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Pain and Therapy

, Volume 4, Issue 1, pp 51–65 | Cite as

Management of Neuropathic Pain Associated with Spinal Cord Injury

  • Ellen M. Hagen
  • Tiina RekandEmail author
Open Access
Review

Abstract

Spinal cord injury (SCI) is an injury to the spinal cord that leads to varying degrees of motor and/or sensory deficits and paralysis. Chronic pain of both neuropathic and nociceptive type is common and contributes to reduced quality of life. The aim of the review is to provide current clinical understanding as well as discuss and evaluate efficacy of pharmacological interventions demonstrated in the clinical studies. The review was based on literature search in PubMed and Medline with words “neuropathic pain” and “spinal cord injury”. The review included clinical studies and not experimental data nor case reports. A limited number of randomized and placebo-controlled studies concerning treatment options of neuropathic pain after SCI were identified. Amitriptyline, a tricyclic antidepressant and the antiepileptic drugs, gabapentin and pregabalin, are most studied with demonstrated efficacy, and considered to be the primary choice. Opioids have demonstrated conflicting results in the clinical studies. In addition, administration route used in the studies as well as reported side effects restrict everyday use of opioids as well as ketamine and lidocaine. Topical applications of capsaicin or lidocaine as well as intradermal injections of Botulinum toxin are new treatment modalities that are so far not studied on SCI population and need further studies. Non-pharmacological approaches may have additional effect on neuropathic pain. Management of pain should always be preceded by thorough clinical assessment of the type of pain. Patients need a follow-up to evaluate individual effect of applied measures. However, the applied management does not necessarily achieve satisfactory pain reduction. Further clinical studies are needed to evaluate the effect of both established and novel management options.

Keywords

Antidepressants Antiepileptics Management Neuropathic pain Opioids Pain Spinal cord injury 

Introduction

A spinal cord injury (SCI) is an injury to the spinal cord that leads to varying degrees of motor and/or sensory deficits and paralysis [1]. Although injury of the cauda equina is included, the definition excludes isolated injuries to other nerve roots [2]. The condition may lead to lifelong loss of function, autonomic disturbances and reduced quality of life, as well as increased morbidity and mortality.

Pain is common in patients with SCI [3, 4, 5]. The pain may be of nociceptive or neuropathic type or a combination of the two. Neuropathic pain following SCI is caused by damage to or dysfunction of the nervous system, while nociceptive pain is caused by damage to non-neural tissue either musculoskeletal due to bone, joint, muscle trauma or inflammation, mechanical instability or muscle spasm. Pain of visceral origin may develop for instance due to renal calculus, bowel, sphincter dysfunction, headache related to autonomic dysreflexia and secondary overuse syndromes [6, 7].

The pain may be localized above, at or below the level of the SCI and may persist for many years after the acute injury [8, 9, 10]. Pain may occur immediately after the acute injury or develop and increase in intensity a long time after the injury [8, 11]. Neuropathic pain is found to contribute to reduce quality of life in patients with SCI [8, 11].

Current review is based on search in PubMed and Medline databases with words “neuropathic pain” and “spinal cord injury”. The review included all clinical studies, but not experimental and case reports, published until December 2015 when the search was conducted. The review included all clinical studies, but not experimental data nor case reports.

The aim is to provide current clinical understanding as well as possible treatment options and initiatives with efficacy evaluation.

This review article is based on previously conducted studies, and does not involve any new studies of human or animal subjects performed by any of the authors.

Epidemiology of SCI and Neuropathic Pain Following SCI

There are large variations in incidence, prevalence, gender distribution, mechanisms, level and completeness of SCI worldwide [12, 13, 14, 15, 16, 17, 18, 19].

The global incidence of traumatic SCI is estimated to be 23 cases per 1,000,000 persons in 2007 and is dependent on regional results [20]. The reported annual incidence ranges from 2.3 per million in one Canadian study to 83 per million in a study from Alaska [18, 19, 20, 21]. Differences in definition, inclusion criteria, classification and procedures for identification of patients as well as geographical and cultural issues may contribute to a vast range of annual incidence reported in the studies [16, 21].

Information about prevalence of traumatic SCI is scarce [18]. The lowest reported prevalence is from India, 236 per million population [22], and the highest from the USA, 4187 per million population [23]. The incidence and prevalence of non-traumatic SCI are very limited and the results are uncertain.

Neuropathic pain is a common complication following SCI. The prevalence of pain in SCI is reported between 18% and 96%, the variation may be explained by differences in selection of study populations [4, 24]. Pain is usually described as present in 60–69% of the SCI population [5]. Most individuals with chronic pain and SCI report more than one pain problem [24]. Prevalence of chronic pain in individuals with SCI is reported to be 11–94%, and severe, disabling pain in 18–63% [24].

Clinical Characteristics of Neuropathic Pain Following SCI

Neuropathic pain above the level of injury is often caused by concomitant compressive radiculopathies or sometimes by complex regional pain syndromes. Neuropathic pain at the level of injury is caused by nerve-root compression development of complications such as syringomyelia or SCI itself, while neuropathic pain below the level of injury is caused by spinal cord trauma or disease [2].

A recent prospective study followed 90 patients with traumatic SCI 1, 6 and 12 months after the injury [7]. Eighty-eight patients completed the 12-month follow-up. Approximately, 80% of the patients reported any type of pain at all periods evaluated. Neuropathic pain related to SCI increased over time, and musculoskeletal pain decreased slightly, with both being present in 59% of patients at 12 months; other neuropathic pain not related to SCI and visceral pain were present in 1–3%. Early sensory changes (particularly cold-evoked dysesthesia) indicated development of neuropathic pain below the level of injury later [7]. The findings demonstrate that examination of sensation may give additional information about prognosis. Trauma in the spinal cord may result in subsequent central neuropathic pain with localization at or below the level of SCI with allodynia, hyperalgesia and sensory deficit in the pain area [25]. There is usually no relation to movement in neuropathic pain. Different descriptive words indicating neuropathic characteristics of sensation such as burning, tingling, pricking, sharpness, shooting, squeezing, cold, electric or shock-like pain have been used by patients [25]. Neuropathic pain at injury level resolved later in 45% of patients and below injury-level pain resolved in 33% of cases. The findings indicate that majority of SCI patients with pain syndromes have long-lasting problems and need follow-up of pain problems.

Classification of Neuropathic Pain in SCI

Neuropathic pain is defined as proposed by the International Association for the Study of Pain (IASP) as “pain initiated or caused by a primary lesion or dysfunction of the nervous system” [25]. Neuropathic pain is divided into peripheral and central pain [25, 26, 27]. Pain after SCI is classified according to type, localization and level of injury [8].

A typical feature of central neuropathic pain following SCI is its localization below the level of the injury combined with sensory phenomena such as allodynia or hyperalgesia in the painful area [8, 9]. Central neuropathic pain may develop months or years after the injury [8, 9, 10]. Development of neuropathic pain a long time after SCI may be a sign of post-traumatic syringomyelia [8].

Neuropathic pain above the level of injury is usually not due to the SCI itself. Patients who use a manual wheelchair may experience carpal tunnel syndrome and peripheral neuropathic pain as a result and shoulder pain due to muscular overuse [28, 29]. Peripheral neuropathic pain at injury level can be due to concomitant injury to the nerve root.

Both nociceptive and neuropathic pain may vary in intensity and may be dependent on daily activities as well as being affected by the individual’s psychosocial environment [30].

Pathophysiology

Numerous and complex changes in the nervous system will take place after development of pain following SCI.

A number of molecular changes will occur after SCI including changes in sodium ion-channels, voltage-gated calcium channels, glutamate and gamma-aminobutyric acid metabolism, serotonergic, noradrenergic, N-methyl-d-aspartate (NMDA) and opioid receptors. Drugs such as antiepileptics, tricyclic antidepressants and opioids have an effect on these changes [8, 31]. Neuroplasticity may contribute to both recovery of neuropathic pain and maintenance and chronification of pain after SCI despite for attempts on medical treatment [31].

Neuropathic pain may also develop because of compression of nerve roots after spinal trauma [31, 32]. Clinically, this pain will often be localized above the level of injury [31].

Clinical Examination

A thorough examination is important to identify any possible somatic cause of the pain other than SCI and to classify the type of pain to optimize therapy. The localization, duration, intensity and characteristics of pain are useful information when assessing the pain [8, 32]. The clinical examination must include a neurological status with a mapping of sensory phenomena in the painful area, indicating the presence of neuropathic pain [32]. It is important to collect data regarding previous surgical and medical treatment [8]. Information will help to find possible underlying causes, classify pain type and relate localization to previous SCI correctly as well as choose appropriate modalities of further management.

Pain intensity can be assessed using a visual analog scale (VAS) or numeric rating scales [8, 33]. Pain characteristics can be mapped using descriptive scales, such as the McGill Pain Questionnaire [34]. The International Spinal Cord Injury Pain Basic Data Set represents an international consensus on clinical data and relevant assessments scales required for pain assessment in SCI patients [35].

Treatment

Established Pharmacological Treatment

Neuropathic pain after SCI often emerges as a chronic condition and responds poorly to a single drug. However, monotherapy will help to identify effectiveness of a single drug. Information about expected effect, the timeline of treatment and need for follow-up should be clearly explained to patients. Freedom from pain is often not realistic, instead modulation of the neuropathic pain may be a more achievable goal. Pharmacological treatment of neuropathic pain following SCI is in general long-lasting process and both expected effect and side effects should be considered before the start and during follow-up. Table 1 gives an overview of randomized clinical studies performed on patients with neuropathic pain following SCI.
Table 1

Randomized clinical studies for neuropathic pain following spinal cord injury

References

Treatment

Dosage

Study design

Sample size

Active substance

Placebo

Antidepressants

 Cardenas et al. [37]

Amitriptyline vs placebo

10–25 mg

Randomized controlled Trial

84

44

40

 Rintala et al. [36]

Amitriptyline vs active placebo vs gabapentin

150 mg amitriptyline vs 3600 mg gabapentin

Randomized, controlled, double blind, triple crossover

38

38

38

 Yang et al. [38]

Lithium vs placebo

0.6–1.2 mmol/l

Randomized, double-blind, placebo-controlled trial

40

20

20

 Davidhoff et al. [39]

Trazodone hydrochloride vs placebo

50–150 mg

Randomized, double-blind, placebo-controlled trial

18

9

9

 Vranken et al. [40]

Duloxetine vs placebo

60-120 mg

Randomized, double-blind, placebo-controlled trial

48a

24

24

Antiepileptics

      

 Rintala et al. [36]

Gabapentin vs active placebo

900–3600 mg

Randomized, controlled, double blind, triple crossover trial

38

38

38

 Levendoglu et al. [43]

Gabapentin vs placebo

1800 mg

Randomized, double blind, placebo-controlled, crossover trial

20

20

20

 Tai et al. [45]

Gabapentin vs placebo

150–600 mg

Prospective, randomized, double-blind, crossover trial

7

7

7

 Ahn et al. [47]

Gabapentin

1800 mg

Evaluation study

31

31

 

 Siddall et al. [48]

Pregabalin

150–600 mg

Randomized, placebo-controlled, multicentre trial

137

70

67

 Vranken et al. [49]

Pregabalin vs placebo

150-600 mg

Randomized, double-blind, placebo-controlled trial

40a

20

20

 Cardenas et al. [50]

Pregabalin vs placebo

150–600 mg

Randomized, double-blind, placebo-controlled trial

220

112

108

 Finnerup et al. [52]

Lamotrigine vs placebo

200–400 mg

Randomized double blind, placebo-controlled, crossover trial

30

27

28

 Drewes et al. [53]

Valproate vs placebo

600–2400 mg

Double-blind, cross-over, placebo-controlled trial

20

20

20

 Finnerup et al. [54]

Levetiracetam

500–3000 mg

Randomized, double-blind, placebo-controlled, crossover, multicentre trial

36

18

18

 Salinas et al. [55]

Carbamazepine vs placebo

600 mg

Randomized, double-blind, placebo-controlled trial

46

24

22

Opioids

 Norrbrink et al. [58]

Tramadol

150 mg

Randomized, double-blind, placebo-controlled trial

35

23

12

 Attal et al. [59]

Morphine vs placebo

2 mg morphine every 10 min intravenous

Double-blind, placebo-controlled, crossover trial

16

8

8

 Siddall et al. [60]

Morphine and clonidine vs placebo

Individual dosage

Randomized, double-blind, placebo-controlled trial

15

15

15

Cannabinoids

 Rintala et al. [68]

Dronabinol vs placebo

5–20 mg

Randomized, controlled, double-blind, crossover trial

7

7

5

 Wade et al. [69]

Cannabis vs placebo

2.5–120 mg

Double-blind, placebo-controlled, crossover trial

24a

24

24

 Karst et al. [70]

Synthetic cannabinoid vs placebo

40 mg

Randomized, double-blind, placebo-controlled trial

21a

21

21

Others

 Eide et al. [66]

Ketamine, alfentanil and placebo

60 + 6 µg/kg and alfentanil (7 + 0.6 µg/kg)

Continuous and evoked pain was examined before and after the intravenous infusion of either ketamine, alfentanil or placebo

9

9

9

 Amr et al. [65]

Ketamine + gabapentin vs gabapentin + placebo

80 mg ketamine + 900 mg gabapentin

Randomized, controlled, double blind trial

40

29

29

 Kvarnstrom et al. [67]

Lidocaine vs ketamine vs placebo

0.4 mg/kg ketamine vs 2.5 mg/kg lidocaine

Randomized, double-blind, three period, three-treatment, cross-over trial

10

10

10

 Finnerup et al. [63]

Lidocaine vs placebo

5 mg/kg

Randomized, double-blind, placebo-controlled, crossover trial

24

24

24

 Chiou-Tan et al. [64]

Mexiletine vs placebo

450 mg

Randomized, placebo-controlled, double-blind, crossover trial

15

11

11

References

Time

Outcomes

Adverse effect active substance

Adverse effect placebo

Dropout

Antidepressants

 Cardenas et al. 37]

6 weeks

No significant between amitriptyline and placebo

43

36

0

 Rintala et al. [36]

8 weeks

Amitriptyline > gabapentin

Amitriptyline > diphenhydramine

No significant difference between gabapentin and diphenhydramine

  

28 completed the amitriptyline phase

25 completed the active placebo phase

16 completed all 3 phases

 Yang et al. [38]

6 weeks

Lithium > placebo

16

14

2 in each group

 Davidhoff et al. [39]

6 weeks

No significant difference between trazodone hydrochloride and diphenhydramine

4

1

5 in active drug group, 1 in placebo group

 Vranken et al. [40]

 

No significant difference between duloxetine vs placebo

30 AE in total

10 AE in total

0

Antiepileptics

 

 Rintala et al. [36]

8 weeks

No significant difference between gabapentin and diphenhydramine

  

26 completed the gabapentin phase

 Levendoglu et al. [43]

18 weeks

Gabapentin > placebo

30 AE in total

 

6

 Tai et al. [45]

10 weeks

Gabapentin > placebo

  

NA

 Ahn et al. [47]

8 weeks

Effect of Gabapentin

15

 

NA

 Siddall et al. [48]

12 weeks

Pregabalin > placebo

15

9

21 in active group, 30 in placebo group

 Vranken et al. [49]

4 weeks

Pregabalin > placebo

3

3

3 in active group, 4 in placebo group

 Cardenas et al. [50]

17 weeks

Pregabalin > placebo

75

50

6 in active group, 5 in placebo group

 Finnerup et al. [52]

21 weeks

No significant difference between lamotrigine and placebo

1

2

3 in active group, 5 in placebo group

 Drewes et al. [53]

8 weeks

No significant difference between valproate and placebo

4

0

0

 Finnerup et al. [54]

12 weeks

No significant effect

7

2

9 in active group, 3 in placebo group

 Salinas et al. [55]

1 month

Carbamazepine > placebo only after 1 monthb

23

21

1 in active group, 1 in placebo group

Opioids

 Norrbrink et al. [58]

4 weeks

Tramadol > placebo

21

7

10 in active group, 1 in placebo group

 Attal et al. [59]

20 min each

Morphine > placebo after 1 month

5

0

1

 Siddall et al. [60]

3 days each

Morphine + clonidine > morphine or clonidine or placebo

Morphine 25 AE, Clonidine 27 AE, Morphine/clonidine 27 AE

4 AE

0

Cannabinoids

 Rintala et al. [68]

17 weeks

No significant difference between dronabinol and placebo

30 AE

18 AE

2 in active group, 0 in placebo group

 Wade et al. [69]

10 weeks

Cannabis > placebo

24

21

3 in active group

 Karst et al. [70]

3 weeks

Synthetic cannabinoid > placebo

2

0

2 in active group, 0 in placebo group

Others

 Eide et al. [66]

2 h each

Ketamine + alfentanil > alfentanil or ketamine or placebo

 Amr et al. [65]

1 week

Ketamine + gabapentin > gabapentin + placebo

 Kvarnstrom et al. [67]

2 weeks

Ketamine > lidocaine or placebo

Ketamine 9, Lidocaine 5

1

 Finnerup et al. [63]

2 weeks

Lidocaine > placebo

9

1

0

 Chiou-Tan et al. [64]

10 weeks

No significant difference between mexiletine and placebo

4

AE adverse events, NA not applicable

aPatients with several diagnoses were included in the study

bCarbamazepine was used as prophylactic treatment

Antidepressants

Amitriptyline, a tricyclic antidepressant showed effect in one study [36], while another randomized study did not confirm this effect [36, 37]. The applied doses varied between 10 and 150 mg in these studies and the studies were designed differently and direct comparison is not possible between these studies. Known adverse effects such as dry mouth, drowsiness or tiredness, constipation, urinary retention and increased spasticity were reported in both studies [36, 37]. Side effect occurred more frequently in the study applying higher doses of amitriptyline [36].

Another antidepressive drug, lithium, has shown favorable effect on neuropathic pain in a placebo-controlled study exploring possible effect on patients with SCI [38]. Oral lithium was titrated to 0.6–1.2 mmol/l for 6 weeks with subsequently 6-month clinical follow-up. The effect of lithium on neuropathic pain was a secondary outcome in this study. A total of 40 patients were enrolled, half of patients suffered from severe neuropathic pain. Significant improvement, measured by visual analog scale (VAS) was recorded after 6 weeks as well as after discontinuation of the 6 months of treatment [38]. However, further studies on neuropathic pain following SCI are needed to confirm the effectiveness of lithium.

Two oral antidepressives, trazodone (50–150 mg) and duloxetine (60–120 mg) have been studied in the randomized, placebo-controlled double-blinded studies without showing any effect in patients with SCI [39, 40].

Other tricyclic antidepressants such as nortriptyline, imipramine, and desipramine are considered to be first-line choice in management of neuropathic pain in general [41, 42]. Other recommended drugs for neuropathic pain include venlafaxine, selective serotonin reuptake inhibitors such as sertraline, paroxetine, fluoxetine and citalopram [41]. All these drugs are not, however, sufficiently studied neither in patients with SCI nor in patients with neuropathic pain [41]. In individual intractable cases, both well-documented and less documented medication may be considered.

Antiepileptics

Pregabalin and gabapentin are the most studied drugs against neuropathic pain following SCI. The analgesic effect of these drugs has been explained by action through multiple pathways [32]. Several studies have reported on the efficacy of gabapentin. [36, 43, 44, 45, 46, 47]. Two studies, including only 27 patients all together, showed better effect than placebo, while two other studies showed conflicting results [36, 43, 44, 45, 46, 47]. The administered doses varied between 300 and 3600 mg. Pregabalin have been studied in three randomized placebo-controlled studies in the doses between 150 and 600 mg [48, 49, 50]. These studies showed that pregabalin has superior effect to placebo [48, 49]. Both pregabalin and gabapentin have similar adverse effect with somnolence, dizziness, edema, dry mouth, and fatigue [36, 50, 51].

Lamotrigine was studied using doses of 200–400 mg in patients with SCI [52]. Thirty patients with complete and incomplete injury were included in the study. Lamotrigine showed effect on neuropathic pain in the group with incomplete injury [52]. Levetiracetam and sodium valproate have been studied in randomized placebo controlled manner in patients with SCI [53, 54]. There was, however, no significant effect on neuropathic pain recorded in these studies. Carbamazepine has been studied in one placebo controlled study on SCI patients. Carbamazepine was administered up to 600 mg daily to SCI patients without pain. The conclusion was that carbamazepine may prevent the early, but not the long-term development of neuropathic pain [55]. Other antiepileptic drugs suggested to have effect on neuropathic pain are phenytoin, oxcarbamazepine and lacosamide. However, the evidence of effect is weak or limited to the specific types of syndromes with neuropathic pain and is not studied on patients with SCI [56]. Phenytoin has been effective on trigeminal neuralgia in doses 15 mg/kg. Also, oxcarbamazepine has reduced significantly the neuropathic pain in doses above 770 mg daily and lacosamide has proven efficacy in doses 15 mg/kg [56]. Gabapentin and pregabalin obviously should be used before other antiepileptics in the SCI-related neuropathic pain. Other studied antiepileptics may be considered in individual cases with intractable neuropathic pain as a last resort.

Opioids

Opioids are potent drugs and recommended as a medication against intractable pain after SCI [32, 56, 57]. Tramadol has been shown to be effective in the randomized placebo-controlled study on 35 patients with SCI-related neuropathic pain [58].

Intravenously given morphine did not show effect in a crossover study in patients with neuropathic pain due to different conditions including SCI [59]. Clonidine together with morphine given intrathecally has been used in two studies including in total of 23 participants [60, 61]. Both studies concluded favorable effect of treatment [60, 61].

The use of Oxycodone, an oral opioid has demonstrated additional improvement of pain in patients with SCI and neuropathic pain pre-treated with antiepileptic drugs [62]. Use of opioids alone or with other medications may be an option. However, side effects such as constipation, nausea and cognitive deprivation along with the risk of drug abuse may complicate a long-term use.

Other Anti-Analgesics

Intravenous lidocaine has shown effect on the patients with SCI and neuropathic pain in a limited study [63]. A per oral analog to lidocaine, mexiletine was, however, not effective in another 4-week placebo-controlled randomized study where only 11 patients completed the study [64].

Ketamine, a NMDA receptor antagonist, was compared with other drugs in three studies [63, 65, 66]. Intravenous ketamine together with oral gabapentin showed better effect than gabapentin and placebo immediately after administration [65]. However, the effect was not present 2 weeks after treatment. Another study compared the effect of ketamine (in dose 0.4 mg/kg) with lidocaine (2.5 mg/kg) and placebo. Ketamine, but not lidocaine, showed significant effect [67]. The third study investigated the effect of ketamine together with µ-receptor agonist alfentanil compared with placebo [66]. This study showed significant effect in patients with SCI and neuropathic pain with dysesthesia. Intravenously administered lidocaine in dosage 5 mg/kg has also shown effect [63]. However, daily intravenous administration will limit the use of these medications on patients with long-lasting pain.

Cannabis-based medications have been studied both in patients with neuropathic pain and also in patients suffering from spasticity related pain in particular. A pilot study on Dronabinol, oral cannabinoid given 5–20 mg daily to patients with SCI and neuropathic pain did not show better effect than placebo [68]. Two studies using cannabis spray on a mixed cohort including patients with SCI demonstrated significant effect on neuropathic pain [69, 70]. The studies are so far too limited and efficacy of cannabinoids and opioids is questionable.

Treatment of neuropathic pain after SCI may include use of topical agents [71]. Topical use of 0.025% capsaicin ointments was studied in a retrospective study including only eight patients, proved effective on neuropathic pain [72]. Topical use of lidocaine or high doses of capsaicin (8%) has not been studied on patients with SCI. These drugs have, however, shown effect on the other types of neuropathic pains [56, 73]. Another new approach for treatment of well-localized neuropathic pain is intradermal use of botulinum toxin A injections [73]. This treatment has not been tried on SCI-related neuropathic pain, but it proved effective in the cases with chronic neuropathic pain after surgery or trauma [74]. The treatment should be studied further on patients with SCI-related neuropathic pain in future.

A recent systematic review compared all available pharmacologic therapies for neuropathic pain following SCI and concluded that available studies are small and cause insufficient data for quantitative comparisons [75].

Other Options of Treatment of Neuropathic Pain Following SCI

Two studies examined the effect of transcutaneous electrical nerve stimulation (TENS) on neuropathic pain following SCI [76, 77]. Low-frequency TENS demonstrated a favorable effect on pain [77]. Transcranial electric stimulation either alone or together with visual illusions was studied in several studies [78, 79, 80, 81]. Favorable effect was demonstrated in all studies. One observational study exploring the effect of visual illusions demonstrated significant reduction of pain as measured by VAS [82]. Transcranial magnetic stimulation did not however show significant effect in two studies on SCI patients [83, 84]. One study, exploring effect of deep brain stimulation did not demonstrate effect of such procedure [85].

Two studies, one of them a mixed cohort, have shown partial effect of DREZotomy (Dorsal Root Entry Zone—a surgical treatment) on neuropathic pain [86, 87].

One observational study investigated the effect of acupuncture or massage on neuropathic pain following SCI [88]. Comparing pain before and after treatment, reduction of pain was reported with both acupuncture and massage. Osteopathic manipulation did not however show any effect in SCI patients with neuropathic pain [89].

Management of Both Neuropathic Pain and Nociceptive Pain

Both nociceptive and neuropathic pain may occur simultaneously in patients with SCI. Given this, management of both types of pain should be addressed. The effect of single pain medication or combinations against mixed types of pain after SCI has not been systematically studied. Non-steroidal anti-inflammatory drugs and opioid medication is widely clinically used [90]. Acupuncture, manual therapy, hypnosis and biofeedback have demonstrated effect on nociceptive pain and should be considered as possible options of non-pharmacological treatment in the cases with mixed pain [91, 92, 93]. Physiotherapy can alleviate nociceptive pain and should be considered, particularly if muscular shoulder pain is present [94, 95, 96].

Recommendations

Based on current knowledge, amitriptyline, gabapentin and pregabalin have the best documented effects on neuropathic pain after SCI and should be considered as the first choice. However, the documentation about efficacy is limited on patients with SCI-related pain in most other options and individual variations in response to treatment are observed. In addition, side effects should be considered, particularly if high doses are used. The available clinical trials demonstrate that use of higher doses results in several and more serious side effects. In the cases of intractable pain, treatments effective on other types of neuropathic pain may be considered. A combination of several drugs or measures, although scarcely studied so far, has probably more pronounced effect than administration of one single drug. Maintenance of treatment effect is not systematically studied. Therefore, the patients should be followed up and treatment should be evaluated continuously. Further studies are needed for evaluation of efficacy of those measures on pain after SCI.

Conclusions

The majority of patients suffer from pain following SCI. Pain has profound impact on many aspects of daily life. The management of pain should be based on clinical findings leading to diagnosis of pain type and evaluation of effect of treatment. Thorough clinical assessment of the condition should precede administration of drugs to make sure of the presence of neuropathic pain.

Evidence of efficacy of pharmacological treatment of neuropathic pain following SCI is limited and available literature does not give enough information about long-term effect or usefulness of combination therapy. Based on current knowledge, tricyclic antidepressant amitriptyline and antiepileptics gabapentin and pregabalin have the best documented effect on neuropathic pain after SCI.

Treatment of topical agents such as capsaicin or lidocaine as well as with intradermal Botulinum toxin injections may be useful approaches but need to be studied on populations with SCI. Further studies are needed for evaluation of efficacy of those measures on pain after SCI.

Notes

Acknowledgments

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. No funding or sponsorship was received for this study or publication of this article. The authors thank Kim Haugen for help with the statistical analyses.

Conflict of interest

E. M. Hagen and T. Rekand have no conflicts of interest to declare.

Compliance with ethics guidelines

This review article is based on previously conducted studies, and does not involve any new studies of human or animal subjects performed by any of the authors.

Open Access

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

References

  1. 1.
    Kraus JF, Franti CE, Riggins RS, Richards D, Borhani NO. Incidence of traumatic spinal cord lesions. J Chronic Dis. 1975;28(9):471–92.PubMedCrossRefGoogle Scholar
  2. 2.
    Maynard FM, Bracken MB, Creasey G, Ditunno JF, Donovan WH, Ducker TB, et al. International standards for neurological and functional classification of spinal cord injury. Spinal Cord. 1997;35(5):266–74.PubMedCrossRefGoogle Scholar
  3. 3.
    Dijkers M, Bryce T, Zanca J. Prevalence of chronic pain after traumatic spinal cord injury: a systematic review. J Rehabil Res Dev. 2009;46(1):13–29.PubMedCrossRefGoogle Scholar
  4. 4.
    Putzke JD, Richards JS, Hicken BL, Ness TJ, Kezar L, DeVivo M. Pain classification following spinal cord injury: the utility of verbal descriptors. Spinal Cord. 2002;40(3):118–27.PubMedCrossRefGoogle Scholar
  5. 5.
    Norrbrink Budh C, Lund I, Hultling C, Levi R, Werhagen L, Ertzgaard P, et al. Gender related differences in pain in spinal cord injured individuals. Spinal Cord. 2003;41(2):122–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Siddall PJ. Management of neuropathic pain following spinal cord injury: now and in the future. Spinal Cord. 2009;47(5):352–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Finnerup NB, Norrbrink C, Trok K, Piehl F, Johannesen IL, Sorensen JC, et al. Phenotypes and predictors of pain following traumatic spinal cord injury: a prospective study. J Pain. 2014;15(1):40–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Siddall PJ, Finnerup NB. Chapter 46: pain following spinal cord injury. Handb Clin Neurol. 2006;81(3rd series):690–703.Google Scholar
  9. 9.
    Calmels P, Mick G, Perrouin-Verbe B, Ventura M. Neuropathic pain in spinal cord injury: identification, classification, evaluation. Ann Phys Rehabil Med. 2009;52(2):83–102.PubMedCrossRefGoogle Scholar
  10. 10.
    Wasner G. Central Pain Syndromes. Curr Pain Headache Rep. 2010;14(6):489–96.PubMedCrossRefGoogle Scholar
  11. 11.
    Jensen MP, Chodroff MJ, Dworkin RH. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology. 2007;68(15):1178–82.PubMedCrossRefGoogle Scholar
  12. 12.
    New PW, Cripps RA, Bonne LB. Global maps of non-traumatic spinal cord injury epidemiology: towards a living data repository. Spinal Cord. 2013;52:97–109.PubMedCrossRefGoogle Scholar
  13. 13.
    Wyndaele M, Wyndaele JJ. Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord. 2006;44(9):523–9.PubMedCrossRefGoogle Scholar
  14. 14.
    van den Berg ME, Castellote JM, Mahillo-Fernandez I, de Pedro-Cuesta J. Incidence of spinal cord injury worldwide: a systematic review. Neuroepidemiology. 2010;34(3):184–92.PubMedCrossRefGoogle Scholar
  15. 15.
    Chiu WT, Lin HC, Lam C, Chu SF, Chiang YH, Tsai SH. Review paper: epidemiology of traumatic spinal cord injury: comparisons between developed and developing countries. Asia Pac J Public Health. 2010;22(1):9–18.PubMedCrossRefGoogle Scholar
  16. 16.
    Ackery A, Tator C, Krassioukov A. A global perspective on spinal cord injury epidemiology. J Neurotrauma. 2004;21(10):1355–70.PubMedCrossRefGoogle Scholar
  17. 17.
    DeVivo MJ. Epidemiology of traumatic spinal cord injury: trends and future implications. Spinal Cord. 2012;50(5):365–72.PubMedCrossRefGoogle Scholar
  18. 18.
    Hagen EM, Rekand T, Gilhus NE, Gronning M. Traumatic spinal cord injuries—incidence, mechanisms and course. Tidsskr Nor Laegeforen. 2012;132(7):831–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Lee BB, Cripps RA, Fitzharris M, Wing PC. The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal Cord. 2014;52:110–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Fitzharris M, Cripps RA, Lee BB. Estimating the global incidence of traumatic cord injury. Spinal Cord. 2014;52:117–22.PubMedCrossRefGoogle Scholar
  21. 21.
    Warren S, Moore M, Johnson MS. Traumatic head and spinal cord injuries in Alaska (1991–1993). Alaska Med. 1995;37(1):11–9.PubMedGoogle Scholar
  22. 22.
    Razdan S, Kaul RL, Motta A, Kaul S, Bhatt RK. Prevalence and pattern of major neurological disorders in rural Kashmir (India) in 1986. Neuroepidemiology. 1994;13(3):113–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Cahill A, Fredine H, Zilberman L. Initial briefing: Prevalence of paralysis including spinal cord injuries in the United States, 2008. Technical Document 41609, 1–60. 2009. The University of New Mexico, School of Medicine, Christopher and Dana Reeve Foundation, Paralysis Resource Foundation.Google Scholar
  24. 24.
    Turner JA, Cardenas DD, Warms CA, McClellan CB. Chronic pain associated with spinal cord injuries: a community survey. Arch Phys Med Rehabil. 2001;82(4):501–9.PubMedCrossRefGoogle Scholar
  25. 25.
    IASP Task Force on Taxonomy, Merskey H, Bogduk N. Classification of chronic pain. Description of chronic pain syndromes and definition of pain terms. 2nd ed. Seattle: IASP Press, Seattle, © 1994; 2005.Google Scholar
  26. 26.
    Jensen TS, Baron R, Haanpaa M, Kalso E, Loeser JD, Rice AS, et al. A new definition of neuropathic pain. Pain. 2011;152(10):2204–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Christensen MD, Hulsebosch CE. Chronic central pain after spinal cord injury. J Neurotrauma. 1997;14(8):517–37.PubMedCrossRefGoogle Scholar
  28. 28.
    Dalyan M, Cardenas DD, Gerard B. Upper extremity pain after spinal cord injury. Spinal Cord. 1999;37(3):191–5.PubMedCrossRefGoogle Scholar
  29. 29.
    McCasland LD, Budiman-Mak E, Weaver FM, Adams E, Miskevics S. Shoulder pain in the traumatically injured spinal cord patient: evaluation of risk factors and function. J Clin Rheumatol. 2006;12(4):179–86.PubMedCrossRefGoogle Scholar
  30. 30.
    Widerstrom-Noga EG, Turk DC. Exacerbation of chronic pain following spinal cord injury. J Neurotrauma. 2004;21(10):1384–95.PubMedCrossRefGoogle Scholar
  31. 31.
    Finnerup NB, Baastrup C. Spinal cord injury pain: mechanisms and management. Curr Pain Headache Rep. 2012;16(3):207–16.PubMedCrossRefGoogle Scholar
  32. 32.
    Rekand T, Hagen EM, Gronning M. Chronic pain following spinal cord injury. Tidsskr Nor Laegeforen. 2012;132(8):974–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Widerstrom-Noga E, Biering-Sorensen F, Bryce T, Cardenas DD, Finnerup NB, Jensen MP, et al. The international spinal cord injury pain basic data set. Spinal Cord. 2008;46(12):818–23.PubMedCrossRefGoogle Scholar
  34. 34.
    Melzack R. The McGill pain questionnaire: major properties and scoring methods. Pain. 1975;1(3):277–99.PubMedCrossRefGoogle Scholar
  35. 35.
    Widerstrom-Noga E, Biering-Sorensen F, Bryce TN, Cardenas DD, Finnerup NB, Jensen MP, et al. The international spinal cord injury pain basic data set (version 2.0). Spinal Cord. 2014.Google Scholar
  36. 36.
    Rintala DH, Holmes SA, Courtade D, Fiess RN, Tastard LV, Loubser PG. Comparison of the effectiveness of amitriptyline and gabapentin on chronic neuropathic pain in persons with spinal cord injury. Arch Phys Med Rehabil. 2007;88(12):1547–60.PubMedCrossRefGoogle Scholar
  37. 37.
    Cardenas DD, Warms CA, Turner JA, Marshall H, Brooke MM, Loeser JD. Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a randomized controlled trial. Pain. 2002;96(3):365–73.PubMedCrossRefGoogle Scholar
  38. 38.
    Yang ML, Li JJ, So KF, Chen JY, Cheng WS, Wu J, et al. Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial. Spinal Cord. 2012;50(2):141–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Davidoff G, Guarracini M, Roth E, Sliwa J, Yarkony G. Trazodone hydrochloride in the treatment of dysesthetic pain in traumatic myelopathy: a randomized, double-blind, placebo-controlled study. Pain. 1987;29(2):151–61.PubMedCrossRefGoogle Scholar
  40. 40.
    Vranken JH, Hollmann MW, van der Vegt MH, Kruis MR, Heesen M, Vos K, et al. Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial. Pain. 2011;152(2):267–73.PubMedCrossRefGoogle Scholar
  41. 41.
    Vranken JH. Elucidation of pathophysiology and treatment of neuropathic pain. Cent Nerv Syst Agents Med Chem. 2012;12(4):304–14.PubMedCrossRefGoogle Scholar
  42. 42.
    O’Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med. 2009;122(10 Suppl):S22–32.PubMedCrossRefGoogle Scholar
  43. 43.
    Levendoglu F, Ogun CO, Ozerbil O, Ogun TC, Ugurlu H. Gabapentin is a first line drug for the treatment of neuropathic pain in spinal cord injury. Spine (Phila Pa 1976). 2004;29(7):743–51.CrossRefGoogle Scholar
  44. 44.
    Putzke JD, Richards JS, Kezar L, Hicken BL, Ness TJ. Long-term use of gabapentin for treatment of pain after traumatic spinal cord injury. Clin J Pain. 2002;18(2):116–21.PubMedCrossRefGoogle Scholar
  45. 45.
    Tai Q, Kirshblum S, Chen B, Millis S, Johnston M, DeLisa JA. Gabapentin in the treatment of neuropathic pain after spinal cord injury: a prospective, randomized, double-blind, crossover trial. J Spinal Cord Med. 2002;25(2):100–5.PubMedGoogle Scholar
  46. 46.
    To TP, Lim TC, Hill ST, Frauman AG, Cooper N, Kirsa SW, et al. Gabapentin for neuropathic pain following spinal cord injury. Spinal Cord. 2002;40(6):282–5.PubMedCrossRefGoogle Scholar
  47. 47.
    Ahn SH, Park HW, Lee BS, Moon HW, Jang SH, Sakong J, et al. Gabapentin effect on neuropathic pain compared among patients with spinal cord injury and different durations of symptoms. Spine (Phila Pa 1976). 2003;28(4):341–6.Google Scholar
  48. 48.
    Siddall PJ, Cousins MJ, Otte A, Griesing T, Chambers R, Murphy TK. Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. Neurology. 2006;67(10):1792–800.PubMedCrossRefGoogle Scholar
  49. 49.
    Vranken JH, Dijkgraaf MG, Kruis MR, van der Vegt MH, Hollmann MW, Heesen M. Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen. Pain. 2008;136(1–2):150–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Cardenas DD, Nieshoff EC, Suda K, Goto S, Sanin L, Kaneko T, et al. A randomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury. Neurology. 2013;80(6):533–9.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Kukkar A, Bali A, Singh N, Jaggi AS. Implications and mechanism of action of gabapentin in neuropathic pain. Arch Pharm Res. 2013;36(3):237–51.PubMedCrossRefGoogle Scholar
  52. 52.
    Finnerup NB, Sindrup SH, Bach FW, Johannesen IL, Jensen TS. Lamotrigine in spinal cord injury pain: a randomized controlled trial. Pain. 2002;96(3):375–83.PubMedCrossRefGoogle Scholar
  53. 53.
    Drewes AM, Andreasen A, Poulsen LH. Valproate for treatment of chronic central pain after spinal cord injury. A double-blind cross-over study. Paraplegia. 1994;32(8):565–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Finnerup NB, Grydehoj J, Bing J, Johannesen IL, Biering-Sorensen F, Sindrup SH, et al. Levetiracetam in spinal cord injury pain: a randomized controlled trial. Spinal Cord. 2009;47(12):861–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Salinas FA, Lugo LH, Garcia HI. Efficacy of early treatment with carbamazepine in prevention of neuropathic pain in patients with spinal cord injury. Am J Phys Med Rehabil. 2012;91(12):1020–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Jensen TS, Madsen CS, Finnerup NB. Pharmacology and treatment of neuropathic pains. Curr Opin Neurol. 2009;22(5):467–74.PubMedCrossRefGoogle Scholar
  57. 57.
    Teasell RW, Mehta S, Aubut JA, Foulon B, Wolfe DL, Hsieh JT, et al. A systematic review of pharmacologic treatments of pain after spinal cord injury. Arch Phys Med Rehabil. 2010;91(5):816–31.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Norrbrink C, Lundeberg T. Tramadol in neuropathic pain after spinal cord injury: a randomized, double-blind, placebo-controlled trial. Clin J Pain. 2009;25(3):177–84.PubMedCrossRefGoogle Scholar
  59. 59.
    Attal N, Guirimand F, Brasseur L, Gaude V, Chauvin M, Bouhassira D. Effects of IV morphine in central pain: a randomized placebo-controlled study. Neurology. 2002;58(4):554–63.PubMedCrossRefGoogle Scholar
  60. 60.
    Siddall PJ, Molloy AR, Walker S, Mather LE, Rutkowski SB, Cousins MJ. The efficacy of intrathecal morphine and clonidine in the treatment of pain after spinal cord injury. Anesth Analg. 2000;91(6):1493–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Uhle EI, Becker R, Gatscher S, Bertalanffy H. Continuous intrathecal clonidine administration for the treatment of neuropathic pain. Stereotact Funct Neurosurg. 2000;75(4):167–75.PubMedCrossRefGoogle Scholar
  62. 62.
    Barrera-Chacon JM, Mendez-Suarez JL, Jauregui-Abrisqueta ML, Palazon R, Barbara-Bataller E, Garcia-Obrero I. Oxycodone improves pain control and quality of life in anticonvulsant-pretreated spinal cord-injured patients with neuropathic pain. Spinal Cord. 2011;49(1):36–42.PubMedCrossRefGoogle Scholar
  63. 63.
    Finnerup NB, Biering-Sorensen F, Johannesen IL, Terkelsen AJ, Juhl GI, Kristensen AD, et al. Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial. Anesthesiology. 2005;102(5):1023–30.PubMedCrossRefGoogle Scholar
  64. 64.
    Chiou-Tan FY, Tuel SM, Johnson JC, Priebe MM, Hirsh DD, Strayer JR. Effect of mexiletine on spinal cord injury dysesthetic pain. Am J Phys Med Rehabil. 1996;75(2):84–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Amr YM. Multi-day low dose ketamine infusion as adjuvant to oral gabapentin in spinal cord injury related chronic pain: a prospective, randomized, double blind trial. Pain Physician. 2010;13(3):245–9.PubMedGoogle Scholar
  66. 66.
    Eide PK, Stubhaug A, Stenehjem AE. Central dysesthesia pain after traumatic spinal cord injury is dependent on N-methyl-d-aspartate receptor activation. Neurosurgery. 1995;37(6):1080–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Kvarnstrom A, Karlsten R, Quiding H, Gordh T. The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury. Acta Anaesthesiol Scand. 2004;48(4):498–506.PubMedCrossRefGoogle Scholar
  68. 68.
    Rintala DH, Fiess RN, Tan G, Holmes SA, Bruel BM. Effect of dronabinol on central neuropathic pain after spinal cord injury: a pilot study. Am J Phys Med Rehabil. 2010;89(10):840–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003;17(1):21–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA. 2003;290(13):1757–62.PubMedCrossRefGoogle Scholar
  71. 71.
    Finnerup NB. Pain in patients with spinal cord injury. Pain. 2013;154(Suppl 1):S71–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Sandford PR, Benes PS. Use of capsaicin in the treatment of radicular pain in spinal cord injury. J Spinal Cord Med. 2000;23(4):238–43.PubMedGoogle Scholar
  73. 73.
    Finnerup NB, Sindrup SH, Jensen TS. Recent advances in pharmacological treatment of neuropathic pain. F1000 Med Rep. 2010;2:52.PubMedCentralPubMedGoogle Scholar
  74. 74.
    Ranoux D, Attal N, Morain F, Bouhassira D. Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol. 2008;64(3):274–83.PubMedCrossRefGoogle Scholar
  75. 75.
    Snedecor SJ, Sudharshan L, Capelleri JS, Sadosky A, Desai P, Jalundhwala YJ, et al. Systematic review and comparison of pharmacologic therapies for neuropathic pain associated with spinal cord injury. J Pain Res. 2013;6:539–47.PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Norrbrink C. Transcutaneous electrical nerve stimulation for treatment of spinal cord injury neuropathic pain. J Rehabil Res Dev. 2009;46(1):85–93.PubMedCrossRefGoogle Scholar
  77. 77.
    Celik EC, Erhan B, Gunduz B, Lakse E. The effect of low-frequency TENS in the treatment of neuropathic pain in patients with spinal cord injury. Spinal Cord. 2013;51(4):334–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, et al. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006;122(1–2):197–209.PubMedCrossRefGoogle Scholar
  79. 79.
    Tan G, Rintala DH, Jensen MP, Richards JS, Holmes SA, Parachuri R, et al. Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase. J Spinal Cord Med. 2011;34(3):285–96.PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Soler MD, Kumru H, Pelayo R, Vidal J, Tormos JM, Fregni F, et al. Effectiveness of transcranial direct current stimulation and visual illusion on neuropathic pain in spinal cord injury. Brain. 2010;133(9):2565–77.PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Kumru H, Soler D, Vidal J, Navarro X, Tormos JM, Pascual-Leone A, et al. The effects of transcranial direct current stimulation with visual illusion in neuropathic pain due to spinal cord injury: an evoked potentials and quantitative thermal testing study. Eur J Pain. 2013;17(1):55–66.PubMedCrossRefGoogle Scholar
  82. 82.
    Moseley GL. Using visual illusion to reduce at-level neuropathic pain in paraplegia. Pain. 2007;130(3):294–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Kang BS, Shin HI, Bang MS. Effect of repetitive transcranial magnetic stimulation over the hand motor cortical area on central pain after spinal cord injury. Arch Phys Med Rehabil. 2009;90(10):1766–71.PubMedCrossRefGoogle Scholar
  84. 84.
    Defrin R, Grunhaus L, Zamir D, Zeilig G. The effect of a series of repetitive transcranial magnetic stimulations of the motor cortex on central pain after spinal cord injury. Arch Phys Med Rehabil. 2007;88(12):1574–80.PubMedCrossRefGoogle Scholar
  85. 85.
    Rasche D, Rinaldi PC, Young RF, Tronnier VM. Deep brain stimulation for the treatment of various chronic pain syndromes. Neurosurg Focus. 2006;21(6):E8.PubMedCrossRefGoogle Scholar
  86. 86.
    Spaic M, Markovic N, Tadic R. Microsurgical DREZotomy for pain of spinal cord and Cauda equina injury origin: clinical characteristics of pain and implications for surgery in a series of 26 patients. Acta Neurochir (Wien). 2002;144(5):453–62.CrossRefGoogle Scholar
  87. 87.
    Kanpolat Y, Tuna H, Bozkurt M, Elhan AH. Spinal and nucleus caudalis dorsal root entry zone operations for chronic pain. Neurosurgery. 2008;62(3 Suppl 1):235–42.PubMedCrossRefGoogle Scholar
  88. 88.
    Norrbrink C, Lundeberg T. Acupuncture and massage therapy for neuropathic pain following spinal cord injury: an exploratory study. Acupunct Med. 2011;29(2):108–15.PubMedCrossRefGoogle Scholar
  89. 89.
    Arienti C, Dacco S, Piccolo I, Redaelli T. Osteopathic manipulative treatment is effective on pain control associated to spinal cord injury. Spinal Cord. 2011;49(4):515–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Cardenas DD, Felix ER. Pain after spinal cord injury: a review of classification, treatment approaches, and treatment assessment. PM R. 2009;1(12):1077–90.PubMedCrossRefGoogle Scholar
  91. 91.
    Dyson-Hudson TA, Shiflett SC, Kirshblum SC, Bowen JE, Druin EL. Acupuncture and Trager psychophysical integration in the treatment of wheelchair user’s shoulder pain in individuals with spinal cord injury. Arch Phys Med Rehabil. 2001;82(8):1038–46.PubMedCrossRefGoogle Scholar
  92. 92.
    Dyson-Hudson TA, Kadar P, LaFountaine M, Emmons R, Kirshblum SC, Tulsky D, et al. Acupuncture for chronic shoulder pain in persons with spinal cord injury: a small-scale clinical trial. Arch Phys Med Rehabil. 2007;88(10):1276–83.PubMedCrossRefGoogle Scholar
  93. 93.
    Jensen MP, Barber J, Romano JM, Hanley MA, Raichle KA, Molton IR, et al. Effects of self-hypnosis training and EMG biofeedback relaxation training on chronic pain in persons with spinal-cord injury. Int J Clin Exp Hypn. 2009;57(3):239–68.PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Curtis KA, Tyner TM, Zachary L, Lentell G, Brink D, Didyk T, et al. Effect of a standard exercise protocol on shoulder pain in long-term wheelchair users. Spinal Cord. 1999;37(6):421–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Nawoczenski DA, Ritter-Soronen JM, Wilson CM, Howe BA, Ludewig PM. Clinical trial of exercise for shoulder pain in chronic spinal injury. Phys Ther. 2006;86(12):1604–18.PubMedCrossRefGoogle Scholar
  96. 96.
    Kemp BJ, Bateham AL, Mulroy SJ, Thompson L, Adkins RH, Kahan JS. Effects of reduction in shoulder pain on quality of life and community activities among people living long-term with SCI paraplegia: a randomized control trial. J Spinal Cord Med. 2011;34(3):278–84.PubMedCentralPubMedCrossRefGoogle Scholar

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© The Author(s) 2015

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.Institute of Clinical MedicineUniversity of BergenBergenNorway
  2. 2.Department of NeurologySpinal Cord Injury Center of Western Denmark, Viborg Regional HospitalViborgDenmark
  3. 3.Institute of Clinical MedicineAarhus UniversityAarhusDenmark
  4. 4.Department of NeurologyHaukeland University HospitalBergenNorway

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