Pulsed radiofrequency of the brachial plexus in the treatment of chemotherapy‐induced peripheral neuropathy of the upper limb

Summary

We describe the treatment of chemotherapy‐induced peripheral neuropathy in the upper limb of a patient via ultrasound‐guided pulsed radiofrequency of the brachial plexus. A 54‐year‐old female, who underwent chemotherapy and mastectomy for left‐sided breast cancer, presented to the pain clinic describing continuous and severe shock‐like pain in the posterolateral aspect of the left upper limb, above the elbow. A diagnosis of chemotherapy‐induced peripheral neuropathy was made. Pain management with multi‐modal analgesia was not fully effective and pulsed radiofrequency was offered as an alternative. Ultrasonography of the supraclavicular region was used to identify the brachial plexus, followed by pulsed radiofrequency using an insulated‐tip needle that produced paraesthesia in the affected area. Onset of pain relief occurred one week post‐procedure and lasted approximately 10 weeks. An estimated 80% decrease in pain intensity was reported by the patient. We propose that pulsed radiofrequency can be offered as a pain management alternative in certain presentations of chemotherapy‐induced peripheral neuropathy.

Introduction

Disease and treatment‐related pain is a significant cause of treatment failure in cancer patients. Analgesic utilisation is not always effective and may be limited by adverse effects. Neurodestructive techniques, such as continuous radiofrequency are limited by potential loss of neurological function and de‐afferentation pain 1. The ideal treatment modality must provide effective pain relief with minimal adverse effects and impairment of function. Pulsed radiofrequency (PRF) is minimally invasive, can be carried out as a day case procedure, is well tolerated with minimal side‐effects and can provide significant pain relief with return to normal functioning and clear improvements in the quality of life of patients. We propose that PRF of the brachial plexus may present a non‐neurodestructive pain management technique in the treatment of chemotherapy‐induced peripheral neuropathy (CIPN) of the upper limb.

Report

A 54‐year‐old female presented to the pain clinic with CIPN of the upper limb. Seven months before presentation, the patient was diagnosed with a T2N1–2M0 grade III invasive ductal carcinoma of the left breast. The patient underwent neoadjuvant chemotherapy, having completed four cycles. Three months later the patient presented with generalised neuropathic pain affecting the lower torso and lower limbs, characterised as intermittent, shooting, severe pain that affected walking, with a numerical rating scale score of 10/10 for intensity. The patient was diagnosed with CIPN secondary to paclitaxel. In the following months, much of the generalised lower torso and limb pain resolved, however, a new focus of pain in the lower aspect of the triceps area was persistent and significant, often triggered by gentle to moderate stimuli. The patient was referred to pain medicine for further management.

Pulsed radiofrequency of the brachial plexus was considered as a treatment modality. Procedural consent and discussion of benefits, risks and treatment alternatives was undertaken. The patient was positioned in the right lateral position and intravenous access secured, with the operator and ultrasound screen positioned behind and in front of the patient, respectively. A high‐frequency (5–10 MHz) linear transducer (SonoSite, Micromaxx, Bothwell, WA, USA) in a sterile sheath (CIVCO Medical instruments, Kalona, IA, USA) was used. Following full aseptic preparation, the ultrasound transducer was oriented transversely on the neck, above the clavicle at the clavicular midpoint. The pulsating subclavian artery, parietal pleura and first rib were identified. The brachial plexus presented as a bundle of hypo‐echoic round nodules lateral and superficial to the artery at a depth of 1–2 cm from the skin. Local anaesthetic was administered subcutaneously at the medial edge of the transducer. A 20‐G, 100‐mm radiofrequency needle with a 10‐mm active tip was inserted in plane with the transducer. The needle was advanced in a medial to lateral direction under direct vision until the needle tip was positioned in close proximity to the brachial plexus. Electrostimulation at 50 Hz with a maximal output of 0.5 V allowed identification of the target site by eliciting paraesthesia over the affected area, in the C5 and C6 regions. Once the target had been identified and the needle appropriately sited, PRF was applied with a current of 2 Hz and output of 44 V with 20‐ms‐long active periods and 480‐ms‐long silent periods over 240 s with a single target. The maximal tip temperature was 42°C.

Onset of pain relief was reported at one week after the procedure, lasting approximately 10 weeks. There was a significantly reduced requirement for breakthrough oral opioid analgesia and improved mobility and sleep. The patient presents for PRF of the brachial plexus every three months, self‐reporting an overall 80% improvement in pain intensity. No post‐procedure complications were reported.

Discussion

We describe the use of ultrasound‐guided PRF of the brachial plexus for the treatment of CIPN of the upper limb. Chemotherapy‐induced peripheral neuropathy is a common and serious side‐effect of cancer treatment. It is often dose‐dependent, progressive and its severity can influence cancer treatment, impacting on patient survival and significantly diminishing quality of life. Chemotherapy‐induced peripheral neuropathy is a challenging and complex pain syndrome for which there are no effective preventive measures and limited treatments options at present. Chemotherapy‐induced peripheral neuropathy is reported to affect 20–100% of patients undergoing cancer treatment, depending on the population studied 2. A recent meta‐analysis identified the prevalence of CIPN to be 68.1% in the first month of treatment, 60% at three months and 30% at six months 3.

The pathogenesis of CIPN has not been fully elucidated, but several classes of chemotherapeutic agents, including taxanes, platinum, proteasome inhibitors and vinca‐alkaloids, have been associated with peripheral nerve degeneration or small fibre neuropathy, the generally accepted underlying mechanisms in the development of CIPN. Peripheral or central injury is potentiated by changes in cellular machinery and innate immune responses 4. Focal or multifocal lesions of the peripheral nervous system are the main cause of neuropathic pain affecting patients with CIPN 4. Changes in the properties of primary afferents and the manner in which stimuli are encoded have been identified 4. For instance, changes in receptor expression on nociceptors alter their firing properties by increasing excitability and neurally encoding hypersensitivity. Other processes associated with CIPN include central sensitisation, upregulation in the cellular machinery producing excitability and a decrease in inhibitory mechanisms or upregulation of diverse inflammatory mediators able to induce neuroplasticity by influencing gene transcription. The blood–brain barrier confers a certain degree of protection to the central nervous system, whereas primary afferent neurons and their cell bodies in the dorsal root ganglion are particularly vulnerable to the toxic effects of chemotherapy 4.

Chemotherapy‐induced peripheral neuropathy affects patients’ hands and feet in a ‘glove and stocking’ pattern, producing a variety of sensory disturbances. Chemotherapy‐induced peripheral neuropathy results in abnormal sensory function, pain and potential loss of motor control secondary to nerve damage, similar to other peripheral neuropathies. Pain, numbness or tingling in the hands or feet are the most common symptoms. Symptoms appear weeks or months after commencing chemotherapy, with presentation and onset being drug‐dependent. Chemotherapy‐induced peripheral neuropathy is thought to improve following dose reduction or discontinuation of the causative agent, compromising the efficacy of cancer treatment. Platinum‐derived compounds are known to exacerbate symptoms after the treatment is stopped, a phenomenon known as ‘coasting’ 5. It is not unusual for pain to persist long after the initial injury and it is generally refractory to treatment. The change in pain phenotype reported in this case report has not been previously described, and one can only speculate that the small area of persistent neuropathic pain may represent irreversible neural changes.

Therapeutic options for the prevention or treatment CIPN are limited and tend to be focused on pharmacotherapy. The use of PRF for the treatment of CIPN has previously been described in one case report 6. Yadav et al. presented the case of a 63‐year‐old man with prostate carcinoma treated with docetaxel who developed CIPN affecting the right hand along the distribution of C5 and C6. The patient received PRF of the median and ulnar nerves, with a self‐reported improvement in symptoms within 4–5 h and 80% relief in symptoms. Case reports outlining the use of PRF for chronic pain exist describing its application to numerous peripheral nerves 7. There is, however, a lack of large randomised controlled trials, contributing to a lack of understanding of the underlying pain and treatment mechanisms 8. The first study using PRF stemmed from the finding that radiofrequency applied adjacent to the dorsal root ganglion caused only a transient sensory loss in the targeted dermatome but was associated with a longer duration of pain relief 9. Pulsed radiofrequency works on the principle that brief pulses of high‐voltage electric current with intermittent pauses allow heat to dissipate from the target tissue, therefore, limiting or even avoiding tissue destruction, the temperature not exceeding 42°C. The exact mechanism of action of PRF is unknown, but heat generation and generation of an electric or electromagnetic fields around the electrode tip may induce changes in neuronal cells 9. Strong electromagnetic fields may interfere with the generation of action potentials and ectopic firing, by disrupting the neuronal membranes. It appears to modulate pain perception rather than destroy neural tissue, with increased expression of c‐Fos, a marker for neuronal activity, detected in the dorsal horn 3 h after PRF treatment, disappearing 7 days after treatment and small histological changes in electron microscopic studies in stark contrast with significant histological changes following continuous radiofrequency 9. Application of PRF on nerve fibres has shown small electron microscopic changes in nociceptive unmyelinated C‐fibres and thinly myelinated Aδ fibres which might explain the sparing of tactile sensory input following PRF application. Endogenous opioids and descending noradrenergic and serotoninergic inhibitory pathways, known to be involved in the modulation of neuropathic pain 10, may also be involved in the analgesic effect of PRF. Pulsed radiofrequency has also been found to be a safe and reproducible procedure if pain recurs 1. A recent systematic review on the use of PRF for the treatment of chronic pain reported no neurological complications in over 200 published articles 5.

Chemotherapy‐induced peripheral neuropathy is a common and significant side‐effect of life‐saving therapy in cancer patients for whom there are limited treatment options available at present. Pulsed radiofrequency comes closest to the ideal treatment modality for CIPN in patients with pain distribution confined to a specific nerve or small group of nerves in dermatomal distribution and has yielded promising results in the treatment of multiple chronic pain conditions. This case report highlights the positive impact PRF can have in the prognosis and quality of life of cancer patients developing more unusual presentations of CIPN, justifying the need for further research in the field.