Lidocaine iontophoresis mediates analgesia in lateral epicondylalgia treatment

152 Physiotherapy Research International

Physiother. Res. Int. 11(3) 152–160 (2006) Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/pri.338

Lidocaine iontophoresis  mediates analgesia in lateral epicondylalgia treatment THOMAS E YARROBINO Optimum Physical Therapy, Smithtown, New York, USA JOHN H KALBFLEISCH, KENNETH E FERSLEW and PETER C PANUS East Tennessee State University, Johnson City, Tennessee, USA ABSTRACT  Background and Purpose.  Iontophoresis transcutaneously delivers antiinflammatory and analgesic drugs for the treatment of musculoskeletal dysfunction. Lidocaine is a local anaesthetic with analgesic but no anti-inflammatory properties. The purpose of this investigation was to examine the clinical use of lidocaine iontophoresis-mediated analgesia in a larger treatment algorithm for five patients with lateral humeral epicondyl­ algia.  Method.  The investigation was a case series design of five subjects, aged 52 (±6) years, with epicondylalgia of 12–393 days’ duration. At each treatment session, the patients received cryotherapy, cross-fibre massage and passive stretch. Between sessions analgesia was provided by an 80 mA-min low-current, long-duration lidocaine iontophoresis (LI) over a 24-hour period. Patients were treated on an every-other-day basis for a total of three treatment sessions. Clinical improvements were determined by triplicate measurements of dolorimetric force over the affected epicondyle prior to treatment 1 (baseline), prior to sessions 2 and 3, and one week following the last session.  Results.  Patients demonstrated an increasing tolerance to dolorimetric force application prior to the next session. The force values prior to session 2 (3.1 (±1.1) Newton (N)) and one week following the third session (3.4 (±0.5) N) were significantly improved from the baseline values (2.1 (±0.9) N).  Conclusions.  Pain associated with lateral epicondylalgia decreased, and function improved in all patients at the final measurement. One patient returned during the 90-day follow-up period to seek additional medical attention. This investigation documents the potential for analgesia provided by LI in the rehabilitation process of musculoskeletal dysfunction. Copyright © 2006 John Wiley & Sons, Ltd. Key words:  drug-delivery, transcutaneous

 Copyright © 2006 John Wiley & Sons, Ltd

iontophoresis,

lateral

epicondylalgia,

lidocaine,

Physiother. Res. Int. 11: 152–160 (2006) DOI: 10.1002/pri

Lidocaine iontophoresis 153 INTRODUCTION

ized anaesthesia provided by lidocaine iontophoresis occurred at systemic drug Iontophoresis is the use of physiologically concentrations equivalent to those associacceptable electrical current to enhance the ated with cutaneous infiltration for localized transcutaneous permeation of drugs (Panus, anaesthesia (Ashburn et al., 1997; Kearns 2006). Initial clinical investigations utilized et al., 2003; Baselt, 2004). Long-duration both sodium-dexamethasone-phosphate and passive lidocaine application also provides lidocaine-hydrochloride for iontophoresis localized analgesia, and was clinically effiin the treatment of pain and functional cacious at improving function in various limitations in musculoskeletal dysfunction neuropathic and musculoskeletal pathophys(Bertolucci, 1982; Harris, 1982). Pharmaco- iologies (Argoff et al., 2004; Burch et al., kinetic data from experimental iontophore- 2004). These lidocaine patches were worn sis of these drugs (Glass et al., 1980) for 18–24 hours per day for several days concluded that the decrease in pain and (Gammaitoni et al., 2003). Again, pharmaimproved function were the result of the ion- cokinetics documented that localized analtophoresis of dexamethasone-phosphate. gesic effects of lidocaine occurred when However, lidocaine iontophoresis also systemic drug concentrations were equivahas clinical applications for anaesthesia and lent to those associated with cutaneous infilanalgesia. Lidocaine is a local anaesthetic tration for localized anaesthesia (Gammaitoni with analgesic properties, used clinically to et al., 2003; Baselt, 2004). decrease local tissue sensation at the treatThe potential value of long-duration pasment site without the loss of consciousness, sively applied lidocaine in providing analgeand as an anti-arrhythmic medication in sia for musculoskeletal and neuropathic cardiac dysfunction (Hume and Grant, 2004; pathophysiologies has led to the clinical White and Katzung, 2004). The proposed application of LI for similar conditions. mechanism of action in both of these clinical There is no literature documenting that LI applications is inhibition of sodium chan- would parallel the clinical efficacy of passive nels. Systemic plasma concentrations of lidocaine application in these pathophysiololidocaine following cutaneous infiltration gies. The purpose of this paper is to present for local anaesthesia peak at 0.42 mg/L, and the outcomes of five patients with lateral plasma concentrations reach 2–5 mg/L when epicondylalgia whose treatment included LI the drug is used as an anti-arrhythmic agent analgesia as part of a larger treatment algo(Baselt, 2004). Signs of toxicity may appear rithm, and to discuss the evidence-based when systemic plasma concentrations exceed clinical use of LI in the treatment of muscu8 mg/L (Baselt, 2004). loskeletal and neuropathic dysfunctions. In solution, lidocaine-hydrochloride will dissociate into positively charged lidocaine METHODS and negatively charged chloride. Anodal lidocaine iontophoresis has been used in the Study design clinic for short-term cutaneous anaesthesia (Kennard and Whitaker, 1992; Sherwin This investigation used a case series design. et al., 2003). The iontophoresis was applied The East Tennessee State University institu≤30 minutes and at a high current of 1–4 mA. tional review board for human research Pharmacokinetics document that the local- approved the research.  Copyright © 2006 John Wiley & Sons, Ltd

Physiother. Res. Int. 11: 152–160 (2006) DOI: 10.1002/pri

154 Yarrobino et al. Subjects Five patients with lateral humeral epicondylalgia all received the same usual standard of care at the clinic. LI was included as a component of that treatment algorithm. None of the patients had a documented previous medical history of arrhythmias, were taking prescribed drugs to prevent arrhythmias, or were currently taking opiate or non-steroidal anti-inflammatory analgesics (traditional non-steroidal anti-inflammatory drugs or cyclo-oxygenase-2 inhibitors) at the time of the treatment. Dolorimetry assessment Dolorimetry measurements were similar to those previously described (Benjamin et al., 1999). The dolorimeter used a 0–20 lb dynamometer (Kom Kare, 1002 North University Blvd, Middletown, OH 45042, USA), modified with the circular rubber tip of surface area 1.77 cm2 to buffer the metal plunger contact on the skin. Each patient was palpated before each treatment session to locate the region of greatest pain at the involved lateral epicondyle for dolorimeter placement. Vertical force was slowly increased until the patient stated that they experienced pain, and the value was recorded in pounds (lb). This protocol was repeated in triplicate, with a 15-second rest interval between replications. Dolorimetry measurements were taken before each of the treatment sessions, and one week after the third session. Procedure

cryotherapy, cross-fibre massage and passive stretch. At the beginning of the treatment session, a cold compress was placed over the lateral epicondyle region for 12 minutes. This was followed by a cross-fibre massage for two minutes to the common extensor tendon. The subject was then instructed to hold a static stretch to the common extensor tendon for one minute. LI was then applied after the stretch. The Iomed Companion 80 (Iomed Inc., 2441 South 3850 West, Salt Lake City, UT 84120, USA) is a constant voltage iontophoretic delivery system preprogrammed to deliver an approximate 80 mA-min dosage. The application sur- face area is 6.45 cm2, with 1.1 mL electrode reservoirs. The iontophoretic system is a self-adhesive disposable design with an approximately 24-hour treatment period. A total of 1.1 mL of 4% (40 mg/mL) lidocaine solution (Roxane Laboratories Inc, 1809 Wilson Rd, Columbus, OH 43326, USA) was applied to the anode, and 1.1 mL of saline was applied to the cathode. If required to improve contact of the iontophoretic system, the treatment area was clipped of hair with scissors. The iontophoretic system was applied evenly with the anode centred over the lateral epicondyle, and the cathode on the forearm. Patients were instructed to wear the iontophoretic system for 24 hours, cautioned not to press on the iontophoretic system and to cover the system with a plastic covering if showering. If the patient used a cock-up splint or aircast strap, they were asked to wear them on non-treatment days. Patients were provided the same treatment protocol on an every-other-day basis, not including weekends, for a total of three sessions.

The treatment protocol for lateral humeral epicondylalgia in these patients was similar Statistical analysis to our previously published treatment algorithm (Benjamin et al., 1999). At each Dolorimetric force measurements were treatment session, the patients received converted to metric units (N = 0.2247 lb).  Copyright © 2006 John Wiley & Sons, Ltd

Physiother. Res. Int. 11: 152–160 (2006) DOI: 10.1002/pri

Lidocaine iontophoresis 155 At each timepoint, measurements were summarized by the mean and standard deviation (SD) of five patient mean values; each patient mean computed from triplicate dolorimetric recordings. Mean for time periods were compared by analysis of variance (ANOVA) and the mean of treatment session 1 (baseline) was compared to the mean of treatment sessions 2 and 3, and at one week after the third session by Dunnett’s procedure. Probability levels of ≤0.05 were used for statistical significance. RESULTS The patient demographics are shown in Table 1. Trends for individual patients (Figure 1) and summary data at each time point (Table 2) are provided. Analysis indicated a significant treatment session effect (Table 3, p = 0.007), which is due mainly to differences between the baseline score and the scores of the following three study timepoints. Statistical effects among the latter three timepoints (sessions 2 and 3, and one week afterwards) were not detected. The significant interaction effect (Subject × Session, p = 0.002) is illustrated by the varying subject response patterns across the treatment sessions (Figure 1). In general, the data reveal an increasing tolerance of force application as the study progresses. Post-treatment, levels for all patients improved and demonstrated the

highest effective mean change from baseline. The increased dolorimetry force levels would suggest decreased sensitivity over the affected epicondyle. Patient interviews during the treatment sessions and at the one-week follow-up showed decreased complaints of pain and improved function. These positive subjective changes accompanied the decreased sensitivity of the treated epicondyles. None of the patients reported anaesthesia at the treatment site during LI. There were no iontophoresis-related adverse events reported by the patients during this period or at the one-week follow-up. One patient returned 88

FIGURE 1:  Changes of dolorimetric force measurements (Newtons) in patients with lateral humeral epicondylalgia immediately before each of the three treatment sessions and one week after the third session. Figure demonstrates individual patient responses (•) and group average responses (—).

TABLE 1:  Demographics for the patients with lateral humeral epicondylalgia PT

Gender

Age (years)

Extremity

Duration of pain (days)

Cause of injury

1 2 3 4 5

F M M M M

47 51 49 62 51

R R R L L

49 393 125 108 12

Insidious Repetitive lifting job Not stated Golfing Repetitive lifting job

PT = patient; M = male; F = female; R = right; L = left.

 Copyright © 2006 John Wiley & Sons, Ltd

Physiother. Res. Int. 11: 152–160 (2006) DOI: 10.1002/pri

156 Yarrobino et al. TABLE 2:  Changes in dolorimetry force measurements (Newtons) in five patients with lateral humeral epicondylalgia

Measurement period 1

Mean (±SD) 2.120 (±0.861) P-level*

2

3

One week post-session

3.093 (±1.117)