Neuromusculoskeletal Pain:Lessons from the Myofascia               Jay P. Shah, MD      Rehabilitation Medicine Department...
Disclosures• Nothing to disclose
NIH Clinical Research Center     “Bench to Bedside - Bedside to Bench”                                     Outpatient     ...
Perception                                                              Sensitization                           Brain area...
Pain MechanismsAdapted from Butler, DS The Sensitive Nervous System
Goals of Discussion•   Review the diagnostic criteria for myofascial pain and    demonstrate the referral patterns of comm...
Goals of Discussion• Introduce novel applications of ultrasound  techniques to visualize MTrPs, measure their  stiffness p...
Myofascial Trigger Points                                 Hans-Werner Weisskircher                                  www.tr...
Essential Clinical Criteria for                  Myofascial Pain        • Palpation of a taut band        • Exquisitely te...
Essential Clinical Criteria for              Myofascial Pain     • Palpation of a taut band     • Exquisitely tender spot ...
Myofascial Trigger Points2-5 areas in hard, palpable  bands of skeletal muscle:Active – cause a clinical pain  complaint o...
Orofacial Pain 2º                    Myofascial Trigger                         Points    Masseter                        ...
Muscle Pain, Inflammation, and Sensitization   Muscle    Injury               Release of Inflammatory                     ...
Muscle Pain, Inflammation, and Sensitization   Muscle                Sensitize wide dynamic range    Injury               ...
Muscle Pain, Inflammation, and Sensitization                         … expansion of the receptive                         ...
Travell JG, Simons DG. Myofascialpain and dysfunction: the trigger pointmanual. Baltimore: Williams &Wilkins; 1992.
Common Referral Diagnoses for Pain Found to be of Myofascial Origin• Angina Pectoris      • Pectoralis Major  (atypical)• ...
“Since no specialty claimsskeletal muscle as their organ, it      is often overlooked”        David G. Simons, MD
Muscle – The “Orphan Organ”• NO specialty claims muscle as its organ  Muscle is ½ of the body  No organized emphasis on mu...
Active MTrPs can only be diagnosed by        systematic palpation                                   Hans-Werner           ...
Apply Firm Pressure        Hans-Werner Weisskircher www.trigger-point.com
Palpation, Palpation, Palpation• Careful palpation of the surface  of the body reveals distinct  differences in the qualit...
Nociceptor Function• Encode Noxious Stimuli  • Possibly leading to pain• Maintain Tissue Health  • Initiate and maintain r...
Nociceptors are Dynamic “Two-way” Structures
A Critical Efferent Nociceptor Function:Neuropeptide (Substance P, CGRP) Production                                  Court...
Unique Neurobiology of Muscle Pain   Muscle pain is NOT skin pain
Muscle Pain is often Overlooked       “I’ll be                   “Ohhh,        Back!”                      my             ...
Unique Characteristics of Muscle Pain •   Aching, cramping pain, difficult to     localize and referred to deep and distan...
Distant Referral Patterns                            Hans-Werner                            Weisskircher                  ...
Powerful Descending Inhibition on Muscle PainFields HL, Basbaum AI: Centralnervous system mechanisms ofpain modualtion. In...
Afferent Bombardment of Muscle Nociceptors:  2nd Messenger Cascades, Induction of Immediate Early Genes and Protein Synthe...
Muscle PainPeripheral Mechanisms
Muscle Nociception – Binding ofSubstances to Matched Chemoreceptors                    (B2→B1)                      BRADYK...
Muscle PainSpinal Mechanisms
Characteristics of Muscle Nociceptor    Projections to Dorsal Horn  • REDUCED SPATIAL RESOLUTION    – Due to lower density...
Dorsal Horn Changes in Pathologic Conditions – Central Sensitization         DIVERGENCE OF SENSORY INPUT• Sustained noxiou...
Expansion of Receptive Field by a               Painful Muscle StimulusCourtesy Jan Dommerholt                            ...
Expansion of Receptive Field by a               Painful Muscle StimulusCourtesy Jan Dommerholt5 min after BK injection in ...
Expansion of Receptive Field by a    Painful Muscle Stimulus                        Hoheisel U, Mense S, Simons DG.       ...
Expansion of Receptive Field by a    Painful Muscle Stimulus                        Hoheisel U, Mense S, Simons DG.       ...
Expansion of Receptive Field by a    Painful Muscle Stimulus                        Hoheisel U, Mense S, Simons DG.       ...
Expansion of Receptive Field by a    Painful Muscle Stimulus                        Hoheisel U, Mense S, Simons DG.       ...
Expansion of Receptive Field by a              Painful Muscle Stimulus                                                    ...
Nociceptive Bombardment causes                          Central Sensitization and NeuroplasticGlutamate   Substance P   Ch...
Pain begins in Calf, Heel and            Foot
Then Develops Pain in SI       Joint too
Then Develops Pain in SI       Joint too                           TrP3
Neuron for SI Joint is  Initially Inactive           Ineffective Synapse                                 TrP3         Dors...
Expansion of the Receptive Field               Effective synapse                                   TrP3
Wide Dynamic Range Neuron                    Excitatory tonus                    via nociceptors              ++          ...
Substances Dynamically Modulating Dorsal Horn Neurons                                          DynorphinImmune system     ...
MTrPs and the Local Twitch Response                        Courtesy Joseph Audette
Myofascial PainHistorical and Regional Confusion Fibrositis         Myofascitis                    Myofibrositis Myositis ...
Historical Context of Trigger Points• Steindler coined the term “trigger points”  when he found he was able to relieve  sc...
Opening of Previously Ineffective Synapses
Treatments for Myofascial Pain                               • Orthotics, shoe•   Spray/Stretch                           ...
“Dry needling MTrPs and  eliciting LTRs is as effective as lidocaine injection in inactivating    a MTrP and relieving pai...
Recent studies comparing MTrP injections with asyringe and MTrP needling with an acupuncture needle showed that MTrP needl...
Trigger Point Needling:Proper Technique to Elicit Local Twitch        Responses is Essential                  Hong CZ Arch...
How does dry needling work?
What is the Pathophysiology of      Myofascial Pain?        UNKNOWN
Simons’ Integrated HypothesisPathophysiology           HistopathologyIncreased Miniature           Increased Endplate Pote...
What is the Biochemical Milieu of MTrPs?                            Clinical findings                            Underlyin...
Myofascial Trigger Points: A Unique Perspective at the NIH In Vivo Microdialysis – A Technique ForAnalysis of the Biochemi...
Microdialysis                                       Low or no                                       solute        Semi-per...
Microdialysis/Acupuncture NeedleCourtesy Terry Phillips
Microdialysis/Acupuncture     Needle – 30 Gauge Hypodermic                      Delivery tubes                            ...
Comparison of Needle Tips                          25G syringe needle                                 32G acupuncture need...
Comparison between a     Standard Acupuncture Needle and             our Needle/Probe                             Needle/P...
Comparison of Needle Tips      Rounded              Sharp beveled      acupuncture needle   hypodermic needle      tip pus...
Microdialysis SamplingCourtesy Sagar Parikh
Microdialysis System                               In-flow                               catheter    Microdialysis    pump...
detector                    capillary           Powercomputer   supply                                CE chamber
Co-investigators• Terry Phillips, PhD, DSc• Jerome Danoff, PT, PhD• Lynn Gerber, MD
Hans-WernerWeisskircherwww.trigger- point.com
Design, Setting, and Patients  Three healthy subjects were selected to be in each of  three groups (total 9 subjects) base...
Initial Analyte Values in TrapeziusAnalyte               Active   Latent   Normal   *P valuepH (pH units)          5.4    ...
400                    Concentration of Substance P over time          350          300          250                Active...
First Phase: What We’ve                      Demonstrated   •     Collect near real-time samples from soft tissue         ...
Purpose of Second Phase1) Determine whether these findings are unique to   the upper trapezius when compared to a remote  ...
Design, Setting, and Patients9 subjects, all of whom had no calf pain or calfMTrPs, were divided into 3 groups based on th...
No                                   MTrP3 Groups of Subjects with following findings in upper                            ...
Exclusion Criteria• Fibromyalgia                   • Other concurrent pain• Cervical radiculopathy           syndromes• At...
Procedure and MeasuresProcedure : Samples were obtained continuously from the trapezius site at regular intervals for 14 m...
Initial Analyte Values in TrapeziusAnalyte               Active   Latent   Normal *P valuepH (pH units)          5.2      ...
Set 1 Active                  Combined Data for Substance P                 Set 1 Latent                                  ...
Concentrations of Analytes in the Active   Group at Initial Needle Insertion Analyte       Trap     GS      *P value pH   ...
Concentrations of Analytes at Initial Needle   Insertion in Gastrocnemius Muscle Analyte       GS (Act)   GS (Lat)   GS (N...
(Normal Muscle)Active                           I = SEELatent                 Active groupNormal
(Normal Muscle)Active                           I = SEELatent                       Active groupNormal
(Normal Muscle)Active                              I = SEE                           Active grou
(Normal Muscle)                              I = SEEActive                           Active group
(Normal Muscle)                                    e                               I = SEEActive                          ...
Active                 Active group                                e         (Normal Muscle)                           I =...
Second Phase: What We’ve Learned•   An active MTrP has a unique biochemical milieu    of substances known to be associated...
Second Phase: What We’ve Learned     •    Subjects with an active MTrP in the upper          trapezius have elevated level...
Biochemical Considerations
H+
“Pro-inflammatory cytokines  increase the sensitivity of all peripheral neural structures andtheir afferent cell bodies, c...
Hypernociceptive role of cytokines         and chemokines:     Targets for analgesic drug           development?    TNF-α,...
Cytokine Cascade and Pain                             Cg, LPS or Ag              Ag                               TNF-α   ...
Moving Ahead: Microanalytic Systems for in-vivoMeasurement of the Biochemical Milieu of Muscle                            ...
The Next Phase:          A Natural History Study•   Does the biochemical milieu at and around the MTrP    change with resp...
Treatment TrialsAssess the local biochemical milieu of MTrPs as an outcomemeasure of efficacy in clinical treatment trials...
A New DirectionTo Address an Old Controversy
Obstacles• There are currently no imaging criteria for  the diagnosis of trigger points or for  assessing clinical outcome...
Our Research Question Can ultrasound imaging be used to develop objectivedescriptions of the tissue and blood flow charact...
Upper Trapezius Muscle with          MTrP                                  Fascia                                Upper    ...
Vibration Sonoelastography         30 kPa63 kPa            44 kPa
Vibration Applicator
Vibration Sonoelastography of         Muscle with MTrP                         Focal decrease of color   Hypoechoeic trigg...
Vibration Sonoelastography of          Uninvolved Muscle                                Uniform color  variance      Unifo...
Vibration Sonoelastography of     Uninvolved Muscle
Sonoelastography Imaging                       Objective                       diagnostic test                       Outco...
Imaging blood flow near MTrPs in          the Upper TrapeziusA              BFS=0B              BFS=1C              BFS=2D...
Observations•   Ultrasound is feasible for imaging MTrPs•   MTrPs exhibit different echogenecity compared to    surroundin...
Observations• Blood flow waveform characteristics can be used  to differentiate Active and Latent MTrPs• Retrograde flow i...
Integrated                     Neuromuscular                        TheoryX     Inflamatory    Mediators, BK,       NE, SP...
Injection Therapies   Where?      Why?What?
2012 aaom shah neuromusculoskeletal pain lessons from the myofascia
2012 aaom shah neuromusculoskeletal pain lessons from the myofascia
2012 aaom shah neuromusculoskeletal pain lessons from the myofascia
2012 aaom shah neuromusculoskeletal pain lessons from the myofascia
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2012 aaom shah neuromusculoskeletal pain lessons from the myofascia

  1. 1. Neuromusculoskeletal Pain:Lessons from the Myofascia Jay P. Shah, MD Rehabilitation Medicine Department National Institutes of Health
  2. 2. Disclosures• Nothing to disclose
  3. 3. NIH Clinical Research Center “Bench to Bedside - Bedside to Bench” Outpatient CareLaboratories Laboratories Inpatient Care
  4. 4. Perception Sensitization Brain areas encoding pain Cultural, experience and behaviors past experience, personality CNS Plasticity attention Pattern- Pathogenic generating inputs mechanism Autonomic (Neuromatrix) endocrine, Visceral immune inputs variables Somatosensory inputsMelzack, Trends Neurosci 1990; 13:88-92
  5. 5. Pain MechanismsAdapted from Butler, DS The Sensitive Nervous System
  6. 6. Goals of Discussion• Review the diagnostic criteria for myofascial pain and demonstrate the referral patterns of common myofascial trigger points (MTrPs)• Examine the unique neurobiology of muscle pain• Discuss the dynamic interplay of muscle nociceptors and endogenous biochemicals in the initiation, amplification and perpetuation of peripheral and central sensitization• Demonstrate that an active myofascial trigger point (MTrP) in the upper trapezius has elevated levels of inflammatory mediators, neuropeptides, and cytokines, etc. – substances known to be associated with persistent pain states, sensitization and inflammation
  7. 7. Goals of Discussion• Introduce novel applications of ultrasound techniques to visualize MTrPs, measure their stiffness properties and local blood flow• Demonstrate that MTrPs in the upper trapezius are stiffer than surrounding tissue and that active MTrPs can be distinguished from latent MTrPs by their high-resistance blood flow
  8. 8. Myofascial Trigger Points Hans-Werner Weisskircher www.trigger-point.comA Very Common, Complex and OverlookedCause of Non-articular Musculoskeletal Pain
  9. 9. Essential Clinical Criteria for Myofascial Pain • Palpation of a taut band • Exquisitely tender spot (a myofascial trigger point) in the taut band • Reproduction of the subject’s symptomatic painGerwin et al. Interrater reliability inmyofascial trigger point examination.Pain. 1997;69(1-2):65-73 Hans-Werner Weisskircher www.trigger-point.com
  10. 10. Essential Clinical Criteria for Myofascial Pain • Palpation of a taut band • Exquisitely tender spot (a myofascial trigger point) in the taut band • Reproduction of the subjects symptomatic pain Gerwin et al. Interrater reliability in myofascial trigger point examination. Pain. 1997;69(1-2):65-73Courtesy Marta Imamura
  11. 11. Myofascial Trigger Points2-5 areas in hard, palpable bands of skeletal muscle:Active – cause a clinical pain complaint or other abnormal sensory symptomsLatent – show all the other characteristics of active MTrPs, except that they’re pain free Travell JG, Simons DG. Myofascial pain and dysfunction: the trigger point manual. Baltimore: Williams & Wilkins; 1992.
  12. 12. Orofacial Pain 2º Myofascial Trigger Points Masseter Medial Pterygoid Upper Trapezius Hans-Werner WeisskircherSCM (sternal division) www.trigger-point.com Lateral Pterygoid
  13. 13. Muscle Pain, Inflammation, and Sensitization Muscle Injury Release of Inflammatory mediators, Neuropeptides and CytokinesCourtesy Marta Imamura
  14. 14. Muscle Pain, Inflammation, and Sensitization Muscle Sensitize wide dynamic range Injury neurons and higher centers leading to allodynia, hyperalgesia and… and…Courtesy Marta Imamura
  15. 15. Muscle Pain, Inflammation, and Sensitization … expansion of the receptive field of pain and referral of painCourtesy Marta Imamura
  16. 16. Travell JG, Simons DG. Myofascialpain and dysfunction: the trigger pointmanual. Baltimore: Williams &Wilkins; 1992.
  17. 17. Common Referral Diagnoses for Pain Found to be of Myofascial Origin• Angina Pectoris • Pectoralis Major (atypical)• Appendicitis • Lower Rectus Abdominis• Atypical Migraine • Sternocleidomastoid,• Tension Headache Temporalis, Mastic.• Occipital Headache Musc, Post. Cervicals, Travell JG, Simons DG. Myofascial pain and dysfunction: the trigger point manual. Baltimore: Williams & Wilkins; 1992.
  18. 18. “Since no specialty claimsskeletal muscle as their organ, it is often overlooked” David G. Simons, MD
  19. 19. Muscle – The “Orphan Organ”• NO specialty claims muscle as its organ Muscle is ½ of the body No organized emphasis on muscle pain (MTrP) research or student training Clinicians focus primarily on treating the SYMPTOMS of myogenic pain, not the CAUSE of the pain (MTrPs)
  20. 20. Active MTrPs can only be diagnosed by systematic palpation Hans-Werner Weisskircher www.trigger-point.com
  21. 21. Apply Firm Pressure Hans-Werner Weisskircher www.trigger-point.com
  22. 22. Palpation, Palpation, Palpation• Careful palpation of the surface of the body reveals distinct differences in the quality and density of the underlying tissue. Many of these areas or points will be tender:• A Shi points in Traditional Chinese Medicine• Kori in Japanese system• Muskelharten in German system
  23. 23. Nociceptor Function• Encode Noxious Stimuli • Possibly leading to pain• Maintain Tissue Health • Initiate and maintain reaction to injury
  24. 24. Nociceptors are Dynamic “Two-way” Structures
  25. 25. A Critical Efferent Nociceptor Function:Neuropeptide (Substance P, CGRP) Production Courtesy Jan Dommerholt
  26. 26. Unique Neurobiology of Muscle Pain Muscle pain is NOT skin pain
  27. 27. Muscle Pain is often Overlooked “I’ll be “Ohhh, Back!” my Back!”
  28. 28. Unique Characteristics of Muscle Pain • Aching, cramping pain, difficult to localize and referred to deep and distant somatic tissues • Muscle pain activates unique cortical structures Svensson P et al. Cerebral processing of acute skin and muscle pain in humans. J Neurophysiology July 1997; 78: 450-460. • Inhibited more strongly by descending pain-modulating pathways XianMin Y, Mense S. Response Properties and descending control of rat dorsal horn neurons with deep receptive fields. Neuroscience 1990; 39:823-831. • Activation of muscle nociceptors is much more effective at inducing neuroplastic changes in dorsal horn neurons Wall PD, Woolf CJ. J Physiol 1984 Nov;356:443-458.
  29. 29. Distant Referral Patterns Hans-Werner Weisskircher www.trigger- point.com
  30. 30. Powerful Descending Inhibition on Muscle PainFields HL, Basbaum AI: Centralnervous system mechanisms ofpain modualtion. In Textbook ofPain; 1999:309-329.
  31. 31. Afferent Bombardment of Muscle Nociceptors: 2nd Messenger Cascades, Induction of Immediate Early Genes and Protein Synthesis, Excitotoxicity and Cell Death Activity Dependent Plasticity Wall PD, Woolf CJ. Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the flexion reflex in the rat. J Physiol. 1984 Nov;356:443-58.
  32. 32. Muscle PainPeripheral Mechanisms
  33. 33. Muscle Nociception – Binding ofSubstances to Matched Chemoreceptors (B2→B1) BRADYKININ RECEPTOR Receptor Bradykinin
  34. 34. Muscle PainSpinal Mechanisms
  35. 35. Characteristics of Muscle Nociceptor Projections to Dorsal Horn • REDUCED SPATIAL RESOLUTION – Due to lower density of muscle sensory afferents compared to the skin • CONVERGENCE OF SENSORY INPUT – Input from skin, bone, viscera, periosteum
  36. 36. Dorsal Horn Changes in Pathologic Conditions – Central Sensitization DIVERGENCE OF SENSORY INPUT• Sustained noxious stimulation (of Group IV fibers in muscle) leads to the opening of previously ineffective connections in dorsal horn neurons• Intramuscular injection of various biochemicals (e.g., bradykinin, prostaglandins, serotonin, acidic saline, etc.) activates muscle nociceptors and causes allodynia and hyperalgesia
  37. 37. Expansion of Receptive Field by a Painful Muscle StimulusCourtesy Jan Dommerholt Biceps Femoris Selected neuron responds Hoheisel U, Mense S, Simons DG. Appearance of new receptive fields in only to deep pressure in rat dorsal horn neurons following noxious stimulation of skeletal muscle: a biceps femoris muscle model for referral of muscle pain? Neurosci lett 153:9-12, 1993
  38. 38. Expansion of Receptive Field by a Painful Muscle StimulusCourtesy Jan Dommerholt5 min after BK injection in TA, the selected neuron can now be excited by additional RF’s located in deep Hoheisel U, Mense S, Simons DG. muscle that normally have high threshold Neurosci lett 153:9-12, 1993
  39. 39. Expansion of Receptive Field by a Painful Muscle Stimulus Hoheisel U, Mense S, Simons DG. Neurosci lett 153:9-12, 1993
  40. 40. Expansion of Receptive Field by a Painful Muscle Stimulus Hoheisel U, Mense S, Simons DG. Neurosci lett 153:9-12, 1993
  41. 41. Expansion of Receptive Field by a Painful Muscle Stimulus Hoheisel U, Mense S, Simons DG. Neurosci lett 153:9-12, 1993
  42. 42. Expansion of Receptive Field by a Painful Muscle Stimulus Hoheisel U, Mense S, Simons DG. Neurosci lett 153:9-12, 1993
  43. 43. Expansion of Receptive Field by a Painful Muscle Stimulus Allodynia (light pressure and muscle movement) Hyperalgesia15 min after BK injection in the TA the selected neuron responds to moderate (innocuous) pressure in its original receptive field - Hoheisel U, Mense S, Simons DG biceps femoris Neurosci lett 153:9-12, 1993
  44. 44. Nociceptive Bombardment causes Central Sensitization and NeuroplasticGlutamate Substance P Changes in Dorsal Horn Neurons
  45. 45. Pain begins in Calf, Heel and Foot
  46. 46. Then Develops Pain in SI Joint too
  47. 47. Then Develops Pain in SI Joint too TrP3
  48. 48. Neuron for SI Joint is Initially Inactive Ineffective Synapse TrP3 Dorsal horn
  49. 49. Expansion of the Receptive Field Effective synapse TrP3
  50. 50. Wide Dynamic Range Neuron Excitatory tonus via nociceptors ++ ---- Inhibitory tonus
  51. 51. Substances Dynamically Modulating Dorsal Horn Neurons DynorphinImmune system Met Leu- enkephalinNeurotrophins SPNeurosteroids GalaninCytokines VIPGlia and Astrocytes NPY GABA, Glycine, Glutamate, SOM ACh, DA, 5-HT, Nitric Oxide
  52. 52. MTrPs and the Local Twitch Response Courtesy Joseph Audette
  53. 53. Myofascial PainHistorical and Regional Confusion Fibrositis Myofascitis Myofibrositis Myositis Myofascial PainMuscular Myelosisrheumatism Radiculitis
  54. 54. Historical Context of Trigger Points• Steindler coined the term “trigger points” when he found he was able to relieve sciatica by injecting Novocain into tender points in muscles in the lumbar and gluteal regions• Travell added the term “myofascial” after performing a biopsy of the infraspinatus muscle and observed that pinching the fasciae produced the same referral pattern as the muscle
  55. 55. Opening of Previously Ineffective Synapses
  56. 56. Treatments for Myofascial Pain • Orthotics, shoe• Spray/Stretch modification• Strain/counterstrain • Counseling• Muscle energy • Behavioral• Myofascial release management• Medications • Relaxation• Dry Needling • Imagery• Trigger point injections • Hypnosis • Coping skills• Botox injections • Acupressure
  57. 57. “Dry needling MTrPs and eliciting LTRs is as effective as lidocaine injection in inactivating a MTrP and relieving pain”Hong CZ. Lidocaine injection versus dry needling tomyofascial trigger point. The importance of the local twitchresponse. Am J Phys Med Rehabil. 1994;73(4):256-63.
  58. 58. Recent studies comparing MTrP injections with asyringe and MTrP needling with an acupuncture needle showed that MTrP needling with an acupneedle does not cause more post-needling soreness Ga H, Choi JH, Park CH, Yoon HJ. Acupuncture needling versus lidocaine injection of trigger points in myofascial pain syndrome in elderly patients - a randomised trial. Acupunct Med. 2007 Dec;25(4):130-6. Ga H, Koh HJ, Choi JH, Kim CH. Intramuscular and nerve root stimulation vs lidocaine injection to trigger points in myofascial pain syndrome. J Rehabil Med. 2007 May;39(5):374-8.
  59. 59. Trigger Point Needling:Proper Technique to Elicit Local Twitch Responses is Essential Hong CZ Arch Phys Med Rehab 1994;73:256 Courtesy Joseph Audette
  60. 60. How does dry needling work?
  61. 61. What is the Pathophysiology of Myofascial Pain? UNKNOWN
  62. 62. Simons’ Integrated HypothesisPathophysiology HistopathologyIncreased Miniature Increased Endplate Potentials Fiber Tension (Endplate Noise) (Taut Band) Histochemistry Release of Sensitizing Substances? (Pain)
  63. 63. What is the Biochemical Milieu of MTrPs? Clinical findings Underlying milieu?
  64. 64. Myofascial Trigger Points: A Unique Perspective at the NIH In Vivo Microdialysis – A Technique ForAnalysis of the Biochemical Milieu of MTrPs
  65. 65. Microdialysis Low or no solute Semi-permeable membrane High concentration soluteCourtesy Terry Phillips
  66. 66. Microdialysis/Acupuncture NeedleCourtesy Terry Phillips
  67. 67. Microdialysis/Acupuncture Needle – 30 Gauge Hypodermic Delivery tubes Fluid in Fluid out Solute exchange surface – dialyzer membrane set 0.2 mm from the needle tipCourtesy Terry Phillips
  68. 68. Comparison of Needle Tips 25G syringe needle 32G acupuncture needleCourtesy Terry Phillips
  69. 69. Comparison between a Standard Acupuncture Needle and our Needle/Probe Needle/Probe Acupuncture needleCourtesy Terry Phillips
  70. 70. Comparison of Needle Tips Rounded Sharp beveled acupuncture needle hypodermic needle tip pushes cells tip acts like a aside rather than miniature scalpel piercing them capable of piercing, cutting and tearing cellsCourtesy Terry Phillips
  71. 71. Microdialysis SamplingCourtesy Sagar Parikh
  72. 72. Microdialysis System In-flow catheter Microdialysis pump Needle Out- flow catheter Soft tissueFractioncollector Courtesy Terry Phillips
  73. 73. detector capillary Powercomputer supply CE chamber
  74. 74. Co-investigators• Terry Phillips, PhD, DSc• Jerome Danoff, PT, PhD• Lynn Gerber, MD
  75. 75. Hans-WernerWeisskircherwww.trigger- point.com
  76. 76. Design, Setting, and Patients Three healthy subjects were selected to be in each of three groups (total 9 subjects) based on history and physical examination of upper trapezius:• Group 1) Normal (no neck pain, no trigger point)• Group 2) Latent (no neck pain, trigger point present)• Group 3) Active (neck pain present [< 3months], trigger point present).
  77. 77. Initial Analyte Values in TrapeziusAnalyte Active Latent Normal *P valuepH (pH units) 5.4 6.3 6.5 P<.03Bradykinin (pm/l) 69 49.6 47.5 P<.01NE (nmol/l) 3.1 2.0 1.8 P<.01Serotonin (nmol/l) 6.6 4.7 4.1 P<.01Substance P (pg/ml) 187 50 34 P<.01CGRP (pg/ml) 172 37.4 25.5 P<.01TNF-α (pg/ml) 173.5 26.5 21.2 P<.001IL-1β (pg/ml) 133.7 19.5 17.7 P<.001 *Active > Latent, Normal (except pH)
  78. 78. 400 Concentration of Substance P over time 350 300 250 Active Ip g /ml 200 I = SEE 150 100 Latent 50 I I Normal 0 0:00 2:24 4:48 7:12 9:36 12:00 14:24 16:48 Time
  79. 79. First Phase: What We’ve Demonstrated • Collect near real-time samples from soft tissue with minimal system perturbation and without harmful effects on subjects • Proof-of-principle of the system’s ability to distinguish among subjects who have clinically distinct soft tissue findings • Active MTrP in the upper trapezius has elevated levels of inflammatory mediators (bradykinin, protons, etc.), catecholamines (norepinephrine and serotonin), neuropeptides (substance P, CGRP) and pro-inflammatory cytokines (TNF-α, IL-1β) Shah J, Phillips T, Danoff J, Gerber L. An in vivo microanalytical technique for measuringthe local biochemical milieu of human skeletal muscle. J Appl Physiol. 2005 99(5): 1977-84.
  80. 80. Purpose of Second Phase1) Determine whether these findings are unique to the upper trapezius when compared to a remote uninvolved site in the medial gastrocnemius muscle2) Measure additional analytes (e.g., IL-6 and IL-8) known to be associated with pain, inflammation and intercellular signaling.
  81. 81. Design, Setting, and Patients9 subjects, all of whom had no calf pain or calfMTrPs, were divided into 3 groups based on thefollowing findings in the trapezius:1) Active (painful MTrP present; 3 subjects)2) Latent (non-painful MTrP present; 3 subjects)3) Normal (no pain, no MTrP present; 3 subjects)
  82. 82. No MTrP3 Groups of Subjects with following findings in upper Hans-Werner trapezius muscle: Weisskircher www.trigger- 1) Active MTrP, 2) Latent MTrP, 3) No MTrP point.com
  83. 83. Exclusion Criteria• Fibromyalgia • Other concurrent pain• Cervical radiculopathy syndromes• Atypical facial neuralgia • Use of tobacco products• History of previous trigger • Any aspirin within 3 days of point injections in the needling upper trapezius and upper • History of bleeding diatheses medial gastrocnemius • Being on anticoagulation• Knee pain therapy• History of cervical spine or • An inordinate fear of needles shoulder surgery • Lumbosacral radiculopathy• On any medications
  84. 84. Procedure and MeasuresProcedure : Samples were obtained continuously from the trapezius site at regular intervals for 14 minutes, and then from the upper medial gastrocnemius site for 10 minutes.Measures :Levels of protons (H+), bradykinin, SP,CGRP, serotonin, norepinephrine, TNF-α,IL-1β, IL-6 and IL-8.
  85. 85. Initial Analyte Values in TrapeziusAnalyte Active Latent Normal *P valuepH (pH units) 5.2 6.6 6.7 P<.001Bradykinin (pm/l) 71.3 39.9 41.5 P<.003NE (nmol/l) 3.0 1.9 1.5 P<.0001Serotonin (nmol/l) 6.9 4.2 3.9 P<.0001Substance P (pg/ml) 169.3 46.7 30.8 P<.0001CGRP (pg/ml) 157.3 49.3 25.8 P<.0001TNF-α (pg/ml) 181.8 30.0 8.9 P<.001IL-1β (pg/ml) 121.9 20.8 9.9 P<.001IL-6 (pg/ml) 130.2 16.7 10.5 P<.0001IL-8 (pg/ml) 61.7 7.7 6.9 P<.0001 *Active > Latent, Normal (except pH)
  86. 86. Set 1 Active Combined Data for Substance P Set 1 Latent Set 1 Normal 600.00 Concentration in Trapezius over Time Set 2 Active Set 2 Latent Set 2 Normal 500.00 400.00pg/L 300.00 200.00 100.00 0.00 0.00 5.00 10.00 15.00 Time (min)
  87. 87. Concentrations of Analytes in the Active Group at Initial Needle Insertion Analyte Trap GS *P value pH 5.5 5.7 NS Bradykinin 63.7 39.7 P<.001 NE 2.8 2.4 P<.001 Serotonin 6.5 6.0 P<.001 Substance P 140.9 52.9 P<.001 CGRP 129.9 46.7 P<.001 TNF-α 143.9 45.5 P<.001 IL-1β 97.1 44.8 P<.001 IL-6 102.5 39.6 P<.001 IL-8 48. 8 21.5 P<.001 *Trapezius > Gastrocnemius
  88. 88. Concentrations of Analytes at Initial Needle Insertion in Gastrocnemius Muscle Analyte GS (Act) GS (Lat) GS (Nor) *P value pH 5.7 6.7 6.8 P<.01 Bradykinin 39.7 37.4 35.3 P<.01(A>N) NE 2.4 1.8 1.5 P<.01 Serotonin 6.0 4.4 3.7 P<.01 Substance P 52.9 18 13.8 P<.01 CGRP 46.7 16.1 12.1 P<.01 TNF-α 45.5 17.1 8.6 P<.01 IL-1β 44.8 23.1 8.5 P<.01 IL-6 39.6 14.9 9.5 P<.01 IL-8 21.5 10.5 5.5 P<.01 *Active > Latent, Normal (except pH)
  89. 89. (Normal Muscle)Active I = SEELatent Active groupNormal
  90. 90. (Normal Muscle)Active I = SEELatent Active groupNormal
  91. 91. (Normal Muscle)Active I = SEE Active grou
  92. 92. (Normal Muscle) I = SEEActive Active group
  93. 93. (Normal Muscle) e I = SEEActive Active group
  94. 94. Active Active group e (Normal Muscle) I = SEE
  95. 95. Second Phase: What We’ve Learned• An active MTrP has a unique biochemical milieu of substances known to be associated with pain states and inflammation• The biochemical milieu of an active MTrP in the upper trapezius differs quantitatively from a remote, uninvolved site in the gastrocnemius muscle.
  96. 96. Second Phase: What We’ve Learned • Subjects with an active MTrP in the upper trapezius have elevated levels of these analytes in a remote, uninvolved muscle compared to latent and normal subjects. This suggests that substances associated with pain are not limited to local areas of MTrPs or a single anatomical locus. • In the trapezius, the concentration of specific analytes dramatically changes in response to initial needle insertion and also following a local twitch response, particularly in active MTrPs Shah JP, Danoff JV, Desai MJ, Parikh S, Nakamura LY, Phillips TM, Gerber LH.Biochemicals assoicated with pain and inflammation are elevated in sites near to and remote from active myofascial trigger points. Archives of Physical Medicine & Rehabilitation 2008 Jan;89(1):16-23
  97. 97. Biochemical Considerations
  98. 98. H+
  99. 99. “Pro-inflammatory cytokines increase the sensitivity of all peripheral neural structures andtheir afferent cell bodies, causing hyperalgesia and thedevelopment of neuropathic pain states” Cytokines and Pain. Watkins and Maier, eds. 2000
  100. 100. Hypernociceptive role of cytokines and chemokines: Targets for analgesic drug development? TNF-α, IL-1β, IL-6 and IL-8 were among the firstcytokines described as participating in the development of inflammatory and neuropathic pain Verri WA, Cunha TM, Parada CA et al Pharmacology and Therapeutics 2006
  101. 101. Cytokine Cascade and Pain Cg, LPS or Ag Ag TNF-α IL-18 ↔ IL-12 IL-1β ↔IL-6 IL-8 ↔CINC-1 ET-1 Prostaglandins Sympathetic amines Cox enzyme β-Blocker Verri WA et. alPharmacology andTherapeutics 2006 Nociceptor Sensitization
  102. 102. Moving Ahead: Microanalytic Systems for in-vivoMeasurement of the Biochemical Milieu of Muscle Shah et al. J. Appl. Physiol. 2005 99:1977-94 30-gauge needle ~0.5 μL sample First Generation Microdialysis Needle 50-μm laser-drilled hole for embedding hydrogel Second Generation Needle with Hydrogel
  103. 103. The Next Phase: A Natural History Study• Does the biochemical milieu at and around the MTrP change with respect to the natural history of myofascial pain in the upper trapezius?• Does the biochemical milieu of the upper trapezius correlate with changes in the severity of pain, presence or absence of physical findings or degree of local tenderness over time?• What are the levels of anti-inflammatory substances (e.g., IL-4, IL-10), neurotrophins (e.g., NGF, NT-3), analgesic substances (e.g., β-endorphin) and substances associated with muscle metabolism and physiology (e.g., creatine kinase, aldolase, ACh esterase, etc.)?
  104. 104. Treatment TrialsAssess the local biochemical milieu of MTrPs as an outcomemeasure of efficacy in clinical treatment trials utilizingpharmacologic and physical medicine approaches
  105. 105. A New DirectionTo Address an Old Controversy
  106. 106. Obstacles• There are currently no imaging criteria for the diagnosis of trigger points or for assessing clinical outcome of treatments.• It remains a clinical diagnosis based exclusively on history and physical examination.
  107. 107. Our Research Question Can ultrasound imaging be used to develop objectivedescriptions of the tissue and blood flow characteristics of myofascial trigger points (MTrPs) and the immediately adjacent structures? In the long term, we want to understand the pathophysiology of myofascial pain and develop clinical outcome measures.
  108. 108. Upper Trapezius Muscle with MTrP Fascia Upper trapezius Hypoechoiec trigger point 3 cm
  109. 109. Vibration Sonoelastography 30 kPa63 kPa 44 kPa
  110. 110. Vibration Applicator
  111. 111. Vibration Sonoelastography of Muscle with MTrP Focal decrease of color  Hypoechoeic trigger  variance indicates a  point  localized stiffer region uppertrapezius
  112. 112. Vibration Sonoelastography of Uninvolved Muscle Uniform color  variance  Uniform echogenecity in  indicates homogeneous   uninvolved muscle  stiffnessuppertrapezius
  113. 113. Vibration Sonoelastography of Uninvolved Muscle
  114. 114. Sonoelastography Imaging Objective diagnostic test Outcome measure to evaluate tissue changes in response to treatment Describe natural history Sikdar et al. Arch. Phys. Me Rehabil., 2009 (in press)
  115. 115. Imaging blood flow near MTrPs in the Upper TrapeziusA BFS=0B BFS=1C BFS=2D BFS=2
  116. 116. Observations• Ultrasound is feasible for imaging MTrPs• MTrPs exhibit different echogenecity compared to surrounding muscle.• Vibration sonoelastography shows differences in relative stiffness between trigger points and normal (uninvolved) muscle. Sikdar et al. Assessment of Myofascial Trigger Points (MTrPs): A New Application of Ultrasound Imaging and Vibration Sonoelastography. Conf Proc. IEEE Eng Med Biol Soc. 2008
  117. 117. Observations• Blood flow waveform characteristics can be used to differentiate Active and Latent MTrPs• Retrograde flow in diastole indicating a very high resistance vascular bed and possible blood vessel compression is associated with Active MTrPs Sikdar S, Shah JP, Gebreab T, Yen R, Gilliams E, Danoff J, Gerber L. Novel Applications of Ultrasound Technology to Visualize and Characterize Myofascial Trigger Point and Surrounding Soft Tissue. Archives of Physical Medicine and Rehabilitation. In press. 2009
  118. 118. Integrated Neuromuscular TheoryX Inflamatory Mediators, BK, NE, SP, Serotonin, Cytokines Courtesy Bryan O’Neill
  119. 119. Injection Therapies Where? Why?What?

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