NECK DISORDERS

Conservative Management of Mechanical Neck Disorders: A Systematic Review

ANITA R. GROSS, CHARLIE GOLDSMITH, JAN L. HOVING, TED HAINES, PAUL PELOSO, PETER AKER, PASQUALINA SANTAGUIDA, CYNTHIA MYERS, and the Cervical Overview Group

ABSTRACT.

Objective. To determine if conservative treatments (manual therapies, physical medicine methods, medication, and patient education) relieved pain or improved function/disability, patient satisfaction, and global perceived effect in adults with acute, subacute, and chronic mechanical neck disorders (MND) by updating 11 systematic reviews of randomized controlled trials (RCT).

Methods. Two independent authors selected studies, abstracted data, and assessed methodological quality from computerized databases. We calculated relative risks and standardized mean differences (SMD) when possible. In the absence of heterogeneity, we calculated pooled effect sizes.

Results. We studied 88 unique RCT. The mean methodological quality scores were acceptable in 59% of the trials. We noted strong evidence of benefit for maintained pain reduction [pooled SMD –0.85 (95% CI –1.20, –0.50)], improvement in function, and positive global perceived effect favoring exercise plus mobilization/manipulation versus control for subacute/chronic MND. We found moderate evidence of longterm benefit for improved function favoring direct neck strengthening and stretching for chronic MND, and for high global perceived effect favoring vertigo exercises. We noted moderate evidence of no benefit for botulinium-A injection [pooled SMD –0.39 (95% CI –01.25, 0.47)]. We found many treatments demonstrating short-term effects.

Conclusion. Exercise combined with mobilization/manipulation, exercise alone, and intramuscular lidocaine for chronic MND; intravenous glucocorticoid for acute whiplash associated disorders; and low-level laser therapy demonstrated either intermediate or longterm benefits. Optimal dosage of effective techniques and prognostic indicators for responders to care should be explored in future research. (First Release Jan 15 2007; J Rheumatol 2007;34:1083-102)

Key Indexing Terms:

NECK
WHIPLASH
DEGENERATIVE
RADICULAR
TREATMENTS
SYSTEMATIC REVIEW

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From the School of Rehabilitation Sciences, Clinical Epidemiology and Biostatistics, and Occupational Health and Environmental Medicine, McMaster University, Hamilton, Ontario, Canada; Coronel Institute of Occupational Health, Academic Medical Center, Universiteit van Amsterdam, Amsterdam, The Netherlands; and the Integrative Medicine Program, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.

Supported by a Problem-based Research Grant from Sunnybrook and Women's Health Sciences Centre, Toronto, Canada.

A.R. Gross, MSc, Associate Clinical Professor; C. Goldsmith, PhD, Professor; T. Haines, MSc, Associate Professor; P. Santaguida, PhD, Associate Professor, School of Rehabilitation Sciences, Clinical Epidemiology and Biostatistics, and Occupational Health and Environmental Medicine, McMaster University; J.L. Hoving, PhD, Senior Research Fellow, Coronel Institute of Occupational Health, Academic Medical Center, Universiteit van Amsterdam, and Department of Epidemiology and Preventive Medicine, Monash University, Australia; P. Peloso, MD, Director, Product Benefit Risk Assessment and Management, Amgen Inc.; P. Aker, MSc, Private Practice, Belleville, ON, Canada; C. Myers, PhD, Director, Integrative Medicine Program, H. Lee Moffitt Cancer Center.

The Cervical Overview Group: T. Kay, P. Kroeling, N. Graham, B. Haraldsson, A.M. Eady, K. Trinh, J. Ezzo, G. Bronfort, A. Morien, E. Wang, I. Cameron.

Address reprint requests to A.R. Gross, School of Rehabilitation Sciences, McMaster University, 1400 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. E-mail: grossa@mcmaster.ca

Accepted for publication October 13, 2006.

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Neck pain is still a major contributor to disability worldwide^1-4 , with about 70% of the population experiencing an episode of neck pain at some point in their lives^1,5 and 15% experiencing chronic neck pain⁶. Chronic pain accounts for $150 to $215 billion US each year in economic loss (i.e., lost workdays, therapy, disability)^7,8 , yet very little is known about the effectiveness of many of the available treatments. In this report, we update our previous systematic reviews from the Cervical Overview Group on conservative management for mechanical neck disorders^9-19.

MATERIALS AND METHODS

The medical and alternative-medicine literature was searched from 1997 to September 2004 with no language restrictions using a sensitive search strategy²⁰. It included computerized bibliographic databases: Cochrane Register of Controlled Trials (Central), Medline, Embase, Manual Alternative and Natural Therapy, Cumulative Index to Nursing and Allied Health Literature, Index to Chiropractic Literature, an acupuncture database in China (root to September 2005). Medical Subject Headings key words included terms related to anatomic, disorder/syndrome, treatment, and methodology. Figure 1 depicts the review retrieval flow from selection to metaanalyses. Two independent reviewers conducted study selection using pilot-tested forms (qw kappa 0.82, SD 0.05)²¹.

Selection criteria

Type of study. Published or unpublished (quasi-) randomized controlled trials.

Type of participant. Adults with acute (< 30 days), subacute (30–90 days), or chronic (> 90 days) neck disorders categorized as: (1) mechanical neck disorders (MND), including whiplash associated disorders (WAD I/II)^22,23 , myofascial neck pain, and degenerative changes or OA²⁴ ; (2) neck disorder with headache (NDH)^25-27 ; and (3) neck disorder with radicular findings (NDR), including WAD III^22,23.

Type of intervention. Medication, medical injections¹⁸ , acupuncture¹⁹ , electrotherapy¹⁷ , exercise¹⁶ , low-level laser therapy¹¹ , orthosis, thermal agents¹² , traction¹³ , massage¹⁵ , mobilization, manipulation¹⁰ , and patient education¹⁴.

The control group consisted of a placebo, wait-list/no treatment control; active treatment control (e.g., exercise and ultrasound vs ultrasound); or inactive treatment control (e.g., sham transcutaneous electrical nerve stimulation). Other comparisons were excluded.

Type of outcome. Pain, disability/function including work related measures, patient satisfaction, and global perceived effect (GPE)²⁸. Followup periods were defined as post-treatment (≤ 1 day), short-term (> 1 day to < 3 months), intermediate term (≥ 3 months to < 1 year), and longterm (≥ 1 year).

Two independent reviewers conducted data abstraction using pilot-tested forms. We calculated standard mean difference (SMD), relative risk (RR), number needed to treat, absolute benefit, and treatment advantage (Table 1, Figures 2 and 3). In the absence of heterogeneity (p ≥ 0.05), data were pooled statistically (random effects model) when we judged the studies to be clinically and statistically similar by Q-test (Figure 4). We categorized our findings using levels of evidence (Table 2)^29,30.

Methodological quality. We had at least 2 authors independently assess each selected study for methodological quality, based on the validated Jadad criteria³¹ (maximum score 5, high/acceptable score ≥ 3) and the van Tulder criteria³⁰ (maximum score 11, high/acceptable score ≥ 6; Table 2). The mean scores were 2.9 (SD 1.2) for Jadad, et al³¹ or 6.0 (SD 2.3) for the van Tulder, et al³⁰ criteria lists. Using a cutoff value of 50% (6/11) on the van Tulder criteria list, 59% of the included studies had "acceptable" methodological quality. Table 3shows methodological quality scores of all studies and Figure 5 the main methodological limitations of the studies by treatment category. Sensitivity analysis for methodological quality using the Jadad scale (high score ≥ 3) upheld our primary analysis. Metaregression was not possible.

RESULTS

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Figure 1. Study selection and metaanalysis for the 2004 Cervical Overview Group update. RCT: randomized controlled trial, MND: mechanical neck disorders, LLLT: low-level laser therapy, neg: negative metaanalysis.

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Figure 2. Intermediate (IT) and longterm (LT) results for continuous data, reported in standard mean difference (SMD), show evidence of benefit favoring pain reduction. In Pettersson's 1998 trial47 , although there was no significant effect on pain reduction, there was a clinically important effect on return to work. Direct comparison across all data is hampered by the various forms of controls (cntl) and would require a head-to-head trial comparing the various treatments. "A": high/acceptable methodological quality (≥ 3), "B": low quality on the Jadad scale31.

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Figure 3. Short (ST) and posttreatment effects across treatment categories are depicted for continuous data on pain relief. "A": high/acceptable methodological quality (≥ 3), "B": low quality on the Jadad scale31. ST: short-term, AROM: active range of motion.

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Figure 4. Metaanalyses for conservative treatments. "A": high/acceptable methodological quality (≥ 3), "B": low quality on the Jadad scale31.

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Figure 5. Proportion of studies (%) meeting quality criteria for concealment, blinding, cointervention, and compliance by treatment category. Proportion of studies meeting the van Tulder 2003 blinding criteria30 across all treatments was: care provider 30%, patient 56%, outcome assessor 67%. DT: drug therapy, PM: physical medicine methods, PE: patient education, MT: manual therapy.

We detailed trial findings by "level of evidence" and "treatment category" in the later sections. Table 1 details the magnitude of the effect in terms of effect size (SMD or RR), number needed to treat, and treatment advantage; Table 4 gives a summary of the level of evidence by treatment category.

Table 1. Evidence of benefit translated into clinically meaningful terms. For example, a multimodal management approach (exercise, mobilization, and manipulation) is compatible with a 28% to 70% treatment advantage over a control and a sustained absolute benefit in pain reduction of 25 mm (0–100 mm numeric rating scale) from baseline for 1 in 2 to 5 patients with subacute or chronic MND/NDH. cntl deteriorated: **baseline values different between treatment and control; LT/IT/ST: longterm/ intermediate/short-term results; SMD: standard mean difference; RR: relative risk; NA: not applicable; NPQ: Nordwick Park Questionnaire 0–36 scale converted to 0–100 scale; NDI: Neck Disability Index 0–50 scale converted to 0–100 scale; NPD: Neck Pain Disability VAS 0–100; MPQ: McGill Pain Questionnaire; DC: degenerative changes; OA: osteoarthritic.

Table 2. Jadad, et al31 and van Tulder, et al30 methodological quality criteria lists and classification of "Level of Evidence"29,30.

Table 3. Methodological quality of selected trials. Agreement between both methodological criteria list scores was acceptable (Spearman rank correlation: rho = 0.76). Specific major gaps continue to be dominant for concealment of treatment allocation, blinding (outcome assessor, patient, and treater), avoiding cointervention, and compliance to intervention (see Figure 5). Mobs/manip: mobilization and/or manipulation.

Table 4. Review article findings by intervention characteristics categorized as showing evidence of benefit/no benefit. Strong level of evidence denotes consistent findings in multiple high-quality randomized controlled trials; Moderate evidence denotes findings in a single, high-quality randomized controlled trial or consistent findings in multiple low-quality trials; Limited evidence indicates a single low-quality randomized trial. The comparisons noted after the author in column 2 are those noted by the author. ST/IT/LT: short-term, intermediate, longterm; neg: negative results; MND: mechanical neck disorder; NDH: neck disorder with headache; NDR: neck disorder with radicular findings; DC: degenerative changes; WAD: whiplash associated disorder; M-A: results based on a metaanalysis; s: session; w: week; Rx: treatment; mobs: mobilizations; manip: manipulation.

Evidence of benefit
Strong evidence
We found that multimodal approaches including stretching/ strengthening exercise and mobilization/manipulation for subacute/chronic MND, NDR, and NDH reduced pain (Figure 4^32-36), improved function, and resulted in favorable GPE in the long term.
Moderate evidence
Exercise. We noted 7 trials that supported various methods of direct neck strengthening and stretching exercises for chronic NDH³⁵ and chronic MND^32,37-39 (Figure 4^40,41 ) in the intermediate or long term for multiple outcomes. However, strengthening and stretching of only the shoulder region plus general conditioning^38,42 did not alter pain in the short or long term, but did assist in improving function in the short term for chronic MND. One study found an effect favoring active range of motion exercises for acute pain reduction of WAD in the short term^43,44. Other studies favored cervical proprioceptive training and eye-fixation exercises to achieve pain reduction, improved function and GPE in the short term, and GPE in the long term for cases of chronic MND^45,46 (Figure 4). The effect for pain was not maintained in the long term.
Medicine. We found 2 controlled trials favoring specific medicines in the intermediate or long term, as follows: intravenous glucocorticoid for pain reduction and reduced sick leave in cases of acute WAD⁴⁷ , and epidural injections for pain reduction and improved function in cases of chronic neck disorder with radiculopathy⁴⁸.
Low-level laser therapy. Using sensitivity analysis by disorder subtype, we found evidence to support the use of low-level laser therapy (830 or 904 nm) for pain reduction and functional improvement in the intermediate term for acute/subacute and chronic MND/degenerative changes^49-52. Although the frequency and duration of treatment were similar, other aspects of dosage (radiant power, energy density, emission frequency, duration of disorder) were diverse and precluded a metaanalysis.
Electrotherapy. We found a short course of low-frequency pulsed electromagnetic field was helpful to palliate pain for acute WAD I and II, acute MND, or chronic MND with associated degenerative changes. We noted an immediate posttreatment effect; this was not maintained into the short term^53-57.
Intermittent traction. For pain, we determined that there was moderate evidence of benefit favoring intermittent traction compared to control or placebo for chronic MND, NDR, degenerative changes^58,59. These were short-term results.
Acupuncture. Acupuncture was found to be effective for pain relief compared to inactive treatments either immediately posttreatment or in short-term followup for chronic MND^60-62 (Figure 4) and NDR⁶³. However, we noted that the evidence suggests no benefit for pain relief in the intermediate and long term and no functional improvements in the short, intermediate, or long term^61,62. Additionally, one high-quality study assessed the traditional Chinese medicine procedure of dry-needling to trigger points⁶⁴ and another low-quality trial on local "standard points"⁶⁵ did not relieve pain in the short term.
Limited evidence
We found limited evidence that suggested there may be benefit in the use of repetitive magnetic stimulation⁶⁶ , traditional Chinese massage⁶⁷ , orthopedic pillow⁶⁸ , and intramuscular injection of local anesthetic (lidocaine)⁶⁹.
Evidence of no benefit
We found evidence that varied between moderate and limited, for both intermediate and longterm use, suggesting that home exercise, hot packs, electromechanical stimulation, ultrasound, and combination of manipulation/mobilization/modalities do not relieve chronic pain or improve function in MND. Additionally, we found that short-term evidence suggests the following treatments do not aid pain reduction: medicines notably botulinum-A^70-75 (Figure 4), morphine added to an epidural injection, manipulation alone, various massage techniques, laser for myofascial pain, infrared light, static traction, spray and stretch^76,77 (Figure 4), electrotherapies (diadynamic current, galvanic current, iontophoresis, magnetic necklace), ultra-reiz, oral splint, neck school, and advice [to rest for acute WAD pain relief was inferior to active treatments in the short term^43,44,78 (Figure 4); advice to activate; or on pain and stress coping skills].
Conflicting evidence
We have recorded numerous trials with conflicting/unclear evidence in Table 5.
Adverse events
We found that minor, transient, and reversible side effects consisting of increased symptoms were occasionally reported. A valid estimate of clinically significant, uncommon, and rare adverse events cannot be made from these trials. Adverse effects of longterm steroid therapy⁸¹ and manipulation⁸² have been well described.

DISCUSSION
For treatment of subacute and chronic MND or NDH, our review found evidence favoring a multimodal strategy (exercise and mobilization/manipulation); exercise alone; intramuscular lidocaine injection; and low level laser therapy (for OA) for pain, function, and GPE in the short and long term. Acupuncture, low-frequency pulse electromagnetic field, repetitive magnetic stimulation, cervical orthopedic pillow, and traditional Chinese massage are favored for either immediate or short-term pain management. For acute WAD, we found that studies of intravenous glucocorticoid show reduction of work disability at 1 year, while stretching exercises and low-frequency pulse electromagnetic field reduce pain. For chronic NDR, we determined that epidural methylprednisolone and lidocaine improved function and pain in the short and long term, while intermittent traction improved pain in the short term. Other commonly used interventions were either not studied, were unclear, or were not compatible with any evidence of benefit.
Interpretation of the magnitude of these treatment effects can benefit communication with our patients, third-party payers, and policy-makers in terms of treatment advantage, expected absolute benefit, and number needed to treat. For example, as shown in Table 1, a multimodal management approach (exercise, mobilization, and manipulation) is compatible with a 28% to 70% treatment advantage over a control, and with a longterm absolute benefit in pain reduction of 25 mm on a numeric rating scale (0-100 mm) from baseline for 1 in 2 to 5 patients with subacute or chronic MND/NDH. Similarly, intramuscular lidocaine injection for chronic myofascial neck pain is associated with a 45% treatment advantage, 40 mm absolute benefit, and a number needed to treat of 3. Table 1 provides corresponding data for treatment types shown to be beneficial.
Despite a large increase in the number of trials since our 1996 review, the advances in our understanding of the effectiveness of treatments are modest. No substantive change in methodological quality has occurred since the 1980s. The main flaws were in concealment of allocation; blinding of patients, caregivers, and outcome assessors; avoidance of cointervention; and compliance. There continues to be ample room for improving the methodological quality of trials, as proposed in the Consolidated Standards of Reporting Trials (CONSORT) statement⁸³.
To date, few trials on neck disorders have looked at costs⁸⁴. However, given the lack of large treatment differences between interventions, economic evaluations are becoming increasingly important and should be performed in randomized clinical trials⁸⁵.
What are the most important unanswered questions with regard to treating mechanical neck disorders? Information on commonly used pain medications (nonsteroidal antiinflammatory drugs, acetaminophen, opioids) is needed. Glucocorticoid studies suggest reduction of work disability at 1 year; if this can be confirmed, it has important public health implications for acute whiplash injury. We need to understand the most effective treatment techniques, combinations, or approaches, and the optimal dosages. This is especially true for different forms of exercise therapy and manual therapy. Are there prognostic indicators for those who will or will not respond to care? Increased insight into compliance with treatments like exercise will help address application barriers. These are the challenging questions requiring focused attention.

REFERENCES

Search PubMed for:

1. Cote P, Cassidy D, Carroll L. The Saskatchewan Health and Back Pain Survey. The prevalence of neck pain and related disability in Saskatchewan adults. Spine 1998;23:1689-98. [MEDLINE]

2. Cote P, Cassidy JD, Carroll L. The factors associated with neck pain and its related disability in the Saskatchewan population. Spine 2000;25:1109-17. [MEDLINE]
3. Linton SJ, Hellsing AL, Hallden K. A population-based study of spinal pain among 35-45 year old individuals. Prevalence, sickleave, and health care use. Spine 1998;23:1457-63. [MEDLINE]
4. Pleis JR, Coles R. Summary health statistics for U.S. adults: National Health Interview Survey, 1998. National Center for Health Statistics. Vital Health Stat 2002;10:1-113.
5. Makela M, Heliovaara M, Sievers K, Impivaara O, Knekt P, Aromaa A. Prevalence determinants and consequences of chronic neck pain in Finland. Am J Epidemiol 1991;134:1356-67.[MEDLINE]
6. Bovim G, Schrader H, Sand T. Neck pain in the general population. Spine 1994;19:1307-9. [MEDLINE]
7. National Research Council. Musculoskeletal disorders and the workplace. Washington, DC: National Academy Press; 2001.
8. United States Bureau of Census. Statistical Abstract of the United States: 1996. 116th ed. Washington, DC: US Bureau of the Census; 1996.
9. Aker P, Gross AR, Goldsmith C, Peloso P. Conservative management of mechanical neck disorders. A systematic overview and meta-analysis. BMJ 1996;313:1291-6. [MEDLINE]
10. Gross AR, Hoving JL, Haines TA, et al. A Cochrane review of manipulation and mobilization for mechanical neck disorders. Spine 2004;29:1541-8. [MEDLINE]
11. Gross A, Kay T, Peloso PM, Goldsmith CH, Haines HT. Laser therapy for mechanical neck disorder: A Cochrane review [abstract]. Arthritis Rheum 2002;46 Suppl:S237.
12. Gross A, Kay T, Peloso PM, Haines T, Kroeling P. Thermal agents for mechanical neck disorders: A Cochrane review [abstract]. Arthritis Rheum 2002;46 Suppl:S237.
13. Graham N, Gross A, Goldsmith C, Cervical Overview Group. Traction for mechanical neck disorders: A systematic review. J Rehabil Med 2006;38:145-52. [MEDLINE]
14. Haines T, Gross AR, Goldsmith CH, Cervical Overview Group. Patient education for mechanical neck disorders. Cochrane Database Syst Rev 2006;in press.
15. Haraldsson BG, Gross AR, Myers CD, et al. Massage for mechanical neck disorders. Cochrane Database Syst Rev 2006;3:CD004871. [MEDLINE]
16. Kay T, Gross A, Santaguida PL, et al. Exercise for mechanical neck disorders. Cochrane Database Syst Rev 2005;3:CD004250.[MEDLINE]
17. Kroeling P, Gross A, Goldsmith CH, Cervical Overview Group. Electrotherapies for mechanical neck disorders. Cochrane Database Syst Rev 2005;2:CD004251. [MEDLINE]
18. Peloso P, Haines T, Gross A, et al. Medicinal and injection therapies for mechanical neck disorders (Cochrane Review). In: The Cochrane Library, 2004. Chichester, UK: John Wiley & Sons Ltd.; 2004.
19. Trinh KV, Graham N, Goldsmith CH, et al. Acupuncture for mechanical neck disorders. Cochrane Database Syst Rev 2006;3:CD004870. [MEDLINE]
20. Higgins JPT, Green S, editors. Locating and selecting studies. In: Cochrane Handbook for Systematic Reviews of Interventions 4.2.5. Section 5, 2005.
21. Cicchetti DV. Assessing inter-rater reliability for rating scales: resolving some basic issues. Br J Psychiatry 1976;129:452-6.
22. Spitzer WO, Leblanc FE, Dupuis M. Scientific approach to the assessment and management of activity related spinal disorders. Spine 1987;7:S1-S59.
23. Spitzer WO, Skovron ML, Salmi LR, et al. Scientific monograph of the Quebec Task Force on Whiplash-Associated Disorders: redefining "whiplash" and its management. Spine 1995;20:1S-73S.[MEDLINE]
24. Schumacher HR, Klippel JH, Koopman WJ, editors. Primer on the rheumatic diseases. 10th ed. Atlanta: The Arthritis Foundation; 1993.
25. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Headache Classification Committee of the International Headache Society Cephalalgia 1988;8 Suppl 7:1-96.
26. Olesen J, Gobel H. ICD-10 Guide for Headaches. Guide to the classification, diagnosis and assessment of headaches in accordance with the tenth revision of the International Classification of Diseases and related health problems and its application to neurology. Cephalgia 1997;17 Suppl 19:29-30.
27. Sjaastad O, Fredriksen TA, Pfaffenrath V. Cervicogenic headache: diagnostic criteria. Headache 1990;30:725-6. [MEDLINE]
28. Turk DC, Dworkin RH. What should be the core outcomes in chronic pain clinical trials? Arthritis Res Ther 2004;6:151-4.[MEDLINE]
29. Sackett DL, Straus SE, Richardson WS, Rosenberg W, Haynes RB. Evidence-based medicine: how to practice and teach EBM. 2nd ed. Edinburgh: Churchill Livingstone; 2000.
30. van Tulder M, Furlan A, Bombardier C, et al. Updated method guidelines for systematic reviews in the Cochrane Collaboration Back Review Group. Spine 2003;28:1290-9. [MEDLINE]
31. Jadad A, Moore A, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996;17:1-12. [MEDLINE]
32. Allison GT, Nagy BM, Hall T. A randomized clinical trial of manual therapy for cervico-brachial pain syndrome -- a pilot study. Manual Therapy 2002;7:95-102. [MEDLINE]
33. Brodin H. Cervical pain and mobilization. Int J Rehabil Res 1984;7:190-1. [MEDLINE]
34. Brodin H. Cervical pain and mobilization. Manual Medicine 1985;2:18-22.
35. Jull G, Trott P, Potter H, et al. A randomized controlled trial of exercise and manipulative therapy for cervicogenic headache. Spine 2001;27:1835-43. [MEDLINE]
36. Karlberg M, Magnusson M, Eva-Maj M, Melander A, Moritz U. Postural and symptomatic improvement after physiotherapy in patients with dizziness of suspected cervical origin. Arch Phys Med Rehabil 1996;77:874-82. [MEDLINE]
37. Gam AN, Warming S, Larsen LH, et al. Treatment of myofascial trigger-points with ultrasound combined with massage and exercise -- a randomised controlled trial. Pain 1998;77:73-9. [MEDLINE]
38. Lundblad I, Elert J, Gerdle B. Randomized controlled trial of physiotherapy and Feldenkrais interventions in female workers with neck-shoulder complaints. J Occup Rehabil 1999;9:179-94.
39. Ylinen J, Takala EP, Nykanen M, et al. Active neck muscle training in the treatment of chronic neck pain in women. JAMA 2003;289:2509-16. [MEDLINE]
40. Bronfort G, Aker PD, Evans R, Goldsmith CH, Nelson B, Vernon H. A randomized controlled clinical trial of rehabilitative exercise and chiropractic spinal manipulation for chronic neck pain. Spine 2001;26:788-99. [MEDLINE]
41. Evans R, Bronfort G, Nelson B, Goldsmith C. Two-year follow-up of a randomized clinical trial of spinal manipulation and two types of exercise for patients with chronic neck pain. Spine 2002;27:2383-9. [MEDLINE]
42. Takala EP, Viikari-Juntura E, Tynkkynen EM. Does group gymnastics at the workplace help in neck pain? A controlled study. Scand J Rehabil Med 1994;26:17-20. [MEDLINE]
43. McKinney LA, Dornan JO, Ryan M. The role of physiotherapy in the management of acute neck sprains following road traffic accidents. Arch Emerg Med 1989;6:27-33. [MEDLINE]
44. McKinney LA. Early mobilisation and outcome in acute sprains of the neck. BMJ 1989;299:1006-8. [MEDLINE]
45. Revel M, Minguet M, Gergoy P, Vaillant J, Manuel JL. Changes in cervicocephalic kinesthesia after a proprioceptive rehabilitation program in patients with neck pain: a randomized controlled study. Arch Phys Med Rehabil 1994;75:895-9. [MEDLINE]
46. Taimela S, Takala EP, Asklof T, Seppala K, Parviainen S. Active treatment of chronic neck pain. Spine 2000;25:1021-7. [MEDLINE]
47. Pettersson K, Toolanen G. High-dose methylprednisolone prevents extensive sick leave after whiplash injury. A prospective, randomized, double-blind study. Spine 1998;23:984-9. [MEDLINE]
48. Stav A, Ovadia L, Sternberg A, Kaadan M, Weksler N. Cervical epidural steroid injection for cervicobrachialgia. Acta Anaesthesiol Scand 1993;37:562-6. [MEDLINE]
49. Ceccherelli F, Altafini L, Lo Castro G, Avila A, Ambrosio F, Giron GP. Diode laser in cervical myofascial pain: A double-blind study versus placebo. Clin J Pain 1989;5:301-4. [MEDLINE]
50. Ozdemir F, Birtane M, Kokino S. The clinical efficacy of low-power laser therapy on pain and function in cervical osteoarthritis. Clin Rheumatol 2001;20:181-4. [MEDLINE]
51. Taverna E, Parrini M, Cabitza P. Laser therapy vs placebo in the treatment of some bone and joints pathology. Minerva Ortop Traumatol 1990;41:631-6.
52. Soriano FS, Rios R, Pedrola M, Giangnorio J, Battagliotti CR. Acute cervical pain is relieved with gallium arsenide (GaAs) laser, a double-blind preliminary study. Laser Therapy 1996;8:149-54.
53. Foley-Nolan D, Barry C, Coughlan RJ, O'Connor P, Roden D. Pulsed high frequency (27 MHz) electromagnetic therapy for persistent neck pain: A double blind, placebo-controlled study of 20 patients. Orthopaedics 1990;13:445-51. [MEDLINE]
54. Foley-Nolan D, Moore K, Codd M, Barry C, O'Connor P, Coughlan RJ. Low energy high frequency pulsed electromagnetic therapy for acute whiplash injuries. A double blind randomized controlled study. Scand J Rehabil Med 1992;24:51-9. [MEDLINE]
55. Rigato M, Battisti E, Fortunato M, Giordano N. Comparison between the analgesic and therapeutic effects of a musically modulated electromagnetic field (TAMMEF) and those of a 100 Hz electromagnetic field: blind experiment on patients suffering from cervical spondylosis or shoulder periarthritis. J Med Eng Technol 2002;26:253-8. [MEDLINE]
56. Thuile C, Walzi M. Evaluation of electromagnetic fields in the treatment of pain in patients with lumbar radiculopathy or the whiplash syndrome. Neurol Rehabil 2002;17:63-7. [MEDLINE]
57. Trock DH, Bollet AJ, Markoll R. The effect of pulsed electromagnetic fields in the treatment of osteoarthritis of the knee and the cervical spine. Report of randomized, double blind, placebo controlled trials. J Rheumatol 1994;21:1903-11. [MEDLINE]
58. Zylbergold RS, Piper MC. Cervical spine disorders: A comparison of three types of traction. Spine 1985;10:867-71.[MEDLINE]
59. Goldie I, Landquist A. Evaluation of the effects of different forms of physiotherapy in cervical pain. Scand J Rehabil Med 1970;2-3:117-21. [MEDLINE]
60. Petrie JP, Hazleman BL. A controlled study of acupuncture in neck pain. Br J Rheumatol 1986;25:271-5. [MEDLINE]
61. Irnich D, Behrens N, Molzen H, et al. Randomized trial of acupuncture compared with conventional massage and "sham" laser acupuncture for treatment of chronic neck pain. BMJ 2001;322:1574-8. [MEDLINE]
62. White P, Lewith G, Prescott P, Conway J. Acupuncture versus placebo for the treatment of chronic mechanical neck pain. Ann Intern Med 2004;141:920-8. [MEDLINE]
63. Coan RM, Wong G, Coan PL. The acupuncture treatment of neck pain: A randomized controlled study. Am J Chinese Med 1982;9:326-32.
64. Irnich D, Behrens N, Gleditsch JM, et al. Immediate effects of dry needling and acupuncture at distant points in chronic neck pain: results of a randomized, double-blind, sham-controlled crossover trial. Pain 2002;99:83-9. [MEDLINE]
65. Petrie JP, Langley GB. Acupuncture in the treatment of chronic cervical pain. A pilot study. Clin Exp Rheumatol 1983;1:333-5.[MEDLINE]
66. Smania N, Corato E, Fiaschi A, Pietropoli P, Aglioti S, Tinazzi M. Therapeutic effects of peripheral repetitive magnetic stimulation on myofascial pain syndrome. Clin Neurophysiol 2003;114:350-8.[MEDLINE]
67. Cen SY, Loy SF, Sletten EG, McLaine A. The effect of traditional Chinese therapeutic massage on individuals with neck pain. Clin Acupuncture Oriental Med 2003;4:88-93.
68. Joechems OB, Vortman BJ, Derde MP. Gerandomiseerd onderzoek naar het effect van The Pillow op de nachtrust, pijn en voorkeur van patienten met klachten van de nek-en schouderregio. :159-163.
69. Esenyel M, Caglar N, Aldemir T. Treatment of myofascial pain. Am J Phys Med Rehabil 2000;79:48-52. [MEDLINE]
70. Cheshire WP, Abashian SW, Mann JD. Botulinum toxin in the treatment of myofascial pain syndrome. Pain 1994;59:65-9.[MEDLINE]
71. Schnider P, Moraru E, Vigl M, et al. Physical therapy and adjunctive botulinum toxin type A in the treatment of cervical headache: a double-blind, randomised placebo-controlled study.
J Headache Pain 2002;3:93-9.
72. Freund BJ, Schwartz M. Treatment of chronic cervical-associated headache with botulinum toxin-A: A pilot study. Headache 2000;40:231-6. [MEDLINE]
73. Freund BJ, Schwartz M. Treatment of whiplash associated neck pain with botulinum toxin-A: A pilot study. J Rheumatol 2000;27:481-4. [MEDLINE]
74. Wheeler AH, Goolkasian P, Gretz SS. A randomized, double-blind prospective pilot study of botulinum toxin injection for refractory, unilateral, cervicothoracic, paraspinal myofascial pain syndrome. Spine 1998;23:1662-7. [MEDLINE]
75. Wheeler AH, Goolkasian P, Gretz SS. Botulinum toxin A for the treatment of chronic neck pain. Pain 2001;94:255-60. [MEDLINE]
76. Hou CR, Tsai LC, Cheng KF, Chung KC, Hong CZ. Immediate effects of various physical therapeutic modalities on cervical myofascial pain and trigger point sensitivity. Arch Phys Med Rehabil 2002;83:1406-14. [MEDLINE]
77. Snow CJ, Aves Wood R, Dowhopoluk V, et al. Randomized controlled clinical trial of spray and stretch for relief of back and neck myofascial pain. Physiother Canada 1992;44:8.
78. Mealy K, Brennan H, Fenelon GC. Early mobilisation of acute whiplash injuries. BMJ 1986;292:656-7. [MEDLINE]
79. Birch S, Jamison R. Controlled trial of Japanese acupuncture for chronic myofascial neck pain: Assessment of specific and nonspecific effects of treatment. Clin J Pain 1998;14:248-55. [MEDLINE]
80. White PF, Craig WF, Vakharia AS, Ghoname EA, Ahmed HE, Hamza MA. Percutaneous neuromodulation therapy: Does the location of electrical stimulation effect the acute analgesic response? Anesth Analg 2000;91:949-54. [MEDLINE]
81. Da Silva JAP, Jacobs JWG, Kirwan JR, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis 2006;65:285-93.[MEDLINE]
82. Haldeman S, Kohlbeck FJ, McGregor M. Stroke, cerebral artery dissection, and cervical spine manipulation therapy. J Neurol 2002;249:1098-104. [MEDLINE]
83. Moher D, Schulz KF, Altman DG, CONSORT Group. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Lancet 2001;357:1191-4. [MEDLINE]
84. Korthals-de Bos IBC, Hoving JL, van Tulder MW, et al. Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomized controlled trial. BMJ 2003;326:1-6. [MEDLINE]
85. van der Roer, Boos N, van Tulder MW. Economic evaluation: a new avenue of outcome assessment in spinal disorders. Eur Spine J 2006;15:109-17. [MEDLINE]
86. Sand T, Bovim G, Held G. Intracutaneous sterile water injections do not relieve pain in cervicogenic headache. Acta Neurol Scand 1992;86:526-8. [MEDLINE]
87. Brockow T, Dillner A, Franke A, Resch KL. Analgesic effectiveness of subcutaneous carbon-dioxide insufflations as an adjunct treatment in patients with non-specific neck or low back pain. Complement Ther Med 2001;9:68-76. [MEDLINE]
88. van Wieringen S, Jansen T, Smits MG, Nagtegaal JF, Coenen AML. Melatonin for chronic whiplash syndrome with delayed melatonin onset. Clin Drug Invest 2001;21:813-20.
89. Castagnera L, Maurette P, Pointellart V, Vital JM, Erny P, Stenegas J. Long-term results of cervical epidural steroid injection with and without morphine in chronic cervical radicular pain. Pain 1994;58:239-43. [MEDLINE]
90. Koes B, Bouter LM, Knipshild PG, et al. The effectiveness of manual therapy, physiotherapy and continued treatment by general practitioner for chronic nonspecific back and neck complaints: design of a randomized clinical trial. J Manipulative Physiol Ther 1991;14:498-502. [MEDLINE]
91. Koes BW, Bouter LM, van Mameren H, et al. Randomized clinical trial of manipulative therapy and physiotherapy for persistent back and neck complaints: results of one year follow up. BMJ 1992;304:601-5. [MEDLINE]
92. Koes BW, Bouter LM, van Mameren H, et al. A blind randomized clinical trial of manual therapy and physiotherapy for chronic back and neck complaints: Physical outcome measures. J Manipulative Physiol Ther 1992;15:16-23. [MEDLINE]
93. Koes BW, Bouter LM, van Mameren H, et al. Randomized clinical trial of manual therapy and physiotherapy for persistent back and neck complaints. Manual Therapy Netherlands 1992;1:7-12.
94. Koes BW, Bouter LM, van Mameren H, et al. A randomized clinical trial of manual therapy and physiotherapy for persistent back and neck complaints. Subgroup analysis and relationship between outcomes measure. J Manipulative Physiol Ther 1993;16:211-19.[MEDLINE]
95. Koes BW, Bouter LM, van Mameren H, et al. The effectiveness of manual therapy, physiotherapy, and treatment by the general practitioner for nonspecific back and neck complaints. Spine 1992;17:28-35. [MEDLINE]
96. Koes BW, den Haag. Cip-Gegevens Koninklijke Bibliotheek; 1992.
97. Horneij E, Hemborg B, Jensen I, Ekdahl C. No significant differences between intervention programmes on neck, shoulder and low back pain: a prospective randomized study among home-care personnel. J Rehabil Med 2001;33:170-6. [MEDLINE]
98. Sloop PR, Smith DS, Goldenberg E, Dore C. Manipulation for chronic neck pain: A double-blind controlled study. Spine 1982;7:532-5. [MEDLINE]
99. Hanten WP, Barret M, Gillespie-Plesko M. Effects of active head retraction with retraction/extension and occipital release on pressure pain threshold of cervical and scapular trigger points. Physiother Theory Pract 1997;13:285-91.
100. Howe DH, Newcombe RG, Wade MT. Manipulation of the cervical spine -- a pilot study. J Roy Coll Gen Pract 1983;33:574-9.[MEDLINE]
101. Bitterli J, Graf R, Robert F, Adler R, Mumenthaler M. Zur objectivierung der manualtherapeutischen beeinflussbarkeit des spondylogenen kopfschmerzes. Nervenarzt 1977;48:259-62.
102. Hanten WP, Olson SL, Butts NL, Nowicki AL. Effectivenes of a home program of ischemic pressure followed by sustained stretch for treatment of myofascial trigger points. Phys Ther 2000;
80:997-1003. [MEDLINE]
103. Flynn T. A comparative study between ultra-reiz and ultra sound in the treatment for relief of pain in whiplash injuries. Physiother Ireland 1987;8:11-4.
104. Lewith GT, Machin D. A randomized trial to evaluate the effect of infra-red stimulation of local trigger points, versus placebo, on the pain caused by cervical osteoarthrosis. Acupunct Electrother Res 1981;6:277-84. [MEDLINE]
105. Philipson T, Haagensen N, Laumann V, Nies M, Thorup K, Hansen TI. Effekten af diadynamisk stroem pa kroniske bloeddelsmerter i nakke-skulderaget [The effect of diadynamic current on chronic soft-tissue pain in the neck and shoulder girdle]. Ugeskr Laeger 1983;145:479-81. [MEDLINE]
106. Fialka V, Preisinger E, Bohler A. Zur physikalischen Diagnostik und physikalischen Therapie der Distorsio columnae vertebralis cervicalis. Z Phys Med Baln Med Klim 1989;18:390-7.
107. Hong CZ, Lin JC, Bender LF, Schaeffer JN, Meltzer RJ, Causin P. Magnetic necklace: Its therapeutic effectiveness on neck and shoulder pain. Arch Phys Med Rehabil 1982;63:462-6. [MEDLINE]
108. Hsueh TC, Cheng PT, Kuan TS, Hong CZ. The immediate effectiveness of electrical nerve stimulation and electrical muscle stimulation on myofascial trigger points. Am J Phys Med Rehabil 1997;76:471-6. [MEDLINE]
109. Thorsen H, Gam AN, Jensen H, Hojmark L, Wahlstrom L. Lav-energi laserbehandling effekt ved lokaliseret fibromyalgi i nakke-og skulderregioner. Ugeskr Laeger 1991;153:1801-4. [MEDLINE]
110. Thorsen H, Gam AN, Svensson BH, et al. Low level laser therapy for myofascial pain in the neck and shoulder girdle. A double-blind, cross-over study. Scand J Rheumatol 1992;21:139-41.[MEDLINE]
111. Seidel U, Uhlemann C. Behandlund der zervikalen Tendomyose [Therapy of cervical tendomyosis]. Deutsche Z Akupunk 2002;12:258-69.
112. Waylonis GW, Wilke S, O'Toole D, Waylonis DA, Waylonis DB. Chronic myofascial pain: Management by low-output helium-neon laser therapy. Arch Phys Med Rehabil 1988;69:1017-20.[MEDLINE]
113. Karppinen K, Eklund S, Suoninen E, Eskelin M, Kirveskari P. Adjustment of dental occlusion in treatment of chronic cervicobrachial pain and headache. J Oral Med 1999;26:715-21.[MEDLINE]
114. Gennis P, Miller L, Gallagher J, Giglio J, Carter W, Nathanson N. The effect of soft cervical collars on persistent neck pain in patients with whiplash injury. Acad Emerg Med 1996;3:568-73.[MEDLINE]
115. Borchgrevink GE, Kaasa A, McDonagh D, Stiles TC, Haraldseth O, Lereim I. Acute treatment of whiplash neck sprain injuries. A randomized trial of treatment during the first 14 days after a car accident. Spine 1998;23:25-31. [MEDLINE]
116. Kamwendo K, Linton SJ. A controlled study of the effect of neck school in medical secretaries. Scand J Rehabil Med 1991;23:143-52. [MEDLINE]
117. Brewerton DA. Pain in the neck and arm: a multicentre trial of the effects of physiotherapy. BMJ 1966;1:253-8.
118. Klaber-Moffett JA, Hughes GI. An investigation of the effects of cervical traction. Part 1: Clinical effectiveness. Clin Rehabil 1990;4:205-11.
119. Schnabel M, Vassiliou T, Schmidt TH, et al. Ergebnisse der frühfunktionellen krankengymnastischen Übungsbehandlung nach HWS-Distorsion [Results of early mobilisation of acute whiplash injuries]. Der Schmerz 2002;16:15–21. [MEDLINE]
120. Chee EK, Walton H. Treatment of trigger point with microamperage transcutaneous electrical nerve stimulation -- The Electro-Acuscope 80. J Manipulative Physiol Ther 1986;9:131-4.[MEDLINE]
121. Nordemar R, Thorner C. Treatment of acute cervical pain -- a comparative group study. Pain 1981;10:93-101. [MEDLINE]
122. Persson L, Karlberg M, Magnusson M. Effects of different treatments on postural performance in patients with cervical root compression. A randomized prospective study assessing the importance of the neck in postural control. J Vestib Res 1996;6:439-53. [MEDLINE]
123. Persson LC, Carlsson CA, Carlsson JY. Long-lasting cervical radicular pain managed with surgery, phyiotherapy or a cervical collar: A prospective, randomized study. Spine 1997;22:751-8.[MEDLINE]
124. Persson LCG, Lilja A. Pain, coping, emotional state and physical function in patients with chronic radicular neck pain. A comparison between patients treated with surgery, physiotherapy or neck collar -- a blinded, prospective randomized study. Disabil Rehabil 2001;23:325-35. [MEDLINE]
125. Persson LCG, Moritz U, Brandt L, Carlsson CA. Cervical radiculopathy: pain, muscle weakness and sensory loss in patients with cervical radiculopathy treated with surgery, physiotherapy or cervical collar. A prospective, controlled study. Eur Spine J 1994;6:256-66. [MEDLINE]
126. Kogstad E. Cervicobrachialgia. Tidsskr Nor Laegeforen nr 1978;16:845-8.
127. Nasswetter G, de los Santos AR, Marti ML, Girolamo GD. Asociacion de clonixinato de lisina con ciclobenzaprina en afecciones dolorosas del raquis con contractura muscular. Pren Med Argent 1998;85:507-14.
128. Basmajian JV. Cyclobenzaprine hydrochloride effect on skeletal muscle spasm in the lumbar region and neck: Two double-blind controlled clinical and laboratory studies. Arch Phys Med Rehabil 1978;59:58-63.
129. Basmajian JV. Reflex cervical muscle spasm: Treatment by diazepam, phenobarbital or placebo. Arch Phys Med Rehabil 1983;64:121-4. [MEDLINE]
130. Thomas M, Eriksson SV, Lundeberg T. A comparative study of diazepam and acupuncture in patients with osteoarthritis pain: A placebo controlled study. Am J Chinese Med 1991;19:95-100.
131. Salzmann VE, Wiedemann O, Loffler L, Sperber H. Tetrazepam in der behandlung akuter zervikalsyndrome, randomisierte doppleblinde pilotstudie zum vergleich von Tetrazepam und plazebo. Fortsch Med 1993;34:544-8. [MEDLINE]
132. Bose K. The efficacy and safety of eperisone in patients with cervical spondylosis: results of a randomized, double-blind, placebo-controlled trial. Methods Find Exp Clin Pharmacol 1999;21:209-13.[MEDLINE]
133. Payne RW, Sorenson EJ, Smalley TK, Brandt EN. Diazepam, meprobamate and placebo in musculoskeletal disorders. JAMA 1964;188:157-60.
134. Dostal C, Pavelka K, Lewit K. Ibuprofen v lecbe cervickokranialniho syndromu v kombinaci manipulacni lecbou. Fysiatricky vestnik 1978;56:258-63.
135. Terzi T, Karakurum B, Ucler S, Inan LE, Tulumay C. Greater occipital nerve blockade in migraine, tension-type headache and cervicogenic headache. J Headache Pain 2002;3:137-41.
136. Castagnera L, Maurette P, Pointellart V, Vital JM, Erny P, Stenegas J. Long-term results of cervical epidural steroid injection with and without morphine in chronic cervical radicular pain. Pain 1994;58:239-43. [MEDLINE]

137. Glossop ES, Goldberg E, Smith DS, Williams HM. Patient