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Neuromusculoskeletal Pain:
Lessons from the Myofascia



               Jay P. Shah, MD
      Rehabilitation Medicine Department
        National Institutes of Health
Disclosures
• Nothing to disclose
NIH Clinical Research Center
     “Bench to Bedside - Bedside to Bench”
                                     Outpatient
                                       Care


Laboratories
                                    Laboratories




                  Inpatient Care
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
                                                inputs

Melzack, Trends Neurosci 1990; 13:88-92
Pain Mechanisms




Adapted from Butler, DS The Sensitive Nervous System
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
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
Myofascial Trigger Points




                                 Hans-Werner Weisskircher
                                  www.trigger-point.com




A Very Common, Complex and Overlooked
Cause of Non-articular Musculoskeletal Pain
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 pain
Gerwin et al. Interrater reliability in
myofascial trigger point examination.
Pain. 1997;69(1-2):65-73




 Hans-Werner Weisskircher
  www.trigger-point.com
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):65-73




Courtesy Marta Imamura
Myofascial Trigger Points
2-5 areas in hard, palpable
  bands of skeletal muscle:
Active – cause a clinical pain
  complaint or other abnormal
  sensory symptoms
Latent – 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.
Orofacial Pain 2Âş
                    Myofascial Trigger
                         Points



    Masseter                                       Medial Pterygoid




                         Upper Trapezius

                              Hans-Werner
                              Weisskircher
SCM (sternal division)     www.trigger-point.com
                                                   Lateral Pterygoid
Muscle Pain, Inflammation, and Sensitization


   Muscle
    Injury               Release of Inflammatory
                         mediators, Neuropeptides
                         and Cytokines




Courtesy Marta Imamura
Muscle Pain, Inflammation, and Sensitization


   Muscle                Sensitize wide dynamic range
    Injury               neurons and higher centers
                         leading to allodynia, hyperalgesia
                         and…
                         and…




Courtesy Marta Imamura
Muscle Pain, Inflammation, and Sensitization



                         … expansion of the receptive
                         field of pain and referral of pain




Courtesy Marta Imamura
Travell JG, Simons DG. Myofascial
pain and dysfunction: the trigger point
manual. Baltimore: Williams &
Wilkins; 1992.
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.
“Since no specialty claims
skeletal 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 muscle pain
  (MTrP) research or student training
  Clinicians focus primarily on treating the
  SYMPTOMS of myogenic pain, not the
  CAUSE of the pain (MTrPs)
Active MTrPs can only be diagnosed by
        systematic palpation




                                   Hans-Werner
                                   Weisskircher
                                www.trigger-point.com
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 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
Nociceptor Function
• Encode Noxious Stimuli
  • Possibly leading to pain
• Maintain Tissue Health
  • Initiate and maintain reaction to injury
Nociceptors are Dynamic “Two-way” Structures
A Critical Efferent Nociceptor Function:
Neuropeptide (Substance P, CGRP) Production




                                  Courtesy Jan Dommerholt
Unique Neurobiology of Muscle Pain




   Muscle pain is NOT skin pain
Muscle Pain is often Overlooked



       “I’ll be                   “Ohhh,
        Back!”                      my
                                   Back!”
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.
Distant Referral Patterns




                            Hans-Werner
                            Weisskircher
                            www.trigger-
                             point.com
Powerful Descending Inhibition on Muscle Pain
Fields HL, Basbaum AI: Central
nervous system mechanisms of
pain modualtion. In Textbook of
Pain; 1999:309-329.
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.
Muscle Pain
Peripheral Mechanisms
Muscle Nociception – Binding of
Substances to Matched Chemoreceptors



                    (B2→B1)
                      BRADYKININ
                      RECEPTOR Receptor
                        Bradykinin
Muscle Pain
Spinal Mechanisms
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
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
Expansion of Receptive Field by a
               Painful Muscle Stimulus
Courtesy 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
Expansion of Receptive Field by a
               Painful Muscle Stimulus
Courtesy Jan Dommerholt




5 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
Expansion of Receptive Field by a
    Painful Muscle Stimulus




                        Hoheisel U, Mense S, Simons DG.
                          Neurosci lett 153:9-12, 1993
Expansion of Receptive Field by a
    Painful Muscle Stimulus




                        Hoheisel U, Mense S, Simons DG.
                          Neurosci lett 153:9-12, 1993
Expansion of Receptive Field by a
    Painful Muscle Stimulus




                        Hoheisel U, Mense S, Simons DG.
                          Neurosci lett 153:9-12, 1993
Expansion of Receptive Field by a
    Painful Muscle Stimulus




                        Hoheisel U, Mense S, Simons DG.
                          Neurosci lett 153:9-12, 1993
Expansion of Receptive Field by a
              Painful Muscle Stimulus



                                                                   Allodynia
                                                              (light pressure and muscle
                                                                       movement)
                                                                Hyperalgesia




15 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
Nociceptive Bombardment causes
                          Central Sensitization and Neuroplastic

Glutamate   Substance P   Changes in Dorsal Horn Neurons
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




         Dorsal horn
Expansion of the Receptive Field




               Effective synapse

                                   TrP3
Wide Dynamic Range Neuron

                    Excitatory tonus
                    via nociceptors

              ++
            ----

                    Inhibitory tonus
Substances Dynamically Modulating Dorsal Horn Neurons

                                          Dynorphin

Immune system                             Met Leu-
                                          enkephalin
Neurotrophins
                                          SP
Neurosteroids
                                          Galanin
Cytokines
                                          VIP
Glia and Astrocytes
                                          NPY
                 GABA, Glycine, Glutamate, SOM
                 ACh, DA, 5-HT, Nitric Oxide
MTrPs and the Local Twitch Response




                        Courtesy Joseph Audette
Myofascial Pain
Historical and Regional Confusion


 Fibrositis         Myofascitis
                    Myofibrositis
 Myositis

         Myofascial
           Pain
Muscular
                      Myelosis
rheumatism
                      Radiculitis
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
Opening of Previously
 Ineffective Synapses
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
“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 to
myofascial trigger point. The importance of the local twitch
response. Am J Phys Med Rehabil. 1994;73(4):256-63.
Recent studies comparing MTrP injections with a
syringe and MTrP needling with an acupuncture
 needle showed that MTrP needling with an acup
needle 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.
Trigger Point Needling:
Proper Technique to Elicit Local Twitch
        Responses is Essential
                  Hong CZ Arch Phys Med Rehab 1994;73:256




                    Courtesy Joseph Audette
How does dry needling work?
What is the Pathophysiology of
      Myofascial Pain?
        UNKNOWN
Simons’ Integrated Hypothesis
Pathophysiology           Histopathology
Increased Miniature           Increased
 Endplate Potentials        Fiber Tension
  (Endplate Noise)           (Taut Band)


               Histochemistry

                  Release of
                 Sensitizing
              Substances? (Pain)
What is the Biochemical Milieu of MTrPs?


                            Clinical findings



                            Underlying milieu?
Myofascial Trigger Points:
 A Unique Perspective at the NIH




 In Vivo Microdialysis – A Technique For
Analysis of the Biochemical Milieu of MTrPs
Microdialysis
                                       Low or no
                                       solute
        Semi-permeable
        membrane




                High concentration solute


Courtesy Terry Phillips
Microdialysis/Acupuncture Needle




Courtesy Terry Phillips
Microdialysis/Acupuncture
     Needle – 30 Gauge Hypodermic
                      Delivery tubes
                                       Fluid in



                                       Fluid
                                       out
           Solute exchange
           surface – dialyzer
           membrane set 0.2
           mm from the
           needle tip
Courtesy Terry Phillips
Comparison of Needle Tips


                          25G syringe needle




                                 32G acupuncture needle


Courtesy Terry Phillips
Comparison between a
     Standard Acupuncture Needle and
             our Needle/Probe




                             Needle/Probe
        Acupuncture needle




Courtesy Terry Phillips
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
                           cells


Courtesy Terry Phillips
Microdialysis Sampling




Courtesy Sagar Parikh
Microdialysis System

                               In-flow
                               catheter
    Microdialysis
    pump

                               Needle
                    Out-
                    flow
                    catheter        Soft tissue

Fraction
collector                          Courtesy Terry Phillips
detector


                    capillary




           Power
computer   supply

                                CE chamber
Co-investigators

• Terry Phillips, PhD, DSc

• Jerome Danoff, PT, PhD

• Lynn Gerber, MD
Hans-Werner
Weisskircher
www.trigger-
 point.com
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).
Initial Analyte Values in Trapezius
Analyte               Active   Latent   Normal   *P value
pH (pH units)          5.4     6.3       6.5      P<.03

Bradykinin (pm/l)      69      49.6     47.5      P<.01

NE (nmol/l)            3.1     2.0       1.8      P<.01

Serotonin (nmol/l)     6.6     4.7       4.1      P<.01

Substance P (pg/ml)   187       50       34       P<.01

CGRP (pg/ml)          172      37.4      25.5     P<.01

TNF-α (pg/ml)         173.5    26.5      21.2     P<.001

IL-1β (pg/ml)         133.7    19.5      17.7     P<.001


 *Active > Latent, Normal (except pH)
400
                    Concentration of Substance P over time

          350



          300



          250


                Active
                               I
p 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
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 measuring
the local biochemical milieu of human skeletal muscle. J Appl Physiol. 2005 99(5): 1977-84.
Purpose of Second Phase
1) Determine whether these findings are unique to
   the upper trapezius when compared to a remote
   uninvolved site in the medial gastrocnemius
   muscle
2) Measure additional analytes (e.g., IL-6 and IL-8)
   known to be associated with pain, inflammation
   and intercellular signaling.
Design, Setting, and Patients
9 subjects, all of whom had no calf pain or calf
MTrPs, were divided into 3 groups based on the
following 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)
No
                                   MTrP




3 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
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
Procedure and Measures
Procedure :
 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.
Initial Analyte Values in Trapezius
Analyte               Active   Latent   Normal *P value
pH (pH units)          5.2      6.6      6.7     P<.001
Bradykinin (pm/l)     71.3     39.9     41.5     P<.003
NE (nmol/l)            3.0      1.9      1.5     P<.0001
Serotonin (nmol/l)     6.9      4.2      3.9     P<.0001
Substance P (pg/ml)   169.3    46.7     30.8     P<.0001
CGRP (pg/ml)          157.3    49.3     25.8     P<.0001
TNF-α (pg/ml)         181.8    30.0      8.9     P<.001
IL-1β (pg/ml)         121.9    20.8      9.9     P<.001
IL-6 (pg/ml)          130.2    16.7     10.5     P<.0001
IL-8 (pg/ml)          61.7     7.7       6.9     P<.0001


 *Active > Latent, Normal (except pH)
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




       400.00
pg/L




       300.00




       200.00




       100.00




          0.00

                 0.00        5.00           10.00       15.00




                                    Time (min)
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
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)
(Normal Muscle)



Active
                           I = SEE
Latent                 Active group
Normal
(Normal Muscle)



Active
                           I = SEE
Latent
                       Active group
Normal
(Normal Muscle)




Active
                              I = SEE

                           Active grou
(Normal Muscle)




                              I = SEE
Active
                           Active group
(Normal Muscle)


                                    e



                               I = SEE

Active
                           Active group
Active                 Active group
                                e
         (Normal Muscle)
                           I = SEE
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.
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
Biochemical Considerations
H+
“Pro-inflammatory cytokines
  increase the sensitivity of all
 peripheral neural structures and
their afferent cell bodies, causing
       hyperalgesia and the
development of neuropathic pain
               states”
                    Cytokines and Pain. Watkins
                       and Maier, eds. 2000
Hypernociceptive role of cytokines
         and chemokines:
     Targets for analgesic drug
           development?
    TNF-α, IL-1β, IL-6 and IL-8 were among the first
cytokines described as participating in the development of
           inflammatory and neuropathic pain


           Verri WA, Cunha TM, Parada CA et al
           Pharmacology and Therapeutics 2006
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. al
Pharmacology and
Therapeutics 2006
                        Nociceptor Sensitization
Moving Ahead: Microanalytic Systems for in-vivo
Measurement of the Biochemical Milieu of Muscle

                                                        Shah et al. J.
                                                        Appl. Physiol.
                                                        2005
                                                        99:1977-94




                             30-gauge needle
                             ~0.5 ÎĽL sample

     First Generation Microdialysis Needle

           50-ÎĽm laser-drilled hole for embedding hydrogel




    Second Generation Needle with Hydrogel
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.)?
Treatment Trials
Assess the local biochemical milieu of MTrPs as an outcome
measure of efficacy in clinical treatment trials utilizing
pharmacologic and physical medicine approaches
A New Direction
To Address an Old Controversy
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.
Our Research Question

 Can ultrasound imaging be used to develop objective
descriptions 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.
Upper Trapezius Muscle with
          MTrP
                                  Fascia




                                Upper
                                trapezius




    Hypoechoiec trigger point




                                    3 cm
Vibration Sonoelastography




         30 kPa




63 kPa            44 kPa
Vibration Applicator
Vibration Sonoelastography of
         Muscle with MTrP
                         Focal decrease of color 
  Hypoechoeic trigger    variance indicates a 
  point                  localized stiffer region 



upper
trapezius
Vibration Sonoelastography of
          Uninvolved Muscle
                                Uniform color  variance 
     Uniform echogenecity in    indicates homogeneous  
     uninvolved muscle          stiffness




upper
trapezius
Vibration Sonoelastography of
     Uninvolved Muscle
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)
Imaging blood flow near MTrPs in
          the Upper Trapezius
A              BFS=0



B              BFS=1




C              BFS=2




D              BFS=2
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
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
Integrated
                     Neuromuscular
                        Theory

X
     Inflamatory
    Mediators, BK,
       NE, SP,
     Serotonin,
      Cytokines




                                    Courtesy Bryan O’Neill
Injection Therapies
   Where?      Why?
What?

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2012 aaom shah neuromusculoskeletal pain lessons from the myofascia

  • 1. Neuromusculoskeletal Pain: Lessons from the Myofascia Jay P. Shah, MD Rehabilitation Medicine Department National Institutes of Health
  • 3. NIH Clinical Research Center “Bench to Bedside - Bedside to Bench” Outpatient Care Laboratories Laboratories Inpatient Care
  • 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 inputs Melzack, Trends Neurosci 1990; 13:88-92
  • 5. Pain Mechanisms Adapted from Butler, DS The Sensitive Nervous System
  • 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. 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. Myofascial Trigger Points Hans-Werner Weisskircher www.trigger-point.com A Very Common, Complex and Overlooked Cause of Non-articular Musculoskeletal Pain
  • 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 pain Gerwin et al. Interrater reliability in myofascial trigger point examination. Pain. 1997;69(1-2):65-73 Hans-Werner Weisskircher www.trigger-point.com
  • 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):65-73 Courtesy Marta Imamura
  • 11. Myofascial Trigger Points 2-5 areas in hard, palpable bands of skeletal muscle: Active – cause a clinical pain complaint or other abnormal sensory symptoms Latent – 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. Orofacial Pain 2Âş Myofascial Trigger Points Masseter Medial Pterygoid Upper Trapezius Hans-Werner Weisskircher SCM (sternal division) www.trigger-point.com Lateral Pterygoid
  • 13. Muscle Pain, Inflammation, and Sensitization Muscle Injury Release of Inflammatory mediators, Neuropeptides and Cytokines Courtesy Marta Imamura
  • 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. Muscle Pain, Inflammation, and Sensitization … expansion of the receptive field of pain and referral of pain Courtesy Marta Imamura
  • 16. Travell JG, Simons DG. Myofascial pain and dysfunction: the trigger point manual. Baltimore: Williams & Wilkins; 1992.
  • 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. “Since no specialty claims skeletal muscle as their organ, it is often overlooked” David G. Simons, MD
  • 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. Active MTrPs can only be diagnosed by systematic palpation Hans-Werner Weisskircher www.trigger-point.com
  • 21. Apply Firm Pressure Hans-Werner Weisskircher www.trigger-point.com
  • 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. Nociceptor Function • Encode Noxious Stimuli • Possibly leading to pain • Maintain Tissue Health • Initiate and maintain reaction to injury
  • 24. Nociceptors are Dynamic “Two-way” Structures
  • 25. A Critical Efferent Nociceptor Function: Neuropeptide (Substance P, CGRP) Production Courtesy Jan Dommerholt
  • 26. Unique Neurobiology of Muscle Pain Muscle pain is NOT skin pain
  • 27. Muscle Pain is often Overlooked “I’ll be “Ohhh, Back!” my Back!”
  • 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. Distant Referral Patterns Hans-Werner Weisskircher www.trigger- point.com
  • 30. Powerful Descending Inhibition on Muscle Pain Fields HL, Basbaum AI: Central nervous system mechanisms of pain modualtion. In Textbook of Pain; 1999:309-329.
  • 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.
  • 33. Muscle Nociception – Binding of Substances to Matched Chemoreceptors (B2→B1) BRADYKININ RECEPTOR Receptor Bradykinin
  • 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. 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. Expansion of Receptive Field by a Painful Muscle Stimulus Courtesy 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. Expansion of Receptive Field by a Painful Muscle Stimulus Courtesy Jan Dommerholt 5 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. Expansion of Receptive Field by a Painful Muscle Stimulus Hoheisel U, Mense S, Simons DG. Neurosci lett 153:9-12, 1993
  • 40. Expansion of Receptive Field by a Painful Muscle Stimulus Hoheisel U, Mense S, Simons DG. Neurosci lett 153:9-12, 1993
  • 41. Expansion of Receptive Field by a Painful Muscle Stimulus Hoheisel U, Mense S, Simons DG. Neurosci lett 153:9-12, 1993
  • 42. Expansion of Receptive Field by a Painful Muscle Stimulus Hoheisel U, Mense S, Simons DG. Neurosci lett 153:9-12, 1993
  • 43. Expansion of Receptive Field by a Painful Muscle Stimulus Allodynia (light pressure and muscle movement) Hyperalgesia 15 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. Nociceptive Bombardment causes Central Sensitization and Neuroplastic Glutamate Substance P Changes in Dorsal Horn Neurons
  • 45. Pain begins in Calf, Heel and Foot
  • 46. Then Develops Pain in SI Joint too
  • 47. Then Develops Pain in SI Joint too TrP3
  • 48. Neuron for SI Joint is Initially Inactive Ineffective Synapse TrP3 Dorsal horn
  • 49. Expansion of the Receptive Field Effective synapse TrP3
  • 50. Wide Dynamic Range Neuron Excitatory tonus via nociceptors ++ ---- Inhibitory tonus
  • 51. Substances Dynamically Modulating Dorsal Horn Neurons Dynorphin Immune system Met Leu- enkephalin Neurotrophins SP Neurosteroids Galanin Cytokines VIP Glia and Astrocytes NPY GABA, Glycine, Glutamate, SOM ACh, DA, 5-HT, Nitric Oxide
  • 52. MTrPs and the Local Twitch Response Courtesy Joseph Audette
  • 53. Myofascial Pain Historical and Regional Confusion Fibrositis Myofascitis Myofibrositis Myositis Myofascial Pain Muscular Myelosis rheumatism Radiculitis
  • 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.
  • 56. Opening of Previously Ineffective Synapses
  • 57. 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
  • 58. “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 to myofascial trigger point. The importance of the local twitch response. Am J Phys Med Rehabil. 1994;73(4):256-63.
  • 59. Recent studies comparing MTrP injections with a syringe and MTrP needling with an acupuncture needle showed that MTrP needling with an acup needle 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.
  • 60. Trigger Point Needling: Proper Technique to Elicit Local Twitch Responses is Essential Hong CZ Arch Phys Med Rehab 1994;73:256 Courtesy Joseph Audette
  • 61. How does dry needling work?
  • 62. What is the Pathophysiology of Myofascial Pain? UNKNOWN
  • 63.
  • 64. Simons’ Integrated Hypothesis Pathophysiology Histopathology Increased Miniature Increased Endplate Potentials Fiber Tension (Endplate Noise) (Taut Band) Histochemistry Release of Sensitizing Substances? (Pain)
  • 65. What is the Biochemical Milieu of MTrPs? Clinical findings Underlying milieu?
  • 66. Myofascial Trigger Points: A Unique Perspective at the NIH In Vivo Microdialysis – A Technique For Analysis of the Biochemical Milieu of MTrPs
  • 67. Microdialysis Low or no solute Semi-permeable membrane High concentration solute Courtesy Terry Phillips
  • 69. Microdialysis/Acupuncture Needle – 30 Gauge Hypodermic Delivery tubes Fluid in Fluid out Solute exchange surface – dialyzer membrane set 0.2 mm from the needle tip Courtesy Terry Phillips
  • 70. Comparison of Needle Tips 25G syringe needle 32G acupuncture needle Courtesy Terry Phillips
  • 71. Comparison between a Standard Acupuncture Needle and our Needle/Probe Needle/Probe Acupuncture needle Courtesy Terry Phillips
  • 72. 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 cells Courtesy Terry Phillips
  • 74. Microdialysis System In-flow catheter Microdialysis pump Needle Out- flow catheter Soft tissue Fraction collector Courtesy Terry Phillips
  • 75.
  • 76. detector capillary Power computer supply CE chamber
  • 77. Co-investigators • Terry Phillips, PhD, DSc • Jerome Danoff, PT, PhD • Lynn Gerber, MD
  • 79. 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).
  • 80. Initial Analyte Values in Trapezius Analyte Active Latent Normal *P value pH (pH units) 5.4 6.3 6.5 P<.03 Bradykinin (pm/l) 69 49.6 47.5 P<.01 NE (nmol/l) 3.1 2.0 1.8 P<.01 Serotonin (nmol/l) 6.6 4.7 4.1 P<.01 Substance P (pg/ml) 187 50 34 P<.01 CGRP (pg/ml) 172 37.4 25.5 P<.01 TNF-α (pg/ml) 173.5 26.5 21.2 P<.001 IL-1β (pg/ml) 133.7 19.5 17.7 P<.001 *Active > Latent, Normal (except pH)
  • 81. 400 Concentration of Substance P over time 350 300 250 Active I p 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
  • 82. 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 measuring the local biochemical milieu of human skeletal muscle. J Appl Physiol. 2005 99(5): 1977-84.
  • 83. Purpose of Second Phase 1) Determine whether these findings are unique to the upper trapezius when compared to a remote uninvolved site in the medial gastrocnemius muscle 2) Measure additional analytes (e.g., IL-6 and IL-8) known to be associated with pain, inflammation and intercellular signaling.
  • 84. Design, Setting, and Patients 9 subjects, all of whom had no calf pain or calf MTrPs, were divided into 3 groups based on the following 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)
  • 85. No MTrP 3 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
  • 86. 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
  • 87. Procedure and Measures Procedure : 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.
  • 88. Initial Analyte Values in Trapezius Analyte Active Latent Normal *P value pH (pH units) 5.2 6.6 6.7 P<.001 Bradykinin (pm/l) 71.3 39.9 41.5 P<.003 NE (nmol/l) 3.0 1.9 1.5 P<.0001 Serotonin (nmol/l) 6.9 4.2 3.9 P<.0001 Substance P (pg/ml) 169.3 46.7 30.8 P<.0001 CGRP (pg/ml) 157.3 49.3 25.8 P<.0001 TNF-α (pg/ml) 181.8 30.0 8.9 P<.001 IL-1β (pg/ml) 121.9 20.8 9.9 P<.001 IL-6 (pg/ml) 130.2 16.7 10.5 P<.0001 IL-8 (pg/ml) 61.7 7.7 6.9 P<.0001 *Active > Latent, Normal (except pH)
  • 89. 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 500.00 400.00 pg/L 300.00 200.00 100.00 0.00 0.00 5.00 10.00 15.00 Time (min)
  • 90. 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
  • 91. 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)
  • 92. (Normal Muscle) Active I = SEE Latent Active group Normal
  • 93. (Normal Muscle) Active I = SEE Latent Active group Normal
  • 94. (Normal Muscle) Active I = SEE Active grou
  • 95. (Normal Muscle) I = SEE Active Active group
  • 96. (Normal Muscle) e I = SEE Active Active group
  • 97. Active Active group e (Normal Muscle) I = SEE
  • 98. 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.
  • 99. 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
  • 100.
  • 102. H+
  • 103. “Pro-inflammatory cytokines increase the sensitivity of all peripheral neural structures and their afferent cell bodies, causing hyperalgesia and the development of neuropathic pain states” Cytokines and Pain. Watkins and Maier, eds. 2000
  • 104. Hypernociceptive role of cytokines and chemokines: Targets for analgesic drug development? TNF-α, IL-1β, IL-6 and IL-8 were among the first cytokines described as participating in the development of inflammatory and neuropathic pain Verri WA, Cunha TM, Parada CA et al Pharmacology and Therapeutics 2006
  • 105. 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. al Pharmacology and Therapeutics 2006 Nociceptor Sensitization
  • 106. Moving Ahead: Microanalytic Systems for in-vivo Measurement of the Biochemical Milieu of Muscle Shah et al. J. Appl. Physiol. 2005 99:1977-94 30-gauge needle ~0.5 ÎĽL sample First Generation Microdialysis Needle 50-ÎĽm laser-drilled hole for embedding hydrogel Second Generation Needle with Hydrogel
  • 107. 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.)?
  • 108. Treatment Trials Assess the local biochemical milieu of MTrPs as an outcome measure of efficacy in clinical treatment trials utilizing pharmacologic and physical medicine approaches
  • 109. A New Direction To Address an Old Controversy
  • 110. 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.
  • 111. Our Research Question Can ultrasound imaging be used to develop objective descriptions 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.
  • 112. Upper Trapezius Muscle with MTrP Fascia Upper trapezius Hypoechoiec trigger point 3 cm
  • 113. Vibration Sonoelastography 30 kPa 63 kPa 44 kPa
  • 115. Vibration Sonoelastography of Muscle with MTrP Focal decrease of color  Hypoechoeic trigger  variance indicates a  point  localized stiffer region  upper trapezius
  • 116. Vibration Sonoelastography of Uninvolved Muscle Uniform color  variance  Uniform echogenecity in  indicates homogeneous   uninvolved muscle  stiffness upper trapezius
  • 117. Vibration Sonoelastography of Uninvolved Muscle
  • 118. 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)
  • 119. Imaging blood flow near MTrPs in the Upper Trapezius A BFS=0 B BFS=1 C BFS=2 D BFS=2
  • 120. 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
  • 121. 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
  • 122. Integrated Neuromuscular Theory X Inflamatory Mediators, BK, NE, SP, Serotonin, Cytokines Courtesy Bryan O’Neill
  • 123. Injection Therapies Where? Why? What?