title: Analgesic Microneedle Patch for Neuropathic Pain Therapy.
abstract: Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.
authors.affiliation: AfaSci Research Laboratories , Redwood City, California 94063, United States.|School of Electronics and Information Technology; State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-Sen University , Guangzhou 510275, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xie
authors.affiliation: AfaSci Research Laboratories , Redwood City, California 94063, United States.|Department of Anesthesia, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Conrado
authors.initials: C
authors.lastname: Pascual
authors.affiliation: AfaSci Research Laboratories , Redwood City, California 94063, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lieu
authors.affiliation: AfaSci Research Laboratories , Redwood City, California 94063, United States.
authors.forename: Seajin
authors.initials: S
authors.lastname: Oh
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: AfaSci Research Laboratories , Redwood City, California 94063, United States.
authors.forename: Bende
authors.initials: B
authors.lastname: Zou
authors.affiliation: AfaSci Research Laboratories , Redwood City, California 94063, United States.
authors.forename: Julian
authors.initials: J
authors.lastname: Xie
authors.affiliation: AfaSci Research Laboratories , Redwood City, California 94063, United States.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Li
authors.affiliation: AfaSci Research Laboratories , Redwood City, California 94063, United States.
authors.forename: James
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Yeomans
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Mei X
authors.initials: MX
authors.lastname: Wu
authors.affiliation: AfaSci Research Laboratories , Redwood City, California 94063, United States.|Department of Anesthesia, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Xinmin Simon
authors.identifier: 0000-0002-4608-3572
authors.initials: XS
authors.lastname: Xie
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009339:Needles; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D014466:Ultraviolet Rays
chemical_list: D000700:Analgesics
keywords: CGRP antagonist peptide; analgesia; drug delivery; microneedle; neuropathic pain