The immediate effects of cervical spine manipulation on pain and biochemical markers in females with acute non-specific mechanical neck pain: a randomized clinical trial

E B Lohman, G R Pacheco, L Gharibvand, N Daher, K Devore, G Bains, M AlAmeri, L S Berk, E B Lohman, G R Pacheco, L Gharibvand, N Daher, K Devore, G Bains, M AlAmeri, L S Berk

Abstract

Study Design: Randomized clinical trial with pre-test, post-test control group design. Objectives: To examine the immediate effects of cervical spinal manipulation (CSM) on serum concentration of biochemical markers (oxytocin, neurotensin, orexin A, and cortisol). Background: Several studies have found an association between spinal manipulation (SM) and pain perception. However, the mechanism by which SM modulates pain remains undefined. Methods: Twenty-eight female subjects with non-specific mechanical neck pain were randomly assigned to one of two interventions (CSM versus sham CSM). Blood samples were drawn before and immediately after the respective interventions. Oxytocin, neurotensin, orexin A, and cortisol were measured from the blood and serum using the Milliplex Map Magnetic Bead Panel Immunoassay on the Luminex 200 Platform. Results: In the CSM group, there were significant increases in pre- versus post-manipulation mean oxytocin (154.5 ± 60.1 vs. 185.1 ± 75.6, p = .012); neurotensin (116.0 ± 26.5 vs.136.4 ± 34.1, p < . 001); orexin A (52.2 ± 31.1 vs. 73.8 ± 38.8, p < .01) serum concentration; but no significant differences in mean cortisol (p = .052) serum concentration. In the sham group, there were no significant differences in any of the biomarkers (p > .05). Conclusion: The results of the current study suggest that the mechanical stimuli provided through a CSM may modify neuropeptide expression by immediately increasing the serum concentration of nociception-related biomarkers (oxytocin, neurotensin, orexin A, but not cortisol) in the blood of female subjects with non-specific mechanical neck pain.

Keywords: Spinal manipulation; cortisol; neck pain; neurotensin; orexin A; oxytocin.

Figures

Figure 1.
Figure 1.
Cervical spinal manipulation.
Figure 2.
Figure 2.
Flow chart of the methodological procedure.
Figure 3.
Figure 3.
Mean and 95% confidence interval error bar for oxytocin, neurotensin, orexin A, cortisol concentration in blood samples.

References

    1. Gross A, Miller J, D’Sylva J, et al. Manipulation or mobilisation for neck pain: a Cochrane review. Manual Ther. 2010;15(4):315–333.
    1. Hoy D, Protani M, De R, et al. The epidemiology of neck pain. Best Pract Res Clin Rheumatol. 2010;24(6):783–792.
    1. Raghavendra MHJ. Gender differences in the prevalence of cervical degenerative disc disease. American Academy of Pain Management Annual Meeting. 2016. [Accessed October 31, 2018]. Available from:
    1. Deyo RA, Von Korff M, Duhrkoop D. Opioids for low back pain. Bmj. 2015;350:g6380.
    1. Kenneth D, Kochanek MA, Sherry L, et al. Mortality in the United States, 2016. 2017. [Accessed October 31, 2018]. Available from:
    1. Abuse NIoD National Survey of Drug Use and Health. 2016.
    1. U.S. Department of Health and Human Services What is the U.S. opioid epidemic? 2018. [Accessed October 31, 2018]. Available from:
    1. Seth P, Rudd RA, Noonan RK, et al. Quantifying the epidemic of prescription opioid overdose deaths. American Public Health Association. 2018.
    1. Kovanur-Sampath K, Mani R, Cotter J, et al. Changes in biochemical markers following spinal manipulation-a systematic review and meta-analysis. Musculoskeletal Sci Pract. 2017;29:120–131.
    1. Hidalgo B, Hall T, Bossert J, et al. The efficacy of manual therapy and exercise for treating non-specific neck pain: a systematic review. J Back Musculoskelet Rehabil. 2017;30(6):1149–1169.
    1. Bronfort G, Haas M, Evans R, et al. Effectiveness of manual therapies: the UK evidence report. Chiropr Osteopat. 2010;18(1):3.
    1. Gross AR, Hoving JL, Haines TA, et al. A Cochrane review of manipulation and mobilization for mechanical neck disorders. Spine (Phila Pa 1976). 2004;29(14):1541–1548.
    1. Carraway R, Leeman SE. The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J Biol Chem. 1973;248(19):6854–6861.
    1. Dorron SL, Losco BE, Drummond PD, et al. Effect of lumbar spinal manipulation on local and remote pressure pain threshold and pinprick sensitivity in asymptomatic individuals: a randomised trial. Chiropr Man Therap. 2016;24(1):47.
    1. Lénárd L, László K, Kertes E, et al. Substance P and neurotensin in the limbic system: their roles in reinforcement and memory consolidation. Neurosci Biobehav Rev. 2017;85:1–20.
    1. Clineschmidt BV, McGuffin JC, Bunting PB. Neurotensin: antinocisponsive action in rodents. Eur J Pharmacol. 1979;54(1–2):129–139.
    1. Hegedus EJ, Goode A, Butler RJ, et al. The neurophysiological effects of a single session of spinal joint mobilization: does the effect last? J Man Manip Ther. 2011;19(3):143–151.
    1. Coronado RA, Gay CW, Bialosky JE, et al. Changes in pain sensitivity following spinal manipulation: a systematic review and meta-analysis. J Electromyogr Kinesiol. 2012;22(5):752–767.
    1. Plaza-Manzano G, Molina F, Lomas-Vega R, et al. Changes in biochemical markers of pain perception and stress response after spinal manipulation. J Orthop Sports Phys Ther. 2014;44(4):231–239.
    1. Bassett J, Marshall P, Spillane R. The physiological measurement of acute stress (public speaking) in bank employees. Int J Psychophysiol. 1987;5(4):265–273.
    1. Matousek RH, Dobkin PL, Pruessner J. Cortisol as a marker for improvement in mindfulness-based stress reduction. Complement Ther Clin Pract. 2010;16(1):13–19.
    1. Jensen MP, Miller L, Fisher LD. Assessment of pain during medical procedures: a comparison of three scales. Clin J Pain. 1998;14(4):343–349.
    1. Audette I, Dumas J-P, Côté JN, et al. Validity and between-day reliability of the cervical range of motion (CROM) device. J Orthop Sports Phys Ther. 2010;40(5):318–323.
    1. Christian GF, Stanton GJ, Sissons D, et al. Immunoreactive ACTH, beta-endorphin, and cortisol levels in plasma following spinal manipulative therapy. Spine (Phila Pa 1976). 1988;13(12):1411–1417.
    1. Ballantyne JC, Shin NS. Efficacy of opioids for chronic pain: a review of the evidence. Clin J Pain. 2008;24(6):469–478.
    1. Hains F, Waalen J, Mior S. Psychometric properties of the neck disability index. J Manipulative Physiol Ther. 1998;21(2):75–80.
    1. Riddle DL, Stratford PW. Use of generic versus region-specific functional status measures on patients with cervical spine disorders. Phys Ther. 1998;78(9):951–963.
    1. Vernon H, Mior S. The neck disability index: a study of reliability and validity. J Manipulative Physiol Ther. 1991;14(7):409–415.
    1. Tsakitzidis G, Remmen R, Dankaerts W, et al. Non-specific neck pain and evidence-based practice. Eur Sci J. 2013;9:3.
    1. Ferraz MB, Quaresma M, Aquino L, et al. Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis. J Rheumatol. 1990;17(8):1022–1024.
    1. Jensen MP, Karoly P, O’riordan EF, et al. The subjective experience of acute pain. An assessment of the utility of 10 indices. Clin J Pain. 1989;5(2):153–159.
    1. Leng G, Sabatier N. Measuring oxytocin and vasopressin: bioassays, immunoassays and random numbers. J Neuroendocrinol. 2016;28:10.
    1. Dunning JR. American academy of manipulative therapy & spinal manipulation institute. 2014. [Accessed November 01, 2018]. Available from:
    1. Pickar JG. Neurophysiological effects of spinal manipulation. Spine J. 2002;2(5):357–371.
    1. Standring S, Ellis H, Healy J, et al. Gray’s anatomy: the anatomical basis of clinical practice. Am J Neuroradiol. 2005;26(10):2703.
    1. Uvnäs-Moberg K, Bruzelius G, Alster P, et al. Oxytocin increases and a specific oxytocin antagonist decreases pain threshold in male rats. Acta Physiol Scand. 1992;144(4):487–488.
    1. Rojas-Piloni G, López-Hidalgo M, Martínez-Lorenzana G, et al. GABA-mediated oxytocinergic inhibition in dorsal horn neurons by hypothalamic paraventricular nucleus stimulation. Brain Res. 2007;1137:69–77.
    1. St-Gelais F, Jomphe C, Trudeau L-É. The role of neurotensin in central nervous system pathophysiology: what is the evidence?. J Psychiatry Neurosci. 2006;31(4):229–245.
    1. Rossi GC, Matulonis JE, Richelson E, et al. Systemically and topically active antinociceptive neurotensin compounds. J Pharmacol Exp Ther. 2010;334(3):1075–1079.
    1. Furutani N, Hondo M, Kageyama H, et al. Neurotensin co-expressed in orexin-producing neurons in the lateral hypothalamus plays an important role in regulation of sleep/wakefulness states. PloS one. 2013;8(4):e62391.
    1. Bingham S, Davey P, Babbs A, et al. Orexin-A, an hypothalamic peptide with analgesic properties. Pain. 2001;92(1–2):81–90.
    1. Yamamoto T, Nozaki‐Taguchi N, Chiba T. Analgesic effect of intrathecally administered orexin‐A in the rat formalin test and in the rat hot plate test. Br J Pharmacol. 2002;137(2):170–176.
    1. Mohamed AR, El-Hadidy WF. Effect of orexin-A (hypocretin-1) on hyperalgesic and cachectic manifestations of experimentally induced rheumatoid arthritis in rats. Can J Physiol Pharmacol. 2014;92(10):813–820.
    1. Feng X-M, Mi W-L, Xia F, et al. Involvement of spinal orexin A in the electroacupuncture analgesia in a rat model of post-laparotomy pain. BMC Complement Altern Med. 2012;12(1):225.
    1. Brennan PC, Kokjohn K, Kaltinger CJ, et al. Enhanced phagocytic cell respiratory burst induced by spinal manipulation: potential role of substance P. J Manipulative Physiol Ther. 1991;14(7):399–408.
    1. Ida T, Nakahara K, Murakami T, et al. Possible involvement of orexin in the stress reaction in rats. Biochem Biophys Res Commun. 2000;270(1):318–323.
    1. Hannibal KE, Bishop MD. Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation. Phys Ther. 2014;94(12):1816–1825.
    1. Teodorczyk-Injeyan JA, Injeyan HS, Ruegg R. Spinal manipulative therapy reduces inflammatory cytokines but not substance P production in normal subjects. J Manipulative Physiol Ther. 2006;29(1):14–21.
    1. Teodorczyk-Injeyan JA, McGregor M, Ruegg R, et al. Interleukin 2-regulated in vitro antibody production following a single spinal manipulative treatment in normal subjects. Chiropr Osteopat. 2010;18(1):26.
    1. Whelan TL, Dishman JD, Burke J, et al. The effect of chiropractic manipulation on salivary cortisol levels. J Manipulative Physiol Ther. 2002;25(3):149–153.
    1. Mirick DK, Bhatti P, Chen C, et al. Night shift work and levels of 6-sulfatoxymelatonin and cortisol in men. Cancer Epidemiol Prev Biomarkers. 2013;22:1079–1087.
    1. Pickar JG, Wheeler JD. Response of muscle proprioceptors to spinal manipulative-like loads in the anesthetized cat. J Manipulative Physiol Ther. 2001;24(1):2–11.

Source: PubMed

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