21
Views
1
CrossRef citations to date
0
Altmetric
Topical review

Going in deeper and deeper: signal transduction pathways in myofacial trigger points – A narrative review

, &
Pages 64-74 | Published online: 18 Jul 2013

References

  • McBeth J, Jones K. Epidemiology of chronic musculoskeletal pain. Best Pract Res Clin Rheumatol 2007;21(3):403–25.
  • Bevan S, Quadrello T, McGee R, Mahdon M, Vavrovsky A, Barham L. Fit for work? Musculoskeletal disorders in the European workforce [accessed 2010 Mar 10]. Available from http://www.theworkfoundation.com/Assets/Docs/Fit%20for%20Work%20pan-European%20report.pdf.
  • Brunelli S, Rovere-Querini P. The immune system and the repair of skeletal muscle. Pharmacol Res 2008;58(2):117–21.
  • Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol 2007;26(4):465–73.
  • Obermann M, Pleger B, de Greiff A, Stude P, Kaube H, Diener HC, et al. Temporal summation of trigeminal pain in human anterior cingulate cortex. Neuroimage 2009;46(1):193–200.
  • Burgmer M, Gaubitz M, Konrad C, Wrenger M, Hilgart S, Heuft G, et al. Decreased gray matter volumes in the cingulo-frontal cortex and the amygdala in patients with fibromyalgia. Psychosom Med 2009;71(5):566–73.
  • Brooks J, Tracey I. From nociception to pain perception: imaging the spinal and supraspinal pathways. J Anat 2005;207(1):19–33.
  • Millan MJ. Descending control of pain. Prog Neurobiol 2002;66(6):355–474.
  • Pinto M, Sousa M, Lima D, Tavares I. Participation of mu-opioid, GABA(B), and NK1 receptors of major pain control medullary areas in pathways targeting the rat spinal cord: implications for descending modulation of nociceptive transmission. J Comp Neurol 2008;510(2):175–87.
  • Dubner R, Ren K. Endogenous mechanisms of sensory modulation. Pain Suppl 1999;82 (Suppl 6):S45–53.
  • Zusman M. Forebrain-mediated sensitization of central pain pathways: ‘non-specific’ pain and a new image for MT. Man Ther 2002;7(2):80–8.
  • Tavares I, Lima D. From neuroanatomy to gene therapy: searching for new ways to manipulate the supraspinal endogenous pain modulatory system. J Anat 2007;211(2):261–8.
  • Kosek E, Ekholm J, Hansson P. Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms. Pain 1996;68(2–3):375–83.
  • Julien N, Goffaux P, Arsenault P, Marchand S. Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain 2005;114(1–2):295–302.
  • Clauw D. Mechanistic studies and their implication for the management of fibromyalgia syndrome. J Musculoskelet Pain 2008;16(1/2):59–66.
  • Baraniuk JN, Whalen G, Cunningham J, Clauw DJ. Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain. BMC Musculoskelet Disord 2004;5:48.
  • Russell IJ, Vaeroy H, Javors M, Nyberg F. Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum 1992;35(5):550–6.
  • Treede RD, Meyer RA, Raja SN, Campbell JN. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol 1992;38(4):397–421.
  • Jankowski MP, Lawson JJ, McIlwrath SL, Rau KK, Anderson CE, Albers KM, et al. Sensitization of cutaneous nociceptors after nerve transection and regeneration: possible role of target-derived neurotrophic factor signaling. J Neurosci 2009;29(6):1636–47.
  • Carlton SM, Du J, Tan HY, Nesic O, Hargett GL, Bopp AC, et al. Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury. Pain 2009;147(1–3):265–76.
  • Jarvis MF, Boyce-Rustay JM. Neuropathic pain: models and mechanisms. Curr Pharm Des 2009;15(15):1711–6.
  • Schmelz M. Translating nociceptive processing into human pain models. Exp Brain Res 2009;196(1):173–8.
  • Graven-Nielsen T, Arendt-Nielsen L. Sensory and motor manifestations of muscle pain. J Musculoskelet Pain 2008;16(1–2):93–105.
  • Nie H, Arendt-Nielsen L, Andersen H, Graven-Nielsen T. Temporal summation of pain evoked by mechanical stimulation in deep and superficial tissue. J Pain 2005;6(6):348–55.
  • Nie H, Arendt-Nielsen L, Madeleine P, Graven-Nielsen T. Enhanced temporal summation of pressure pain in the trapezius muscle after delayed onset muscle soreness. Exp Brain Res 2006;170(2):182–90.
  • Staud R, Cannon RC, Mauderli AP, Robinson ME, Price DD, Vierck CJ. Temporal summation of pain from mechanical stimulation of muscle tissue in normal controls and subjects with fibromyalgia syndrome. Pain 2003;102(1–2):87–95.
  • Raphael KG. Temporal summation of heat pain in temporomandibular disorder patients. J Orofac Pain 2009;23(1):54–64.
  • Drewes AM, Pedersen J, Reddy H, Rasmussen K, Funch-Jensen P, Arendt-Nielsen L, et al. Central sensitization in patients with non-cardiac chest pain: a clinical experimental study. Scand J Gastroenterol 2006;41(6):640–9.
  • Woolf CJ. Windup and central sensitization are not equivalent. Pain 1996;66(2–3):105–8.
  • Hoheisel U, Koch K, Mense S. Functional reorganization in the rat dorsal horn during an experimental myositis. Pain 1994;59(1):111–8.
  • Mense S, Hoheisel U. Central nervous sequelae of local muscle pain. J Musculoskelet Pain 2004;12(3–4):101–9.
  • Shah JP, Gilliams EA. Uncovering the biochemical milieu of myofascial trigger points using in vivo microdialysis: an application of muscle pain concepts to myofascial pain syndrome. J Bodyw Mov Ther 2008;12(4):371–84.
  • Mense S. The pathogenesis of muscle pain. Curr Pain Headache Rep 2003;7(6):419–25.
  • Sorensen J, Bengtsson A, Backman E, Henriksson KG, Bengtsson M. Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Scand J Rheumatol 1995;24(6):360–5.
  • Crombez G, Baeyens F, Eelen P. Sensory and temporal information about impending pain: the influence of predictability on pain. Behav Res Ther 1994;32(6):611–22.
  • Waylonis GW, Heck W. Fibromyalgia syndrome. New associations. Am J Phys Med Rehabil 1992;71(6):343–8.
  • Martin MY, Bradley LA, Alexander RW, Alarcon GS, Triana-Alexander M, Aaron LA, et al. Coping strategies predict disability in patients with primary fibromyalgia. Pain 1996;68(1):45–53.
  • Hassett AL, Cone JD, Patella SJ, Sigal LH. The role of catastrophizing in the pain and depression of women with fibromyalgia syndrome. Arthritis Rheum 2000;43(11):2493–500.
  • Turk DC, Robinson JP, Burwinkle T. Prevalence of fear of pain and activity in patients with fibromyalgia syndrome. J Pain 2004;5(9):483–90.
  • Schmitter M, Keller L, Giannakopoulos N, Rammelsberg P. Chronic stress in myofascial pain patients. Clin Oral Investig 2009;14(5):593–7.
  • Vedolin GM, Lobato VV, Conti PC, Lauris JR. The impact of stress and anxiety on the pressure pain threshold of myofascial pain patients. J Oral Rehabil 2009;36(5):313–21.
  • Nifosi F, Violato E, Pavan C, Sifari L, Novello G, Guarda Nardini L, et al. Psychopathology and clinical features in an Italian sample of patients with myofascial and temporomandibular joint pain: preliminary data. Int J Psychiatry Med 2007;37(3):283–300.
  • Manfredini D, Bandettini di Poggio A, Cantini E, Dell'Osso L, Bosco M. Mood and anxiety psychopathology and temporomandibular disorder: a spectrum approach. J Oral Rehabil 2004;31(10):933–40.
  • Dohrenwend BP, Raphael KG, Marbach JJ, Gallagher RM. Why is depression comorbid with chronic myofascial face pain? A family study test of alternative hypotheses. Pain 1999;83(2):183–92.
  • Bruehl S, Chung OY, Burns JW. Differential effects of expressive anger regulation on chronic pain intensity in CRPS and non-CRPS limb pain patients. Pain 2003;104(3):647–54.
  • Gerwin R. The taut band and other mysteries of the trigger point: an examination of the mechanisms relevant to the development and maintenance of the trigger point. J Musculoskelet Pain 2008;16(1–2):115–21.
  • Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev 2004;68(2):320–44.
  • Gaestel M, Kotlyarov A, Kracht M. Targeting innate immunity protein kinase signalling in inflammation. Nat Rev Drug Discov 2009;8(6):480–99.
  • Ji RR, Gereau RW, Malcangio M, Strichartz GR. MAP kinase and pain. Brain Res Rev 2009;60(1):135–48.
  • Chen Q, Basford J, An KN. Ability of magnetic resonance elastography to assess taut bands. Clin Biomech (Bristol, Avon) 2008;23(5):623–9.
  • Travell J, Simons D. Travell and Simons’ myofascial pain and dysfunction: the trigger point manual, Vol 1. Upper half of the body. Baltimore: Williams & Wilkins; 1983.
  • Mense S, Simons D. Muscle pain. Understanding its nature, diagnosis, and treatment. Baltimore and Philadelphia: Lippincott, Williams & Wilkins; 2001.
  • Gerwin RD, Dommerholt J, Shah JP. An expansion of Simons’ integrated hypothesis of trigger point formation. Curr Pain Headache Rep 2004;8(6):468–75.
  • Simons D, Travell J, Simons L. Myofascial pain and dysfunction: the trigger point manual, Vol 1. 2nd ed. Baltimore: Williams and Wilkins; 1999.
  • Andrews C, Ho PD, Dillmann WH, Glembotski CC, McDonough PM. The MKK6-p38 MAPK pathway prolongs the cardiac contractile calcium transient, downregulates SERCA2, and activates NF-AT. Cardiovasc Res 2003;59(1):46–56.
  • Hägg G. Static work loads and occupational myalgia—a new explanation model. In: , Anderson P, Hobart D, JV D (eds) Electromyographical kinesiology, Vol 1. Amsterdam: Elsevier Science; 1991. p.141–3.
  • Treaster D, Marras WS, Burr D, Sheedy JE, Hart D. Myofascial trigger point development from visual and postural stressors during computer work. J Electromyogr Kinesiol 2006;16(2):115–24.
  • Edwards J. The importance of postural habits in perpetuating myofascial trigger point pain. Acupunct Med 2005;23(2):77–82.
  • Fernandez-de-las-Penas C, Alonso-Blanco C, Cuadrado ML, Gerwin RD, Pareja JA. Trigger points in the suboccipital muscles and forward head posture in tension-type headache. Headache 2006;46(3):454–60.
  • Lucas N, Macaskill P, Irwig L, Moran R, Bogduk N. Reliability of physical examination for diagnosis of myofascial trigger points: a systematic review of the literature. Clin J Pain 2009;25(1):80–9.
  • Alvarez DJ, Rockwell PG. Trigger points: diagnosis and management. Am Fam Phys 2002;65(4):653–60.
  • Chen Q, Bensamoun S, Basford JR, Thompson JM, An KN. Identification and quantification of myofascial taut bands with magnetic resonance elastography. Arch Phys Med Rehabil 2007;88(12):1658–61.
  • Shah J. Uncovering the biochemical milieu of myofascial trigger points using in vivo microdialysis. J Musculoskelet Pain 2008;16(1–2):17–20.
  • Shah JP, Danoff JV, Desai MJ, Parikh S, Nakamura LY, Phillips TM, et al. Biochemicals associated with pain and inflammation are elevated in sites near to and remote from active myofascial trigger points. Arch Phys Med Rehabil 2008;89(1):16–23.
  • Shah JP, Phillips TM, Danoff JV, Gerber LH. An in vivo microanalytical technique for measuring the local biochemical milieu of human skeletal muscle. J Appl Physiol 2005;99(5):1977–84.
  • Skyba DA, King EW, Sluka KA. Effects of NMDA and non-NMDA ionotropic glutamate receptor antagonists on the development and maintenance of hyperalgesia induced by repeated intramuscular injection of acidic saline. Pain 2002;98(1–2):69–78.
  • Sluka KA, Kalra A, Moore SA. Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia. Muscle Nerve 2001;24(1):37–46.
  • Sluka KA, Rohlwing JJ, Bussey RA, Eikenberry SA, Wilken JM. Chronic muscle pain induced by repeated acid Injection is reversed by spinally administered mu- and delta-, but not kappa-, opioid receptor agonists. J Pharmacol Exp Ther 2002;302(3):1146–50.
  • Schafers M, Sorkin LS, Sommer C. Intramuscular injection of tumor necrosis factor-alpha induces muscle hyperalgesia in rats. Pain 2003;104(3):579–588.
  • Widmann C, Gibson S, Jarpe MB, Johnson GL. Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 1999;79(1):143–80.
  • Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 2002;298(5600):1911–2.
  • Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 2001;22(2):153–83.
  • Ono K, Han J. The p38 signal transduction pathway: activation and function. Cell Signal 2000;12(1):1–13.
  • Puri PL, Wu Z, Zhang P, Wood LD, Bhakta KS, Han J, et al. Induction of terminal differentiation by constitutive activation of p38 MAP kinase in human rhabdomyosarcoma cells. Genes Dev. 2000;14(5):574–84.
  • Kumar S, Boehm J, Lee JC. p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov 2003;2(9):717–26.
  • Saklatvala J. The p38 MAP kinase pathway as a therapeutic target in inflammatory disease. Curr Opin Pharmacol 2004;4(4):372–7.
  • Kotlyarov A, Neininger A, Schubert C, Eckert R, Birchmeier C, Volk HD, et al. MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis. Nat Cell Biol 1999;1(2):94–7.
  • Chen CY, Shyu AB. AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem Sci 1995;20(11):465–70.
  • Clark A, Dean J, Tudor C, Saklatvala J. Post-transcriptional gene regulation by MAP kinases via AU-rich elements. Front Biosci 2009;14:847–71.
  • Hitti E, Iakovleva T, Brook M, Deppenmeier S, Gruber AD, Radzioch D, et al. Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor mRNA stability and translation mainly by altering tristetraprolin expression, stability, and binding to adenine/uridine-rich element. Mol Cell Biol 2006;26(6):2399–407.
  • Rousseau S, Morrice N, Peggie M, Campbell DG, Gaestel M, Cohen P. Inhibition of SAPK2a/p38 prevents hnRNP A0 phosphorylation by MAPKAP-K2 and its interaction with cytokine mRNAs. EMBO J 2002;21(23):6505–14.
  • Ronkina N, Kotlyarov A, Dittrich-Breiholz O, Kracht M, Hitti E, Milarski K, et al. The mitogen-activated protein kinase (MAPK)-activated protein kinases MK2 and MK3 cooperate in stimulation of tumor necrosis factor biosynthesis and stabilization of p38 MAPK. Mol Cell Biol 2007;27(1):170–81.
  • Neininger A, Kontoyiannis D, Kotlyarov A, Winzen R, Eckert R, Volk HD, et al. MK2 targets AU-rich elements and regulates biosynthesis of tumor necrosis factor and interleukin-6 independently at different post-transcriptional levels. J Biol Chem 2002;277(5):3065–8.
  • Zarubin T, Han J. Activation and signaling of the p38 MAP kinase pathway. Cell Res 2005;15(1):11–8.
  • Gaestel M. MAPKAP kinases – MKs – two's company, three's a crowd. Nat Rev Mol Cell Biol 2006;7(2):120–30.
  • Engel K, Plath K, Gaestel M. The MAP kinase-activated protein kinase 2 contains a proline-rich SH3-binding domain. FEBS Lett 1993;336(1):143–7.
  • Ronkina N, Kotlyarov A, Gaestel M. MK2 and MK3 – a pair of isoenzymes? Front Biosci 2008;13:5511–21.
  • Kontoyiannis D, Boulougouris G, Manoloukos M, Armaka M, Apostolaki M, Pizarro T, et al. Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn's-like inflammatory bowel disease. J Exp Med 2002;196(12):1563–74.
  • Lehner MD, Schwoebel F, Kotlyarov A, Leist M, Gaestel M, Hartung T. Mitogen-activated protein kinase-activated protein kinase 2-deficient mice show increased susceptibility to Listeria monocytogenes infection. J Immunol 2002;168(9):4667–73.
  • Rousseau S, Papoutsopoulou M, Symons A, Cook D, Lucocq JM, Prescott AR, et al. TPL2-mediated activation of ERK1 and ERK2 regulates the processing of pre-TNF alpha in LPS-stimulated macrophages. J Cell Sci 2008;121(Pt 2):149–54.
  • Dumitru CD, Ceci JD, Tsatsanis C, Kontoyiannis D, Stamatakis K, Lin JH, et al. TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell 2000;103(7):1071–83.
  • Gaestel M. Specificity of signaling from MAPKs to MAPKAPKs: kinases’ tango nuevo. Front Biosci 2008;13:6050–9.
  • Ji RR, Baba H, Brenner GJ, Wolf CJ. Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity. Nat Neurosci 1999;2(12):1114–9.
  • Widegren U, Ryder JW, Zierath JR. Mitogen-activated protein kinase signal transduction in skeletal muscle: effects of exercise and muscle contraction. Acta Physiol Scand 2001;172(3):227–38.
  • Akimoto T, Pohnert SC, Li P, Zhang M, Gumbs C, Rosenberg PB, et al. Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway. J Biol Chem 2005;208(20):19587–93.
  • Puigserver P, Rhee J, Lin J, Wu Z, Yoon JC, Zhang CY, et al. Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Mol Cell 2001;8(5):971–82.
  • Aronson D, Wojtaszewski JF, Thorell A, Nygren J, Zangen D, Richter EA, et al. Extracellular-regulated protein kinase cascades are activated in response to injury in human skeletal muscle. Am J Physiol 1998;275(2 Pt 1):C555–61.
  • Pedersen BK, Akerström TC, Nielsen AR, Fischer CP. Role of myokines in exercise and metabolism. J Appl Physiol 2007;103(3):1093–98.
  • Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol 2005;98(4):1154–62.
  • Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature 2008;454(7203):463–9.
  • Kramer HF, Goodyear LJ. Exercise, MAPK, and NF-kappaB signaling in skeletal muscle. J Appl Physiol 2007;103(1):388–95.
  • Ji LL. Antioxidant signaling in skeletal muscle: a brief review. Exp Gerontol 2007;42(7):582–93.
  • Schaeffer C, Vandroux D, Thomassin L, Athias P, Rochette L, Connat JL. Calcitonin gene-related peptide partly protects cultured smooth muscle cells from apoptosis induced by an oxidative stress via activation of ERK1/2 MAPK. Biochim Biophys Acta 2003;1643(1–3):65–73.
  • Lee MR, Dominguez C. MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alpha protein. Curr Med Chem 2005;12(25):2979–94.
  • Kuma Y, Sabio G, Bain J, Shpiro N, Márquez R, Cuenda A. BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo. J Biol Chem 2005;280(20):19472–9.
  • Dominguez C, Powers DA, Tamayo N. p38 MAP kinase inhibitors: many are made, but few are chosen. Curr Opin Drug Discov Devel 2005;8(4):421–30.
  • Dambach DM. Potential adverse effects associated with inhibition of p38alpha/beta MAP kinases. Curr Top Med Chem 2005;5(10):929–39.
  • Ding C. Drug evaluation: VX-702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronary syndrome. Curr Opin Investig Drugs 2006;7(11):1020–5.
  • Ji RR, Suter MR. p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain 2007;3:33.
  • Damjanov N, Kauffman RS, Spencer-Green GT. Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum 2009;60(5):1232–41.
  • Suckfuell M, Canis M, Strieth S, Scherer H, Haisch A. Intratympanic treatment of acute acoustic trauma with a cell-permeable JNK ligand: a prospective randomized phase I/II study. Acta Otolaryngol 2007;127(9):938–42.
  • Xu JJ, Hendriks BS, Zhao J, de Graaf D. Multiple effects of acetaminophen and p38 inhibitors: towards pathway toxicology. FEBS Lett 2008;582(8):1276–82.
  • Duraisamy S, Bajpai M, Bughani U, Dastidar SG, Ray A, Chopra P. MK2: a novel molecular target for anti-inflammatory therapy. Expert Opin Ther Targets 2008;12(8):921–36.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.