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Acupuncture for neuropathic pain due to bortezomib in a patient with multiple myeloma
  1. Sibel Mandıroğlu1,
  2. Cemal Çevik2,
  3. Meltem Aylı3
  1. 1Department of Physical Medicine and Rehabilitation, Ankara Physical Medicine and Rehabilitation Training and Research Hospital, Ankara, Turkey
  2. 2Medicine Faculty, Department of Biochemistry, Gazi University, Ankara, Turkey
  3. 3Medicine Faculty, Department of Hematology, Ufuk University, Ankara, Turkey
  1. Correspondence to Sibel Mandıroğlu, Department of Physical Medicine and Rehabilitation, Ankara Physical Medicine and Rehabilitation Training and Research Hospital, 0600 Ankara, Turkey; sblmandir{at}hotmail.com

Abstract

Multiple myeloma (MM) is characterised by an increase in plasma cells, particularly in the bone marrow but also in other organs and systems, and with the abnormal production of immunoglobulin. Bortezomib, a current treatment option, inhibits angiogenesis by proteasome inhibition and is known to be effective in the treatment of MM. Peripheral neuropathy (PN) is a common dose-related side effect of bortezomib in patients with MM. We describe a case of PN due to bortezomib treatment which responded dramatically to acupuncture treatment, enabling his bortezomib treatment to continue. The patient was a 74-year-old man with pain, numbness, tingling and weakness in his hands and feet after 22 days of bortezomib treatment given by the haematology clinic. His neuropathic pain score was 8/10. There were no autonomic symptoms. Electroneurophysiological testing confirmed sensorimotor PN. Acupuncture treatment was planned as his neuropathic pain continued. Acupuncture was administered bilaterally to ST36, SP6 and LI4 15 times (every other day in the first five sessions and then twice a week). The numbness, tingling and pain symptoms substantially decreased after the first two treatments. After the 15th session acupuncture treatment was continued once a month. At the end of the sixth month the neuropathic pain assessment score was 0/10. There was no side effect of acupuncture treatment. Acupuncture seems promising as a complementary medical treatment for neuropathic pain from bortezomib-induced PN. Clinical studies involving more cases and electrophysiological studies are necessary to investigate the effectiveness of acupuncture.

  • Acupuncture

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Introduction

Bortezomib, a proteasome inhibitor, is used for multiple myeloma (MM) and commonly causes peripheral neuropathy (PN). We describe the case history of a patient with PN who responded to acupuncture, enabling his treatment to continue.

Case history

A 74-year-old man with pain, numbness, tingling and weakness in his hands and feet for 4 weeks was referred to our department by the haematology clinic. His medical history included no cause for PN such as metabolic, endocrine, infectious or neurological disease. Bortezomib treatment (1.3 mg/m2 on days 1, 4, 8 and 11 followed by a 10-day rest period) was started by the haematology clinic. His complaints started at the beginning of the second 22-day period. Muscle strength was 5/5 in both proximal and distal muscles of the upper and lower extremities. The Achilles reflex was reduced bilaterally. His neuropathic pain score was 8/10.1 There were no autonomic symptoms. Electroneurophysiological testing confirmed sensorimotor PN. Pregabalin 150 mg daily was started for PN but it was stopped 1 week later because of severe dizziness and sedation.

Acupuncture treatment was offered as the neuropathic pain continued. The patient was informed of the risks (local pain, bruising, minor bleeding and light-headedness). The treatment used a protocol of points selected on the basis of our clinical experience and Traditional Chinese Medicine (TCM) principles. Acupuncture was given 15 times (every other day in the first five treatments and then twice a week) to ST36, SP6 and LI4 bilaterally. Disposable sterilised acupuncture needles (0.25×25 mm, Shangai Kangnian Medical Device Co, China) were used. When the patient felt dull pain or the acupuncture sensation (de qi), the manipulation was stopped and the needle was left in place for 20 min to a depth of 10–20 mm. Numbness, tingling and pain symptoms distinctly decreased after the first two treatments, as shown in figure 1. At the end of the 15th treatment, peripheral neuropathic pain symptoms had completely recovered. After the 2nd, 5th and 15th sessions, neuropathic pain symptoms were 4/10, 3/10 and 0/10, respectively. At the end of the sixth month the neuropathic pain score was 0/10. During the acupuncture treatment bortezomib treatment was continued and it was not necessary to limit the dose. There was no side effect during or after treatment.

Figure 1

Treatment with bortezomib and acupuncture and changes in the neuropathic pain score.

Discussion

MM is characterised by an increase of plasma cells, particularly in bone marrow, in other organs and systems and by the abnormal production of immunoglobulin. MM accounts for 4% of all types of malignancy. The annual incidence rate is approximately five cases per 100 000.2 Recurrent bacterial infections, anaemia, osteolytic bone lesions, widespread pain, renal failure and thromboembolism may occur in the course of the disease. Thalidomide, bortezomib, lenalidomid and a combination of these drugs with dexamethasone are the preferred treatment options.3 ,4 Bortezomib, which inhibits angiogenesis with proteasome inhibition, is effective. Its most frequent side effects are weakness, nausea, diarrhoea, constipation, anorexia, thrombocytopenia and leucopenia, and PN is a common and severe dose-limiting side effect.5 The symptoms due to PN may negatively affect quality of life for a long time, even if the drug is stopped.6 We describe a case of PN due to bortezomib treatment which responded dramatically to acupuncture.

PN can occur in patients with MM due to an autoimmune mechanism such as plasma cell dyscrasia, direct compression of the medial and radial nerves, cryoglobulinaemia and amyloidosis as a result of light chain deposits. Thalidomide and bortezomib, which are used in the treatment of MM, also cause PN, affecting the quality of life negatively.3 ,4 The pathological mechanism of PN caused by bortezomib is incompletely understood, although it is suggested that autoimmune and inflammatory factors trigger changes at the molecular level.5 Bortezomib-induced PN (BIPN) is known to be associated with the cumulative dose of the drug. The symptoms generally occur after 3 or 4 weeks.6 BIPN can be very painful or not painful. Painful BIPN is often seen at the end of the first three treatments. The regression of symptoms can take a long time after cessation of drug.7 Sensorial-axonal type of PN occurs electrophysiologically. Spontaneous pain, paraesthesiae (numbness, tingling), hyperalgesia, allodynia and decrease of physical activity can be seen clinically.8 Narcotic analgesics, antidepressants and anticonvulsants have a limited effect on the symptoms of BIPN, and adverse effects such as dizziness, sedation, xerostomia and constipation limit the use of these drugs.9–11 BIPN can be diagnosed easily from the history and physical examination.

Electrophysiological studies on the analgesic effects of acupuncture are mostly related to nociceptive pain, but there are studies in recent years suggesting that acupuncture is effective in PN pain from diabetes and chemotherapeutic agents.12–15 Schroeder et al16 suggest that acupuncture has a positive effect on chemotherapy-induced PN as measured by objective electrophysiological parameters. Litscher et al17 showed that acupuncture may increase the blood flow in the lower extremities, which increases blood flow to the vasa nervorum and dependent capillary beds supplying the neurons and may contribute to nerve repair with measurable improvement of axons or myelin sheaths.

The analgesic effect of acupuncture has been shown in animal studies, and stimulating nerves which innervate muscles causes release of neurotransmitters such as endorphin and enkephalin which modulate spinal cord, midbrain and hypothalomo-hypophyseal pathways.18 These changes activate descending pain pathways and modulate the limbic system.19 The effect of acupuncture on BIPN can be explained by similar mechanisms, including opioid peptide release and reduction of proinflammatory cytokines.20

In a previous similar case, Bao et al21 administered acupuncture to two cases with MM and BIPN and observed regression of symptoms such as numbness, tingling and burning due to PN. In another series of acupuncture for five cases with MM and BIPN, Bao et al22 detected marked relief of numbness, tingling and pain in all cases. In four of the five cases there was no recurrence of neuropathic pain symptoms during the 6-month follow-up period.

The spontaneous recovery of BIPN after reducing therapy limits the evidence of case reports for the effectiveness of acupuncture. BIPN can seriously affect daily activities and recovery can occur after months. However, the 50% decrease in the neuropathic pain score after the first acupuncture treatment supports the effectiveness of acupuncture.

This case suggests that acupuncture might be an effective and safe complementary medical method for neuropathic pain from BIPN. Clinical studies with more cases and electrophysiological assessment are necessary to investigate the effectiveness of acupuncture.

References

View Abstract

Footnotes

  • Contributors All authors assisted in the direct management of the patient. SM drafted the manuscript and reviewed the literature. All authors read and approved the final manuscript.

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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