. Histamine (5–5,000 nmol), serotonin (5-HT, 10–300 nmol) and a PAR-2 agonist (SLIGRL-NH2, 10–300 μg) were injected intradermally as a purtitogen into the hindpaw in HR-1 and ICR mice, and biting behavior and spinal neuronal response were measured for 30 minutes. Biting behaviors were dose-depen-dently observed after 5-HT and SLIGRL-NH2 but not histamine injections in HR-1 mice. The 5-HT and SLIGRL-NH2-induced biting behaviors were more prominent in HR-1 mice than ICR mice. An excitation of spinal dorsal horn neurons were evoked by the 5-HT and SLIGRL-NH2 injections in HR-1 mice, and the frequency of action potentials were also dose-dependently increased. There was a positive correlation between the duration of biting behavior and the frequency of action potentials. These results indicate that the present recordings of itch-related beha-vioral and neuronal responses elicited in HR-1 mice enable us to study detailed mechanisms for topical antipruritic drug action on histamine-independent itch.PP2[LEU11]-HK-1-DERIVED PEPTIDES WITH D-TRP PROLONG ANTIPRURICEPTIVE EFFECTS IN RATSHideki Funahashi1, Rumi Naono-Nakayama2, Yu Miyahara1, Yasushi Ishida1, Toshikazu Nishimori11Dep. psychiatry Psychiatry, Fac. Medicine, Univ. Miyazaki, 2Div. Integra-tive Physiology, Fac. Medicine, Univ. Miyazaki, Miyazaki, JapanHemokinin-1 (HK-1) is a mammalian tachykinin peptide con-sisting of 11 amino acids. Recently, it was demonstrated that the previous treatment with [Leu11]-HK-1, in which Met at the C-terminal of HK-1 was replaced by Leu, reduced scratching induced by intrathecal injection of HK-1. Additionally, the pre-treatment with [Leu11]-HK-1 attenuated the induction of scrat-ching behavior by pruritogens, suggesting that [Leu11]-HK-1 may have an inhibitory effect on itch processing. Furthermore, it is believed that replacement of amino acids by D-tryptophan (D-Trp), prolongs the effective period. Therefore, to clarify the effective period of [Leu11]-HK-1-derived peptides, the effect of previous treatment with [D-Trp7]-[Leu11]-HK-1, [D-Trp9]-[Leu11]-HK-1 and [D-Trp7,9]-[Leu11]-HK-1 on the induction of scratching behavior by the intrathecal injection of HK-1 and by the intradermal administration of chloroquine and hista-mine was evaluated. The induction of scratching by intrathecal injection of HK-1 was significantly suppressed until 24 hours after pretreatment with [D-Trp7]-[Leu11]-HK-1 and [D-Trp9]-[Leu11]-HK-1 and 4 hours after [D-Trp7,9]-[Leu11]-HK-1 treatment. On the other hand, intrathecal administration of [D-Trp7,9]-[Leu11]-HK-1 and [D-Trp9]-[Leu11]-HK-1 similarly inhibited the induction of scratching behavior by intradermal injection of a pruritogen, chloroquine and histamine. Taken together, these results suggest that the antipruriceptive effects of [Leu11]-HK-1-derived peptides replaced by D-Trp may be unrelated to the number of D-Trp.BASIC RESEARCH TRACK – RECEPTORS AND CHANNELSPP3STIMULUS-RESPONSE EVALUATION OF THE ANTIPRURITIC EFFECT OF HOMOTOPIC, MONOPHASIC COLD AND TRP-AGONIST COUNTER-STIMULATION ON HISTAMINE-INDUCED ITCH IN HEALTHY VOLUNTEERSHjalte H. Andersen1, Amalie Randers1, Amalie H. Simoni1, Anne Jerwiarz1, Camilla Melholt1, Jacob B. Pedersen1, Sigurd D. Hilborg1, Jesper Elberling2, Lars Arendt-Nielsen11Center for Sensory-Motor Interactions, Department of Health Science and Technology, Aalborg University, Aalborg, 2The Allergy Clinic, Copenhagen University Hospital, Gentofte, Copenhagen, DenmarkThe alleviating effect of cold on itch is a common clinical obser-vation. Contradictory results of the antipruritic effect of biphasic cold-modulation exist. We evaluated the counter-stimulatory efficacy of 3-min monophasic cold-stimulation and the effect of pretreatment with topical TRPA1- and TRPM8-agonists. In a two-session, randomized, single-blinded study in 13 volunteers (age: 22.8±3) superficial skin-puncture through a 1% histamine droplet was performed 12 times at their volar forearms. Thermal stimulation was performed 2 minutes after histamine applica-tion (3×3cm ATS-probe, Medoc). Applied temperatures were: 4, 12, 22, 28, 32 and 37°C. Chemical counter-stimulation was conducted with 40% l-menthol and 10% trans-cinnamaldehyde and compared to the effects of 5% topical doxepin. Cold de-tection and pain thresholds were assessed. Outcome measures were itch intensity (VAS 0–10), wheal-size and flare-response. Cold-stimulation alleviated histamine-induced itch in a stimulus-intensity-dependent manner with the temperatures; 4, 12 and 22°C having a significant inhibitory effect, p<0.05, compared to 32°C. L-menthol, CA and doxepin reduced itch intensity but trans-cinnamaldehyde also gave rise to pain (VAS 1.6±0.47). Homotopic cold- or cold-like-stimulations in the lower innocuous or noxious range has an inhibitory effect on histaminergic itch. Selective and potent agonists of receptors conveying innocuous cold could be of potential therapeutic value as antipruritics.

Stimulus-response evaluation of the antipruritic effect of homotopic, monophasic cold and TRP-agonist counter-stimulation on histamine-induced itch in healthy volunteers

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Stimulus-response evaluation of the antipruritic effect of homotopic, monophasic cold and TRP-agonist counter-stimulation on histamine-induced itch in healthy volunteers

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