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Case Report

J Acupunct Meridian Stud 2023; 16(5): 183-187

Published online October 31, 2023 https://doi.org/10.51507/j.jams.2023.16.5.183

Copyright © Medical Association of Pharmacopuncture Institute.

Can Electroacupuncture Be Useful in Opioid-Induced Hyperalgesia? A Case Report

Marco Di Carlo* , Antonio D’Addario, Fausto Salaffi

Rheumatology Clinic, “Carlo Urbani” Hospital, Polytechnic University of the Marche, Jesi, Italy

Correspondence to:Marco Di Carlo
Rheumatology Clinic, “Carlo Urbani” Hospital, Polytechnic University of the Marche, Jesi, Italy
E-mail dica.marco@yahoo.it

Received: July 24, 2023; Revised: August 29, 2023; Accepted: October 10, 2023

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Opioid-induced hyperalgesia (OIH) is characterized by a paradoxical increase in pain sensitivity following opioid exposure. Although animal models indicate that electroacupuncture (EA) is effective against pain sensitization, there are no reports of its clinical application in OIH treatment. This case report involves an adult patient with osteomalacia complicated by multiple vertebral fragility fractures. The patient developed OIH following the use of oxycodone to treat severe disabling lower back pain that was refractory to nonsteroidal anti-inflammatory drugs. After hospitalization and treatment with low EA-frequency (2-10 Hz) sessions, the patient exhibited significant pain reduction and functional recovery after the first session, which was accompanied by steady progressive improvement as the treatment continued. This case report illustrates the clinical efficacy of EA in OIH treatment and indicates that EA, which has multiple modes of action on the neurobiology of chronic pain, has potential applications in the management of complex and difficult-to-manage conditions, such as OIH.

Keywords: Opioid-induced hyperalgesia, Electroacupuncture, Chronic noncancer pain, Musculoskeletal pain

INTRODUCTION

Chronic pain exerts a heavy burden on individuals and society, worldwide. In the United States, chronic pain has a prevalence of 20.4%, which is increasing with advancing age [1]. Chronic musculoskeletal pain is a major reason for seeking medical care and is often accompanied by reduced functional capacity, decreased quality of life, and the risks associated with opioid pain therapy [2]. The use of opioids to treat conditions like chronic low back pain has increased in recent years, although such use is not supported by guidelines and clinical trial findings [3]. The use of opioids to manage chronic, noncancer pain is controversial and about one-third of patients discontinue long-term oral opioid therapy because of adverse events [4]. Randomized controlled trials indicate that 71.5% of patients discontinue opioid treatment mainly because of the occurrence of adverse events between the randomization and open-label phases [5].

Opioid therapy has several risks, including opioid-induced hyperalgesia (OIH), which is characterized by nociceptive sensitization because of opioid exposure. However, the neurobiology of OIH is not fully understood and it may involve multiple intricate neuronal mechanisms, including neuroexcitatory factors, long-term potentiation, and descending pain facilitation. Additionally, non-neuronal mechanisms, such as neuroinflammation involving glial cells may also play a role in OIH [6]. Sensitization can occur in different areas of the central nervous system involved in pain processing. Of the several proposed OIH mechanisms, the most plausible one suggests the central glutamatergic system with the excitatory neurotransmitter N-methyl-D-aspartate (NMDA) as the main player [7]. The pathophysiological mechanisms result in an imbalance between pro- and anti-nociceptive pathways.

Clinically, OIH is characterized by the development of diffuse pain that cannot be explained by the extension or worsening of an underlying disease. Such pain is distributed across the body to regions that were previously unaffected and lack a clear qualitative definition. Paradoxically, the pain intensifies with increasing opioid dosage [8]. OIH development does not necessarily result from chronic opioid therapy since it has also been observed in patients who undergo a short course of opioid treatment, such as in perioperative settings [9]. Currently, OIH diagnosis is completely clinical and it lacks defined classification criteria.

OIH management is not standardized and there are several pharmacological approaches. One therapeutic option is the use of NMDA antagonists (mainly ketamine), which have been shown to prevent tolerance. Methadone and dextromethorphan, which exhibit NMDA antagonist activity, and sublingual buprenorphine, which seems to have anti-hyperalgesic effects, may also be used. Another strategy involves rotation between opioids. Because molecules like pregabalin and cyclooxygenase-2 (COX-2) inhibitors might have opioid-sparing effects, they may be effective in modulating OIH. However, OIH treatment is challenging, time-consuming, and often requires the use of nonpharmacological strategies, such as psychotherapy [10].

Acupuncture and electroacupuncture (EA) are complementary techniques of Traditional Chinese Medicine, which have gained significant popularity for the treatment of chronic pain. Acupuncture is efficacious and rarely has side effects. For some patients, such as those who are not unresponsive or intolerant to pharmacologic treatments, acupuncture may be a feasible treatment strategy [11]. Acupuncture has also been shown to be effective in the treatment of conditions with central pain sensitization (nociplastic pain), such as fibromyalgia [12]. For over 30 years, it has been known that EA, in which electrical stimulation is applied to acupuncture needles, is effective against this condition [13].

However, to the best of our knowledge, no studies have investigated the potential of using EA to treat conditions of increased pain sensitivity, such as OIH.

CASE PRESENTATION

This clinical case involved an adult patient in their 30 s, who had been diagnosed with osteomalacia, a metabolic bone disorder, in October 2019 upon observation of a fragility deformity on the L5 vertebra that occurred following minor work trauma. The condition was assessed and diagnosed through consultation between endocrinology and nephrology experts and was associated with the patient’s loss of 25 kg (from 75 kg to 50 kg, equivalent to a body mass index of 19.5 kg/m2) over six months in 2018 following a restrictive, self-imposed diet. At the time of diagnosis, the patient had serum vitamin D levels of 7.7 ng/ml and notably, did not have hypophosphatemic rickets and had normal FGF-23 values. Over the years, the patient was treated with daily cholecalciferol supplements (dosage at admission: 8,750 U/day). At the time when the L5 vertebral fracture was identified, the patient had been treated with etoricoxib (120 mg/day) for 14 days and experienced a slow but progressive reduction in lumbar pain. Consultation with a geneticist ruled out X-linked hereditary rickets.

In September 2022, the patient experienced recurrent lumbar pain and was treated again with etoricoxib (120 mg/day) for 14 days but it was not associated with any benefit. In October 2022, because of persistently progressive lumbar pain worsening, the patient began taking oxycodone (5 mg × 2/day). Magnetic resonance imaging of the lumbar spine revealed fragility deformities on vertebrae T12, L1, L2, L3, L4, and L5 (Fig. 1). As of November 2022, despite the use of opioid therapy, the patient experienced worsening lumbar pain. Moreover, gradually raising the dose of oxycodone to 20 mg × 2/day did not have any benefit and paradoxically, it was associated with worsening pain, which was characterized by the development of severe diffuse pain, marked hyperalgesia, and cutaneous allodynia. The patient started to lose the ability to engage in independent ambulation, common daily activities, and maintain a sitting position, eventually becoming completely dependent on caregivers even to have meals.

Figure 1. Magnetic resonance imaging of the dorsal and the lumbosacral spine. (A) A T2-weighted image reveals the presence of inveterate biconcave lens vertebral deformities on the vertebral bodies of all dorsal and lumbar vertebrae, with an inversion of the physiological lumbar lordosis. (B) A short tau inversion recovery (STIR) image showing details of the lumbar vertebrae and the posterior bulging of the posterior somatic wall of the L5 vertebra.

In February 2023, the patient was admitted for rheumatology inpatient care because of their persistent clinical condition. Based on clinical, laboratory, and instrumental assessment, as well as the paradoxical pain exacerbation with increasing oxycodone dosage and the development of central sensitization, the patient was diagnosed with OIH and started on daily EA treatment sessions as an alternative to oxycodone.

The 10 EA sessions were conducted in the same manner and were performed by MDC, a rheumatologist with decades of experience in acupuncture, who is licensed in Italy to practice EA. EA was done using an SDZ-V electrostimulator, which was equipped with six output channels and generated a bidirectional asymmetrical wave. First, single-use acupuncture needles with guide tubes (size: 0.25 × 25 mm, TeWa - Asiamed) were bilaterally placed at points located in pairs in the lower limb (LV3, GB34), upper limb bilaterally (LI4, LI11), abdomen (CV6, CV12), and head (GV20, EX-HN3 [Yintang]). Next, the pairs of points located on the same limb, abdomen, and head were connected and then electrically stimulated in the same way using a dense-dispersed frequency of 2-10 Hz with a gradual intensity increase to 3 mA in the first 10 minutes. Each session lasted 40 minutes and 400 EA minutes were administered over 14 days (Table 1). No adverse events were observed during the EA treatment.

NRS = numerical rating scale..

&md=tbl&idx=1' data-target="#file-modal"">Table 1

Summary of the main characteristics of inpatient care.

Day of hospitalizationElectroacupunture sessionPharmacological treatmentNRS pain (0-10 range)Activities
Day 1Oxycodone 10 mg + 10 mg10At the end of the first electroacupuncture session, the patient returns to moving the arms in the absence of pain
Day 2Oxycodone 10 mg + 10 mg8At the end of the second acupuncture session, the patient is able to assume the sitting position in bed
Day 3Oxycodone 10 mg + 5 mg7Same activities as the previous day, plus the patient returns to independent feeding from a seated position
Day 4Oxycodone 5 mg + 5 mg6Same activities as the previous day
Day 5Oxycodone 5 mg4Patient resumes upright position with spinal orthosis
Day 6-Oxycodone 5 mg + pregabalin 75 mg4Same activities as the previous day
Day 7-Stop oxycodone, pregabalin 75 mg + 75 mg3Same activities as the previous day
Day 8Pregabalin 75 mg + 75 mg3Resume walking with a spinal orthosis and with the support of a physical therapist
Day 9Pregabalin 75 mg + 150 mg3Same activities as the previous day
Day 10Pregabalin 75 mg + 150 mg3Same activities as the previous day
Day 11-Pregabalin 150 mg + 150 mg2Same activities as the previous day
Day 12Pregabalin 150 mg + 150 mg2Same activities as the previous day
Day 13-Pregabalin 150 mg + 150 mg2Same activities as the previous day
Day 1410°Pregabalin 150 mg + 150 mg2The patient is discharged and transferred to a rehabilitation unit
Two months after discharge-Pregabalin 150 mg + 150 mg, neridronate 100 mg monthly0The patient has regained complete independence in all activities of daily living

NRS = numerical rating scale..



By the end of the first EA session, the patient exhibited significant clinical improvement and regained upper limb mobility without pain. Over the next sessions, the patient continued to exhibit reduced pain and progressively recovered function. By the end of the fifth session, the patient had regained an upright gait after more than two months. This allowed the gradual reduction of oxycodone until it was completely withdrawn, after which the patient was started on pregabalin because the residual pain was mainly characterized by neuropathic symptoms in the lower limbs. The patient was also started on a physio-kinesitherapy rehabilitation course. Two months after discharge, the patient did not experience pain flare-ups, and therefore continued rehabilitation therapy and regained complete independence in all daily activities. The patient was prescribed bone anti-resorptive therapy using neridronate (100 mg per month, off-label therapy) to prevent new vertebral fractures.

DISCUSSION

EA may be effective in the management of complex conditions, such as OIH. In this case report, EA achieved remarkable improvements after one session, thereby allowing the progressive reduction of oxycodone dosage until its complete withdrawal.

Although opioids are important in the management of chronic pain, they cause adverse events in a significant proportion of patients, including those with OIH. A 2020 survey indicated that experts consider oxycodone to be the most frequent cause of OIH. The same study observed considerable heterogeneity in the management of OIH [14]. For patients who benefit from treatment with opioids, the primary objective should be to gradually reduce the dose, before ultimately withdrawing the treatment. However, no treatments have been definitively proven to effectively and safely reduce the need for opioid therapy in the treatment of chronic noncancer pain [15].

Acupuncture has many benefits, including analgesic effects without significant adverse side effects. Several mechanisms are thought to underlie the analgesic effects of acupuncture, including effects on purinergic signaling through the local production of adenosine, effects on mast cell degranulation via processes that involve the transient receptor potential cation channel subfamily V member 2 (TRPV2), and effects on the production of endorphins, serotonin, and norepinephrine at the spinal and supraspinal level. Acupuncture is also thought to suppress the inflammatory effects on COX-2 by inhibiting prostaglandin E2 production, and acting on the hypothalamic–pituitary–adrenal axis by stimulating the release of catecholamines from adrenal glands [16]. The use of electrically-stimulated acupuncture needles has additional benefits in some conditions. For instance, low stimulation frequencies are more effective against neuropathic pain when compared with high frequencies. Stimulation at 10 Hz acts on neuropathic pain through the mechanisms already listed as well as by inhibiting NMDA receptor activation. In contrast, stimulation at 2 Hz inhibits the upregulation of acid-sensing ion channel 3 (ASIC3) in the dorsal root ganglia. EA also reduces the affective dimension of pain [17].

Studies of the effects of EA against OIH have been mainly done using animal models. In rats with remifentanil infusion- and surgical incision-induced hyperalgesia, intraoperative EA at 2 Hz on ST36 inhibits glial cell activation and the upregulation of proinflammatory cytokines and MPAK/ERK signaling in the spine [18]. Another study showed that treating rats with EA at 2 Hz on ST36 + SP6 for five sessions starting on the day before remifentanil infusion is effective in reducing the paw withdrawal threshold in response to mechanical stimulus, and paw withdrawal latency in response to thermal stimulus while decreasing spontaneous opioid-induced neuronal activity [19]. A clinical trial found that an EA session on the day before thyroidectomy significantly reduces the risk of remifentanil-induced post-infusion hyperalgesia [20].

The limitations of this study include that it involves a single clinical case that was treated with an EA protocol that is subject to numerous potential modifications.

In conclusion, this case report provides clinical evidence that EA, a widely applicable therapeutic method with minimal side effects, may be effective against complex and difficult-to-manage conditions, such as OIH. The study’s findings highlight the potential value of EA in the management of musculoskeletal noncancer pain.

FUNDING

The Authors has not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

AUTHORS' CONTRIBUTIONS

Marco Di Carlo - Conceptualization, Methodology, Validation, Writing original draft; Fausto Salaffi - Conceptualization, Resources, Writing – Review & Editing; Antonio D’Addario - Resources, Writing – Review & Editing.

STATEMENT OF ETHICS

This research complied with the guidelines for human studies and was conducted ethically, following the World Medical Association Declaration of Helsinki. Written informed consent was obtained from the patient to publish this case report and any accompanying images.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Fig 1.

Figure 1.Magnetic resonance imaging of the dorsal and the lumbosacral spine. (A) A T2-weighted image reveals the presence of inveterate biconcave lens vertebral deformities on the vertebral bodies of all dorsal and lumbar vertebrae, with an inversion of the physiological lumbar lordosis. (B) A short tau inversion recovery (STIR) image showing details of the lumbar vertebrae and the posterior bulging of the posterior somatic wall of the L5 vertebra.
Journal of Acupuncture and Meridian Studies 2023; 16: 183-187https://doi.org/10.51507/j.jams.2023.16.5.183

Table 1 . Summary of the main characteristics of inpatient care.

Day of hospitalizationElectroacupunture sessionPharmacological treatmentNRS pain (0-10 range)Activities
Day 1Oxycodone 10 mg + 10 mg10At the end of the first electroacupuncture session, the patient returns to moving the arms in the absence of pain
Day 2Oxycodone 10 mg + 10 mg8At the end of the second acupuncture session, the patient is able to assume the sitting position in bed
Day 3Oxycodone 10 mg + 5 mg7Same activities as the previous day, plus the patient returns to independent feeding from a seated position
Day 4Oxycodone 5 mg + 5 mg6Same activities as the previous day
Day 5Oxycodone 5 mg4Patient resumes upright position with spinal orthosis
Day 6-Oxycodone 5 mg + pregabalin 75 mg4Same activities as the previous day
Day 7-Stop oxycodone, pregabalin 75 mg + 75 mg3Same activities as the previous day
Day 8Pregabalin 75 mg + 75 mg3Resume walking with a spinal orthosis and with the support of a physical therapist
Day 9Pregabalin 75 mg + 150 mg3Same activities as the previous day
Day 10Pregabalin 75 mg + 150 mg3Same activities as the previous day
Day 11-Pregabalin 150 mg + 150 mg2Same activities as the previous day
Day 12Pregabalin 150 mg + 150 mg2Same activities as the previous day
Day 13-Pregabalin 150 mg + 150 mg2Same activities as the previous day
Day 1410°Pregabalin 150 mg + 150 mg2The patient is discharged and transferred to a rehabilitation unit
Two months after discharge-Pregabalin 150 mg + 150 mg, neridronate 100 mg monthly0The patient has regained complete independence in all activities of daily living

NRS = numerical rating scale..


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