Hypoalgesic Effect of Neural Mobilization

The purpose of these study is to compare the effectivity of the Cervical Lateral Glide physical therapy neural mobilization technique to the complete absence of treatment in a group of patients who suffer cervicobrachial pain.

The Cervical Lateral Glide (CLG) is a neural tissue mobilization technique capable of achieving a hypoalgesic effect during the onset of cervicobrachial pain symptoms. This happens through a series of complex physiologic interactions which are not fully understood. The CLG Physical therapy technique consists of controlled movements of the cervical and brachial plexus neural tissue. Hypoalgesic effect produced by CLG is associated to an increase in neural tissue mobility, edema, inflammation and intraneural pressure reduction, without any known side effects when applied properly, except for a momentary worsening of symptoms (the only known side effect of CLG), which is an important contrast to the wide and sometimes severe spectrum of side effects derived from drug therapy used to treat cervicobrachial pain. It is believed that the hypoalgesic effect offered by neural tissue mobilization is a consequence of descending nervous system pain modulation activity and an improvement in the distinct biomechanical properties of the involved neural tissue.Despite the increase in scientific interest in evidence based options to treat pain and neural tissue mobilization techniques there is a current lack of enough controlled double blind clinical trials that measure the effectiveness of neural tissue mobilization techniques such as the CLG and its specific effect over cervicobrachial pain. For this reason the present investigation consisted in the application of a treatment protocol based on CLG neural tissue mobilization in a controlled double blind clinical trial with the aim to assess its clinical effectiveness in treating pain symptoms

15 minutes Cervical Lateral Glide neural mobilization 5 times a week During 6 weeks Patient's adequate cervical spine linear alignment was determined through the baseline use of a Universal Goniometer Device in each application of Cervical Lateral Glide neural mobilization.

Non-surgical non-invasive Cervical Lateral Glide neural mobilization procedure was applied by a physical therapist continuously during 2 minutes in 5 different occasions with 1 minute of rest between each 2 minute application of the Neural Mobilization technique. The intervention was applied during a period of 6 weeks. The correct linear alignment of patient's cervical spine was determined through the baseline use of a Universal Goniometer Device in each application of Cervical Lateral Glide neural mobilization.

the Numeric Rating scale for Pain (NRS) is an 11 point scale for patient self reporting of pain in which 0 points represents the total absence of pain and 10 points the worst state of pain, it was employed to evaluate the presence and relieve of cervicobrachial pain symptoms.

at baseline for both arms and 1 hour after the application of treatment only in the experimental arm, corresponding to intervention days 1, 15 and 30

Change from baseline of the Physical function involving the affected upper limb using the Quik DASH Scale

The disabilities of the arm quick test (Quick DASH) is a self report short questionnaire designed to measure physical function and symptoms in people with any or several musculoskeletal disorders of the upper limb.

Cervical rotation was assessed in units of rotation degrees, using the cervical range-of-motion device (CROM).

at baseline for both arms and 1 hour after the application of treatment only in the experimental arm, corresponding to intervention days 1 and 30

Inclusion Criteria: Clinical diagnosis of cervicobrachial pain confirmed by magnetic resonance imaging Presence of unilateral symptoms of arm pain, paresthesia or numbness in the upper extremity during at least 3 continuous months previous to the application of treatment. Positive results in all of the following tests: Spurling, Distraction, and Upper Limb Exclusion Criteria: Contraindication in the use of nonsteroidal anti inflammatory drugs (NSAIDs) The use of any type of treatment, therapy, procedure or drug to relieve pain Patients who are under anticonvulsant, antidepressant or psychotropic medication Vertebral instability Vertebral osteoporosis Vertebral or spine infection. Neurologic diseases of genetic, infectious or neoplastic origin Cervical stenosis myelopathy Pregnancy Kinesiophobia Endocrine disorders and menopause History of spine surgery Intellectual disability, severe mental illness, intoxication, severe sleep deprivation, Alzheimer's disease.

Schug SA, Goddard C. Recent advances in the pharmacological management of acute and chronic pain. Ann Palliat Med. 2014 Oct;3(4):263-75. doi: 10.3978/j.issn.2224-5820.2014.10.02.

Cowell IM, Phillips DR. Effectiveness of manipulative physiotherapy for the treatment of a neurogenic cervicobrachial pain syndrome: a single case study -- experimental design. Man Ther. 2002 Feb;7(1):31-8. doi: 10.1054/math.2001.0429.

Salt E, Wright C, Kelly S, Dean A. A systematic literature review on the effectiveness of non-invasive therapy for cervicobrachial pain. Man Ther. 2011 Feb;16(1):53-65. doi: 10.1016/j.math.2010.09.005. Epub 2010 Nov 12.

Allison GT, Nagy BM, Hall T. A randomized clinical trial of manual therapy for cervico-brachial pain syndrome -- a pilot study. Man Ther. 2002 May;7(2):95-102. doi: 10.1054/math.2002.0453.

Huisstede BM, Bierma-Zeinstra SM, Koes BW, Verhaar JA. Incidence and prevalence of upper-extremity musculoskeletal disorders. A systematic appraisal of the literature. BMC Musculoskelet Disord. 2006 Jan 31;7:7. doi: 10.1186/1471-2474-7-7.

Radhakrishnan K, Litchy WJ, O'Fallon WM, Kurland LT. Epidemiology of cervical radiculopathy. A population-based study from Rochester, Minnesota, 1976 through 1990. Brain. 1994 Apr;117 ( Pt 2):325-35. doi: 10.1093/brain/117.2.325.

Daffner SD, Hilibrand AS, Hanscom BS, Brislin BT, Vaccaro AR, Albert TJ. Impact of neck and arm pain on overall health status. Spine (Phila Pa 1976). 2003 Sep 1;28(17):2030-5. doi: 10.1097/01.BRS.0000083325.27357.39.

Isabel de-la-Llave-Rincon A, Puentedura EJ, Fernandez-de-Las-Penas C. Clinical presentation and manual therapy for upper quadrant musculoskeletal conditions. J Man Manip Ther. 2011 Nov;19(4):201-11. doi: 10.1179/106698111X13129729551985.

Antonelli BA, de Paula Xavier AA, Oenning P, Baumer MH, da Silva TF, Pilatti LA. Prevalence of cervicobrachial discomforts in elementary school teachers. Work. 2012;41 Suppl 1:5709-14. doi: 10.3233/WOR-2012-0927-5709.

Dillingham TR. Evaluating the patient with suspected radiculopathy. PM R. 2013 May;5(5 Suppl):S41-9. doi: 10.1016/j.pmrj.2013.03.015. Epub 2013 Mar 19.

Boyles R, Toy P, Mellon J Jr, Hayes M, Hammer B. Effectiveness of manual physical therapy in the treatment of cervical radiculopathy: a systematic review. J Man Manip Ther. 2011 Aug;19(3):135-42. doi: 10.1179/2042618611Y.0000000011.

Eubanks JD. Cervical radiculopathy: nonoperative management of neck pain and radicular symptoms. Am Fam Physician. 2010 Jan 1;81(1):33-40.

Peolsson A, Soderlund A, Engquist M, Lind B, Lofgren H, Vavruch L, Holtz A, Winstrom-Christersson A, Isaksson I, Oberg B. Physical function outcome in cervical radiculopathy patients after physiotherapy alone compared with anterior surgery followed by physiotherapy: a prospective randomized study with a 2-year follow-up. Spine (Phila Pa 1976). 2013 Feb 15;38(4):300-7. doi: 10.1097/BRS.0b013e31826d2cbb.

Caridi JM, Pumberger M, Hughes AP. Cervical radiculopathy: a review. HSS J. 2011 Oct;7(3):265-72. doi: 10.1007/s11420-011-9218-z. Epub 2011 Sep 9.

Young IA, Michener LA, Cleland JA, Aguilera AJ, Snyder AR. Manual therapy, exercise, and traction for patients with cervical radiculopathy: a randomized clinical trial. Phys Ther. 2009 Jul;89(7):632-42. doi: 10.2522/ptj.20080283. Epub 2009 May 21. Erratum In: Phys Ther. 2009 Nov;89(11):1254-5. Phys Ther. 2010 May;90(5):825.

Campbell WW. Evaluation and management of peripheral nerve injury. Clin Neurophysiol. 2008 Sep;119(9):1951-65. doi: 10.1016/j.clinph.2008.03.018. Epub 2008 May 14.

Nikolaidis I, Fouyas IP, Sandercock PA, Statham PF. Surgery for cervical radiculopathy or myelopathy. Cochrane Database Syst Rev. 2010 Jan 20;2010(1):CD001466. doi: 10.1002/14651858.CD001466.pub3.

Legakis A, Boyd BS. The influence of scapular depression on upper limb neurodynamic test responses. J Man Manip Ther. 2012 May;20(2):75-82. doi: 10.1179/2042618611Y.0000000020.

McGregor AH, Probyn K, Cro S, Dore CJ, Burton AK, Balague F, Pincus T, Fairbank J. Rehabilitation following surgery for lumbar spinal stenosis. Cochrane Database Syst Rev. 2013 Dec 9;(12):CD009644. doi: 10.1002/14651858.CD009644.pub2.

Cleland JA, Whitman JM, Fritz JM, Palmer JA. Manual physical therapy, cervical traction, and strengthening exercises in patients with cervical radiculopathy: a case series. J Orthop Sports Phys Ther. 2005 Dec;35(12):802-11. doi: 10.2519/jospt.2005.35.12.802.

Beneciuk JM, Bishop MD, George SZ. Effects of upper extremity neural mobilization on thermal pain sensitivity: a sham-controlled study in asymptomatic participants. J Orthop Sports Phys Ther. 2009 Jun;39(6):428-38. doi: 10.2519/jospt.2009.2954.

Elvey R HT. Neural tissue evaluation and treatment, Donatelli R, Physical Therapy of the Shoulder,. 3rd ed. Livingstone C, editor. New York; 1997

Fritz JM, Thackeray A, Brennan GP, Childs JD. Exercise only, exercise with mechanical traction, or exercise with over-door traction for patients with cervical radiculopathy, with or without consideration of status on a previously described subgrouping rule: a randomized clinical trial. J Orthop Sports Phys Ther. 2014 Feb;44(2):45-57. doi: 10.2519/jospt.2014.5065. Epub 2014 Jan 9.

Persson LC, Carlsson CA, Carlsson JY. Long-lasting cervical radicular pain managed with surgery, physiotherapy, or a cervical collar. A prospective, randomized study. Spine (Phila Pa 1976). 1997 Apr 1;22(7):751-8. doi: 10.1097/00007632-199704010-00007.

Carlesso LC, Macdermid JC, Gross AR, Walton DM, Santaguida PL. Treatment preferences amongst physical therapists and chiropractors for the management of neck pain: results of an international survey. Chiropr Man Therap. 2014 Mar 24;22(1):11. doi: 10.1186/2045-709X-22-11.

Coppieters MW, Stappaerts KH, Wouters LL, Janssens K. The immediate effects of a cervical lateral glide treatment technique in patients with neurogenic cervicobrachial pain. J Orthop Sports Phys Ther. 2003 Jul;33(7):369-78. doi: 10.2519/jospt.2003.33.7.369.

Garland EL. Treating chronic pain: the need for non-opioid options. Expert Rev Clin Pharmacol. 2014 Sep;7(5):545-50. doi: 10.1586/17512433.2014.928587. Epub 2014 Jun 11.

Santos FM, Grecco LH, Pereira MG, Oliveira ME, Rocha PA, Silva JT, Martins DO, Miyabara EH, Chacur M. 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. Behav Brain Funct. 2014 May 13;10:19. doi: 10.1186/1744-9081-10-19.

Ogneva IV. Cell mechanosensitivity: mechanical properties and interaction with gravitational field. Biomed Res Int. 2013;2013:598461. doi: 10.1155/2013/598461. Epub 2012 Dec 26.

Bonin RP, Bories C, De Koninck Y. A simplified up-down method (SUDO) for measuring mechanical nociception in rodents using von Frey filaments. Mol Pain. 2014 Apr 16;10:26. doi: 10.1186/1744-8069-10-26.

Moriarty O, Finn DP. Cognition and pain. Curr Opin Support Palliat Care. 2014 Jun;8(2):130-6. doi: 10.1097/SPC.0000000000000054.

Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011 Mar;152(3 Suppl):S2-S15. doi: 10.1016/j.pain.2010.09.030. Epub 2010 Oct 18.

Courtney CA, Clark JD, Duncombe AM, O'Hearn MA. Clinical presentation and manual therapy for lower quadrant musculoskeletal conditions. J Man Manip Ther. 2011 Nov;19(4):212-22. doi: 10.1179/106698111X13129729552029.

Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472):1765-9. doi: 10.1126/science.288.5472.1765.

Woolf CJ. Central sensitization: uncovering the relation between pain and plasticity. Anesthesiology. 2007 Apr;106(4):864-7. doi: 10.1097/01.anes.0000264769.87038.55. No abstract available.

Santos FM, Silva JT, Giardini AC, Rocha PA, Achermann AP, Alves AS, Britto LR, Chacur M. Neural mobilization reverses behavioral and cellular changes that characterize neuropathic pain in rats. Mol Pain. 2012 Jul 29;8:57. doi: 10.1186/1744-8069-8-57.

Villafane JH. Botulinum toxin type A combined with neurodynamic mobilization for lower limb spasticity: a case report. J Chiropr Med. 2013 Mar;12(1):39-44. doi: 10.1016/j.jcm.2013.01.001.

Villafane JH, Pillastrini P, Borboni A. Manual therapy and neurodynamic mobilization in a patient with peroneal nerve paralysis: a case report. J Chiropr Med. 2013 Sep;12(3):176-81. doi: 10.1016/j.jcm.2013.10.007.

Ellis RF, Hing WA, McNair PJ. Comparison of longitudinal sciatic nerve movement with different mobilization exercises: an in vivo study utilizing ultrasound imaging. J Orthop Sports Phys Ther. 2012 Aug;42(8):667-75. doi: 10.2519/jospt.2012.3854. Epub 2012 Jun 18.

Shacklock M. Neural mobilization: a systematic review of randomized controlled trials with an analysis of therapeutic efficacy. J Man Manip Ther. 2008;16(1):23-4. doi: 10.1179/106698108790818602. No abstract available.

Lin PL, Shih YF, Chen WY, Ma HL. Neurodynamic responses to the femoral slump test in patients with anterior knee pain syndrome. J Orthop Sports Phys Ther. 2014 May;44(5):350-7. doi: 10.2519/jospt.2014.4781. Epub 2014 Apr 14.

Franze K. The mechanical control of nervous system development. Development. 2013 Aug;140(15):3069-77. doi: 10.1242/dev.079145.

Livne A, Bouchbinder E, Geiger B. Cell reorientation under cyclic stretching. Nat Commun. 2014 May 30;5:3938. doi: 10.1038/ncomms4938.

Lopez-Fagundo C, Bar-Kochba E, Livi LL, Hoffman-Kim D, Franck C. Three-dimensional traction forces of Schwann cells on compliant substrates. J R Soc Interface. 2014 Aug 6;11(97):20140247. doi: 10.1098/rsif.2014.0247.

Nee RJ, Vicenzino B, Jull GA, Cleland JA, Coppieters MW. Neural tissue management provides immediate clinically relevant benefits without harmful effects for patients with nerve-related neck and arm pain: a randomised trial. J Physiother. 2012;58(1):23-31. doi: 10.1016/S1836-9553(12)70069-3.

Savva C, Giakas G. The effect of cervical traction combined with neural mobilization on pain and disability in cervical radiculopathy. A case report. Man Ther. 2013 Oct;18(5):443-6. doi: 10.1016/j.math.2012.06.012. Epub 2012 Jul 18.

Ellis RF, Hing WA. Neural mobilization: a systematic review of randomized controlled trials with an analysis of therapeutic efficacy. J Man Manip Ther. 2008;16(1):8-22. doi: 10.1179/106698108790818594.

Cueco T. La columna cervical ; Sindromes clínicos y su tratamiento manipulativo. Panamericano E, editor. 2008. 40-41 p.

Basson A, Olivier B, Ellis R, Coppieters M, Stewart A, Mudzi W. The effectiveness of neural mobilizations in the treatment of musculoskeletal conditions: a systematic review protocol. JBI Database System Rev Implement Rep. 2015 Jan;13(1):65-75. doi: 10.11124/jbisrir-2015-1401.

Niemisto L, Kalso E, Malmivaara A, Seitsalo S, Hurri H. Radiofrequency denervation for neck and back pain. A systematic review of randomized controlled trials. Cochrane Database Syst Rev. 2003;(1):CD004058. doi: 10.1002/14651858.CD004058.

van Tulder M, Malmivaara A, Koes B. Repetitive strain injury. Lancet. 2007 May 26;369(9575):1815-1822. doi: 10.1016/S0140-6736(07)60820-4.

Salommon L W. Aply´s concise system of orthopedics and fractures. 3rd ed. Taylor Francis Group; 2005. 105-106 p

Mico JA, Ardid D, Berrocoso E, Eschalier A. Antidepressants and pain. Trends Pharmacol Sci. 2006 Jul;27(7):348-54. doi: 10.1016/j.tips.2006.05.004. Epub 2006 Jun 9.

van der Velde G, Hogg-Johnson S, Bayoumi AM, Cassidy JD, Cote P, Boyle E, Llewellyn-Thomas H, Chan S, Subrata P, Hoving JL, Hurwitz E, Bombardier C, Krahn M. Identifying the best treatment among common nonsurgical neck pain treatments: a decision analysis. J Manipulative Physiol Ther. 2009 Feb;32(2 Suppl):S209-18. doi: 10.1016/j.jmpt.2008.11.021.

Sella G. Practical Guide to Chronic Pain Syndromes Compression Neuropathies Chap 8. Press C, editor. 2009. 85-98 p.

Borenstein D. Low Back and Neck Pain. Low Back and Neck Pain [Internet]. 2004. p. 771-849. Available from: http://www.sciencedirect.com/science/article/pii/B9780721692777500283

Sniezek PJ, Brodland DG, Zitelli JA. A randomized controlled trial comparing acetaminophen, acetaminophen and ibuprofen, and acetaminophen and codeine for postoperative pain relief after Mohs surgery and cutaneous reconstruction. Dermatol Surg. 2011 Jul;37(7):1007-13. doi: 10.1111/j.1524-4725.2011.02022.x. Epub 2011 May 11.

Jeyakumar A, Brickman TM, Williamson ME, Hirose K, Krakovitz P, Whittemore K, Discolo C. Nonsteroidal anti-inflammatory drugs and postoperative bleeding following adenotonsillectomy in pediatric patients. Arch Otolaryngol Head Neck Surg. 2008 Jan;134(1):24-7. doi: 10.1001/archoto.2007.11.

Kanabar D. A practical approach to the treatment of low-risk childhood fever. Drugs R D. 2014 Jun;14(2):45-55. doi: 10.1007/s40268-014-0052-x.

Moore RA, Derry S, Wiffen PJ, Straube S, Aldington DJ. Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions. Eur J Pain. 2015 Oct;19(9):1213-23. doi: 10.1002/ejp.649. Epub 2014 Dec 22.

Kissin I. Scientometric assessment of drugs for chronic pain, 1979-2013: rapid growth of publications, paucity of successful drugs. J Pain Res. 2014 Aug 20;7:505-14. doi: 10.2147/JPR.S67479. eCollection 2014.

Nasca RJ. Cervical radiculopathy: current diagnostic and treatment options. J Surg Orthop Adv. 2009 Spring;18(1):13-8.

Fountas KN, Kapsalaki EZ, Nikolakakos LG, Smisson HF, Johnston KW, Grigorian AA, Lee GP, Robinson JS Jr. Anterior cervical discectomy and fusion associated complications. Spine (Phila Pa 1976). 2007 Oct 1;32(21):2310-7. doi: 10.1097/BRS.0b013e318154c57e.

Ghobrial GM, Viereck MJ, Margiotta PJ, Beygi S, Maulucci CM, Heller JE, Vaccaro AR, Harrop JS. Surgical management in 40 consecutive patients with cervical spinal epidural abscesses: shifting toward circumferential treatment. Spine (Phila Pa 1976). 2015 Sep 1;40(17):E949-53. doi: 10.1097/BRS.0000000000000942.

Persson LC, 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. 1997;6(4):256-66. doi: 10.1007/BF01322448.

Imani F, Motavaf M, Safari S, Alavian SM. The therapeutic use of analgesics in patients with liver cirrhosis: a literature review and evidence-based recommendations. Hepat Mon. 2014 Oct 11;14(10):e23539. doi: 10.5812/hepatmon.23539. eCollection 2014 Oct.

Asghar W, Jamali F. The effect of COX-2-selective meloxicam on the myocardial, vascular and renal risks: a systematic review. Inflammopharmacology. 2015 Feb;23(1):1-16. doi: 10.1007/s10787-014-0225-9. Epub 2014 Dec 17.

Unzueta A, Vargas HE. Nonsteroidal anti-inflammatory drug-induced hepatoxicity. Clin Liver Dis. 2013 Nov;17(4):643-56, ix. doi: 10.1016/j.cld.2013.07.009. Epub 2013 Sep 4.

Herndon CM, Dankenbring DM. Patient perception and knowledge of acetaminophen in a large family medicine service. J Pain Palliat Care Pharmacother. 2014 Jun;28(2):109-16. doi: 10.3109/15360288.2014.908993. Epub 2014 May 12.

Zadrazil J. [Nonsteroidal antiinflammatory drugs and the kidney]. Vnitr Lek. 2006 Jul-Aug;52(7-8):686-90. Czech.

Waddington F, Naunton M, Thomas J. Paracetamol and analgesic nephropathy: Are you kidneying me? Int Med Case Rep J. 2014 Dec 15;8:1-5. doi: 10.2147/IMCRJ.S71471. eCollection 2015.

Whelton A, Hamilton CW. Nonsteroidal anti-inflammatory drugs: effects on kidney function. J Clin Pharmacol. 1991 Jul;31(7):588-98. doi: 10.1002/j.1552-4604.1991.tb03743.x.

Turajane T, Wongbunnak R, Patcharatrakul T, Ratansumawong K, Poigampetch Y, Songpatanasilp T. Gastrointestinal and cardiovascular risk of non-selective NSAIDs and COX-2 inhibitors in elderly patients with knee osteoarthritis. J Med Assoc Thai. 2009 Dec;92 Suppl 6:S19-26.

van der Linden MW, van der Bij S, Welsing P, Kuipers EJ, Herings RM. The balance between severe cardiovascular and gastrointestinal events among users of selective and non-selective non-steroidal anti-inflammatory drugs. Ann Rheum Dis. 2009 May;68(5):668-73. doi: 10.1136/ard.2007.087254. Epub 2008 May 21.

Ingrasciotta Y, Sultana J, Giorgianni F, Caputi AP, Arcoraci V, Tari DU, Linguiti C, Perrotta M, Nucita A, Pellegrini F, Fontana A, Cavagna L, Santoro D, Trifiro G. The burden of nephrotoxic drug prescriptions in patients with chronic kidney disease: a retrospective population-based study in Southern Italy. PLoS One. 2014 Feb 18;9(2):e89072. doi: 10.1371/journal.pone.0089072. eCollection 2014.

Pfizer Inc. Neurontin ® ( gabapentin ) Capsules Neurontin ® ( gabapentin ) Tablets Neurontin ® ( gabapentin ) Oral Solution. Neurontin Packag Inser. 2009;(LAB-01069.1):1-29.

Aronson JK. Side Effects of Drugs Annual: A World Wide Yearly Survey of New Data in Adverse Drug Reactions. Newnes. 2014. p.1056-137

Rodriguez SC, Olguin AM, Miralles CP, Viladrich PF. Characteristics of meningitis caused by Ibuprofen: report of 2 cases with recurrent episodes and review of the literature. Medicine (Baltimore). 2006 Jul;85(4):214-220. doi: 10.1097/01.md.0000229757.78057.50.

Auriel E, Regev K, Korczyn AD. Nonsteroidal anti-inflammatory drugs exposure and the central nervous system. Handb Clin Neurol. 2014;119:577-84. doi: 10.1016/B978-0-7020-4086-3.00038-2.

Bancos S, Bernard MP, Topham DJ, Phipps RP. Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells. Cell Immunol. 2009;258(1):18-28. doi: 10.1016/j.cellimm.2009.03.007. Epub 2009 Apr 5.

Moriarty O, McGuire BE, Finn DP. The effect of pain on cognitive function: a review of clinical and preclinical research. Prog Neurobiol. 2011 Mar;93(3):385-404. doi: 10.1016/j.pneurobio.2011.01.002. Epub 2011 Jan 7.

Krenkel O, Mossanen JC, Tacke F. Immune mechanisms in acetaminophen-induced acute liver failure. Hepatobiliary Surg Nutr. 2014 Dec;3(6):331-43. doi: 10.3978/j.issn.2304-3881.2014.11.01.

Jann MW, Slade JH. Antidepressant agents for the treatment of chronic pain and depression. Pharmacotherapy. 2007 Nov;27(11):1571-87. doi: 10.1592/phco.27.11.1571.

Salerno SM, Browning R, Jackson JL. The effect of antidepressant treatment on chronic back pain: a meta-analysis. Arch Intern Med. 2002 Jan 14;162(1):19-24. doi: 10.1001/archinte.162.1.19.

Fragemann K, Wiese C. Pain education policies and initiatives in Europe. J Pain Palliat Care Pharmacother. 2014 Dec;28(4):402-3. doi: 10.3109/15360288.2014.972004. Epub 2014 Oct 28.

Wagner JG, Albert KS, Szpunar GJ, Lockwood GF. Pharmacokinetics of ibuprofen in man IV: absorption and disposition. J Pharmacokinet Biopharm. 1984 Aug;12(4):381-99. doi: 10.1007/BF01062664.

Rasu RS, Vouthy K, Crowl AN, Stegeman AE, Fikru B, Bawa WA, Knell ME. Cost of pain medication to treat adult patients with nonmalignant chronic pain in the United States. J Manag Care Spec Pharm. 2014 Sep;20(9):921-8. doi: 10.18553/jmcp.2014.20.9.921.

Chaparro LE, Wiffen PJ, Moore RA, Gilron I. Combination pharmacotherapy for the treatment of neuropathic pain in adults. Cochrane Database Syst Rev. 2012 Jul 11;2012(7):CD008943. doi: 10.1002/14651858.CD008943.pub2.

Cohen SP, Hayek S, Semenov Y, Pasquina PF, White RL, Veizi E, Huang JH, Kurihara C, Zhao Z, Guthmiller KB, Griffith SR, Verdun AV, Giampetro DM, Vorobeychik Y. Epidural steroid injections, conservative treatment, or combination treatment for cervical radicular pain: a multicenter, randomized, comparative-effectiveness study. Anesthesiology. 2014 Nov;121(5):1045-55. doi: 10.1097/ALN.0000000000000409.

Schmid A, Brunner F, Wright A, Bachmann LM. Paradigm shift in manual therapy? Evidence for a central nervous system component in the response to passive cervical joint mobilisation. Man Ther. 2008 Oct;13(5):387-96. doi: 10.1016/j.math.2007.12.007. Epub 2008 Mar 3.

Harvey MP, Descarreaux M. Short term modulation of trunk neuromuscular responses following spinal manipulation: a control group study. BMC Musculoskelet Disord. 2013 Mar 13;14:92. doi: 10.1186/1471-2474-14-92.

McReynolds TM, Sheridan BJ. Intramuscular ketorolac versus osteopathic manipulative treatment in the management of acute neck pain in the emergency department: a randomized clinical trial. J Am Osteopath Assoc. 2005 Feb;105(2):57-68.

Dabbs V, Lauretti WJ. A risk assessment of cervical manipulation vs. NSAIDs for the treatment of neck pain. J Manipulative Physiol Ther. 1995 Oct;18(8):530-6.

Sheather-Reid RB, Cohen M. Efficacy of analgesics in chronic pain: a series of N-of-1 studies. J Pain Symptom Manage. 1998 Apr;15(4):244-52. doi: 10.1016/s0885-3924(98)00369-8.

Rainsford KD. Ibuprofen: from invention to an OTC therapeutic mainstay. Int J Clin Pract Suppl. 2013 Jan;(178):9-20. doi: 10.1111/ijcp.12055.

Vicenzino B, Collins D, Benson H, Wright A. An investigation of the interrelationship between manipulative therapy-induced hypoalgesia and sympathoexcitation. J Manipulative Physiol Ther. 1998 Sep;21(7):448-53.

X. Casado-Zumeta. Efectividad de la fisioterapia manual en el dolor cervicobraquial neuropático: una revisión sistematica. Fisioterapia. 2015;37(4).

Brochwicz P, von Piekartz H, Zalpour C. Sonography assessment of the median nerve during cervical lateral glide and lateral flexion. Is there a difference in neurodynamics of asymptomatic people? Man Ther. 2013 Jun;18(3):216-9. doi: 10.1016/j.math.2012.10.001. Epub 2013 Jan 11.

Wang WT, Olson SL, Campbell AH, Hanten WP, Gleeson PB. Effectiveness of physical therapy for patients with neck pain: an individualized approach using a clinical decision-making algorithm. Am J Phys Med Rehabil. 2003 Mar;82(3):203-18; quiz 219-21. doi: 10.1097/01.PHM.0000052700.48757.CF.

Freburger JK, Carey TS, Holmes GM. Effectiveness of physical therapy for the management of chronic spine disorders: a propensity score approach. Phys Ther. 2006 Mar;86(3):381-94.

Hinkelmann K. Designe and análisis of experiments, Volume I, Introduction to experiment designe. 2, editor. Wiley; 2008.

Elliott SA, Brown JS. What are we doing to waiting list controls? Behav Res Ther. 2002 Sep;40(9):1047-52. doi: 10.1016/s0005-7967(01)00082-1.

Angst F, Schwyzer HK, Aeschlimann A, Simmen BR, Goldhahn J. Measures of adult shoulder function: Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) and its short version (QuickDASH), Shoulder Pain and Disability Index (SPADI), American Shoulder and Elbow Surgeons (ASES) Society standardized shoulder assessment form, Constant (Murley) Score (CS), Simple Shoulder Test (SST), Oxford Shoulder Score (OSS), Shoulder Disability Questionnaire (SDQ), and Western Ontario Shoulder Instability Index (WOSI). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S174-88. doi: 10.1002/acr.20630. No abstract available.

Moshe S, Izhaki R, Chodick G, Segal N, Yagev Y, Finestone AS, Juven Y. Predictors of return to work with upper limb disorders. Occup Med (Lond). 2015 Oct;65(7):564-9. doi: 10.1093/occmed/kqv100. Epub 2015 Jul 20.