Acute neck pain is a common problem seen in both young and older populations (Hogg-Johnson 2008). It is estimated that one-third of American and European adults may suffer from neck pain (Croft 2001). It is said that the lifetime incidence of neck pain is 67% (Cote 1998).The incidence of neck pain is greater among women than men (Fejer 2006). Factors that contribute to neck pain include poor posture, an occupation involving desktop work, injury and psychological stress (Ariens 2001; Croft 2001; Hoy 2010; McLean 2010). Among the various types of neck pain, 'non-specific neck pain' is one of the most common patterns of neck disorder. Persistent neck pain can result in disability, stress, loss of work hours and economic burden to society (Borghouts 1998; Cote 1998). Various options are available for managing neck pain (Hurwitz 2008), ranging from exercise and manual therapy (D'Sylva 2010) to cognitive-behavioural therapy. Reviews have examined the role of exercise (Kay 2005), manipulation (Miller 2010), mobilisation (Gross 2010), electrotherapy (Kroeling 2009), traction (Graham 2006), education (Haines 2009), acupuncture (Trinh 2007) and massage (Ezzo 2007) in the management of neck pain. Cryotherapy or cold therapy is widely used for acute soft tissue injury (Hubbard 2004). However, the effect of cryotherapy (ice therapy) in the management of acute non-specific neck pain is not clear.
Description of the condition
'Non-specific neck pain', also known as 'mechanical neck pain', is neck pain with no specific underlying pathology (e.g. fracture, dislocation, neoplasm, disc disease, degeneration) or systemic disease (Bogduk 1984; Borghouts 1998). The onset of neck pain is usually sudden and accompanied by stiffness of the neck. Individuals with non-specific neck pain complain of pain in the neck with or without pain in the shoulder and arm regions. In some individuals, the pain may be referred to the head and thorax. In the acute stage, which is less than six weeks (Furlan 2009), the neck pain may be more disabling, leading to absence from work. It has been noted that people with greater severity of pain in the acute stage and with a previous history of neck pain seem to have a poor prognosis (Borghouts 1998). Hence, it is important to manage neck pain effectively in the acute stage.
Description of the intervention
Cold therapy or cryotherapy is defined as the application of substances that remove heat from the body for therapeutic purposes (Nadler 2004). The application of such substances causes a reduction in the tissue temperature, which, in turn, gives rise to the desired physiological and therapeutic effects (discussed in the next section). Cryotherapy is applied by various methods including the use of ice packs, ice towels, ice massage, frozen peas, gel packs, vapo-coolant sprays, ice immersion and cold whirlpool bath. It is considered an effective modality for pain relief that is inexpensive and easily available. The duration of cold application varies with the method of cryotherapy, ranging from a few seconds (vapocoolant sprays) to 20 minutes (cold whirlpool, ice packs). In addition, cold application can be continuous (e.g. ice packs, ice immersion) or intermittent (e.g. ice massage, intermittent cold compression).
How the intervention might work
Cryotherapy reduces the temperature of the tissues to which it is being applied. This produces vasoconstriction and leads to a decrease in the metabolic rate of the tissues. These physiological effects result in control of inflammation and edema, which leads to reductions in pain and spasm－the main therapeutic effects of cold therapy. Moreover, cryotherapy is said to produce an analgesic effect by reducing the nerve conduction velocity (Chesterton 2002; Algafly 2007). In cases of acute injury, cryotherapy has been found to reduce recovery time (Swenson 1996) and enhance return to normal activity and participation in sports.
The effects of cryotherapy vary with the method of application. For instance, it is said that ice massage decreases the muscle temperature at a faster rate when compared with ice packs or a cold whirlpool. Similarly, continuous application and intermittent application have diverse effects on tissue temperature, pain and recovery (Myrer 1998; Zemke 1998; Dykstra 2009).
Although its effects vary depending on the mode of application, cryotherapy is said to provide benefits, both physiological and therapeutic, leading to better functional recovery. It has been suggested that the skin temperature should drop by at least 15°C to achieve the desired effects (Auley 2001). However, if not applied with adequate caution, cryotherapy may lead to adverse effects such as frost bite, nerve injury and reduced reflex activity (Swenson 1996; Auley 2001). Unmonitored and prolonged exposure when the skin temperature falls to below 20°C can result in frostbite, and prolonged application of cryotherapy with compression in the areas where nerves are superficial (e.g. median nerve at the wrist) can lead to nerve injury.
Why it is important to do this review
Cryotherapy is widely used in managing acute sports injuries and post surgery when post-traumatic or postoperative inflammation is predominantly manifested. However, in acute non-specific neck pain, the causative factors and the sources of symptoms are varied. Pain may arise from any mechanical dysfunction (e.g. facet joint dysfunction, muscle dysfunction), resulting in inflammation of the affected area. It is important to know whether cryotherapy, a simple, safe tool, can ease acute pain by reducing inflammation and metabolic rate, thereby preventing long-term disability. Very limited evidence has been found on the effect of cryotherapy in acute non-specific neck pain.
To assess the effects of cryotherapy on pain and functional limitation in adults with acute non-specific neck pain.
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs) that assess the effects of cryotherapy in adults with acute non-specific neck pain will be included in the review. Quasi-randomised controlled trials (QRCTs) will also be included because it is anticipated that RCTs relevant to this review will be limited. QRCTs are clinical controlled trials in which allocation has been done through quasi-random methods, such as alternation, date of birth, participant register number and days of the week.
Types of participants
Trials that include participants who are 18 years of age or older with complaints of "acute non-specific neck pain" will be included in the review. Participants who complain of (i) pain over the neck (ii) with/without referred pain over the head, thorax, shoulder and arm regions will be considered as those experiencing "neck pain". "Non-specific" pain is defined as pain without detection of a specific systemic disease as the underlying cause of the complaints. Participants with radicular pain and pathological causes of neck pain will be excluded. Studies that have included participants with spinal pain, in general, will be included if the neck pain was analysed separately. Participants with a first episode or recurrent episodes of acute non-specific neck pain will be included in the review. For the purposes of this review, the term "acute" is defined as symptom duration of "less than six weeks", according to the Updated Method Guidelines for Systematic Reviews in the Cochrane Back Review Group (CBRG; Furlan 2009). Studies with a mixed sample of participants with both acute and non-acute neck pain will be included if the authors have done a group-wise analysis (e.g. acute vs non-acute neck pain) and have presented separate results for each group.
Types of interventions
Studies that have investigated the effects of cryotherapy, in any form (e.g. ice pack, ice cubes, vapocoolant sprays), with any method of application (e.g. ice pack, ice massage, immersion), at any dosage and in any treatment setting (e.g. clinic, home), will be included in the review.
Studies designed to investigate the distinctive contribution of cryotherapy will be included.
The following comparisons would be considered appropriate for the review.
- Cryotherapy versus no treatment, placebo treatment or wait-list control.
- Cryotherapy versus any other therapy,
- Cryotherapy plus any other therapy versus the same therapy without cryotherapy of any type.
Types of outcome measures
Primary outcomes of interest will be one or more of the following.
- Pain intensity.
- Patient-reported (e.g. visual analogue scale (VAS)).
- Clinically evaluated (e.g. pressure pain threshold).
- Functional activity limitation (e.g. Neck Disability Index).
- Global perceived effect or global improvement.
Work-related outcomes (e.g. return to work, absenteeism) and adverse effects (e.g. increase in symptoms) will be considered as secondary outcomes.
Studies reporting immediate and short-term (˜ 4 weeks) effects of treatment will be included in the review. Long-term effects on function (longer than 4 weeks) will be considered if they are reported in any of the included studies.
Search methods for identification of studies
All available evidence relevant to the research question will be included in the review with no language restrictions.
A computer-aided search of the following databases will be conducted since their inception.
- CBRG (Cochrane Back Review Group) Trials Register.
- The Cochrane Register of Controlled Trials (CENTRAL).
- Index to Chiropractic Literature.
- Australasian Medical Index.
General search engines.
- Google Scholar.
- Turning Research Into Practice database.
Subject headings (MeSH) and keywords, including anatomical terms, disorder terms, treatments and methodological terms, will be used in identifying relevant trials according to the recommendations given by the Cochrane Back Review Group (Furlan 2009). The MEDLINE strategy is shown in Appendix 1 and will be modified for the other databases.
Searching other resources
In addition to the databases mentioned above, the review authors will search the reference lists of relevant reviews and trials to identify appropriate articles. They will look through conference abstracts and proceedings to locate published and unpublished articles on cryotherapy for neck pain. The expertise of a research librarian will be used in conducting the search.
Data collection and analysis
Selection of studies
Two review authors (JRW and SS) with expertise in the field of musculoskeletal physiotherapy will independently assess the titles and abstracts of studies retrieved from the literature search on the basis of selection criteria. Reports that are obviously irrelevant will be excluded. The review authors will then independently examine the full text of the identified reports and will include the studies that meet the selection criteria. The reliability of study selection between the two review authors will be assessed using the Kappa statistic (Orwin 1994). Disagreements between the review authors will be resolved by discussion, and a third review author will be consulted if disagreements persist.
Data extraction and management
The two review authorsers (JRW and SS) will perform data extraction using standardised data extraction forms. Data on study characteristics (e.g. source or setting, funding, study design), participants (e.g. number, age, gender, diagnostic criteria, duration of disorder), interventions (e.g. number of interventions, control and experimental interventions, co-interventions, duration, type and dosage of the intervention), outcomes (types of outcomes, frequency and duration of follow-up, change scores or final value scores of the outcomes) and results and the authors' conclusions will be extracted. In case of multiple reports, data from each report will be extracted separately and then combined across multiple data collection forms. Any disagreements between the review authors will be resolved by discussion. A third review author will be consulted if unresolved disagreements persist.
Assessment of risk of bias in included studies
The risk of bias assessment will be performed by the two review authors independently using the updated Cochrane Back Review Group criteria, which are shown in Appendix 2 and are based on criteria in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (Higgins 2011). Criteria will be scored as "low risk", "high risk" or "unclear" and will be reported in the 'risk of bias table'. If any information on methodological issues is unclear or missing, an attempt will be made to obtain additional information from authors of the studies. Studies satisfying at least six of the 12 criteria and having no serious flaws will be considered to have a "low" risk of bias (Furlan 2009).
Measures of treatment effect
Outcomes on pain intensity (i.e. VAS, numerical rating scale (NRS), pressure-pain threshold) and functional activities will be examined as standardized mean differences (SMDs) between treatment groups. An attempt will be made, if possible, to transform the effect back to the units used in the studies, so that interpretation of the effect can be easier for clinicians. For dichotomous outcomes (i.e. recovery, return-to-work, absenteeism, adverse effects), a risk ratio (RR) will be calculated. If global perceived effect or global improvement is assessed using a measurement scale, this information will be summarised as a dichotomous outcome, and the intervention effect will be described as a risk ratio. A fixed-effect model will be used for all analyses. However, if a substantial amount of heterogeneity remains unexplained by the subgroup or sensitivity analyses, results will be reported using a random-effects model. For comparisons where studies are too heterogeneous, a meta-analysis will not be performed, and the treatment effect will be analysed by means of narrative synthesis. In situations where only one study measures the outcome, data will be considered to be "indirect" and "sparse" (if fewer than 400 participants are included in cases of continuous outcomes, or if fewer than 300 events are included in cases of dichotomous outcomes).
The clinical relevance of included studies will be independently scored by the two review authors according to the guidelines put forth by the CBRG (Furlan 2009; Appendix 3). Each of the five questions will be scored positively (+) if the clinical relevance item was fulfilled, negatively (-) if the item was not fulfilled and as unclear (?) if data were not available. The following cut-offs will be considered as minimal clinically important changes for neck pain and function: 30% change on VAS (Lee 2003) and a change of 3.5 points on the Neck Disability Index (Pool 2007).
Unit of analysis issues
To minimise unit-of-analysis errors, data from cross-over trials will be included, only if data are available before the cross-over of the intervention is done. Cluster-randomised trials will be included in the analysis and will be analysed appropriately. In cases of studies involving repeated measurements, the data from each time frame (e.g. immediate effect, short-term effect) will be analysed separately for each outcome measure. If more than two interventions are evaluated in a single study, multiple “pair-wise” comparisons between all possible pairs will be performed. In cases in which an outcome measure such as an adverse effect may recur, the count data will not be considered as dichotomous data, hence the summary statistic for the meta-analysis will be the rate ratio.
Dealing with missing data
In cases where data are missing, the original authors would be contacted to request the required information. If data from the original authors could not be sought, the data would be assumed to be 'missing at random', and possible assumptions will be made as follows. In cases where follow-up data are not available, baseline measurements will be used as measures for subsequent follow-up, assuming that the intervention produces no effect.
Assessment of heterogeneity
Clinical homogeneity in the included RCTs will be examined by considering whether the studies are similar in terms of setting, participants, interventions and outcomes. Heterogeneity in methodology will be assessed by examining the variability in study design and in risk of bias. Statistical heterogeneity will be determined using a Chi² test with level of significance at 0.05. Values of I² that are greater than 75% will be considered to show "a very high" level of heterogeneity, in which case pooling of studies will not be done. If values of I² are 40% to 74%, studies will be pooled in a random-effects model. Values less than 40% will be considered as "low or no" heterogeneity, and the studies will be analysed using a fixed-effect model (Higgins 2011).
Assessment of reporting biases
Funnel plots will be constructed to assess the presence of any reporting or publication bias, if sufficient studies are available.
The overall quality of the evidence for each outcome measure will be analysed using the adapted GRADE approach, as recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and by the updated CBRG method guidelines (Furlan 2009). The quality of the evidence on a specific outcome is based on performance against five factors: study design, risk of bias and consistency of results, directness (generalisability), precision (sufficient data) and reporting of results across all studies that measure that particular outcome. The quality starts at high when high-quality RCTs provide results for the outcome and is reduced by one level for each of the factors not met.
High-quality evidence: Findings are consistent among at least 75% of RCTs with no limitations in study design, with consistent, direct and precise data and with no known or suspected publication biases. Further research is unlikely to change the estimate of effect or our confidence in the results.
Moderate-quality evidence: One of the domains is not met. Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low-quality evidence: Two of the domains are not met. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low-quality evidence: three of the domains are not met. We are very uncertain about the results.
No evidence: No RCTs were identified that addressed this outcome.
The analyses mentioned above will be done even if insufficient data are available. According to the GRADE Working Group, no precise cut-off level is available to define 'insufficient' data; N < 300 events for dichotomous data and N < 400 for continuous data are generally considered 'insufficient' (Furlan 2009).
Subgroup analysis and investigation of heterogeneity
If a sufficient number of studies are retrieved, subgroup analyses will be performed to examine the effects of the study method (e.g. study design, risk of bias), treatment differences (e.g. type or mode of cryotherapy, dosage) and time frame.
Sensitivity analysis will be done to determine whether results on effectiveness of cryotherapy are influenced by studies that have a high risk of bias or by those that do not have adequate concealment of allocation. If the studies including participants with acute and non-acute neck pain are included, a sensitivity analysis will be done to assess the influence of those studies on the overall findings. In cases for which missing data are being imputed or assumed, sensitivity analysis will be performed to discover the effect of the assumption or imputation on the results of the review.
We would like to acknowledge the efforts of Dr Prathap Tharyan (Director, South Asian Cochrane Network, Prof. B.V. Moses and ICMR Advanced Centre for Research and Training in Evidence-Informed Health Care, Christian Medical College, Vellore) and his team for inspiring and training us regarding the Cochrane Collaboration and methods used in performing a systematic review. We would also like to thank Ms Victoria Pennick (former CBRG Managing Editor), Allison Kelly (CBRG Editorial Assistant), Rachal Couban (CBRG Trials Search Co-ordinator) and their respective teams for their valuable guidance and support from the start and throughout the process of submitting this protocol. We are grateful to Mrs Savita Ravindra (Principal and Head, Department of Physiotherapy, M.S. Ramaiah Medical College) for her continuous support and encouragement towards submitting this protocol.
Appendix 1. MEDLINE search strategy
1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
5. drug therapy.fs.
10. (animals not (humans and animals)).sh.
11. 9 not 10
13. Neck Muscles/
14. Cervical Plexus/
15. exp Cervical Vertebrae/
16. Atlanto-Axial Joint/
17. Atlanto-Occipital Joint/
18. Spinal Nerve Roots/
19. exp Brachial Plexus/
21. Neck Pain/
22. acute cervical pain.mp.
23. non-specific neck pain.mp.
24. nonspecific neck pain.mp.
25. mechanical neck pain.mp.
30. exp Arthritis/
31. exp Myofascial Pain Syndromes/
34. exp Spinal Osteophytosis/
35. exp Spondylosis/
36. Intervertebral Disk Degeneration/
37. Intervertebral Disk Displacement/
38. "Ossification of Posterior Longitudinal Ligament"/
39. Whiplash Injuries/
40. Cervical Rib Syndrome/
42. Brachial Plexus Neuritis/
46. Thoracic Outlet Syndrome/
47. Post-Traumatic Headache/
48. cervicogenic headache.mp.
50. 29 and 49
51. 26 or 50
52. exp Cryotherapy/
53. (cryotherapy or ice or cool or cold).mp.
54. 52 or 53
55. 11 and 51 and 54
Appendix 2. Criteria for assessing risk of bias
Random sequence generation (selection bias)
Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
Risk of selection bias is low if the investigators describe a random component in the sequence generation process, such as referring to a random number table, using a computer random number generator, coin tossing, shuffling cards or envelopes, throwing dice, drawing lots or minimising (minimisation may be implemented without a random element, and this is considered equivalent to being random).
Risk of selection bias is high if the investigators describe a non-random component in the sequence generation process, such as sequence generated by odd or even date of birth, date (or day) of admission, hospital or clinic record number or allocation by judgement of the clinician, preference of the participant, results of a laboratory test or a series of tests or availability of the intervention.
Allocation concealment (selection bias)
Selection bias (biased allocation to interventions) due to inadequate concealment of allocations before assignment
Risk of selection bias is low if participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: central allocation (including telephone, Web-based and pharmacy-controlled randomisation); sequentially numbered drug containers of identical appearance or sequentially numbered, opaque, sealed envelopes.
Risk of bias is high if participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation based on using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes used without appropriate safeguards (e.g. if envelopes were unsealed or non-opaque or were not sequentially numbered); alternation or rotation; date of birth; case record number or other explicitly unconcealed procedures.
Blinding of participants
Performance bias due to knowledge of the allocated interventions by participants during the study
Risk of performance bias is low if blinding of participants was ensured and it was unlikely that the blinding could have been broken; or if no blinding or incomplete blinding was used, but the review authors judge that the outcome is not likely to be influenced by lack of blinding.
Blinding of personnel/care providers (performance bias)
Performance bias due to knowledge of the allocated interventions by personnel/care providers during the study
Risk of performance bias is low if blinding of personnel was ensured and it was unlikely that the blinding could have been broken; or if no blinding or incomplete blinding was used, but the review authors judge that the outcome is not likely to be influenced by lack of blinding.
Blinding of outcome assessor (detection bias)
Detection bias due to knowledge of the allocated interventions by outcome assessors
Risk of detection bias is low if blinding of the outcome assessment was ensured and it was unlikely that the blinding could have been broken; or if no blinding or incomplete blinding was used, but the review authors judge that the outcome is not likely to be influenced by lack of blinding, or:
- for participant-reported outcomes in which the participant was the outcome assessor (e.g. pain, disability): Risk of bias for outcome assessors is low if risk of bias for participant blinding is low (Boutron 2005);
- for outcome criteria that are clinical or therapeutic events that will be determined by the interaction between participants and care providers (e.g. co-interventions, length of hospitalisation, treatment failure), in which the care provider is the outcome assessor: Risk of bias for outcome assessors is low if risk of bias for care providers is low (Boutron 2005); and
- for outcome criteria that are assessed from data from medical forms: Risk of bias is low if the treatment or adverse effects of the treatment could not be noticed in the extracted data (Boutron 2005).
Incomplete outcome data (attrition bias)
Attrition bias due to amount, nature or handling of incomplete outcome data
Risk of attrition bias is low if no outcome data were missing; reasons for missing outcome data were unlikely to be related to the true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data were balanced in numbers, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with the observed event risk was not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, the plausible effect size (difference in means or standardised difference in means) among missing outcomes was not enough to have a clinically relevant impact on observed effect size, or missing data were imputed using appropriate methods (if dropouts are very large, imputation using even "acceptable" methods may still suggest a high risk of bias) (van Tulder 2003). The percentage of withdrawals and dropouts should not exceed 20% for short-term follow-up and 30% for long-term follow-up and should not lead to substantial bias (these percentages are commonly used but arbitrary and are not supported by the literature) (van Tulder 2003).
Selective reporting (reporting bias)
Reporting bias due to selective outcome reporting
Risk of reporting bias is low if the study protocol is available and all of the study's prespecified (primary and secondary) outcomes that are of interest in the review have been reported in the prespecified way, or if the study protocol is not available, but it is clear that the published reports include all expected outcomes, including those that were prespecified (convincing text of this nature may be uncommon).
Risk of reporting bias is high if not all of the study's prespecified primary outcomes have been reported; one or more primary outcomes are reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not prespecified; one or more reported primary outcomes were not prespecified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely, so that they cannot be entered in a meta-analysis or the study report fails to include results for a key outcome that would be expected to have been reported for such a study.
Group similarity at baseline (selection bias)
Bias due to dissimilarity at baseline for the most important prognostic indicators
Risk of bias is low if groups are similar at baseline for demographic factors, value of main outcome measure(s) and important prognostic factors (examples in the field of back and neck pain are duration and severity of complaints, vocational status and percentage of participants with neurological symptoms) (van Tulder 2003).
Co-interventions (performance bias)
Bias because co-interventions were different across groups
Risk of bias is low if no co-interventions were provided, or if they were similar between index and control groups (van Tulder 2003).
Compliance (performance bias)
Bias due to inappropriate compliance with interventions across groups
Risk of bias is low if compliance with the interventions was acceptable (i.e. completion of more than 80% of scheduled sessions across all groups). We will check clinical trials registries when assessing the possibility of a publication bias based on reported intensity/dosage, duration, number and frequency for both index and control intervention(s). For single-session interventions (e.g. surgery), this item is irrelevant (van Tulder 2003).
Risk of bias is low if all randomly assigned participants were reported/analysed in the group to which they were allocated by randomisation.
Timing of outcome assessments (detection bias)
Bias because important outcomes were not measured at the same time across groups
Risk of bias is low if all important outcome assessments for all intervention groups were measured at the same time (van Tulder 2003).
Bias due to problems not covered elsewhere in the table
Risk of bias is low if the study appears to be free of other sources of bias not addressed elsewhere (e.g. study funding).
Appendix 3. Assessing the clinical relevance
1. Are the participants described in detail so that you can decide whether they are comparable with patients that you see in your practice?
2. Are the interventions and treatment settings described well enough that you can provide the same for your patients?
3. Were all clinically relevant outcomes measured and reported?
4. Is the size of the effect clinically important?
5. Are the likely treatment benefits worth the potential harms?
Contributions of authors
Conceiving of the protocol - Williams JR
Designing, drafting and writing the protocol - Williams JR and Srikantaiah S
Reading and providing expert advice on the protocol - Mani R
Providing final approval of the protocol - All authors
Declarations of interest
Sources of support
- Department of Physiotherapy, M. S. Ramaiah Medical College, Bangalore, India.
- Indian Council for Medical Research, India.