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.

Role of Keap1-Nrf2 Signaling in Anhedonia Symptoms in a Rat Model of Chronic Neuropathic Pain: Improvement With Sulforaphane

“…In the present study, hierarchical cluster analysis was used to divide SNI rats into two clusters: one group (approximately 68%; anhedonia-like phenotype) with reduced sucrose preference in the SPT and the other (approximately 32%; without anhedonia-like phenotype) with sucrose preference similar to that in sham-operated rats, consistent with our previous report ( Fang et al, 2018 ). In the current study, we also found that rats, regardless of the presence or absence of anhedonia-like phenotype, exhibited similar MWT scores, suggesting that alterations in mood-related behaviors were independent of the degree of nociceptive damage, which was consistent with previous studies ( Monassi et al, 2003 ; Austin and Moalem-Taylor, 2010 ; Austin et al, 2015 ; Gui et al, 2016 ; Xie et al, 2017 ; Fang et al, 2018 ).…”

Hyaluronic acid microneedle patch for the improvement of crow's feet wrinkles

“…Microneedle patch vaccines can be used to target not just infectious viruses but also cancer, and microneedle patch‐assisted delivery of anti‐cancer immunotherapeutic agents have been developed (Ita, ). A range of drugs, such as analgesics or medication for dementia, could be delivered by microneedle patch (Kathuria et al, ; Kearney et al, ; Xie et al, ). In the field of dermatology, several reports have shown that the active cosmetic ingredients, such as retinoic acid and ascorbic acid, can be loaded onto the microneedle patch, and these cosmetic patches were found to be safe and effective for pigmented lesions or wrinkles (Hirobe, Otsuka, & Iioka, ; Kim, Yang, Kim, & Jung, ; Lee, Yang, & Kim, ).…”

“…Microneedle patches have been used for transdermal delivery in different medical fields (Hirobe, Azukizawa, & Hanafusa, ; Kearney, Caffarel‐Salvador, Fallows, McCarthy, & Donnelly, ; Wang, Ye, & Hochu, ; Xie, Pascual, & Lieu, ). To increase the permeability of active agents such as drugs or vaccines across skin, the formulation of microneedle patches has been technologically developed (Kathuria, Li, & Pan, ; Lau, Fei, Liu, Chen, & Liu, ).…”

3D Printed Microheater Sensor‐Integrated, Drug‐Encapsulated Microneedle Patch System for Pain Management

“…Fabrication of Microneedle Patch : The fabrication of microneedle was conducted by following the protocol published in this paper . In brief, ≈2 mg Cy5 (gift from Dr. Zhang lab at Cedars‐Sinai, CA) was dissolved in 500 µL 8% (w/w) sodium carboxylmethyl cellulose (SCMC, Sigma‐Aldrich, MO, USA) solution.…”