{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T03:20:06Z","timestamp":1787973606963,"version":"build-2784847793"},"reference-count":217,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Pain and itch are both important manifestations of various disorders, such as herpes zoster, atopic dermatitis, and psoriasis. Growing evidence suggests that both sensations have shared mediators, overlapping neural circuitry, and similarities in sensitization processes. In fact, pain and itch coexist in some disorders. Determining pharmaceutical agents and targets for treating pain and itch concurrently is of scientific and clinical relevance. Here we review the neurobiology of pain and itch and discuss the pharmaceutical targets as well as novel compounds effective for the concurrent treatment of these sensations.<\/jats:p>","DOI":"10.3390\/ph15070892","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T23:10:22Z","timestamp":1658272222000},"page":"892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Druggable Targets and Compounds with Both Antinociceptive and Antipruritic Effects"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7006-7599","authenticated-orcid":false,"given":"Hao-Jui","family":"Weng","sequence":"first","affiliation":[{"name":"Department of Dermatology, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan"},{"name":"Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4648-3445","authenticated-orcid":false,"given":"Quoc Thao Trang","family":"Pham","sequence":"additional","affiliation":[{"name":"International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Dermatology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 70000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4763-4137","authenticated-orcid":false,"given":"Chia-Wei","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1498-1474","authenticated-orcid":false,"given":"Tsen-Fang","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, National Taiwan University Hospital, Taipei 100225, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jdermsci.2022.02.005","article-title":"Itching and skin pain in real-life patients with plaque psoriasis: Baseline analysis of the ProLOGUE study","volume":"105","author":"Honma","year":"2022","journal-title":"J. Dermatol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s41687-019-0128-z","article-title":"Exploring content and psychometric validity of newly developed assessment tools for itch and skin pain in atopic dermatitis","volume":"3","author":"Newton","year":"2019","journal-title":"J. Patient-Rep. Outcomes"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/S1526-5900(03)00637-0","article-title":"Herpes zoster itch: Preliminary epidemiologic data","volume":"4","author":"Oaklander","year":"2003","journal-title":"J. Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1097\/DER.0000000000000406","article-title":"Pain and itch are dual burdens in atopic dermatitis","volume":"29","author":"Maarouf","year":"2018","journal-title":"Dermatitis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/j.1365-2133.2008.08941.x","article-title":"Itch characteristics in atopic dermatitis: Results of a web-based questionnaire","volume":"160","author":"Dawn","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/papr.12518","article-title":"Pain, itch, quality of life, and costs after herpes zoster","volume":"17","author":"Aerssens","year":"2017","journal-title":"Pain Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.mayocp.2012.08.020","article-title":"Why patients visit their doctors: Assessing the most prevalent conditions in a defined American population","volume":"88","author":"Sauver","year":"2013","journal-title":"Mayo Clin. Proc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/S0140-6736(16)31678-6","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990\u20132015: A systematic analysis for the Global Burden of Disease Study 2015","volume":"388","author":"Vos","year":"2016","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1046\/j.1087-0024.2003.09111.x","article-title":"Self-reported skin morbidity among adults: Associations with quality of life and general health in a Norwegian survey","volume":"9","author":"Dalgard","year":"2004","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.pain.2005.09.032","article-title":"The role of threat-expectancy in acute pain: Effects on attentional bias, coping strategy effectiveness and response to pain","volume":"119","author":"Boston","year":"2005","journal-title":"Pain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S1090-3801(02)00021-6","article-title":"Selective attention for pain-related information in healthy individuals: The role of pain and fear","volume":"6","author":"Roelofs","year":"2002","journal-title":"Eur. J. Pain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1023\/A:1023408503807","article-title":"Attentional bias for psoriasis-specific and psychosocial threat in patients with psoriasis","volume":"26","author":"Fortune","year":"2003","journal-title":"J. Behav. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.2340\/00015555-0743","article-title":"Role of attentional focus on bodily sensations in sensitivity to itch and pain","volume":"90","author":"Kraaimaat","year":"2010","journal-title":"Acta Derm. Venereol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1152\/jn.01210.2006","article-title":"Pain enhances functional connectivity of a brain network evoked by performance of a cognitive task","volume":"97","author":"Seminowicz","year":"2007","journal-title":"J. Neurophysiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.pain.2008.12.009","article-title":"The effect of attentional re-training and threat expectancy in response to acute pain","volume":"142","author":"McGowan","year":"2009","journal-title":"Pain"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.pain.2009.03.001","article-title":"Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhage","volume":"144","author":"Sikand","year":"2009","journal-title":"Pain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1136\/jnnp.27.5.483","article-title":"Substances producing pain and itch","volume":"27","author":"Whitty","year":"1964","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.tins.2010.09.002","article-title":"The multiple pathways for itch and their interactions with pain","volume":"33","author":"Davidson","year":"2010","journal-title":"Trends Neurosci."},{"key":"ref_19","first-page":"129","article-title":"Pain and the Neurosurgeon a Forty-Year Experience","volume":"33","author":"Simpson","year":"1970","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1001\/archsurg.1961.01300090110023","article-title":"Use of cordotomy in the relief of intractable pain","volume":"82","author":"Clark","year":"1961","journal-title":"Arch. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"E311","DOI":"10.1093\/neuros\/nyy330","article-title":"Somatotopy and organization of spinothalamic tracts in the human cervical spinal cord","volume":"84","author":"Vedantam","year":"2019","journal-title":"Neurosurgery"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1001\/archneurpsyc.1943.02290200029002","article-title":"Anterior chordotomy: Further observations on physiologic results and optimum manner of performance","volume":"50","author":"Hyndman","year":"1943","journal-title":"Arch. Neurol. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/nn.3289","article-title":"A subpopulation of nociceptors specifically linked to itch","volume":"16","author":"Han","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1152\/jn.00431.2001","article-title":"Responses of superficial dorsal horn neurons to intradermal serotonin and other irritants: Comparison with scratching behavior","volume":"87","author":"Jinks","year":"2002","journal-title":"J. Neurophysiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7659","DOI":"10.1523\/JNEUROSCI.1760-08.2008","article-title":"A role for polymodal C-fiber afferents in nonhistaminergic itch","volume":"28","author":"Johanek","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrn3641","article-title":"Sensory neurons and circuits mediating itch","volume":"15","author":"LaMotte","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1172\/JCI43426","article-title":"Labeled lines meet and talk: Population coding of somatic sensations","volume":"120","author":"Ma","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.neuron.2010.10.018","article-title":"An itch to be scratched","volume":"68","author":"Patel","year":"2010","journal-title":"Neuron"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1007\/s00424-013-1284-2","article-title":"New insights into the mechanisms of itch: Are pain and itch controlled by distinct mechanisms?","volume":"465","author":"Liu","year":"2013","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1111\/j.1365-2133.2009.09628.x","article-title":"Ethnic differences in pain, itch and thermal detection in response to topical capsaicin: African Americans display a notably limited hyperalgesia and neurogenic inflammation","volume":"162","author":"Wang","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1152\/jn.00668.2013","article-title":"Characterization of pruriceptive trigeminothalamic tract neurons in rats","volume":"111","author":"Moser","year":"2014","journal-title":"J. Neurophysiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1152\/jn.00302.2011","article-title":"Facial injections of pruritogens or algogens elicit distinct behavior responses in rats and excite overlapping populations of primary sensory and trigeminal subnucleus caudalis neurons","volume":"106","author":"Klein","year":"2011","journal-title":"J. Neurophysiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s12264-012-1202-1","article-title":"Peripheral mechanisms of itch","volume":"28","author":"McNeil","year":"2012","journal-title":"Neurosci. Bull."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.pain.2007.04.017","article-title":"Chronic itch and chronic pain: Analogous mechanisms","volume":"131","author":"Yosipovitch","year":"2007","journal-title":"Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1111\/j.1468-3083.2007.02215.x","article-title":"Generalized and symptom-specific sensitization of chronic itch and pain","volume":"21","author":"Kraaimaat","year":"2007","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1037\/0033-2909.126.6.890","article-title":"Emotion, plasticity, context, and regulation: Perspectives from affective neuroscience","volume":"126","author":"Davidson","year":"2000","journal-title":"Psychol. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/1467-9450.00276","article-title":"Cognitive-emotional sensitization and somatic health complaints","volume":"43","author":"Brosschot","year":"2002","journal-title":"Scand. J. Psychol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0022-3999(03)00011-4","article-title":"Exaggerated perception of normal physiological responses to stress and hypercapnia in young women with numerous functional somatic symptoms","volume":"55","author":"Houtveen","year":"2003","journal-title":"J. Psychosom. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0005-7967(03)00104-9","article-title":"Acquired sensitivity to relevant physiological activity in patients with chronic health problems","volume":"42","author":"Rietvelt","year":"2004","journal-title":"Behav. Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/1467-9450.00280","article-title":"Learning subjective health complaints","volume":"43","author":"Winters","year":"2002","journal-title":"Scand. J. Psychol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1093\/ndt\/gfl461","article-title":"Pruritus in haemodialysis patients: International results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)","volume":"21","author":"Pisoni","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1002\/art.11272","article-title":"Subgrouping of fibromyalgia patients on the basis of pressure-pain thresholds and psychological factors","volume":"48","author":"Giesecke","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/art.20063","article-title":"Evidence of augmented central pain processing in idiopathic chronic low back pain","volume":"50","author":"Giesecke","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1212\/WNL.62.2.212","article-title":"Painful stimuli evoke itch in patients with chronic pruritus: Central sensitization for itch","volume":"62","author":"Ikoma","year":"2004","journal-title":"Neurology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jpsychores.2006.07.004","article-title":"Psychophysiological responses in patients with fibromyalgia syndrome","volume":"61","author":"Thieme","year":"2006","journal-title":"J. Psychosom. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/ncprheum0091","article-title":"Mechanisms of disease: Pain in fibromyalgia syndrome","volume":"2","author":"Staud","year":"2006","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/bja\/87.1.3","article-title":"Mechanisms of inflammatory pain","volume":"87","author":"Kidd","year":"2001","journal-title":"Br. J. Anaesth."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1152\/jn.01139.2002","article-title":"Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens","volume":"89","author":"Schmelz","year":"2003","journal-title":"J. Neurophysiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.chom.2016.05.010","article-title":"Pain and itch: Beneficial or harmful to antimicrobial defense?","volume":"19","author":"Baral","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1046\/j.1365-2133.2002.04803.x","article-title":"Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis","volume":"147","author":"Toyoda","year":"2002","journal-title":"Br. J. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s004410000202","article-title":"Increase in NGF content and nerve fiber sprouting in human allergic contact eczema","volume":"302","author":"Kinkelin","year":"2000","journal-title":"Cell Tissue Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1007\/s00403-001-0285-8","article-title":"Increased nerve growth factor-and tyrosine kinase A-like immunoreactivities in prurigo nodularis skin\u2013an exploration of the cause of neurohyperplasia","volume":"293","author":"Johansson","year":"2002","journal-title":"Arch. Dermatol. Res."},{"key":"ref_53","first-page":"769","article-title":"Pruritus and nerve growth factor in psoriasis","volume":"43","author":"Choi","year":"2005","journal-title":"Korean J. Dermatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1159\/000010045","article-title":"Increased intraepithelial innervation in women with vulvar vestibulitis syndrome","volume":"46","author":"Hilliges","year":"1998","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"9426","DOI":"10.1158\/0008-5472.CAN-05-0826","article-title":"A blocking antibody to nerve growth factor attenuates skeletal pain induced by prostate tumor cells growing in bone","volume":"65","author":"Halvorson","year":"2005","journal-title":"Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1097\/j.pain.0000000000001625","article-title":"Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: Mechanism of action in the context of efficacy and safety","volume":"160","author":"Schmelz","year":"2019","journal-title":"Pain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/08990229970357","article-title":"Enhancement of experimental pruritus and mechanically evoked dysesthesiae with local anesthesia","volume":"16","author":"Atanassoff","year":"1999","journal-title":"Somatosens. Mot. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/1058-9139(92)90040-J","article-title":"Subpopulations of \u201cnocifensor neurons\u201d contributing to pain and allodynia, itch and alloknesis","volume":"1","author":"LaMotte","year":"1992","journal-title":"APS J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.jaci.2018.09.005","article-title":"Itch: From mechanism to (novel) therapeutic approaches","volume":"142","author":"Yosipovitch","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3109\/08990229109144750","article-title":"Psychophysical studies of the itch sensation and itchy skin (\u201calloknesis\u201d) produced by intracutaneous injection of histamine","volume":"8","author":"Simone","year":"1991","journal-title":"Somatosens. Mot. Res."},{"key":"ref_61","unstructured":"Torebj\u00f6rk, H., Schmelz, M., and Handwerker, H. (1996). Functional Properties of Human Cutaneous Nociceptors and Their Role in Pain and Hyperalgesia. Neurobiology of Nociceptors, Oxford University Press."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1152\/jn.1991.66.1.190","article-title":"Neurogenic hyperalgesia: Psychophysical studies of underlying mechanisms","volume":"66","author":"LaMotte","year":"1991","journal-title":"J. Neurophysiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.1097\/00002508-200009001-00004","article-title":"Neural mechanisms of cutaneous nociceptive pain","volume":"16","author":"Koltzenburg","year":"2000","journal-title":"Clin. J. Pain"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1113\/jphysiol.1992.sp019069","article-title":"Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans","volume":"448","author":"Lundberg","year":"1992","journal-title":"J. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/brain\/124.9.1754","article-title":"Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary hyperalgesia","volume":"124","author":"Magerl","year":"2001","journal-title":"Brain"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1093\/brain\/122.12.2245","article-title":"Secondary hyperalgesia to punctate mechanical stimuli: Central sensitization to A-fibre nociceptor input","volume":"122","author":"Ziegler","year":"1999","journal-title":"Brain"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0304-3959(99)00194-3","article-title":"Secondary hyperalgesia persists in capsaicin desensitized skin","volume":"84","author":"Fuchs","year":"2000","journal-title":"Pain"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1097\/00001756-200111160-00020","article-title":"Histamine-induced itch converts into pain in neuropathic hyperalgesia","volume":"12","author":"Baron","year":"2001","journal-title":"Neuroreport"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1002\/(SICI)1097-4598(199711)20:11<1389::AID-MUS6>3.0.CO;2-6","article-title":"Effects of cutaneous histamine application in patients with sympathetic reflex dystrophy","volume":"20","author":"Birklein","year":"1997","journal-title":"Muscle Nerve"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.jaad.2012.11.026","article-title":"Brachioradial pruritus: A trigger for generalization of itch","volume":"68","author":"Kwatra","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.pain.2006.06.003","article-title":"Bradykinin is a potent pruritogen in atopic dermatitis: A switch from pain to itch","volume":"126","author":"Hosogi","year":"2006","journal-title":"Pain"},{"key":"ref_72","first-page":"78","article-title":"Repetitive scratching and noxious heat do not inhibit histamine-induced itch in atopic dermatitis","volume":"158","author":"Ishiuji","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0304-3959(98)00205-X","article-title":"Differential inhibitory effect on human nociceptive skin senses induced by local stimulation of thin cutaneous fibers","volume":"80","author":"Nilsson","year":"1999","journal-title":"Pain"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0304-3959(01)00400-6","article-title":"Intractable postherpetic itch and cutaneous deafferentation after facial shingles","volume":"96","author":"Oaklander","year":"2002","journal-title":"Pain"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"156","DOI":"10.11154\/pain.31.156","article-title":"Investigation of neuropathic pain component by the stage of a disease of the herpes zoster associated pain patients received pain clinic treatments","volume":"31","author":"Ishikawa","year":"2016","journal-title":"Pain Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1468-3083.1999.tb00890.x","article-title":"Gabapentin treatment for brachioradial pruritus","volume":"13","author":"Bueller","year":"1999","journal-title":"J. Eur. Acad. Derm. Venereol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/39807","article-title":"The capsaicin receptor: A heat-activated ion channel in the pain pathway","volume":"389","author":"Caterina","year":"1997","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0896-6273(00)80564-4","article-title":"The cloned capsaicin receptor integrates multiple pain-producing stimuli","volume":"21","author":"Tominaga","year":"1998","journal-title":"Neuron"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1126\/science.288.5464.306","article-title":"Impaired nociception and pain sensation in mice lacking the capsaicin receptor","volume":"288","author":"Caterina","year":"2000","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4122","DOI":"10.1038\/ncomms5122","article-title":"Three functionally distinct classes of C-fibre nociceptors in primates","volume":"5","author":"Wooten","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"11330","DOI":"10.1073\/pnas.0905605106","article-title":"TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms","volume":"106","author":"Imamachi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s12272-012-0321-6","article-title":"Development of PAC-14028, a novel transient receptor potential vanilloid type 1 (TRPV1) channel antagonist as a new drug for refractory skin diseases","volume":"35","author":"Lim","year":"2012","journal-title":"Arch. Pharmacal Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1038\/jid.2011.87","article-title":"Antipruritic effects of TRPV1 antagonist in murine atopic dermatitis and itching models","volume":"131","author":"Yun","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1016\/j.jaci.2021.09.024","article-title":"Asivatrep, a TRPV1 antagonist, for the topical treatment of atopic dermatitis: Phase 3, randomized, vehicle-controlled study (CAPTAIN-AD)","volume":"149","author":"Park","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s41598-020-80725-z","article-title":"A capsaicinoid-based soft drug, AG1529, for attenuating TRPV1-mediated histaminergic and inflammatory sensory neuron excitability","volume":"11","author":"Butron","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/j.1526-4637.2009.00793.x","article-title":"NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: A randomized, double-blind, controlled study with an open-label extension","volume":"11","author":"Backonja","year":"2010","journal-title":"Pain Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1517\/14656566.2010.481670","article-title":"Topical capsaicin. The fire of a \u2018hot\u2019medicine is reignited","volume":"11","author":"Papoiu","year":"2010","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1111\/ced.13114","article-title":"Topical capsaicin 8% for the treatment of neuropathic itch conditions","volume":"42","author":"Andersen","year":"2017","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_89","unstructured":"Dellavalle, R.P., and Callen, J. (2022). Pruritus: Therapies for Localized Pruritus, Uptodate."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature00894","article-title":"TRPV3 is a temperature-sensitive vanilloid receptor-like protein","volume":"418","author":"Smith","year":"2002","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1126\/science.1108609","article-title":"Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin","volume":"307","author":"Moqrich","year":"2005","journal-title":"Science"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/jid.2008.245","article-title":"Impact of the Gly573Ser substitution in TRPV3 on the development of allergic and pruritic dermatitis in mice","volume":"129","author":"Yoshioka","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1111\/bph.15390","article-title":"A plant-derived TRPV3 inhibitor suppresses pain and itch","volume":"178","author":"Han","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e68128","DOI":"10.7554\/eLife.68128","article-title":"Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine","volume":"10","author":"Liu","year":"2021","journal-title":"eLife"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1001\/archderm.1955.01540300050013","article-title":"Evaluation of a new topical anesthetic, dyclonine hydrochloride","volume":"71","author":"Shelmire","year":"1955","journal-title":"AMA Arch. Dermatol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Broad, L.M., Mogg, A.J., Eberle, E., Tolley, M., Li, D.L., and Knopp, K.L. (2016). TRPV3 in drug development. Pharmaceuticals, 9.","DOI":"10.3390\/ph9030055"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1111\/bph.12303","article-title":"Pharmacological profiling of the TRPV3 channel in recombinant and native assays","volume":"171","author":"Grubisha","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S0092-8674(00)00143-4","article-title":"Vanilloid receptor\u2013related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor","volume":"103","author":"Liedtke","year":"2000","journal-title":"Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.pain.2005.07.016","article-title":"TRPV4 mediates pain-related behavior induced by mild hypertonic stimuli in the presence of inflammatory mediator","volume":"118","author":"Joseph","year":"2005","journal-title":"Pain"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.1016\/j.pain.2014.09.033","article-title":"TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor","volume":"155","author":"Chen","year":"2014","journal-title":"Pain"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/JID.2015.388","article-title":"Involvement of TRPV4 in serotonin-evoked scratching","volume":"136","author":"Akiyama","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"ra71","DOI":"10.1126\/scisignal.aaf1047","article-title":"Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations","volume":"9","author":"Kim","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1080\/13543776.2021.1903432","article-title":"TRPV4 antagonists: A patent review (2015\u20132020)","volume":"31","author":"Lawhorn","year":"2021","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0092-8674(03)00158-2","article-title":"ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures","volume":"112","author":"Story","year":"2003","journal-title":"Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fpain.2021.638620","article-title":"The TRPA1 Channel Mediates Mechanical Allodynia and Thermal Hyperalgesia in a Rat Bone Cancer Pain Model","volume":"2","author":"Liu","year":"2021","journal-title":"Front. Pain Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0896-6273(04)00150-3","article-title":"Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin","volume":"41","author":"Bandell","year":"2004","journal-title":"Neuron"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4808","DOI":"10.1523\/JNEUROSCI.5380-08.2009","article-title":"TRPA1 modulates mechanotransduction in cutaneous sensory neurons","volume":"29","author":"Kwan","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/nn.2789","article-title":"TRPA1 is required for histamine-independent, Mas-related G protein\u2013coupled receptor\u2013mediated itch","volume":"14","author":"Wilson","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.neuron.2010.04.030","article-title":"A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome","volume":"66","author":"Kremeyer","year":"2010","journal-title":"Neuron"},{"key":"ref_110","first-page":"798","article-title":"A human surrogate model of itch utilizing the TRPA1 agonist trans-cinnamaldehyde","volume":"95","author":"Rosengaard","year":"2015","journal-title":"Acta Derm."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1080\/13543776.2020.1797679","article-title":"Transient receptor potential ankyrin 1 (TRPA1) antagonists: A patent review (2015\u20132019)","volume":"30","author":"Chen","year":"2020","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.neuron.2014.12.065","article-title":"Tmem100 is a regulator of TRPA1-TRPV1 complex and contributes to persistent pain","volume":"85","author":"Weng","year":"2015","journal-title":"Neuron"},{"key":"ref_113","unstructured":"Dong, X., and Weng, H.-J. (2021). Tmem100 Peptides and Variants Thereof and Their Use in Treating or Preventing Diseases or Conditions. (US11066455B2)."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.neuron.2007.02.024","article-title":"TRPM8 is required for cold sensation in mice","volume":"54","author":"Dhaka","year":"2007","journal-title":"Neuron"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nature719","article-title":"Identification of a cold receptor reveals a general role for TRP channels in thermosensation","volume":"416","author":"McKemy","year":"2002","journal-title":"Nature"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Mu\u00f1iz, R., Bonache, M.A., Mart\u00edn-Escura, C., and G\u00f3mez-Monterrey, I. (2019). Recent progress in TRPM8 modulation: An update. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112618"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/00002508-200205000-00011","article-title":"A novel treatment of postherpetic neuralgia using peppermint oil","volume":"18","author":"Davies","year":"2002","journal-title":"Clin. J. Pain"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/jcpt.12679","article-title":"The role and mechanism of action of menthol in topical analgesic products","volume":"43","author":"Pergolizzi","year":"2018","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/bph.13760","article-title":"Transient receptor potential cation channel subfamily M member 8 channels mediate the anti-inflammatory effects of eucalyptol","volume":"174","author":"Caceres","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1523\/JNEUROSCI.1943-12.2013","article-title":"A sensory-labeled line for cold: TRPM8-expressing sensory neurons define the cellular basis for cold, cold pain, and cooling-mediated analgesia","volume":"33","author":"Knowlton","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.jpain.2016.05.004","article-title":"High-concentration L-menthol exhibits counter-irritancy to neurogenic inflammation, thermal and mechanical hyperalgesia caused by trans-cinnamaldehyde","volume":"17","author":"Andersen","year":"2016","journal-title":"J. Pain"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1200\/JCO.2008.18.5017","article-title":"From bench to bedside: A case of rapid reversal of bortezomib-induced neuropathic pain by the TRPM8 activator, menthol","volume":"26","author":"Colvin","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/j.jid.2017.12.025","article-title":"Cooling relief of acute and chronic itch requires TRPM8 channels and neurons","volume":"138","author":"Palkar","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_124","unstructured":"Wei, E.T. (2021). Di-Isopropyl-Phosphinoyl-Alkanes (Dapa) Compounds as Topical Agents for the Treatment of Sensory Discomfort. (US20210401857A1)."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1016\/j.pain.2013.06.043","article-title":"TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain","volume":"154","author":"Liu","year":"2013","journal-title":"Pain"},{"key":"ref_126","unstructured":"Liu, Y., Liu, Y., Narang, C., Limjunyawong, N., Jamaldeen, H., Yu, S., Patiram, S., Nie, H., Caterina, M.J., and Dong, X. (2022, June 04). Sensory Neuron Expressed TRPC3 Mediates Acute and Chronic Itch. Available online: https:\/\/assets.researchsquare.com\/files\/rs-1021582\/v1\/e34a7342-53a2-4e30-9468-4fa4759b6152.pdf?c=1648558243."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Ko, M.-C. (2015). Neuraxial Opioid-Induced Itch and Its Pharmacological Antagonism. Pharmacology of Itch, Springer.","DOI":"10.1007\/978-3-662-44605-8_17"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1124\/jpet.103.061101","article-title":"The role of central \u03bc opioid receptors in opioid-induced itch in primates","volume":"310","author":"Ko","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.jaad.2007.01.007","article-title":"Treatment of pruritus with topically applied opiate receptor antagonist","volume":"56","author":"Bigliardi","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1056\/NEJMoa1912770","article-title":"A phase 3 trial of difelikefalin in hemodialysis patients with pruritus","volume":"382","author":"Fishbane","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1016\/j.jpain.2015.01.341","article-title":"(422) CR845, a peripheral kappa opioid, provides better pain relief with less nausea and vomiting than placebo in patients after bunionectomy","volume":"16","author":"Menzaghi","year":"2015","journal-title":"J. Pain"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"773204","DOI":"10.3389\/fphar.2021.773204","article-title":"Antinociceptive and antipruritic effects of HSK21542, a peripherally-restricted kappa opioid receptor agonist, in animal models of pain and itch","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"ra117","DOI":"10.1126\/scisignal.aai8441","article-title":"Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria","volume":"9","author":"Brust","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1016\/j.jaad.2018.12.031","article-title":"The uses of naltrexone in dermatologic conditions","volume":"80","author":"Lee","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"159","DOI":"10.5021\/ad.2016.28.2.159","article-title":"Clinical efficacy and safety of naltrexone combination therapy in older patients with severe pruritus","volume":"28","author":"Lee","year":"2016","journal-title":"Ann. Dermatol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/272826a0","article-title":"The narcotic antagonist naloxone enhances clinical pain","volume":"272","author":"Levine","year":"1978","journal-title":"Nature"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1097\/ALN.0000000000000170","article-title":"Buprenorphine\u2013naloxone therapy in pain management","volume":"120","author":"Chen","year":"2014","journal-title":"Anesthesiology"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jaad.2005.12.010","article-title":"Butorphanol for treatment of intractable pruritus","volume":"54","author":"Dawn","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1007\/s10620-020-06392-2","article-title":"Use of butorphanol as treatment for cholestatic itch","volume":"66","author":"Golpanian","year":"2021","journal-title":"Dig. Dis. Sci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1159\/000484573","article-title":"A multicenter, randomized, double-blind, placebo-controlled trial of nalbuphine ER tablets for uremic pruritus","volume":"46","author":"Mathur","year":"2017","journal-title":"Am. J. Nephrol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1097\/AJP.0000000000000211","article-title":"Nalbuphine for treatment of opioid-induced pruritus","volume":"32","author":"Jannuzzi","year":"2016","journal-title":"Clin. J. Pain"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1080\/13543784.2018.1548606","article-title":"Novel drugs for the treatment of chronic pruritus","volume":"27","author":"Pereira","year":"2018","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.3389\/fimmu.2018.01873","article-title":"The role of histamine and histamine receptors in mast cell-mediated allergy and inflammation: The hunt for new therapeutic targets","volume":"9","author":"Thangam","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1136\/bmj.2.3418.61","article-title":"The blood vessels of the human skin","volume":"2","author":"Lewis","year":"1926","journal-title":"Br. Med. J."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3109\/07367228709144620","article-title":"The magnitude and duration of itch produced by intracutaneous injections of histamine","volume":"5","author":"Simone","year":"1987","journal-title":"Somatosens. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1111\/bph.14696","article-title":"Histamine, histamine receptors, and neuropathic pain relief","volume":"177","author":"Obara","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S0885-3924(01)00311-6","article-title":"Diphenhydramine as an analgesic adjuvant in refractory cancer pain","volume":"22","author":"Fischberg","year":"2001","journal-title":"J. Pain Symptom Manag."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jaci.2006.08.034","article-title":"Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus","volume":"119","author":"Dunford","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1600-0625.2008.00762.x","article-title":"Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation","volume":"18","author":"Wendorff","year":"2009","journal-title":"Exp. Dermatol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ejphar.2007.02.026","article-title":"Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenan-induced acute inflammation","volume":"563","author":"Coruzzi","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1111\/bph.14185","article-title":"Antinociceptive effects of novel histamine H3 and H4 receptor antagonists and their influence on morphine analgesia of neuropathic pain in the mouse","volume":"175","author":"Latacz","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s00213-011-2224-5","article-title":"CB1 receptors mediate rimonabant-induced pruritic responses in mice: Investigation of locus of action","volume":"216","author":"Schlosburg","year":"2011","journal-title":"Psychopharmacology"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0304-3959(01)00454-7","article-title":"CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain","volume":"96","author":"Clayton","year":"2002","journal-title":"Pain"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/ced.13398","article-title":"Involvement of spinal cannabinoid receptors in the antipruritic effects of WIN 55,212-2, a cannabinoid receptor agonist","volume":"43","author":"Bilir","year":"2018","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1007\/s00894-011-0986-7","article-title":"Modeling of ligand binding to G protein coupled receptors: Cannabinoid CB1, CB2 and adrenergic \u03b22AR","volume":"17","author":"Latek","year":"2011","journal-title":"J. Mol. Model."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.jaad.2020.01.036","article-title":"Cannabinoids for the treatment of chronic pruritus: A review","volume":"82","author":"Avila","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jdermsci.2005.01.007","article-title":"Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin","volume":"38","author":"Schmelz","year":"2005","journal-title":"J. Dermatol. Sci."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.beem.2008.09.003","article-title":"Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: Focus on anxiety and depression","volume":"23","author":"Moreira","year":"2009","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1111\/j.1572-0241.2002.05852.x","article-title":"Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease","volume":"97","author":"Neff","year":"2002","journal-title":"Am. J. Gastroenterol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jpain.2007.10.018","article-title":"Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy","volume":"9","author":"Narang","year":"2008","journal-title":"J. Pain"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1007\/s00011-003-1162-z","article-title":"Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin","volume":"52","author":"Dvorak","year":"2003","journal-title":"Inflamm. Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.2147\/CIA.S65448","article-title":"N-palmitoylethanolamine and N-acetylethanolamine are effective in asteatotic eczema: Results of a randomized, double-blind, controlled study in 60 patients","volume":"9","author":"Yuan","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_163","first-page":"97","article-title":"Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: A preliminary study","volume":"13","author":"Szepietowski","year":"2005","journal-title":"Acta Dermatovenerol. Croat."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1046\/j.1460-9568.2003.02681.x","article-title":"Expression of oncostatin M receptor \u03b2 in a specific subset of nociceptive sensory neurons","volume":"17","author":"Tamura","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1523\/JNEUROSCI.4975-03.2004","article-title":"Essential function of oncostatin m in nociceptive neurons of dorsal root ganglia","volume":"24","author":"Morikawa","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1111\/jnc.15172","article-title":"Oncostatin M induces hyperalgesic priming and amplifies signaling of cAMP to ERK by RapGEF2 and PKA","volume":"157","author":"Ebersberger","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1111\/exd.14279","article-title":"Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor alpha and oncostatin M receptor beta","volume":"30","author":"Hashimoto","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"eabe3037","DOI":"10.1126\/scitranslmed.abe3037","article-title":"Oncostatin M can sensitize sensory neurons in inflammatory pruritus","volume":"13","author":"Tseng","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"8555","DOI":"10.1073\/pnas.87.21.8555","article-title":"ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains","volume":"87","author":"Fu","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1073\/pnas.86.5.1603","article-title":"Two putative protein-tyrosine kinases identified by application of the polymerase chain reaction","volume":"86","author":"Wilks","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.3389\/fimmu.2019.02342","article-title":"Targeting the Janus kinase family in autoimmune skin diseases","volume":"10","author":"Howell","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.jaci.2020.06.039","article-title":"Astrocytic STAT3 activation and chronic itch require IP3R1\/TRPC-dependent Ca2+ signals in mice","volume":"147","author":"Yamaguchi","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.cell.2017.08.006","article-title":"Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch","volume":"171","author":"Oetjen","year":"2017","journal-title":"Cell"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Kim, B.S. (2022). The translational revolution of itch. Neuron, in press.","DOI":"10.1016\/j.neuron.2022.03.031"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/brain\/awr025","article-title":"JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats","volume":"134","author":"Tsuda","year":"2011","journal-title":"Brain"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1471-4159.2008.05566.x","article-title":"JAK\/STAT3 pathway is activated in spinal cord microglia after peripheral nerve injury and contributes to neuropathic pain development in rat","volume":"107","author":"Dominguez","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"668","DOI":"10.55563\/clinexprheumatol\/e7ayu8","article-title":"JAK\/STAT pathway and nociceptive cytokine signalling in rheumatoid arthritis and psoriatic arthritis","volume":"39","author":"Crispino","year":"2021","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s10787-022-00995-z","article-title":"Early response to JAK inhibitors on central sensitization and pain catastrophizing in patients with active rheumatoid arthritis","volume":"30","author":"Salaffi","year":"2022","journal-title":"Inflammopharmacology"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1098\/rstb.2006.1894","article-title":"Neurotrophin-regulated signalling pathways","volume":"361","author":"Reichardt","year":"2006","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1146\/annurev.neuro.24.1.1217","article-title":"Nerve growth factor signaling, neuroprotection, and neural repair","volume":"24","author":"Sofroniew","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"294","DOI":"10.2174\/1570159X13666150403231920","article-title":"Nerve growth factor: A focus on neuroscience and therapy","volume":"13","author":"Aloe","year":"2015","journal-title":"Curr. Neuropharmacol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/1479-5876-10-239","article-title":"Nerve growth factor: From the early discoveries to the potential clinical use","volume":"10","author":"Aloe","year":"2012","journal-title":"J. Transl. Med."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S1359-6101(03)00047-9","article-title":"New insights on the involvement of Nerve Growth Factor in allergic inflammation and fibrosis","volume":"14","author":"Micera","year":"2003","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/00130832-200410000-00015","article-title":"Nerve growth factor and the immune system: Old and new concepts in the cross-talk between immune and resident cells during pathophysiological conditions","volume":"4","author":"Lambiase","year":"2004","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jdermsci.2008.08.011","article-title":"Quantitative analysis of nerve growth factor (NGF) in the atopic dermatitis and psoriasis horny layer and effect of treatment on NGF in atopic dermatitis","volume":"53","author":"Yamaguchi","year":"2009","journal-title":"J. Dermatol. Sci."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2147\/TCRM.S144125","article-title":"Tanezumab: A selective humanized mAb for chronic lower back pain","volume":"14","author":"Webb","year":"2018","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1136\/annrheumdis-2020-217259","article-title":"Efficacy and safety of fasinumab in patients with chronic low back pain: A phase II\/III randomised clinical trial","volume":"80","author":"Dakin","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"C1429","DOI":"10.1152\/ajpcell.1998.274.6.C1429","article-title":"Proteinase-activated receptors: Novel mechanisms of signaling by serine proteases","volume":"274","author":"Corvera","year":"1998","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/72247","article-title":"Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism","volume":"6","author":"Steinhoff","year":"2000","journal-title":"Nat. Med."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00281-011-0289-1","article-title":"Protease-activated receptor 2 signaling in inflammation","volume":"34","author":"Rothmeier","year":"2012","journal-title":"Proc. Semin. Immunopathol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.it.2007.09.001","article-title":"Protease-activated receptors: Novel PARtners in innate immunity","volume":"28","author":"Shpacovitch","year":"2007","journal-title":"Trends Immunol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"ra45","DOI":"10.1126\/scisignal.2001925","article-title":"The distinct roles of two GPCRs, MrgprC11 and PAR2, in itch and hyperalgesia","volume":"4","author":"Liu","year":"2011","journal-title":"Sci. Signal."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/j.jid.2020.01.012","article-title":"PAR2 mediates itch via TRPV3 signaling in keratinocytes","volume":"140","author":"Zhao","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"7477","DOI":"10.1021\/jm400638v","article-title":"Toward drugs for protease-activated receptor 2 (PAR2)","volume":"56","author":"Yau","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0165-6147(00)01932-5","article-title":"Role of PAR2 in pain and inflammation","volume":"23","author":"Fiorucci","year":"2002","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/89945","article-title":"Proteinase-activated receptor-2 and hyperalgesia: A novel pain pathway","volume":"7","author":"Vergnolle","year":"2001","journal-title":"Nat. Med."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.pain.2010.02.010","article-title":"Serine proteases and protease-activated receptor 2-dependent allodynia: A novel cancer pain pathway","volume":"149","author":"Lam","year":"2010","journal-title":"PAIN"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.3389\/fimmu.2020.01740","article-title":"Protease-activated receptor-2 regulates neuro-epidermal communication in atopic dermatitis","volume":"11","author":"Buhl","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"14178","DOI":"10.1523\/JNEUROSCI.2399-12.2012","article-title":"Novel animal models of acute and chronic cancer pain: A pivotal role for PAR2","volume":"32","author":"Lam","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1042\/BST20200191","article-title":"The development of proteinase-activated receptor-2 modulators and the challenges involved","volume":"48","author":"McIntosh","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"145","DOI":"10.33549\/physiolres.933104","article-title":"Blocking proteinase-activated receptor 2 alleviated neuropathic pain evoked by spinal cord injury","volume":"65","author":"Wei","year":"2016","journal-title":"Physiol. Res."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1124\/jpet.112.195222","article-title":"Involvement of serine protease and proteinase-activated receptor 2 in dermatophyte-associated itch in mice","volume":"343","author":"Andoh","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"716","DOI":"10.3389\/fneur.2020.00716","article-title":"Botulinum neurotoxin for the treatment of neuropathic pain","volume":"11","author":"Egeo","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1002\/ejp.1941","article-title":"Efficacy and safety of botulinum A toxin for the treatment of chronic peripheral neuropathic pain: A systematic review of randomized controlled trials and meta-analysis","volume":"26","author":"Hary","year":"2022","journal-title":"Eur. J. Pain"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1097\/MRR.0000000000000495","article-title":"Botulinum toxin type A therapy for bilateral focal neuropathic pruritus in multiple sclerosis: A case report","volume":"44","author":"Portugal","year":"2021","journal-title":"Int. J. Rehabil. Res."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.jaad.2013.12.006","article-title":"Treatment of notalgia paresthetica with botulinum toxin A: A double-blind randomized controlled trial","volume":"70","author":"Maari","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/jocd.12134","article-title":"Intralesional botulinum toxin type A equally effective and better tolerated than intralesional steroid in the treatment of keloids: A randomized controlled trial","volume":"14","author":"Shaarawy","year":"2015","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1111\/pde.14552","article-title":"Treatment of pruritus with botulinum toxin in a pediatric patient with Fox-Fordyce disease","volume":"38","author":"Klager","year":"2021","journal-title":"Pediatric Dermatol."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Meixiong, J., Dong, X., and Weng, H.-J. (2020). Neuropathic itch. Cells, 9.","DOI":"10.3390\/cells9102263"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jaad.2017.08.001","article-title":"Botulinum toxin type A for the treatment of localized recalcitrant chronic pruritus","volume":"78","author":"Boozalis","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.amjmed.2005.05.031","article-title":"Efficacy of lidocaine in the treatment of pruritus in patients with chronic cholestatic liver diseases","volume":"118","author":"Villamil","year":"2005","journal-title":"Am. J. Med."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.jaad.2016.10.030","article-title":"Topical ketamine-amitriptyline-lidocaine for chronic pruritus: A retrospective study assessing efficacy and tolerability","volume":"76","author":"Lee","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1097\/00004630-200105000-00010","article-title":"Safety and pharmacokinetics of EMLA in the treatment of postburn pruritus in pediatric patients: A pilot study","volume":"22","author":"Kopecky","year":"2001","journal-title":"J. Burn Care Rehabil."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1080\/09546630802441218","article-title":"A pramoxine-based anti-itch lotion is more effective than a control lotion for the treatment of uremic pruritus in adult hemodialysis patients","volume":"20","author":"Young","year":"2009","journal-title":"J. Dermatol. Treat."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/sj.bjp.0704439","article-title":"Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones","volume":"135","author":"Sutton","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.jaad.2016.02.1237","article-title":"Gabapentin and pregabalin for the treatment of chronic pruritus","volume":"75","author":"Matsuda","year":"2016","journal-title":"J. Am. Acad. Dermajtol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/7\/892\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:54:02Z","timestamp":1760140442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/7\/892"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,19]]},"references-count":217,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ph15070892"],"URL":"https:\/\/doi.org\/10.3390\/ph15070892","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,19]]}}}