Authors: Gulseren Akyuz, MD Ozge Kenis, MD Pain Affiliations: From the Department of Physical Medicine and Rehabilitation (GA, OK) and Department of Algology (GA), Marmara University, School of Medicine, Istanbul, Turkey. Correspondence: All correspondence and requests for reprints should be addressed to: Fevzi Cakmak Mah, Mimar Sinan Cad, Marmara Üniversitesi, Hastanesi No: 41, 34899 Üst Kaynarca, Istanbul, Turkey. LITERATURE REVIEW Physical Therapy Modalities and Rehabilitation Techniques in the Management of Neuropathic Pain Disclosures: ABSTRACT Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. Akyuz G, Kenis O: Physical therapy modalities and rehabilitation techniques in the management of neuropathic pain. Am J Phys Med Rehabil 2014;93:253Y259. 0894-9115/14/9303-0253 American Journal of Physical Medicine & Rehabilitation Copyright * 2013 by Lippincott Williams & Wilkins DOI: 10.1097/PHM.0000000000000037 Neuropathic pain is an important problem because of its complex natural history, unclear etiology, and poor response to standard physical therapy agents. It causes severe disability unrelated to its etiology. The primary goals of the management of neuropathic pain are to detect the underlying cause, to define the differential diagnosis and eliminate risk factors, and to reduce the pain. The physician should also know the functional and psychologic conditions of the patient. Therefore, a multimodal management plan in neuropathic pain is essential. This review aimed to reflect a diverse point of view about various physical therapy modalities and rehabilitation techniques. Physical therapy modalities and rehabilitation techniques are important options and must be considered when pharmacotherapy alone is not sufficient. In addition, psychosocial support and cognitive behavioral therapy could also be taken into consideration. It has been suggested that the importance of pain rehabilitation techniques will increase in time and these will take a larger part in the management of neuropathic pain. However, it is now early to comment on these methods because of the lack of adequate publications. Key Words: Management www.ajpmr.com Physical Therapy Modalities, Rehabilitation Techniques, Neuropathic Pain, Management of Neuropathic Pain Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 253 N europathic pain can be defined as pain caused by a lesion or a disease of the somatosensory system.1 It can last a long time and increase gradually, leading to serious disability.2 There are many causes of neuropathic pain, which can be classified according to etiology, localization, or anatomy3 (Table 1). As it is well known, neuropathic pain affects the quality-oflife, decreases physical functionality and activities of daily living, and creates severe difficulties in both professional and personal life. It also causes psychologic problems resulting in sleep disorders, anxiety, and depression. There are also some consequences associated with neuropathic pain, such as deterioration in sexual and marital life and family relationships, that lead to social isolation. These problems increase over time, which, in turn, worsen the pain and cause a vicious circle. Neuropathic pain also has a bad impact on the economy because of considerable loss in working days, disability, and increasing healthcare costs.4 Therefore, neuropathic pain must be approached as a big health problem that has to be resolved as quickly and as efficiently as possible. At the beginning of the treatment of neuropathic pain, pain must be defined and goals of treatment must be established. Comorbidities and psychosocial factors, which can be related to pain, should also be evaluated. It is important to determine an underlying cause of neuropathic pain and the functional status of the patient. As a result, a target-based treatment algorithm must be planned and executed step by step. In a well designed management plan of neuropathic pain, pharmacotherapy, physical therapy modalities, rehabilitation techniques, cognitive behavioral therapy/psychotherapy/relaxation therapy methods, and invasive procedures should all be taken into consideration. In pharmacologic treatment, the European Federation of Neurological Societies guideline suggests the use of antiepileptic drugs such as gabapentin and pregabalin and antidepressants such as duloxetine, venlafaxine, and tricyclic antidepressants as first-line drugs.5 Namaka et al.6 also advocate topical analgesics such as capsaicin and lidocaine as an addition to first-line drugs. As a second-line drug, weak opioids such as tramadol are preferred. Physical Therapy Modalities Physical therapy modalities include pain modulators such as hot and cold packs, ultrasound, short-wave diathermy, low-frequency currents (trancutaneous electrical nerve stimulation [TENS], diadynamic currents, and interferential currents), high-voltage galvanic stimulation, laser, and neurostimulation techniques such as deep brain stimulation and transcranial magnetic stimulation (Table 2). Hot and cold applications could also be used together as in contrast baths. Sometimes, fluidotherapy or whirlpool could also be chosen for this purpose. All these superficial heat agents should not be applied in high degrees because of possible risk for increase in pain. Although TABLE 1 Main causes of neuropathic pain Central Causes of Neuropathic Pain Peripheral Causes of Neuropathic Pain Compression myelopathy caused by spinal stenosis HIV myelopathy Multiple sclerosis pain Pain of Parkinson disease Myelopathy after ischemia or radiation Pain after stroke Pain caused by posttraumatic medulla spinalis injury Syringomyelia Acute and chronic inflammatory demyelinating polyradiculoneuropathy Alcohol-induced polyneuropathy Chemotherapy-induced polyneuropathy CRPS Compression neuropathies HIV sensory neuropathy Idiopathic sensory neuropathy Tumor infiltration of nerves Neuropathy of nutrition deficiency Diabetic neuropathy Phantom pain of extremity Postherpetic neuralgia Plexopathy after radiation Radiculopathy (cervical, thoracic, lumbosacral) Neuropathy caused by toxic exposure Trigeminal neuralgia Posttraumatic neuralgia Peripheral nerve injury Bogduk and Merskey.2 HIV, human immunodeficiency virus. 254 Akyuz and Kenis Am. J. Phys. Med. Rehabil. & Vol. 93, No. 3, March 2014 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. TABLE 2 Physical therapy modalities used in neuropathic pain and their main indications Physical Therapy Modalities Heat and cold applications Fluidotherapy Whirlpool Massage TENS Indications Chronic pain SCI SCI Acute, subacute, and chronic postoperative pain Radiculopathy Diabetic neuropathy Transcranial magnetic SCI stimulation Stroke Brachial plexus lesions Trigeminal nerve lesions CES SCI these modalities have been found effective in chronic pain, there is a definite need of studies that support their effectiveness.7 In general, deep heating agents such as ultrasound and short-wave diathermy should not be recommended in the treatment of neuropathic pain. Although these are helpful especially in the improvement of joint contractures and adhesions by increasing the flexibility of collagen fibers and circulation of connective tissues, these might increase neuropathic pain. Massage is also not proven to be effective in neuropathic pain. In acquired immunodeficiency syndrome patients with neuropathic pain, massage therapy has been applied, but there have been no significant changes on pain intensity.8 There is another study that has investigated the role of massage in spinal cord injury (SCI) patients. Although the study claims that massage seems as one of the effective therapies, it does not specify the type of pain.9 Pieber et al.10 have evaluated the effectiveness of different types of electrotherapy. In that review, the studies that involve the largest groups are usually about TENS in addition to other studies with smaller groups that investigate other techniques such as electromagnetic neural stimulation, pulse and static electromagnetic field application, and high-frequency external muscle stimulation. Possible action mechanisms of electrotherapy have been suggested to be local release of neurotransmitters such as serotonin, raised levels of adenosine triphosphate, release of endorphins, and its own anti-inflammatory effects. Dorsal column activation is another mechanism of electrotherapy. It has been shown that lowfrequency currents increase microcirculation and www.ajpmr.com endoneural blood flow. Electrotherapy could also be effective in correcting the disrupted microcirculation in diabetic polyneuropathy and increase oxidative capacity in muscles via metabolic effect. TENS is one of the best modalities that has been shown to be effective in the treatment of neuropathic pain.11 It has been suggested that TENS activates central mechanisms to provide analgesia. Lowfrequency TENS activates K-opioid receptors in the spinal cord and the brainstem, whereas highfrequency TENS produces its effect via C-opioid receptors. The European Federation of Neurological Societies has published a guideline about the use of therapeutic electrical neurostimulation techniques in chronic neuropathic pain.12 The guideline suggests that the effectiveness of TENS depends on the intensity, frequency, duration, and number of sessions. McQuay et al.13 have published a review about the use of TENS in outpatient conditions for nonspecific chronic pain, which suggests that it is effective in chronic nonspecific pain. Randomized controlled trials that were done by Akyuz et al.14 and Guven et al.15 have also shown the efficacy of TENS in fibromyalgia and postoperative pain. In another study investigating the effect of different TENS applications compared with placebo in 11 radiculopathy patients, TENS has been found effective when compared with placebo.16 Cheing and Luk17 found that highfrequency TENS is significantly effective in reducing the hypersensitivity of the hand. In a randomized controlled trial, low-frequency TENS (G2 Hz) and placebo (4 wks, 30 mins daily) have been compared in patients with diabetic neuropathy. Eighty-three percent of the patients in the treatment group have reported sudden decrease in pain and discomfort.18 Forst et al.19 compared the effects of low-frequency TENS and placebo TENS in a randomized controlled trial and showed that visual analog scale (VAS) and NTSS-6 [Neuropathy Total Symptom Score 6] scores have improved significantly in the treatment group. Acupuncture-type TENS (0Y4 Hz) has been found more acceptable when compared with high-frequency TENS because of increased sensation of numbness, but there is no sufficient evidence.12 As a result, TENS can be effective in the treatment of painful peripheral neuropathy. However, inadequate trial designs and short follow-up durations still prevent the authors to comment on TENS objectively. There is need for more randomized, double-blind studies done with larger patient groups. Laser is another physical therapy agent that can be used in the treatment of neuropathic pain. Very low level of laser has been shown effective in patients with neuropathic pain.20 When very low laser therapy Management of Neuropathic Pain Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 255 is applied, it decreases pain and inflammation, in addition to improving functional ability. In rats, low-level laser therapy decreases the level of hypoxia-induced factor 1->, which is an important modulator in inflammation and released after chronic constrictive nerve injury.21 There are other studies that study the effectiveness of laser therapy in neuropathic pain that are also done in rats.22,23 In humans, the effectiveness of helium-neon laser therapy was studied. In a study, it has been shown to induce a 55.3% pain decrease in 36 patients who have been experiencing postherpetic neuralgia.24 Another study that had investigated the effects of helium-neon therapy in 18 postherpetic neuralgia patients found a 44% decrease in pain after 50 sessions of therapy.25 A study also points out a good improvement rate of 60% among postherpetic neuralgia patients who have received low-level laser therapy.26 Still, there is not enough evidence to suggest that it is effective in neuropathic pain. Neurostimulation techniques including transcranial magnetic stimulation and cortical electrical stimulation (CES), spinal cord stimulation, and deep brain stimulation have also been found effective in the treatment of neuropathic pain. In the Cochrane review published in 2011, the effects of repetetive transcranial magnetic stimulation (rTMS) and CES over chronic pain such as neuropathic pain, chronic neck and back pain, osteoarthritis, and fibromyalgia were investigated and found to be not significantly different from those of sham stimulation.27 Lefaucheur et al.28 investigated 60 patients with chronic unilateral neuropathic pain caused by one of the following lesions: thalamic stroke, brainstem stroke, spinal cord lesion, brachial plexus lesion, or trigeminal nerve lesion. Transcranial magnetic stimulation was applied 3 wks apart in two sessions, with a 10-Hz frequency. The patients’ pain level was assessed with the VAS. Thirtynine patients reported a decrease in pain depending on the localization and the cause of pain. Capel et al.29 have done a randomized, placebo- controlled study and evaluated the effects of CES in 27 patients with SCI. Fourteen patients received CES for 2 hrs, two times a day, for 4 days, whereas 13 patients received placebo CES at the same protocol. Pain was assessed with the VAS and the McGill Pain Questionnaire, but other functional-related factors such as depression, anxiety, and analgesic use were also monitored. In this study, patients receiving CES reported decrease in pain intensity and the need for pain medication. However, in both groups, there was no significant functional improvement. Another randomized placebo-controlled trial was done by Tan et al.30 in 38 SCI patients who had chronic neuropathic and musculoskeletal pain for at least 3 mos. CES was 256 Akyuz and Kenis applied to 18 patients for 21 days at a maximum of 100 KA. Twenty patients received placebo. The patients in the CES group reported a decrease in pain intensity immediately, and this decrease did not change over time. However, there was no statistically significant difference between the groups. Although there are many studies that have been done about neurostimulation techniques, these are far from giving a definite result with patient groups being so small and mainly including patients with SCI. There is need for further research in the efficacy of neurostimulation techniques in other causes of neuropathic pain. Rehabilitation Techniques Rehabilitation is also an essential part of treatment in neuropathic pain (Table 3). The main aims of rehabilitation are to decrease pain and amount of medication, improve dysfunction, increase quality-of-life and physical activity, and bring the patient’s self-esteem back. Although one of the major parts of rehabilitation methods is therapeutic exercise, there is no sufficient evidence supporting this idea in the treatment of neuralgia. Many kinds of therapeutic exercises have already been used in the rehabilitation program such as conditioning, strengthening, and stretching exercises. Kuphal et al.31 developed a neuropathic pain model in rodents by making a peripheral nerve injury in their sciatic nerve and showed that 25 days of exercises in water and swimming decreased pain. In this study, extended exercises in water and swimming have been shown to reduce edema, inflammation, and peripheral neuropathic pain in this animal model. The purposes of psychotherapy are to treat emotional, behavioral, or mental dysfunction; remove negative symptoms such as anxiety or depression; modify or reverse problem behaviors; help the individual cope with situational crises such as bereavement, pain, or prolonged medical illnesses; TABLE 3 Rehabilitation techniques used in neuropathic pain and their indications Rehabilitation Techniques Cognitive behavioral therapy Relaxation techniques Acupuncture Mirror therapy GMI Visual illusion Indications Elderly patients with neuropathic pain Chronic pain SCI Phantom pain CRPS Stroke Stroke SCI Am. J. Phys. Med. Rehabil. & Vol. 93, No. 3, March 2014 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. improve the individual’s relationships; manage conflict; and enhance positive personality growth and development. In a study done by Turk et al.,32 psychosocial treatment approaches, cognitive behavioral methods, and the prevalence of emotional stress have been investigated and the effectiveness of psychologic treatment has been evaluated. It showed that psychosocial support increases the efficacy of treatment. Psychosocial management programs should be added to standard therapy regimens in neuropathic pain. The primary goal of cognitive behavioral therapy is to find and correct the negative, irregular, and irrational thoughts that have become automatic by being repeated. Automatic thoughts come into mind when a person experiences a new thing or recalls a past event. In persons with depression and anxiety, negative automatic thoughts are experienced more often. The use of cognitive behavioral therapy is gradually increasing in neuropathic pain. Especially in elderly patients, relaxation techniques, the accurate planning of activity-rest cycles, cognitive reconstruction, meditation, and distraction techniques can be used.33 Relaxation therapy is a process that focuses on using a combination of breathing and muscle relaxation to deal with stress. Relaxation therapy is useful in decreasing anxiety, autonomic hyperactivity, and muscle tension. Their adaptability for use at home and in other environments is another advantage. Progressive muscle relaxation, imaging, controlled breathing, or listening to relaxation tapes has been started to be used in chronic pain although there is still not enough evidence for its effects on neuropathic pain. There is no clear evidence about the effectiveness of acupuncture on neuropathic pain as well. Cha et al.34 investigated the healing effect of acupuncture in neuropathic pain induced in rats and found out that acupuncture is effective in the treatment of neuropathic pain. Rapson et al.35 applied electroacupuncture to 36 SCI patients with neuropathic pain five times a week for 30 mins and suggested that pain intensity decreased after therapy and that there were no side effects. It is now well known that in various cases of chronic pain such as phantom limb pain and chronic low back pain, the organization of the primary somatosensory cortex changes.36 Mirror therapy and graded motor imagery (GMI) are rehabilitation procedures developed with the hope of correcting this disorganization and thus decreasing the pain. Mirror therapy is one of the rehabilitation methods that is widely used in patients with neuropathic pain. In mirror therapy, the patient puts his/her affected limb into a mirror box and keeps the unaffected side in front of the mirror. The unaffected limb in front of the mirror makes simple movements, and the pawww.ajpmr.com tient imagines doing the same movements with the affected limb. Although the pain may increase at the time, the patient tries to tolerate it. This method has been used in patients with stroke, phantom limb pain, and complex regional pain syndrome (CRPS) and found effective in increasing upper extremity functionality.37 During these studies, decrease in pain accompanied functional improvement. Therefore, studies have been designed to further investigate the effect of mirror therapy in neuropathic pain. McCabe et al.38 did a study on eight patients with CRPS type 1, in whom mirror therapy has been applied. They found that it was effective in decreasing pain in the patients who had the condition for less than 8 wks, whereas it was effective in reducing only stiffness in the patients who had this condition for less than a year. However, in cases of CRPS lasting more than 1 yr, it was not effective. In another randomized controlled trial with 22 patients with amputated limbs, 4 wks of mirror therapy were compared with covered mirror therapy (sham mirror therapy) and mental imagery.39 There was a significant decrease in the VAS in the mirror therapy group compared with the others. In a similarly designed study done by Caccio,40 24 patients with stroke were given 4 wks of mirror therapy, sham mirror therapy, and mental imagery. There was also a significant difference only with mirror therapy. GMI is a comprehensive program designed to sequentially activate cortical motor networks and improve cortical organization in three steps: laterality training, imagined hand movements, and mirror visual feedback.41 There is one randomized controlled trial done by Moseley42 in CRPS type 1 patients who received GMI for 6 wks, 2 wks in each step, and compared with conventional physical therapy and medication. The study was done with 51 patients and showed significant decrease in pain in the GMI group compared with other groups. However, a study by Johnson et al.43 failed to show the effectiveness of GMI in CRPS patients. Instead, in this study, one patient even reported an increase in pain intensity. Although mirror therapy and GMI are promising new ways of rehabilitation in the treatment of neuropathic pain, there is definitely a need for more evidence. Moseley44 has done another interesting study that uses visual feedback through creating a visual illusion and compares its effectiveness with other experimental therapies such as guided imagery and watching another person walking. This study is also based on the principle of disorganization of the primary somatosensory cortex. In this study, five paraplegic patients with SCI were taken, and first, the three different therapies mentioned above were Management of Neuropathic Pain Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 257 applied. In visual illusion, the patients’ body from waist above were reflected in a mirror and the legs of the patients were blocked. Instead, an image of a man walking on a treadmill was reflected where the patients’ legs were supposed to be. The patients were also encouraged to move their body accordingly. The pain, foreignness, and heaviness levels were all measured by the VAS, and these were all decreased in the visual illusion technique compared with others. After this, four patients received visual illusion therapy for 15 days consecutively; their pretask pain and the duration of pain relief all increased during these 15 days. This study also shows that there is much area for improvement of these kinds of problems, and many techniques can be developed using visual feedback. As a conclusion, physical therapy modalities such as superficial and deep heat agents, analgesic currents, and laser are not sufficient in the management of neuropathic pain when applied alone. Even though neurostimulation techniques are being used more frequently, their effectiveness in the treatment of neuropathic pain are still disputed. Rehabilitation programs must be emphasized and combined with pharmacotherapy in daily practice. The emotional component of neuropathic pain is more striking and cannot be controlled by pharmacotherapy alone. Rehabilitative methods that are effective in treating pain behavior such as cognitive behavioral therapy, psychotherapy, virtual reality, and GMI increase overall treatment success. Pain rehabilitation techniques seem promising in the management of neuropathic pain; however, there is a requirement for more randomized controlled trials with larger patient groups. REFERENCES 1. 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