Clinical trial NCT03531541: Hypoalgesic Effect of Electrical Current and Cervical Manipulation
Official title: Transcutaneous Electrical Nerve Stimulation and Cervical Joint Manipulation on Pressure Pain Threshold
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain
Keywords: TENS
cervical manipulation
pressure pain
Lead sponsor: Universidade Federal de Sao Carlos
Sponsor class: OTHER
First posted: 2018-05-21
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: The participants will be randomly allocated into 4 groups: (G1) active TENS and CJM, (G2) placebo TENS and CJM, (G3) placebo TENS and active CJM, (G4) active TENS and placebo CJM.
Primary purpose: BASIC_SCIENCE

Brief summary: This study evaluates the hypoalgesic effect of the TENS application associated with joint manipulation of the cervical region in healthy individuals. One group had both active treatments, the other group received both placebo treatments, the third and fourth group received only one of the two treatments actively and the other placebo

Detailed description: Transcutaneous Electrical Nerve Stimulation (TENS) and Cervical Joint Manipulation (CJM) are often used for pain treatment.

TENS also promotes analgesia by activating a descending pathway, which originates in the periaqueductal grey (PAG) and in the rostroventromedial medulla (RVM) to inhibit the excitability of nociceptive neurons in the dorsal horn of the spinal cord.

Joint manipulation generates a series of stimuli within the central nervous system through the activation of proprioceptors located in the joint capsule or muscles, stimulates the PAG, causing pain inhibition by activation of non-opioid descending inhibitory pathways

Eligibility criteria: Inclusion Criteria:

* healthy subjects
* no pain complaints from the last 90 days

Exclusion Criteria:

* previous spinal surgeries
* spinal canal stenosis
* vertebral fracture
* spondylolisthesis
* cancer
* acute infections
* hemorrhagic disorders
* active tuberculosis
* deep vein thrombosis
* osteoporosis
* diseases rheumatic
* diseases metabolic
* cardiorespiratory diseases
* headache in the last seven days
* smoking
* changes in skin sensitivity
* use of pacemaker
* women in menstrual period
* pregnant women
* use of pain-killers in the last 48 hours
* use of anti-inflammatory drugs in the last 48 hours
* previous electrostimulation
* previous cervical joint manipulation treatments
* hypersensitivity to TENS application
* aversion to cervical joint manipulation
* positive test for vertebral artery.

Primary outcomes:
measure: Pressure Pain Threshold of the posterior region of the forearm
timeFrame: 1 minute after the end of the intervention.
Secondary outcomes:
measure: Pressure Pain Threshold of the posterior region of the forearm
timeFrame: 20 minutes after the end of the intervention
measure: Pressure Pain Threshold of the tibialis anterior muscle
timeFrame: 1 minute after the end of the intervention.
measure: Pressure Pain Threshold of the tibialis anterior muscle
timeFrame: 20 minutes after the end of the intervention
Other outcomes:
Locations:
city: Lins
country: Brazil
facility: Centro Universitário Católico Salesiano Auxilium de Lins
state: São Paulo
city: São Carlos
country: Brazil
facility: Ufscar - Universidade Federal de São Carlos
state: São Paulo
Study officials:
affiliation: Universidade Federal de São Carlos - UFScar
name: Richard E Liebano, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sluka KA, Deacon M, Stibal A, Strissel S, Terpstra A. Spinal blockade of opioid receptors prevents the analgesia produced by TENS in arthritic rats. J Pharmacol Exp Ther. 1999 May;289(2):840-6.
citation: Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965 Nov 19;150(3699):971-9. doi: 10.1126/science.150.3699.971. No abstract available.
citation: Mayer DJ, Price DD, Rafii A. Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxone. Brain Res. 1977 Feb;121(2):368-72. doi: 10.1016/0006-8993(77)90161-5. No abstract available.
citation: Ha H, Tan EC, Fukunaga H, Aochi O. Naloxone reversal of acupuncture analgesia in the monkey. Exp Neurol. 1981 Jul;73(1):298-303. doi: 10.1016/0014-4886(81)90063-7. No abstract available.
citation: Citak Karakaya I, Karakaya MG, Ergun E, Elmali S, Firat T. Effects of different frequencies of conventional transcutaneous electrical nerve stimulation on pressure pain threshold and tolerance. J Back Musculoskelet Rehabil. 2014;27(2):197-201. doi: 10.3233/BMR-130436.
citation: Dailey DL, Rakel BA, Vance CGT, Liebano RE, Amrit AS, Bush HM, Lee KS, Lee JE, Sluka KA. Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia. Pain. 2013 Nov;154(11):2554-2562. doi: 10.1016/j.pain.2013.07.043. Epub 2013 Jul 27.
citation: Sabino GS, Santos CM, Francischi JN, de Resende MA. Release of endogenous opioids following transcutaneous electric nerve stimulation in an experimental model of acute inflammatory pain. J Pain. 2008 Feb;9(2):157-63. doi: 10.1016/j.jpain.2007.09.003. Epub 2007 Nov 7.
citation: Chandran P, Sluka KA. Development of opioid tolerance with repeated transcutaneous electrical nerve stimulation administration. Pain. 2003 Mar;102(1-2):195-201. doi: 10.1016/s0304-3959(02)00381-0.
citation: Han JS, Chen XH, Sun SL, Xu XJ, Yuan Y, Yan SC, Hao JX, Terenius L. Effect of low- and high-frequency TENS on Met-enkephalin-Arg-Phe and dynorphin A immunoreactivity in human lumbar CSF. Pain. 1991 Dec;47(3):295-298. doi: 10.1016/0304-3959(91)90218-M.
citation: Flynn TW, Childs JD, Fritz JM. The audible pop from high-velocity thrust manipulation and outcome in individuals with low back pain. J Manipulative Physiol Ther. 2006 Jan;29(1):40-5. doi: 10.1016/j.jmpt.2005.11.005.
citation: Dunning J, Rushton A. The effects of cervical high-velocity low-amplitude thrust manipulation on resting electromyographic activity of the biceps brachii muscle. Man Ther. 2009 Oct;14(5):508-13. doi: 10.1016/j.math.2008.09.003. Epub 2008 Nov 21.
citation: DeVocht JW, Pickar JG, Wilder DG. Spinal manipulation alters electromyographic activity of paraspinal muscles: a descriptive study. J Manipulative Physiol Ther. 2005 Sep;28(7):465-71. doi: 10.1016/j.jmpt.2005.07.002.
citation: Evans DW. Mechanisms and effects of spinal high-velocity, low-amplitude thrust manipulation: previous theories. J Manipulative Physiol Ther. 2002 May;25(4):251-62. doi: 10.1067/mmt.2002.123166.
citation: Achalandabaso A, Plaza-Manzano G, Lomas-Vega R, Martinez-Amat A, Camacho MV, Gasso M, Hita-Contreras F, Molina F. Tissue damage markers after a spinal manipulation in healthy subjects: a preliminary report of a randomized controlled trial. Dis Markers. 2014;2014:815379. doi: 10.1155/2014/815379. Epub 2014 Dec 25.
citation: Wright A. Hypoalgesia post-manipulative therapy: a review of a potential neurophysiological mechanism. Man Ther. 1995 Nov;1(1):11-6. doi: 10.1054/math.1995.0244.
citation: Pickar JG, Wheeler JD. Response of muscle proprioceptors to spinal manipulative-like loads in the anesthetized cat. J Manipulative Physiol Ther. 2001 Jan;24(1):2-11. doi: 10.1067/mmt.2001.112017.
citation: Maigne JY, Vautravers P. Mechanism of action of spinal manipulative therapy. Joint Bone Spine. 2003 Sep;70(5):336-41. doi: 10.1016/s1297-319x(03)00074-5.
citation: Randoll C, Gagnon-Normandin V, Tessier J, Bois S, Rustamov N, O'Shaughnessy J, Descarreaux M, Piche M. The mechanism of back pain relief by spinal manipulation relies on decreased temporal summation of pain. Neuroscience. 2017 May 4;349:220-228. doi: 10.1016/j.neuroscience.2017.03.006. Epub 2017 Mar 11.
citation: Bialosky JE, Bishop MD, Price DD, Robinson ME, George SZ. The mechanisms of manual therapy in the treatment of musculoskeletal pain: a comprehensive model. Man Ther. 2009 Oct;14(5):531-8. doi: 10.1016/j.math.2008.09.001. Epub 2008 Nov 21.
citation: Coronado RA, Gay CW, Bialosky JE, Carnaby GD, Bishop MD, George SZ. Changes in pain sensitivity following spinal manipulation: a systematic review and meta-analysis. J Electromyogr Kinesiol. 2012 Oct;22(5):752-67. doi: 10.1016/j.jelekin.2011.12.013. Epub 2012 Jan 30.
citation: Savva C, Giakas G, Efstathiou M. The role of the descending inhibitory pain mechanism in musculoskeletal pain following high-velocity, low amplitude thrust manipulation: a review of the literature. J Back Musculoskelet Rehabil. 2014;27(4):377-82. doi: 10.3233/BMR-140472.
citation: Gay CW, Robinson ME, George SZ, Perlstein WM, Bishop MD. Immediate changes after manual therapy in resting-state functional connectivity as measured by functional magnetic resonance imaging in participants with induced low back pain. J Manipulative Physiol Ther. 2014 Nov-Dec;37(9):614-27. doi: 10.1016/j.jmpt.2014.09.001. Epub 2014 Oct 3.
citation: Jordon MK, Beattie PF, D'Urso S, Scriven S. Spinal manipulation does not affect pressure pain thresholds in the absence of neuromodulators: a randomized controlled trial. J Man Manip Ther. 2017 Sep;25(4):172-181. doi: 10.1080/10669817.2016.1230352. Epub 2016 Sep 12.
citation: Boal RW, Gillette RG. Central neuronal plasticity, low back pain and spinal manipulative therapy. J Manipulative Physiol Ther. 2004 Jun;27(5):314-26. doi: 10.1016/j.jmpt.2004.04.005.
citation: Molina-Ortega F, Lomas-Vega R, Hita-Contreras F, Plaza Manzano G, Achalandabaso A, Ramos-Morcillo AJ, Martinez-Amat A. Immediate effects of spinal manipulation on nitric oxide, substance P and pain perception. Man Ther. 2014 Oct;19(5):411-7. doi: 10.1016/j.math.2014.02.007. Epub 2014 Mar 5.
citation: Nakatsuka T, Chen M, Takeda D, King C, Ling J, Xing H, Ataka T, Vierck C, Yezierski R, Gu JG. Substance P-driven feed-forward inhibitory activity in the mammalian spinal cord. Mol Pain. 2005 Jun 29;1:20. doi: 10.1186/1744-8069-1-20.
citation: Wu LJ, Xu H, Ko SW, Yoshimura M, Zhuo M. Feed-forward inhibition: a novel cellular mechanism for the analgesic effect of substance P. Mol Pain. 2005 Nov 18;1:34. doi: 10.1186/1744-8069-1-34.
citation: Pantaleao MA, Laurino MF, Gallego NL, Cabral CM, Rakel B, Vance C, Sluka KA, Walsh DM, Liebano RE. Adjusting pulse amplitude during transcutaneous electrical nerve stimulation (TENS) application produces greater hypoalgesia. J Pain. 2011 May;12(5):581-90. doi: 10.1016/j.jpain.2010.11.001. Epub 2011 Feb 1.
citation: Doig GS, Simpson F. Randomization and allocation concealment: a practical guide for researchers. J Crit Care. 2005 Jun;20(2):187-91; discussion 191-3. doi: 10.1016/j.jcrc.2005.04.005.
citation: Liebano RE, Rakel B, Vance CGT, Walsh DM, Sluka KA. An investigation of the development of analgesic tolerance to TENS in humans. Pain. 2011 Feb;152(2):335-342. doi: 10.1016/j.pain.2010.10.040. Epub 2010 Dec 8.
citation: Leffler AS, Hansson P, Kosek E. Somatosensory perception in patients suffering from long-term trapezius myalgia at the site overlying the most painful part of the muscle and in an area of pain referral. Eur J Pain. 2003;7(3):267-76. doi: 10.1016/S1090-3801(02)00138-6.
citation: Liebano RE, Vance CG, Rakel BA, Lee JE, Cooper NA, Marchand S, Walsh DM, Sluka KA. Transcutaneous electrical nerve stimulation and conditioned pain modulation influence the perception of pain in humans. Eur J Pain. 2013 Nov;17(10):1539-46. doi: 10.1002/j.1532-2149.2013.00328.x. Epub 2013 May 6.
citation: Walton DM, Macdermid JC, Nielson W, Teasell RW, Chiasson M, Brown L. Reliability, standard error, and minimum detectable change of clinical pressure pain threshold testing in people with and without acute neck pain. J Orthop Sports Phys Ther. 2011 Sep;41(9):644-50. doi: 10.2519/jospt.2011.3666. Epub 2011 Sep 1.
citation: Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Kosek E, Lavand'homme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ. A classification of chronic pain for ICD-11. Pain. 2015 Jun;156(6):1003-1007. doi: 10.1097/j.pain.0000000000000160. No abstract available.
citation: Staud R. Treatment of fibromyalgia and its symptoms. Expert Opin Pharmacother. 2007 Aug;8(11):1629-42. doi: 10.1517/14656566.8.11.1629.
citation: Moran F, Leonard T, Hawthorne S, Hughes CM, McCrum-Gardner E, Johnson MI, Rakel BA, Sluka KA, Walsh DM. Hypoalgesia in response to transcutaneous electrical nerve stimulation (TENS) depends on stimulation intensity. J Pain. 2011 Aug;12(8):929-35. doi: 10.1016/j.jpain.2011.02.352. Epub 2011 Apr 9.
citation: Rakel B, Cooper N, Adams HJ, Messer BR, Frey Law LA, Dannen DR, Miller CA, Polehna AC, Ruggle RC, Vance CG, Walsh DM, Sluka KA. A new transient sham TENS device allows for investigator blinding while delivering a true placebo treatment. J Pain. 2010 Mar;11(3):230-8. doi: 10.1016/j.jpain.2009.07.007. Epub 2009 Nov 27.
citation: Fernandez-Carnero J, Fernandez-de-Las-Penas C, de la Llave-Rincon AI, Ge HY, Arendt-Nielsen L. Widespread mechanical pain hypersensitivity as sign of central sensitization in unilateral epicondylalgia: a blinded, controlled study. Clin J Pain. 2009 Sep;25(7):555-61. doi: 10.1097/AJP.0b013e3181a68a040.
citation: Saiz-Llamosas JR, Fernandez-Perez AM, Fajardo-Rodriguez MF, Pilat A, Valenza-Demet G, Fernandez-de-Las-Penas C. Changes in neck mobility and pressure pain threshold levels following a cervical myofascial induction technique in pain-free healthy subjects. J Manipulative Physiol Ther. 2009 Jun;32(5):352-7. doi: 10.1016/j.jmpt.2009.04.009.
citation: Fernandez-de-las-Penas C, Perez-de-Heredia M, Brea-Rivero M, Miangolarra-Page JC. Immediate effects on pressure pain threshold following a single cervical spine manipulation in healthy subjects. J Orthop Sports Phys Ther. 2007 Jun;37(6):325-9. doi: 10.2519/jospt.2007.2542.
citation: Vernon HT, Triano JJ, Ross JK, Tran SK, Soave DM, Dinulos MD. Validation of a novel sham cervical manipulation procedure. Spine J. 2012 Nov;12(11):1021-8. doi: 10.1016/j.spinee.2012.10.009. Epub 2012 Nov 15.
citation: Gomes Ade O, Silvestre AC, Silva CF, Gomes MR, Bonfleur ML, Bertolini GR. Influence of different frequencies of transcutaneous electrical nerve stimulation on the threshold and pain intensity in young subjects. Einstein (Sao Paulo). 2014 Sep;12(3):318-22. doi: 10.1590/s1679-45082014ao3092.
citation: Wassinger CA, Rich D, Cameron N, Clark S, Davenport S, Lingelbach M, Smith A, Baxter GD, Davidson J. Cervical & thoracic manipulations: Acute effects upon pain pressure threshold and self-reported pain in experimentally induced shoulder pain. Man Ther. 2016 Feb;21:227-32. doi: 10.1016/j.math.2015.08.009. Epub 2015 Aug 28.
citation: Chesterton LS, Foster NE, Wright CC, Baxter GD, Barlas P. Effects of TENS frequency, intensity and stimulation site parameter manipulation on pressure pain thresholds in healthy human subjects. Pain. 2003 Nov;106(1-2):73-80. doi: 10.1016/s0304-3959(03)00292-6.
citation: Tanaka K, Ikeuchi M, Izumi M, Aso K, Sugimura N, Enoki H, Nagano Y, Ishida K, Tani T. Effects of two different intensities of transcutaneous electrical nerve stimulation on pain thresholds of contralateral muscles in healthy subjects. J Phys Ther Sci. 2015 Sep;27(9):2771-4. doi: 10.1589/jpts.27.2771. Epub 2015 Sep 30.
citation: Fernandez-Carnero J, Fernandez-de-las-Penas C, Cleland JA. Immediate hypoalgesic and motor effects after a single cervical spine manipulation in subjects with lateral epicondylalgia. J Manipulative Physiol Ther. 2008 Nov-Dec;31(9):675-81. doi: 10.1016/j.jmpt.2008.10.005.
citation: Desantana JM, Sluka KA, Lauretti GR. High and low frequency TENS reduce postoperative pain intensity after laparoscopic tubal ligation: a randomized controlled trial. Clin J Pain. 2009 Jan;25(1):12-9. doi: 10.1097/AJP.0b013e31817d1070.
citation: Telles JD, Gabanela Schiavon MA, Rampazo da Silva EP, Liebano RE. Transcutaneous electrical nerve stimulation and cervical joint manipulation on pressure pain threshold. Pain Manag. 2018 Jul 1;8(4):263-269. doi: 10.2217/pmt-2017-0069. Epub 2018 Jun 1.