The Management of Carpal Tunnel Syndrome

The Management of Carpal Tunnel Syndrome by Vinoth Ketheeswaran

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy where there is a compression of the median nerve at the wrist as it passes through an osteofibrous canal known as the carpal tunnel. In addition to the median nerve, the carpal tunnel contains the carpal bones, transverse carpal ligament, the flexor carpi radialis, flexor pollicis longus, flexor digitorum profundus, and flexor digitorum superficialis tendons.  Symptoms include pain in the hand and wrist, paraesthesia usually in the thumb, index finger, middle finger, and medial half of the ring finger, hand weakness, and dexterity loss.

CTS has substantial physical and psychological consequences such as depression and anxiety (Fernandez-de-las-Penas 2015) alongside a significant socioeconomic burden due to its impact on function, productivity, and costs associated with its management (Keith et al. 2010, Foley et al. 2007). CTS is managed conservatively via drugs, wrist splints, exercises, activity modification, injections, or non-conservatively via surgery with stronger evidence supporting the latter (Shi and MacDermid 2011). Despite the significant socioeconomic impact of CTS, it is considered a low surgical priority (Jerosch-Herold et al. 2014), with the waiting list for surgery being as long as ten months (Duquette 2015), with the demand for surgery anticipated to double over the next decade (Bebbington 2015). With this in mind, in addition to CTS surgery being a ‘restricted procedure’ on the NHS (Acobucci 2018), alternative management options with desired outcomes need to be considered.

Shared decision making (SDM) is when the care receiver and the clinician collaboratively make a health-related decision after discussing all the options, the likely harms, and benefits of the options, considering the individual’s preferences and values (Hoffman et al. 2014). SDM has been shown to increase patients’ knowledge of treatment options (Stacey et al. 2014), improve engagement in healthcare decision making (LeBlanc et al. 2015), improve clinical outcomes (Lindhiem 2014), and improve treatment decision satisfaction and overall care (Nota et al. 2014, Lofland 2017). SDM is underutilised within physiotherapy and healthcare generally; a systematic review of SDM in the rehabilitation setting showed that patients often reported minimal involvement in their care decisions (Rose et al. 2017).

Limited health literacy is a common issue with individuals with CTS (Rosebaum et al. 2016), and to facilitate SDM, all the management options need to be presented. The infographic that has been designed aims to provide the common management options of CTS to facilitate SDM with the person receiving care. This written justification aims critically evaluate the evidence for the conservative and non-conservative management of CTS.

The Management of CTS 

Inadequate access to conservative care is a common issue for individuals with CTS (Burke 2007). The usual conventional treatment from physiotherapy involves advice, splinting, manual therapy, and exercises. A recent randomised control trial revealed nocturnal splinting, education, and home exercises reduced conversion to surgery for CTS patients by 21% by 24 weeks (Lewis et al. 2020).

Splinting for CTS

Splinting is most commonly used at night to keep the wrist in a neutral position. It is attributed to preventing end range positions related to high carpal tunnel and median nerve pressures. There are links between increased pressure in the carpal tunnel and the development of CTS (Okutsu et al. 2004) with the pressure of the median nerve lowest in a neutral wrist position (Luchetti 1998, Weiss 1995). Keeping the wrist neutral is thought to cause a therapeutic effect by reducing oedema and promoting adequate blood circulation, subsequently reducing the pressure (Sugimoto 1994). Schmid et al. (2012) further supported this by conducting a study where twenty patients with mild to moderate CTS were randomly allocated a nocturnal splinting or exercise group for one week with MRI confirming the reduction in intraneural oedema in both groups. Although splinting was shown to reduce intraneural oedema within one week from ten minutes of nocturnal splinting, it would have been beneficial to see if there were any changes in oedema through the course of six to eight weeks that is typically advised for nocturnal splinting alongside wearing the splint overnight rather than ten minutes. However, it can be counterargued that the beneficial effects of the one-week splinting period in these patients are associated with the splinting itself rather than the natural course of CTS. It would be challenging to validate the study as it did not mention how long these patients had CTS, in addition to questioning the external validity of the finding due to the low number of participants.

Regarding the clinical efficacy of splinting, a Cochrane review has shown limited evidence of the short-term benefit (two to four weeks) of splinting compared to no treatment (Page et al. 2012). These results have to be interpreted with caution as out of the nineteen studies, only one study was blinded, only three studies concealed the allocation sequence, and some did not report the duration of the splinting. There was insufficient evidence of the efficacy of splinting over other non-surgical interventions such as oral steroids or exercises.

Exercises and manual therapy for CTS

Exercises and manual therapy focusing on influencing the median nerve are commonly used for CTS. There are predominately two main types of nerve treatment technique; neurodynamic mobilisations (NDM), which aims to move the nerve through the tissue, and interface techniques, which aims to modify the structures such as soft tissue and bone through which the nerve passes.  Both NDM and interface techniques have been shown to reduce the symptoms of CTS (Huisstede et al. 2010) with better efficacy of these interventions over other conservative management options, specifically electrophysical modalities (Wolny 2017) and clinical benefit to surgery (Fernandez-de-las-Penas et al. 2017).

Specific to CTS, the median nerve may be compromised as its passes into the carpal tunnel of the wrist; therefore, the carpal bones could be subjected to joint accessory mobilisations, aiming to increase the space within the carpal tunnel. Tal-Akabi and Rushton (2000) compared the effectiveness of carpal bone mobilisations and NDM for the treatment of CTS, comparing these two intervention groups with a control group that received no treatment. Although the treatment groups had a favourable outcome in symptom reduction, there was no statistical difference in the effectiveness between the two treatment groups. This research has shown that interface treatment can be just as effective in individuals with CTS. However, there was a small sample size of seven participants in each group, and no conclusion can be drawn regarding the long-term effects as there was only a three week follow up. A placebo effect may have also contributed to the positive results from the carpal bone mobilisation group. There is indirect evidence to support this, showing manual therapy having the highest proportion of patients who expected this type of treatment to significantly improve their neck pain (Bishop et al. 2013).

On the contrary, it has been shown that median nerve NDMs were no more effective than sham techniques in people with CTS (Bialosky et al. 2009). However, there were a few flaws to this randomised control trial. There was a small sample size of fourty, and generalisability could be questioned as the participants only consisted of women. In addition, a true control group was absent, and the findings could not be compared to natural history. Both the NDM group and the sham group received wrist splints, and its favourable outcomes in both groups could have been down to the splint rather than the specific intervention.

A combination of an NDM and interface treatment may be used. Although this evidence is scarce, De-la-Llave-Rincorn et al (2012) revealed that a median nerve slider with soft tissue mobilisations decreased pain in women with CTS. A combination of nerve and tendon gliding exercises for patients waiting for CTS surgery lowered the percentage of patients requiring surgery by 28.2% in a clinical trial involving hundred ninety-seven patients with a two-year follow-up (Rozmaryn et al. 1998).

The biomechanical effects of neurodynamic mobilisations

Due to extraneural and intraneural fibrosis from undispersed oedema, a nerve’s ability to glide through the interfacing structures may be restricted (Mackinnon 2002). The nerve’s inability to glide effectively from this restriction is likely to result in pain as the nerve is moved through the interfaces. Creep and hysteresis are one way in which the connective tissue properties of the nerve may be influenced; however, in the literature, there is uncertainty whether the nervous tissue becomes restricted post-injury.

Evidence has shown no difference in restriction in sciatic nerve excursion during a modified straight leg raise between individuals with spinally referred leg pain and asymptomatic individuals (Ridehalgh et al. 2015).  In support and specifically to the median nerve, Dilley et al (2008) also demonstrated no difference in restriction in median nerve excursion in individuals with non-specific arm pain. Although it can be argued that the non-specific arm pain was not specific to a particular aetiology, changes were also not seen in restriction in the median nerve with individuals with CTS (Erel et al. 2003).

Opposingly, Hough et al (2007) revealed a restriction in median nerve excursion at the carpal tunnel in a significant number of individuals with CTS. In further support, Korstanje et al (2012) also showed a greater reduction in median nerve excursion in the most affected hand than the least affected hand in individuals with bilateral CTS.

The neurophysiological effects of neurodynamic mobilisations

There is evidence suggesting clinically relevant neurophysiological effects that follow after NDM. Conventionally nerve treatment focused on the biomechanical effects, and although there has been a drive away from this over the years, it mustn’t be forgotten that the stimulus for the neurophysiological effects is via the biomechanical events that occur during the NDM positions.

The peripheral nerve sheaths of the peripheral nerves provide the most tensile strength to the nerve and provide an efficient diffusion barrier, preventing oedema from entering the endoneurial space. The nerve root and dorsal horn ganglion may be more susceptible to oedema entering the endoneurial space as they have a less effective barrier. This oedema may increase compression on the nerve and maintain an acidic nerve environment which may enhance peripheral nerve sensitivity (Steen et al. 1996). If the oedema is present for prolonged periods, it is likely to cause irreversible fibrotic changes, which have shown to be severe in individuals with severe CTS (Kleindienst et al. 1996). Therefore, reducing oedema would be favourable in individuals with CTS.

The dispersion of oedema could be attainable via the pumping effects caused by the NDM, as described by Coppieters and Butler 2008. There is evidence to support NDM dispersing oedema along the course of the nerve; cadaveric studies involving injecting dye into the tibial nerve showed significant fluid dispersion in an experimental group with NDM using ankle dorsiflexion and plantarflexion (Brown et al. 2011). Specifically, to CTS, cadaveric studies have shown five minutes of NDM promoted significant fluid dispersion in the median nerve at the carpal tunnel (Boudier-Reveret 2017). However, unlike the study by Brown et al 2011 a control limb was not used. There is further support from a human study by Schmid et al 2012 where a reduction in intraneural oedema was evident via nerve and tendon gliding exercises and nocturnal splinting.

Supraspinal modulation of pain via descending pain inhibition has been postulated as a mechanism from NDM. There is evidence of descending pain inhibition following NDM of the sciatic nerve in rat studies. Neurodynamic tensioners following chronic constriction injury of the sciatic nerve in rats, increased the expression of opioid receptors levels in the periaqueductal grey (Santos et al. 2014), suggesting that NDM facilitates pain relief by endogenous analgesic modulation.

Inflammation is common in entrapment neuropathies. It has been shown that nerve compression results in immune-mediated inflammation when the sciatic nerves of rats are progressively and mildly compressed (Schmid et al. 2013), with the degree of inflammation being dependent on the degree of compression. In neuropathic pain conditions, there is an activation of glial cells that synthesise inflammatory mediators and an increase in nerve growth factor production, which is influential in the development of hyperalgesia (Milligan and Watkins 2009). An increase in glial cells is responsible for heightened nerve sensitivity. There have been suggestions that NDM may lead to a dampening down effect in the immune response following a peripheral nerve injury. This has been backed up with evidence showing a reduction in glial cell activation from NDM in rats with chronic constriction injury of the sciatic nerve where the rats were subjected to NDM every other day (Santos et al. 2012).

Injections for CTS

Corticosteroid injections are another alternative management option for CTS. Corticosteroid injections have shown to have a more significant effect in symptom relief in mild or moderate CTS compared to night splinting at six weeks (Chesterton et al. 2018). However, at twenty-four weeks, the outcomes were similar. A systematic review of corticosteroid injections (Huisstede et al. 2010) and a Cochrane systematic review (Marshall et al. 2007) have further supported their effectiveness in the short term at one month compared to placebo, with inadequate evidence for the long-term. A randomised placebo-control trial showed the effectiveness of corticosteroid injection over ten weeks compared to placebo, with no support over the long term (Atroshi et al. 2013), reinforcing the short-term benefits of a corticosteroid injection.

 A randomised control trial has shown that a combination of splinting alongside a corticosteroid injection could be more effective in the long term for severe CTS (Khosrawi et al. 2016). However, these results have to be taken with caution due to the small sample size of fourty three, short intervention duration and follow up period of twelve weeks. A prospective study also exploring a combination of splinting and corticosteroid injection with a bigger sample size of seventy-three patients over a longer period of nine weeks with a longer one-year follow-up showed splinting and injections were effective in only 10% of patients (Graham et al. 2004).

Surgery for CTS

Surgical treatment is usually offered when adequate relief is not achieved with conservative management, or a presence of severe sensory disturbance, or thenar motor weakness. Surgery aims to increase the carpal tunnel volume by transection of the flexor retinaculum to release the pressure on the median nerve. A systematic review comparing surgical with non-surgical intervention demonstrated a slight benefit in favour of surgery regarding symptom relief and functional improvement at six and twelve months. A Cochrane systematic review (Verdugo et al. 2008) included a randomised control trial comparing surgery with nocturnal splinting, showing that there was better clinical improvement in favour of the surgery at three and six months follow up. At one year follow up it showed that there was significantly better relief of symptoms from surgical treatment. In a randomised trial comparing surgery with corticosteroid injection, both treatments were equally effective in short-term follow-up at three months, with surgery having an additional long-term benefit of symptom resolution at a two-year follow-up (Ly-Pen et al. 2012). Although not being a double-blind study is a limit to the study, it can be argued that it would have been unethical to have sham surgery. Given these short-term and long-term treatment differences and the potential for surgical complications, the evidence supports initial non-surgical management in individuals with mild or moderate CTS.

 

References

 Atroshi, I., Flondell, M., Hofer, M. and Ranstam, J. (2013). Methylprednisolone Injections for the Carpal Tunnel Syndrome: a randomized, placebo-controlled trial. Annals of Internal Medicine, 159(5), pp.309–17.

Bebbington, E. and Furniss, D. (2015). Linear regression analysis of Hospital Episode Statistics predicts a large increase in demand for elective hand surgery in England. Journal of Plastic, Reconstructive & Aesthetic Surgery, 68(2), pp.243–251.

Bialosky, J.E., Bishop, M.D., Price, D.D., Robinson, M.E., Vincent, K.R. and George, S.Z. (2009). A Randomized Sham-Controlled Trial of a Neurodynamic Technique in the Treatment of Carpal Tunnel Syndrome. Journal of Orthopaedic & Sports Physical Therapy, 39(10), pp.709–723.

Bishop, M.D., Mintken, P.E., Bialosky, J.E. and Cleland, J.A. (2013). Patient expectations of benefit from interventions for neck pain and resulting influence on outcomes. The Journal of Orthopaedic and Sports Physical Therapy, 43(7), pp.457–465.

Boudier-Revéret, M., Gilbert, KK., Allégue, DR., Moussadyk, M., Brismée, JM., Sizer, PS., Feipel, V., Dugailly, PM. and Sobczak, S. (2017). Effect of neurodynamic mobilization on fluid dispersion in median nerve at the level of the carpal tunnel: A cadaveric study. Musculoskeletal Science and Practice, 31, pp.45–51.

Brown, C.L., Gilbert, K.K., Brismee, J., Sizer, P.S., Roger James, C. and Smith, M.P. (2011). The effects of neurodynamic mobilization on fluid dispersion within the tibial nerve at the ankle: an unembalmed cadaveric study. Journal of Manual & Manipulative Therapy, 19(1), pp.26–34.

Burke, F.D., Bradley, M.J., Sinha, S., Wilgis, E.F.S. and Dubin, N.H. (2007). Primary care management of patients with carpal tunnel syndrome referred to surgeons: are non-operative interventions effectively utilised? Postgraduate Medical Journal, 83(981), pp.498–501.

Chesterton, L.S., Blagojevic-Bucknall, M., Burton, C., Dziedzic, K.S., Davenport, G., Jowett, S.M., Myers, H.L., Oppong, R., Rathod-Mistry, T., van der Windt, D.A., Hay, E.M. and Roddy, E. (2018). The clinical and cost-effectiveness of corticosteroid injection versus night splints for carpal tunnel syndrome (INSTINCTS trial): an open-label, parallel group, randomised controlled trial. The Lancet, 392(10156), pp.1423–1433.

Coppieters, M.W. and Butler, D.S. (2008). Do “sliders” slide and “tensioners” tension? An analysis of neurodynamic techniques and considerations regarding their application. Manual Therapy, 13(3), pp.213–221.

De-la-Llave-Rincon, A.I., Ortega-Santiago, R., Ambite-Quesada, S., Gil-Crujera, A., Puentedura, E.J., Valenza, M.C. and Fernández-de-las-Peñas, C. (2012). Response of Pain Intensity to Soft Tissue Mobilization and Neurodynamic Technique: A Series of 18 Patients With Chronic Carpal Tunnel Syndrome. Journal of Manipulative and Physiological Therapeutics, 35(6), pp.420–427.

Dilley, A., Odeyinde, S., Greening, J. and Lynn, B. (2008). Longitudinal sliding of the median nerve in patients with non-specific arm pain. Manual Therapy, 13(6), pp.536–543.

Duquette, S., Nosrati, N., Cohen, A., Munshi, I. and Tholpady, S. (2015). Decreased Wait Times After Institution of Office-Based Hand Surgery in a Veterans Administration Setting. JAMA Surgery, 150(2), p.182.

Erel, E., Dilley, A., Greening, J., Morris, V., Cohen, B. and Lynn B. (2003). Longitudinal Sliding of the Median Nerve in Patients with Carpal Tunnel Syndrome. Journal of Hand Surgery, 28(5), pp.439–443.

Fernández-de-las-Peñas, C., Cleland, J., Palacios-Ceña, M., Fuensalida-Novo, S., Alonso-Blanco, C., Pareja, J.A. and Alburquerque-Sendín, F. (2017). Effectiveness of manual therapy versus surgery in pain processing due to carpal tunnel syndrome: A randomized clinical trial. European Journal of Pain, 21(7), pp.1266–1276.

Fernández-de-las-Peñas, C., Fernández-Muñoz, J.J., Palacios-Ceña, M., Navarro-Pardo, E., Ambite-Quesada, S. and Salom-Moreno, J. (2015). Direct and Indirect Effects of Function in Associated Variables Such as Depression and Severity on Pain Intensity in Women with Carpal Tunnel Syndrome. Pain Medicine, 16(12), pp.2405–2411.

Foley, M., Silverstein, B. and Polissar, N. (2007). The economic burden of carpal tunnel syndrome: long-term earnings of CTS claimants in Washington State. American journal of industrial medicine, 50(3), pp.155–72.

Graham, R.G., Hudson, D.A., Solomons, M. and Singer, M. (2004). A Prospective Study to Assess the Outcome of Steroid Injections and Wrist Splinting for the Treatment of Carpal Tunnel Syndrome. Plastic and Reconstructive Surgery, 113(2), pp.550–556.

Hoffmann, T.C., Légaré, F., Simmons, M.B., McNamara, K., McCaffery, K., Trevena, L.J., Hudson, B., Glasziou, P.P. and Del Mar, C.B. (2014). Shared decision making: what do clinicians need to know and why should they bother? Medical Journal of Australia, 201(1), pp.35–39.

Hough, A.D., Moore, A.P. and Jones, M.P. (2007). Reduced longitudinal excursion of the median nerve in carpal tunnel syndrome. Archives of Physical Medicine and Rehabilitation, 88(5), pp.569–576.

Huisstede, B.M., Hoogvliet, P., Randsdorp, M.S., Glerum, S., van Middelkoop, M. and Koes, B.W. (2010). Carpal Tunnel Syndrome. Part I: Effectiveness of Nonsurgical Treatments–A Systematic Review. Archives of Physical Medicine and Rehabilitation, 91(7), pp.981–1004.

Jerosch-Herold, C., Shepstone, L., Wilson, E.C., Dyer, T. and Blake, J. (2014). Clinical course, costs and predictive factors for response to treatment in carpal tunnel syndrome: the PALMS study protocol. BMC Musculoskeletal Disorders, 15(1).

Keith, M.W., Masear, V., Chung, K.C., Amadio, P.C., Andary, M., Barth, R.W., Maupin, K., Graham, B., Watters, W.C., Turkelson, C.M., Haralson, R.H., Wies, J.L. and McGowan, R. (2010). American Academy of Orthopaedic Surgeons Clinical Practice Guideline on The Treatment of Carpal Tunnel Syndrome. The Journal of Bone and Joint Surgery-American Volume, 92(1), pp.217–219.

Kleindienst, A., Hamm, B., Hildebrandt, G. and Klug, N. (1996). Diagnosis and staging of carpal tunnel syndrome: Comparison of magnetic resonance imaging and intra-operative findings. Acta Neurochirurgica, 138(2), pp.228–233.

Korstanje, J.-W.H., Boer, M.S.-D., Blok, J.H., Amadio, P.C., Hovius, S.E.R., Stam, H.J. and Selles, R.W. (2012). Ultrasonographic assessment of longitudinal median nerve and hand flexor tendon dynamics in carpal tunnel syndrome. Muscle & Nerve, 45(5), pp.721–729.

Khosrawi, S., Mahmoodian, A. and Emadi, M. (2016). Effectiveness of splinting and splinting plus local steroid injection in severe carpal tunnel syndrome: A Randomized control clinical trial. Advanced Biomedical Research,5(1), p.16.

LeBlanc, A., Wang, A.T., Wyatt, K., Branda, M.E., Shah, N.D., Van Houten, H., Pencille, L., Wermers, R. and Montori, V.M. (2015). Encounter Decision Aid vs. Clinical Decision Support or Usual Care to Support Patient-Centered Treatment Decisions in Osteoporosis: The Osteoporosis Choice Randomized Trial II. PLOS ONE, 10(5): e0128063.

Lewis, K.J., Coppieters, M.W., Ross, L., Hughes, I., Vicenzino, B. and Schmid, A.B. (2020). Group education, night splinting and home exercises reduce conversion to surgery for carpal tunnel syndrome: a multicentre randomised trial. Journal of Physiotherapy, 66(2).

Lindhiem, O., Bennett, C.B., Trentacosta, C.J. and McLear, C. (2014). Client preferences affect treatment satisfaction, completion, and clinical outcome: A meta-analysis. Clinical Psychology Review, 34(6), pp.506–517.

Lofland, J., Johnson, P., Ingham, M., Rosemas, S., White, J.C. and Ellis, L. (2017). Shared decision-making for biologic treatment of autoimmune disease: influence on adherence, persistence, satisfaction, and health care costs. Patient Preference and Adherence, 18(11), pp.947–958.

Luchetti, R., Schoenhuber, R. and Nathan, P. (1998). Correlation of Segmental Carpal Tunnel Pressures with Changes in Hand and Wrist Positions in Patients with Carpal Tunnel Syndrome and Controls. Journal of Hand Surgery, 23(5), pp.598–602.

Ly-Pen, D., Andreu, J.L., Millan, I., de Blas, G. and Sanchez-Olaso, A. (2012). Comparison of surgical decompression and local steroid injection in the treatment of carpal tunnel syndrome: 2-year clinical results from a randomized trial. Rheumatology, 51(8), pp.1447–1454.

Mackinnon, S.E. (2002). Pathophysiology of nerve compression. Hand Clinics, 18(2), pp.231–241.

Marshall, S.C., Tardif, G. and Ashworth, N.L. (2007). Local corticosteroid injection for carpal tunnel syndrome. Cochrane Database of Systematic Reviews, 18(2).

Milligan, E.D. and Watkins, L.R. (2009). Pathological and protective roles of glia in chronic pain. Nature Reviews Neuroscience, 10(1), pp.23–36.

Nota, I., Drossaert, C.H., Taal, E., Vonkeman, H.E. and van de Laar, M.A. (2014). Patient participation in decisions about disease modifying anti-rheumatic drugs: a cross-sectional survey. BMC Musculoskeletal Disorders, 15(1).

Okutsu, I., Ninomiya, S., Yoshida, A., Hamanaka, I. and Kitajima, I. (2004). Measurement of Carpal Canal and Median Nerve Pressure in Patients With Carpal Tunnel Syndrome. Techniques in Hand & Upper Extremity Surgery, 8(2), pp.124–128.

Page, M.J., Massy-Westropp, N., O’Connor, D. and Pitt, V. (2012). Splinting for carpal tunnel syndrome. Cochrane Database of Systematic Reviews.

Ridehalgh, C., Moore, A. and Hough, A. (2015). Sciatic nerve excursion during a modified passive straight leg raise test in asymptomatic participants and participants with spinally referred leg pain. Manual Therapy, 20(4), pp.564–569.

Rose, A., Rosewilliam, S. and Soundy, A. (2017). Shared decision making within goal setting in rehabilitation settings: A systematic review. Patient Education and Counseling, 100(1), pp.65–75.

Rosenbaum, A.J., Dunkman, A., Goldberg, D., Uhl, R.L. and Mulligan, M. (2016). A Cross-Sectional Study of Musculoskeletal Health Literacy in Patients With Carpal Tunnel Syndrome. HAND, 11(3), pp.330–335.

Rozmaryn, L.M., Dovelle, S., Rothman, E.R., Gorman, K., Olvey, K.M. and Bartko, J.J. (1998). Nerve and tendon gliding exercises and the conservative management of carpal tunnel syndrome. Journal of Hand Therapy, 11(3), pp.171–179.

Santos, F.M., Silva, J.T., Giardini, A.C., Rocha, P.A., Achermann, A.P., Alves, A.S., Britto, L.R. and Chacur, M. (2012). Neural Mobilization Reverses Behavioral and Cellular Changes That Characterize Neuropathic Pain in Rats. Molecular Pain, 8, pp.1744–8069.

Santos, F., Grecco, L., Pereira, M., Oliveira, M., Rocha, P., Silva, J., Martins, D., Miyabara, E. and Chacur, M. (2014). The neural mobilization technique modulates the expression of endogenous opioids in the periaqueductal gray and improves muscle strength and mobility in rats with neuropathic pain. Behavioral and Brain Functions, 10(1), p.19.

Schmid, A.B., Coppieters, M.W., Ruitenberg, M.J. and McLachlan, E.M. (2013). Local and Remote Immune-Mediated Inflammation After Mild Peripheral Nerve Compression in Rats. Journal of Neuropathology & Experimental Neurology, 72(7), pp.662–680.

Schmid, A.B., Elliott, J.M., Strudwick, M.W., Little, M. and Coppieters, M.W. (2012). Effect of splinting and exercise on intraneural edema of the median nerve in carpal tunnel syndrome–an MRI study to reveal therapeutic mechanisms. Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society, 30(8), pp.1343–1350.

Shi, Q. and MacDermid, J.C. (2011). Is surgical intervention more effective than non-surgical treatment for carpal tunnel syndrome? a systematic review. Journal of Orthopaedic Surgery and Research, 11(6), p.17.

Stacey, D., Légaré, F., Lewis, K., Barry, M.J., Bennett, C.L., Eden, K.B., Holmes-Rovner, M., Llewellyn-Thomas, H., Lyddiatt, A., Thomson, R. and Trevena, L. (2017). Decision aids for people facing health treatment or screening decisions. Cochrane Database of Systematic Reviews, 4(4).

Steen, K.H., Steen, A.E., Kreysel, H.-W. and Reeh, P.W. (1996). Inflammatory mediators potentiate pain induced by experimental tissue acidosis. Pain, 66(2), pp.163–170.

Sugimoto, H., Miyaji, N. and Ohsawa, T. (1994). Carpal tunnel syndrome: evaluation of median nerve circulation with dynamic contrast-enhanced MR imaging. Radiology, 190(2), pp.459–466.

Tal-Akabi, A. and Rushton, A. (2000). An investigation to compare the effectiveness of carpal bone mobilisation and neurodynamic mobilisation as methods of treatment for carpal tunnel syndrome. Manual Therapy, 5(4), pp.214–222.

Verdugo, R.J., Salinas, R.A., Castillo, J.L. and Cea, G. (2008). Surgical versus non-surgical treatment for carpal tunnel syndrome. Cochrane Database of Systematic Reviews.

Weiss, N.D., Gordon, L., Bloom, T., So, Y. and Rempel, D.M. (1995). Position of the wrist associated with the lowest carpal-tunnel pressure. The Journal of Bone & Joint Surgery, 77(11), pp.1695–1699.

Wolny, T., Saulicz, E., Linek, P., Shacklock, M. and Myśliwiec, A. (2017). Efficacy of Manual Therapy Including Neurodynamic Techniques for the Treatment of Carpal Tunnel Syndrome: A Randomized Controlled Trial. Journal of Manipulative and Physiological Therapeutics, 40(4), pp.263–272.