Patch Adhesion Research Articles

Skin adhesion of a newly developed, bioequivalent rotigotine patch formulation in comparison to the originator product: Results of a multi-center, randomized, crossover trial in patients with Parkinson's disease.

To demonstrate adequate skin adhesion of a new once-daily rotigotine transdermal patch (ROT-TDS) compared to the originator product (reference) in patients with Parkinson's disease (PD). Pharmacokinetic bioequivalence (PK BE) was assessed with the 4 mg/24h patches in healthy adults in a single-/multiple-dose, crossover trial. The trial investigating skin adhesion in PD patients (stable dose ≥ 8 mg/day rotigotine) was performed with the 8 mg/24h patches as a multiple-dose, crossover trial (4 alternating once-daily patch applications). Skin status (seborrhea, sweating) was characterized at screening. Adhesion was assessed 5 minutes after application and 5 minutes before removal of each patch. Systemic safety and skin irritation/sensitization were monitored. ROT-TDS was bioequivalent to the reference product in the PK BE trial in 48 randomized healthy subjects. In the skin adhesion trial in 43 randomized PD patients, the cumulative mean percentage of adhesion (90% CI) at the end-of-dosing interval was 92.948% (90.156 - 95.740%) for ROT-TDS and 90.471% (87.574 - 93.367%) for the reference. For ROT-TDS, 80.23% of patches were ≥ 90% adhered at the end-of-dosing interval, while this was the case for 67.44% of the reference patches. Safety and skin tolerability of both products were comparable; the most frequent treatment-related adverse event was application-site pruritus for both treatments at comparable extent. ROT-TDS - with shown BE to the originator reference product - displayed similar safety and local tolerability as the reference product in patients with PD. The results show a trend to improved skin adhesion of the new patch compared to the reference in the target population.

Electrospun Polymeric Fiber Systems Inoculated with Cyanoacrylate Tissue Adhesive: A Novel Hemostatic Alternative during Open Surgery.

Natural-based and synthetic tissue adhesives have attracted extensive attention in the last two decades for their ability to stabilize uncontrolled bleeding instances. However; these materials present several drawbacks during use that scientists have tried to minimize in order to optimize their usage. This study comprises the development of a novel wound dressing, combining the excellent properties of polylactic acid (PLA) non-woven textile, as substrate, obtained through electrospinning, and a cyanoacrylate-based (CA) tissue adhesive, for rapid hemostatic action. Thus, the fabrication of electrospun PLA membranes at three different PLA concentrations, the design and manufacturing of the support system and the production of surgical patches were carried out. SEM and FT-IR methods were employed for analyzing the morphology as well as the indicative markers for the shelf life evolution of the obtained patches. PLA fibers with well-defined structures and a mean diameter varying between 4.6 and 7.24 μm were obtained with the increase of the concentration of the PLA solutions. In vivo tests on a rat model as well as peeling tests for good patch adhesion on liver fragments harvested from the test animals, with a limit for the strength of the liver tissue of 1.5 N, were carried out. The devices exhibited excellent adhesion to the parenchymal tissue and a long enough shelf life to be used with success in surgical procedures, also facilitating prompt hemostatic action.

First promising non-stimulant (guanfacine) transdermal patch for long-acting treatment of ADHD by solid dispersion technique

Guanfacine (GFC) extended-release tablet (Intuniv®) is an effective non-stimulant medication prescribed for attention deficit hyperactivity disorder (ADHD), presenting limitations regarding patient compliance and safety risks. The study aimed to design a novel long-acting transdermal delivery system of GFC to address these issues. Polyvinylpyrrolidone (PVP)-GFC solid dispersions were constructed by the co-evaporation method to improve drug-loading capacity to approximately 10 % (w/w). A PVP-GFC ratio of 3:1 was determined to prevent drug crystallization and promote rapid dissolution. The mechanisms underlying solid dispersion formation were revealed by XRD, DSC, molecular docking, FTIR, and Raman imaging. Hydrogen-bond interactions between PVP and GFC played a crucial role. The prescription and preparation process were optimized using single-factor and Box-Behnken design experiments. The optimized patch exhibited excellent crystallization resistance and adhesion for at least six months. Additionally, superior rheology, mechanical strength, in vitro drug release, and percutaneous permeation characteristics were observed. In human pharmacokinetic studies, the therapeutic efficacy, skin safety, and adhesion of transdermal patches were initially demonstrated for the three-day treatment of ADHD. Therefore, the innovative work expands the comprehension of solid dispersion techniques and facilitates the industrialization and commercialization of the first non-stimulant transdermal patches, providing a promising alternative for ADHD therapy.

A qualitative evaluation of a fentanyl patch safer supply program in Vancouver, Canada

BackgroundThe ongoing overdose crisis in Canada has prompted efforts to increase access to a “safer supply” of prescribed alternatives to the unregulated drug supply. While safer supply programs predominantly distribute hydromorphone tablets, the Safer Alternatives for Emergency Response (SAFER) program in Vancouver, Canada offers a range of prescribed alternatives, including fentanyl patches. However, little is known about the effectiveness of fentanyl patches as safer supply. Drawing on the perspectives and experiences of program participants, we sought to qualitatively evaluate the effectiveness of the SAFER fentanyl patch program in meeting its intended aims, including reducing risk of overdose by decreasing reliance on the unregulated drug supply. MethodsAs part of a larger mixed-methods evaluation of SAFER, semi-structured qualitative interviews were conducted with 17 fentanyl patch program participants between February 2022 and April 2023. Thematic analysis of interview data focused on program engagement, experiences, impacts, and challenges. ResultsThe flexible program structure, including lack of need for daily dispensation, the extended missed dose protocol, and community pharmacy patch distribution fostered engagement and enhanced autonomy. Improved management of withdrawal symptoms and cravings due to steady transdermal dosing led to reduced unregulated drug use and overdose risk. Participants also experienced economic benefits and improvements in overall health and quality of life. However, skin irritation and patch adhesion issues were key barriers to program retention. ConclusionOur findings demonstrate the value of including fentanyl patch safer supply in the substance use continuum of care and offer insights for innovations in delivery of this intervention.

Black phosphorus boosts wet-tissue adhesion of composite patches by enhancing water absorption and mechanical properties

Wet-tissue adhesives have long been attractive materials for realizing complicated biomedical functions. However, the hydration film on wet tissues can generate a boundary, forming hydrogen bonds with the adhesives that weaken adhesive strength. Introducing black phosphorus (BP) is believed to enhance the water absorption capacity of tape-type adhesives and effectively eliminate hydration layers between the tissue and adhesive. This study reports a composite patch integrated with BP nanosheets (CPB) for wet-tissue adhesion. The patch’s improved water absorption and mechanical properties ensure its immediate and robust adhesion to wet tissues. Various bioapplications of CPB are demonstrated, such as rapid hemostasis (within ~1-2 seconds), monitoring of physical-activity and prevention of tumour-recurrence, all validated via in vivo studies. Given the good practicability, histocompatibility and biodegradability of CPB, the proposed patches hold significant promise for a wide range of biomedical applications.

Wet environment-induced adhesion and softening of coenzyme-based polymer elastic patch for treating periodontitis

Periodontitis, a common chronic inflammatory disease caused by pathogenic bacteria, can be treated with diverse biomaterials by loading drugs, cytokines or proteins. However, these biomaterials often show unsatisfactory therapeutic efficiency due to their poor adhesion, short residence time in the wet and dynamic oral cavity and emerging drug resistance. Here we report a wet-responsive methacrylated gelatin (GelMA)-stabilized co-enzyme polymer poly(α-lipoic acid) (PolyLA)-based elastic patch with water-induced adhesion and softening features. In PolyLA-GelMA, the multiple covalent and hydrogen-bonding crosslinking between PolyLA and GelMA prevent PolyLA depolymerization and slow down the dissociation of PolyLA in water, allowing durable adhesion to oral periodontal tissue and continuous release of LA-based bioactive small molecule in periodontitis wound without resorting external drugs. Compared with the undifferentiated adhesion behavior of traditional adhesives, this wet-responsive patch demonstrates a favorable periodontal pocket insertion ability due to its non-adhesion and rigidity in dry environment. In vitro studies reveal that PolyLA-GelMA patch exhibits satisfactory wet tissue adhesion, antibacterial, blood compatibility and ROS scavenging abilities. In the model of rat periodontitis, the PolyLA-GelMA patch inhibits alveolar bone resorption and accelerates the periodontitis healing by regulating the inflammatory microenvironment. This biomacromolecule-stabilized coenzyme polymer patch provides a new option to promote periodontitis treatment.

Comparative effectiveness of myocardial patches and intramyocardial injections in treating myocardial infarction with a MitoQ/hydrogel system.

In cardiac tissue engineering, myocardial surface patches and hydrogel intramyocardial injections represent the two primary hydrogel-based strategies for myocardial infarction (MI) treatment. However, the comparative effectiveness of these two treatments remains uncertain. Therefore, this study aimed to compare the effects of the two treatment modalities by designing a simple and reproducible hydrogel cross-linked with γ-PGA and 4-arm-PEG-SG. To improve mitochondrial damage in cardiomyocytes (CMs) during early MI, we incorporated the mitochondria-targeting antioxidant MitoQ into the hydrogel network. The hydrogel exhibited excellent biodegradability, biocompatibility, adhesion, and injectability in vitro. The hydrogel was utilized for rat MI treatment through both patch adhesion and intramyocardial injections. In vivo results demonstrated that the slow release of MitoQ peptide from the hydrogel hindered ROS production in CM, alleviated mitochondrial damage, and enhanced CM activity within 7 days, effectively inhibiting MI progression. Both hydrogel intramyocardial injections and patches exhibited positive therapeutic effects, with intramyocardial injections demonstrating superior efficacy in terms of cardiac function and structure in equivalent treatment cycles. In conclusion, we developed a MitoQ/hydrogel system that is easily prepared and can serve as both a myocardial patch and an intramyocardial injection for MI treatment, showing significant potential for clinical applications.

Experimental evaluation of interface adhesion of a flax fiber composite patch with epoxy and polyurethane adhesives for the reinforcement of steel structures

Using fiber-reinforced composite patches for repairing damaged structures made of metal or/and concrete is an interesting and widely available solution on the market using synthetic materials. These repairing patches are bonded on the structures’ surfaces to increase their strength against internal stresses, as well as protect them from external physico-chemical attacks, thereby limiting crack propagation. Natural fibers offer a potential alternative to replacing glass or carbon fibers commonly used for bonded repair patches. Similarly, bio-based polymers represent an important sustainable alternative for partially or entirely replacing the petroleum-based polymers. In this study, an epoxy matrix reinforced with flax fiber is proposed as the material for the patches, and bonded to a steel plate using four different types of adhesive materials, including a castor-oil derived polyurethane resin. Floating roller peel tests were performed to assess the adhesion and viability of these new patches. The resulting peeling loads and fracture surface analysis are presented. Polyurethane demonstrates promising performance for epoxy-to-steel joints, but major improvements of the bio-based polyurethane application process and curing conditions may be necessary for its successful industrial implementation.

The Impact of Liquid Components on Alteration of the Adhesion of Polyacrylate and Silicone Patches.

Polyacrylates and polysiloxanes are polymers used in pressure-sensitive adhesive (PSA) patches. Liquid additives are co-solvents of the active substances or permeation enhancers, and their compatibility with the polymeric matrix and the effect on adhesive properties should be considered. The patches were prepared from commercial polyacrylates (three types of Duro-Tak®) and siloxanes (Bio-PSA® and Soft Skin Adhesive®). Propylene glycol, polyoxyethylene glycol, isopropyl myristate, triacetin, triethyl citrate and silicone oil were added (10% w/w). Formulations were evaluated microscopically and with a texture analyzer in terms of in vitro adhesiveness and hardness. Only silicone oil was compatible with the silicone matrices. The best compatibility of acrylic PSA was observed with triethyl citrate; one out of three Duro-Tak matrices was incompatible with every additive. In all compositions, the adhesiveness was impaired by the liquid additives. A significant drop in adhesiveness was noted after immersion of the patches in buffer and drying. The probe tack test was considered as the most useful for evaluation of the effect of the liquid additive on adhesiveness, but the results obtained with a spherical and cylindrical probe were contradictory. The structural changes caused by the additives were also demonstrated by a 90° peel test, considered as complementary to the tack test.

DoE-based formulation, physicochemical properties, and anti-inflammatory investigation of a topical patch preparing by partially neutralized polyacrylate-based adhesive hydrogel

A capsaicin patch was formulated by optimizing the adhesion, the release behavior of the patch, and the pharmacological effect. The aims of study were to 1) apply the design of experiments approach for investigating the simultaneous effect of Viscomate (partially neutralized polyacrylate)-based adhesive, glycerin plasticizing excipient and permeation enhancers on patch adhesion, and the permeation rate of model drug (capsaicin) and then 2) compare the optimal formulation with the reference product (Wellpatch®, Metholatum, U.S.A.) in terms of pharmacological effect. The topical patch was prepared by casting the drug-loaded adhesive hydrogel on the backing layer. The adhesive ability of patches was determined by testing a 90° peel rig on a texture analyzer, and the permeation rate of capsaicin (CAP) through mouse skin was evaluated using Franz diffusion cells. The effects of these critical factors on patch adhesion, CAP flux, and permeation enhancer interaction with the stratum corneum were analyzed using ANOVA and ATR-FTIR/skin hydration tests, respectively. Accordingly, Viscomate (adhesion excipient) and glycerin (plasticizing excipient) had a significant impact on patch adhesion (p < 0.05). Meanwhile, N-methyl pyrrolidone, the permeation enhancer, had a better permeation rate and higher hydration level of the stratum corneum than did Transcutol. The partially neutralized polyacrylate-based optimal formulation had a higher permeation rate of CAP, equal adhesion and comparable anti-inflammatory effects to those of the reference product which was also in agreement with the analysis of anatomical images of tissue structure and inflammatory cells. This study successfully integrated DoE method, release behavior and pharmacological research to develop a stable and highly effective topical product containing capsaicin.

Bionic artificial penile Tunica albuginea

Bionic artificial penile Tunica albuginea

Development and Characterisation of a Topical Methyl Salicylate Patch: Effect of Solvents on Adhesion and Skin Permeation.

The advent of skin patch formulation design and technology has enabled the commercialisation of methyl salicylate (MS) as a topical patch. However, the most fundamental aspect of skin permeation is unknown at present. The study aims to investigate the effect of solvent choice on the skin permeation of MS in a neat solvent system and patch formulation with an emphasis on patch adhesion. MS in six selected solvents (propylene glycol (PG), Transcutol®, isopropyl myristate, Labrasol®, Plurol® oleique CC 497 and Maisine® CC) was characterised and in vitro permeation studies were also performed. An ATR-FTIR analysis on solvent-treated skin was conudcted. Patch formulation was prepared and characterised for adhesion, in vitro drug release and skin permeation studies. The highest MS permeation was found in neat PG over 24 h (~90 μg/cm2) due to its strong skin protein conformation effect. Transcutol® and isopropyl myristate showed better skin deposition and formulation retention, respectively. Nevertheless, PG enhanced the patch adhesion despite having a lower cumulative amount of MS permeated (~80 μg/cm2) as compared with Transcutol® and Maisine® (~110-150 μg/cm2). These two solvents, however, demonstrated better skin deposition and formulation retention but a lower patch adhesion. The unpredictable influence of the solvent on patch adhesion highlights the importance of the trade-off between patch adhesion and skin permeation during formulation design.

Adhesive polyethylene glycol-based hydrogel patch for tissue repair

Polyethylene glycol (PEG)-based tissue glue has been widely used in surgery, but the sealants were weak in strength and could not be in place of sutures. This paper prepared a PEG-based tissue patch made of F127-DA hydrogel and PEG-DA as adhesive. For the patch adhesion on tissues, photoinitiator of lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP, 0.1 % w/v) and UV flashlight at 395 nm for 30 s irradiation was used. The adhesion energy on pig skin, lung, heart, liver, kidney and stomach was 85.33, 56.40, 75.56, 70.22, 66.67 and 36.89 N/m, indicating the well stitching to different tissues. The hydrogel patch could also seal the punched tissues to prevent the leakage of liquid or air. Finally, the patch showed good tissue compatibility after 2 days adhesion on pig skin. In this regard, the hydrogel patch is expected to repair the wounded tissues without suture, being a biocompatible adhesive for wound healing of various tissues.

Bioavailability Study of a Transdermal Patch Formulation of Rivastigmine Compared with Exelon in Healthy Subjects.

Rivastigmine is a reversible cholinesterase inhibitor indicated for the treatment of all stages of Alzheimer's disease (AD). Transdermal patch formulation allows smooth and continuous drug delivery. Its tolerability, efficacy and convenience of use increase treatment compliance. This study was designed to evaluate the bioavailability and to assess the bioequivalence of two rivastigmine transdermal patches at steady state (RIV-TDS Test Product versus Exelon Marketed Reference Product), with a release rate of 13.3mg/24h, after multiple patch applications. As secondary objectives, safety, patch adhesion and skin irritation were evaluated. This was an open-label, randomized, balanced, two-period, two-sequence, cross-over study of healthy adults (n=31). The treatment period consisted of two 5-day study periods during which consecutive daily application of the investigational patches with a release rate of 13.3mg/24h rivastigmine took place. Serial blood samples were collected to measure plasma concentrations. Adhesion and skin irritation assessments were performed after application of patches. Point estimates and 90% confidence intervals of pharmacokinetic parameters at steady state, viz. area under the plasma concentration versus time curve from dosing time to the end of the dosing interval τ (profile day) at steady state [AUC0-τ,ss] (97.4; 88.8-106.9), maximum plasma concentration within the dosing interval τ (profile day) at steady state [Cmax,ss] (99.6; 90.4-109.7) and trough plasma concentration at the end of the dosing interval τ (profile day) at steady state [Cτ,ss] (96.8; 86.2-108.9), demonstrated that both patches were bioequivalent. Evaluation of patch adhesion showed better skin adherence for RIV-TDS as well as dermal response scores (skin tolerability after removal). For both products, bioequivalence was shown andsystemic tolerability was in accordance with the safety profile of the drug substance. The trial is registered in ClinicalTrials.gov: NCT03573050 and EudraCT: 2018-000968-28.

Development and In Vitro Testing of a Novel Universal Transdermal Drug Delivery Platform to Reduce Medication Nonadherence

Medication nonadherence results in avoidable symptom exacerbations and hospitalization, causing thousands of deaths and billions of dollars in healthcare costs annually. Although pharmacological therapies are present for chronic diseases, lengthy and complicated medication regimens often have high rates of nonadherence. Transdermal drug delivery is a potential method of reducing medication nonadherence as it allows for long-course medication regimens to be simplified to a one-time epidermal patch. We have engineered a transdermal drug delivery system on a customizable platform to longitudinally deliver a wide variety of soluble small-molecule drugs. As a proof of concept, we have chosen to administer long-course corticosteroids for chronic inflammatory disease via epidermal patch. A drug-in-adhesive matrix consisting of the drug, adhesive, solvents, and penetration enhancers, was cured onto a fluoropolymer release liner. The transdermal drug delivery system has an integrated tapering mechanism to avoid end-of-course steroid dependence and can incorporate other small-molecule medications required for cases of polypharmacy. To date, there have been no successful attempts to develop long-term steroid patches for systemic delivery, which may be attributed to issues with patch adhesion and skin irritation over extended periods of time. We have analyzed such challenges and have designed a proof of concept system to overcome these obstacles in order to provide patients with a simple, inexpensive, and effective solution to complicated and long-term treatment regimens.

Dorsolateral prefrontal cortex sensing analgesia.

Chronic pain often has an unknown cause, and many patients with chronic pain learn to accept that their pain is incurable and pharmacologic treatments are only temporarily effective. Complementary and integrative health approaches for pain are thus in high demand. One such approach is soft touch, e.g., adhesion of pyramidal thorn patches in a pain region. The effects of patch adhesion on pain relief have been confirmed in patients with various types of pain. A recent study using near-infrared spectroscopy revealed that the dorsolateral prefrontal cortex (DLPFC), especially the left side, is likely to be inactivated in patients experiencing pain relief during patch treatment. Mindfulness meditation is another well-known complementary and integrative approach for achieving pain relief. The relation between pain relief due to mindfulness meditation and changes in brain regions, including the DLPFC, has long been examined. In the present review article, we survey the literature describing the effects of the above-mentioned complementary and integrative treatments on pain relief, and outline the important brain regions, including the DLPFC, that are involved in analgesia. We hope that the present article will provide clues to researchers who hope to advance neurosensory treatments for pain relief without medication.

Detection and Analysis of Drug Crystals in Medical Transdermal Patches by Using X-ray Diffraction Measurement

The crystallization of active pharmaceutical ingredients (APIs) in matrix-type transdermal patches has implications for the rate of drug absorption through the skin and patch adhesion strength. Therefore, the presence or absence and the degree of API crystallinity must be controlled to guarantee the quality of patches. In this study, the utility of laboratory-level X-ray diffractometers for the detection and analysis of crystalline APIs in transdermal patches was investigated using medical patches of tulobuterol and isosorbide dinitrate. Several matrix-type patches employ a controlled drug delivery system containing intentionally crystallized API. Both benchtop and high-resolution laboratory X-ray diffractometers can detect several characteristic peaks of the APIs in these patches even if the patches are wrapped in an outer bag, although a benchtop model provides peak heights one-seventh to one-fifth that of a high-resolution instrument. An isosorbide dinitrate patch containing an unintentionally crystallized spot was wrapped in an outer bag, followed by measurements using both X-ray diffractometers. For both instruments, several isosorbide dinitrate-derived peaks were detected only at the crystallized spot, although the signal-to-noise ratio was poorer for the benchtop model. These results show that a high-resolution X-ray diffractometer is advantageous for high-detection sensitivity and offers a high degree of freedom of the measurement position on the sample. It was concluded that a laboratory-level high-resolution X-ray diffractometer can be used to examine the crystalline state of APIs in patches inside an unopened outer bag.

Review on Transdermal drug delivery system

Transdermal drug delivery system offers best way of drug delivery through skin than compared to oral route of administration by overcoming side-effects.Drug delivery is done through adhesion of transdermal patches to skin surface.Novel application techniques have been employed for better therapeutic response for various drug in treatment of several disease using dermal route of administration.This is best non-invasive method of drug delivery by reducing frequency of administration to achieve complete action of action of drug with maximum benefits to patients .These patches are formulated using various permeation enhancers that are compatible to skins surface .The dermal route of delivery is best suited for therapy to patient for certain diseases.

Randomized, double-blind, two-way crossover bioequivalence and adhesion study, in healthy women, of a transdermal contraceptive patch with a newly sourced adhesive component at the end of shelf life vs. the EVRA patch at the beginning of shelf life.

Objective: Evaluate bioequivalence, based on norelgestromin (NGMN) and ethinyl estradiol (EE) plasma concentrations, and adhesion of a transdermal contraceptive patch containing a newly sourced adhesive component (test) at end of shelf life (EOSL) vs. the marketed EVRA patch (reference) at beginning of shelf life (BOSL). Materials and methods: In this randomized, double-blind, two-way crossover study, healthy women received a single, 7-day application of test and reference patches in 4 sequences: two 11-day treatment periods separated by a 21-day washout. Assessments included NGMN and EE pharmacokinetics (PK), adhesion (per European Medicines Agency (EMA) 5-point scale), irritation potential and application-site reactions, and tolerability. Patches were bioequivalent if 90% CIs of geometric mean ratios (GMRs) of test/reference for Cmax, AUC168h, AUC0–tlast, and AUC∞ were 80 – 125%. Patch adhesion was comparable if ratios of geometric mean cumulative adhesion percentages were ≥ 90%. Results: 68 women were randomized, and 62 completed both treatments. 55 and 59 participants in the reference and test group, respectively, had patch adhesion ≥ 80% (EMA score 0 – 1) at end of treatment. Bioequivalence was demonstrated: GMRs for pharmacokinetic (PK) parameters ranged from 102.76 to 105.57% for NGMN and 93.78 – 94.80% for EE, and associated 90% CIs were fully within the bioequivalence acceptance range (80 – 125%) for both. The patches had comparable adhesion properties (GMR, 101.4% (90% CI: 99.2 – 103.6)) and incidences of treatment-emergent adverse events. Conclusion: NGMN-EE transdermal test patch at EOSL was bioequivalent to the marketed patch at BOSL, supporting widening the product’s shelf-life specification. Adhesive properties and safety profiles were comparable between patches.

Pain relief associated with decreased oxyhemoglobin level in left dorsolateral prefrontal cortex.

Pain in the elbow, shoulder, knee, lower back, and various other joints is relieved by adhesion of pyramidal thorn patches. To elucidate the pain relief mechanism induced by the patches, we established a quantitative method for estimating the pain reduction and investigated the brain regions that change in association with pain relief. We first attempted to quantify the pain relief using transcutaneous electric stimulation (TCES) and a visual analog scale (VAS), and then applied near-infrared spectroscopy (NIRS) to the prefrontal cortex, including the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC). We also examined the salivary oxytocin levels, which are thought to reflect oxytocin secretion levels from the posterior pituitary in the brain. Application of pyramidal thorn patches to pain regions decreased the pain degree estimated using TCES and VAS. Oxyhemoglobin levels were likely to be decreased in the left DLPFC on the basis of NIRS measurements during patch treatment, suggesting that the left DLPFC is involved in pain relief. On the other hand, the salivary oxytocin levels varied widely. A potential reason for the varying salivary oxytocin levels is its utilization in the pain region as an analgesic agent. Our results suggest that the left DLPFC will become a target brain region for pain therapy.