Title: Management strategies for phantom limb pain
Funder: Department of Health and Social Care

Abstract: To determine which types of brain and spinal stimulation therapy are likely to be the most promising for treating phantom limb pain. This will be done by undertaking a systematic review to assess the research evidence on treatment effectiveness and safety. A review of the epidemiology and characteristics of patients with PLP and a survey of practicing NHS clinicians will also be undertaken.

Lay abstract: Phantom limb pain (PLP) is defined as persistent painful sensations perceived in the missing portion of an amputated limb. Common reasons for limb amputations include circulatory disorders, severe trauma events, cancer and persistent limb infections. Although not fully understood, it is thought that PLP is caused by cortical changes in the brain i.e. by disorganised brain mapping, with alterations at other levels of the central nervous system, such as the dorsal root ganglion, having a role.1 Also as the nerves heal following amputation the ‘wrong connections’ can be formed such that the sense of touch is perceived as pain, and this in turn can result in central sensitisation.2, 3 Post amputation phenomena can consist of three elements:4 • Phantom limb pain: Painful sensations referred to the absent limb • Phantom limb sensation: Any sensation in the absent limb, except pain • Stump pain: Pain localized in the stump Several surveys have reported on PLP incidence with most rates ranging between around 60-80% of amputees.5 Risk factors include female sex,6, 7 pre-amputation pain,8 and depression.9 Phantom limb pain may be severe in around a third of patients.9, 10 However, the frequency and duration of pain can vary and for many patients the pain may be episodic and not particularly disabling. For example, in one survey half of patients with PLP reported one or fewer episodes of PLP a week, with most episodes lasting between a few minutes and an hour.10 Another survey reported that around a fifth of patients always experience PLP.9 The presence, duration and severity of phantom limb pain are therefore all important determinants of health-related quality of life.11, 12 There appears to be no single best treatment for PLP, although the options seem many and varied. As far back as 1980 a literature review and survey identified 68 different methods of treating PLP, 50 of which were still in use at that time.13 A pharmacological focus on treatment prevails in primary care settings, though amputees with PLP rarely report satisfactory pain management.14 A recent systematic review of pharmacologic interventions found the randomised trial evidence for the medications reviewed to be inconclusive. This was mainly due to the limited outcomes reported and the small trial sample sizes: 14 trials were identified, covering seven different types of treatment, and the total number of participants across all trials was only 269 (sample sizes ranged from 8 to 36).15 Other treatments have also been studied in systematic reviews, although they are often based on even more limited evidence. They include perioperative interventions,16 TENS17, 18 acupuncture,19 mirror therapy,20 and myoelectric and body-powered prostheses.21 This combination of limited evidence together with a lack of guidelines for the management of PLP represents a major challenge for the clinician. Brain, spinal cord and dorsal root ganglion neurostimulation therapies are among some of the more recently investigated treatments for PLP. These neurostimulation therapies are targeted at patients with chronic pain which is refractory to pharmacologic treatment. Deep brain stimulation (DBS) is a neurosurgical procedure in which electrodes are implanted into certain parts of the brain. The amount of stimulation the brain receives is controlled by a pacemaker-like device, called a neurostimulator, which is implanted under the skin in the chest or abdomen. The stimulation may alter the electrical signals in the brain which are responsible for pain. Motor cortex stimulation (MCS) - a therapy which is equally as invasive as DBS - involves placing electrodes on the surface of the brain. Other brain stimulation therapies are non-invasive, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial current stimulation. In spinal cord stimulation (SCS), and dorsal root ganglion (DRG) stimulation, electrodes are implanted near the spinal cord or the DRG and connected to a neurostimulator which is inserted under the skin in the abdomen, chest wall or in the buttock area. This generates an electrical pulse which can provide analgesia through different mechanisms. The National Institute for Health and Care Excellence (NICE) recommends that: • DBS should only be used in patients with refractory chronic pain syndromes that other treatments have failed to control; patient selection should be carried out by a multidisciplinary team specialising in pain management22 • SCS should only be used in adults with chronic pain of neuropathic origin if they continue to experience chronic pain (measuring at least 50 mm on a 0–100 mm visual analogue scale) for at least 6 months despite appropriate conventional medical management and who have had a successful trial of SCS. This is providing that patients are assessed by a multidisciplinary team experienced in chronic pain assessment and management of people with SCS devices23 Although there are other neurosurgical means of relieving phantom limb pain, such as dorsal root entry zone lesioning (DREZ), these surgeries are irreversible and have higher risk profiles. They should only be considered for patients refractory to the reversible neuromodulation therapies outlined above, and are therefore beyond the scope of this review.

Research activity codes: 6.7 PHYSICAL
Health categories: NEUROLOGICAL