Randomised controlled trial of a microneedle patch with a topical anaesthetic for relieving the pain of dental injections

Abstract

Objectives

To determine whether a microneedle patch combined with 5% topical lidocaine reduces dental injection pain more than a patch without microneedles combined with 5% topical lidocaine.

Methods

This proof of principle randomised, two-treatment, double-blind, crossover split-unit design study in 16 healthy participants investigated levels of perceived pain from 3 increasing pain provoking challenges, when topical 5% lidocaine dental gel was applied to the oral mucosa with a microneedle patch and a patch with no microneedles, prior to infiltration with local anaesthesia on 2 visits. Pain was assessed by visual analogue scale (VAS) and 4-point verbal rating scale (VRS).

Results

15 participants completed the study. Mean pain scores, lower at buccal sites, increased in both groups across challenges 1−3: Test palatal 5.1, 11.9, 26.8; buccal 0.7, 2.8, 18.3; Control palatal 12.3, 18.7, 39.5; buccal 4.0, 6.9, 30.6. The microneedle patch plus lidocaine significantly lowered VAS pain scores at both sites for all challenges, the biggest mean difference seen palatally after challenge 3 (12.7, p < 0.001). VRS pain scores were also significantly reduced for test compared to control for all 3 challenges (p = 0.014). Buccal scores favoured the microneedle patch, significantly for pain challenge 3 (p = 0.025). No adverse events occurred.

Conclusions

Prior oral application of a microneedle patch combined with 5% topical lidocaine gel reduced the pain experienced from dental infiltration. Microneedle patch use in the dental setting offers the prospect of improving degree and depth of anaesthesia from topically applied anaesthetic gel, without itself causing any pain.

Clinical Significance

Dental injections are associated with fear and anxiety. Application of a microneedle patch, combined with topical anaesthetic, to the oral mucosa prior to delivery of the injection reduces the pain from this dental procedure. This novel technique may allay patients’ apprehension of local anaesthesia and improve quality of life outcomes.

Introduction

Dental treatment is recognised to be associated with pain and anxiety [[1], [2], [3]] and according to the American Dental Association, fear of pain can prevent patients from visiting their dentists [4,5]. To minimise the discomfort derived from invasive dental procedures, patients routinely receive local infiltration anaesthesia so that treatment may be undertaken in a relatively painless manner. However, dental injections per se provoke pain [5,6], and indeed local anaesthetic injection has been demonstrated to be the most anxiety-provoking procedure for some patients [7,8]. Furthermore, because local anaesthetic is provided at a point of maximum apprehension, it can impart a powerful patient stimulus [9] which itself is a source of distress and may contribute to an overall state of dental anxiety. A number of procedural factors have been identified as drivers of pain derived from the delivery oral local infiltration anaesthesia, including the mechanical trauma of needle insertion, rapid distention of the soft tissues by the anaesthetic solution [10] and anatomical location of the injection site.

Topical anaesthetic agents may be applied to the oral mucosa to inure the patient to the discomfort of the subsequent infiltration. However, pain stimuli are blocked only in the superficial mucosal layer, due to poor drug penetration of soft tissues. Used alone, they do not provide sufficient depth of anaesthesia for operative dento-alveolar procedures. However, both direct chemical effects [11] and placebo effects [12,13] produce relief thereby contributing to positive responses from patients undergoing dental treatment. Lidocaine is widely used for its potent topical anaesthetic effect and low toxicity [11].

Despite pre-treatment of the oral mucosa with anaesthetic gels, pain may still be experienced by the patient upon subsequent injection infiltration, impacting on the overall pain experience. Some areas of the oral cavity are difficult to pre-anaesthetise with topical anaesthesia to acceptable levels prior to infiltration injection. Two areas that are particularly difficult to pre-anaesthetise are the mucosa covering the hard palate and the upper anterior labial region. The palatal mucosa is tightly bound to the palatal shelf of the maxilla and drugs have been shown to be poorly absorbed through this highly keratinised tissue [14,15], while the upper anterior labial region has a high density of nerve endings [16]. The oral sites chosen for the study were the mucosa adjacent to the upper labial incisors and upper palatal premolars, representing these sites.

Recently, there has been significant growth in the area of microneedle assisted drug delivery. Advances in micro-fabrication technology have led to the development of several delivery devices, with industry, healthcare professionals and researchers closely following this pioneering field. Microneedles were developed in part to overcome patients’ fear of needles. Microneedle patches create minute channels in the surface of the treated area through which topically applied drugs can pass more readily than by permeation alone. Human skin studies in vitro have shown that a microneedle patch increases permeation of lidocaine and inulin through the skin [17]. The permeation of lidocaine also showed a large reduction in lag time which, in a clinical setting, hastens the onset of local anaesthesia [17].

The microneedles mucosal patch investigated in this study is designed to accelerate and improve the pain preventive outcome of pre-treatment anaesthetic gels by enhanced delivery and uptake, with minimum discomfort to the patient [[18], [19], [20]]. The authors consider that the use of microneedle patches combined with topical anaesthetic gel will result in increased effectiveness in reducing the discomfort associated with delivery of a local anaesthetic injection. Furthermore, the use of the microneedle device may result in an improved quality of life experience for the patient. The aim of this proof of concept study is to compare the level of perceived pain from a lidocaine local infiltration injection, after the oral mucosa was topically treated with lidocaine applied to a mucosal patch either with or without microneedles. The study hypothesis is that pain experience is reduced by topically treating the oral mucosa with lidocaine on a mucosal patch with microneedles, compared to lidocaine delivered on a mucosal patch without microneedles, prior to local infiltration of lidocaine.