Articles Dry Needling Certification 232 / The Journal of Manual & Manipulative Therapy, 2006 The Journal of Manual & Manipulative Therapy Vol. 14 No. 4 (2006), 232 - 239 Myofascial Trigger Points: Translating Molecular Theory into Manual Therapy Address all correspondence and request for reprints to: John M. McPartland 53 Washington Street Ext Middlebury, VT 05753 USA mcpruitt@verizon.net Abstract: Theories regarding the molecular pathophysiology of myofascial trigger points (MFTrPs) have undergone fundamental revisions in recent years. New research suggests that MFTrPs are evoked by the abnormal depolarization of motor endplates. The motor endplate transduces electrical potential into muscle contraction. This review article expands the proposed etiology to include presynaptic, synaptic, and postsynaptic mechanisms, such as excessive release of acetycholine (ACh), defects of acetylcholinesterase, and upregulation of nicotinic ACh receptors, respectively. Dysfunctional motor endplates and sustained muscular contraction give rise to a localized “ATP energy crisis” associated with sensory and autonomic reflex arcs that is sustained by central sensitization. This working hypothesis has given rise to several new approaches in the treatment of MFTrPs. K e y Wo rd s : M y o f a s c i a l Tr i g g e r P o i n t s , M o t o r E n d p l a t e , A c e t y c h o l i n e R e c e p t o r, Acetylcholinesterase John M. McPartland, DO, MS David G. Simons, MD Simons, Travell, and Simons1 defined the myofascial trigger point (MFTrP) as “…a hyperirritable spot in skeletal muscle that is associated with a hypersensitive palpable nodule in a taut band. The spot is tender when pressed, and can give rise to characteristic referred pain, motor dysfunction, and autonomic phenomena…” Thus each MFTrP contains a sensory component, a motor component, and an autonomic component. These components comprise a new “integrated hypothesis” regarding the etiology of MFTrPs1. This hypothesis involves local myofascial tissues, the central nervous system (CNS), and systemic biomechanical factors. The “integrated hypothesis” has changed our approach to treating MFTrPs. The purpose of this paper is to review new concepts concerning MFTrPs and to describe our evolving approach to their treatment. Motor Endplate: Epicenter of the Myofascial Trigger point Simons2 implicated the motor endplate as the central etiology of MFTrPs. The motor endplate is synonymous with the neuromuscular junction (the first term de- scribes structure, the latter term describes function); it is the site where an -motor neuron synapses with its target muscle fibers. The -motor neuron terminates in multiple swellings termed presynaptic boutons. Each bouton contains many acetylcholine (ACh) vesicles, clustered around structures called dense bars (Figure 1). Voltage-sensitive calcium channels (VsCCs, specifi- cally P/Q-type VsCCs) also cluster near dense bars. When voltage running down an -motor neuron reaches VsCCs in the bouton, the VsCC channels open, leading to an influx of calcium ions (Ca2+) into the bouton from the extracellular space. The influx of Ca2+ causes the ACh vesicles to release their transmitter into the synaptic cleft (Figure 1). Across the synaptic cleft, the postsynaptic muscle cell membrane forms junctional folds that are lined with nicotinic ACh receptors (nAChs). The nACh is a ligand- gated cation channel, and ACh is its ligand. Binding of Myofascial Trigger Points: Translating Molecular Theory into Manual Therapy / 233 ACh to nACh opens its channel, allowing sodium ions (Na+) and potassium ions (K+) to move in and out of the muscle cell membrane. Movement of Na+ and K+ depolar- izes the postsynaptic cell, forming a miniature endplate potential (MEPP). A sufficient number of MEPPs activate VsCCs (specifically L-type VsCCs), which subsequently trigger another Ca2+ channel, the ryanodine receptor. The ryanodine receptor is imbedded in the membrane of an intracellular structure called the sarcoplasmic reticulum, which houses intracellular stores of Ca2+. Activation of the ryanodine receptor releases Ca2+ from the sarcoplasmic reticulum into the cytoplasm of the muscle cell. This triggers the interaction between actin and myosin, and the sarcomere contracts. Electromyography (EMG) studies of MFTrPs have reported spontaneous electrical activity (SEA) in MFTrPs, while adjacent muscle tissues are electrically silent3. Hubbard and Berkoff3 originally attributed the source of SEA action potentials to sympathetically activated intrafusal muscle spindles. These researchers were unaware of previous work by Liley of New Zealand, who had demonstrated that SEA was a consequence of ACh release at motor endplates4. Simons5 “connected the dots” by correlating SEA with “endplate noise” that had been described by electromyographers, and he linked SEA to excessive ACh release, which he proposed as the primary cause of MFTrP development. This “motor endplate” hypothesis was tested in Hong’s laboratory6, where MFTrPs were injected with botulinum toxin type A, which blocks ACh release at the motor endplate. This treatment significantly decreased SEA activity. Mense et al7 confirmed the hypothesis using a rat MFTrP model. They injected diisopropylfluorophosphate (DFP), a drug that increases synaptic ACh, into the proximal half of the gastrocnemius muscle, and the motor nerve was electrically stimulated for 30-60 min to induce muscle contractions. The distal half of the muscle, which performed the same contractions, served as a control. Proximal and distal sections of the muscle were then examined for morphological changes. The DFP-injected proximal half exhibited significantly more contracted and torn muscle fibers compared to the distal half of the muscle. Myofascial tension may play a role in excess ACh release. Chen and Grinnell8 showed that a 1% increase in muscle stretch at the motor endplate evoked a 10% increase in ACh release. These researchers postulated that tension upon integrins (cell-surface proteins that bind connective tissues) in the presynaptic membrane was transduced mechanically into ACh vesicle release. Expanding the Endplate Hypothesis Simons’ description of a presynaptic dysfunction (excessive ACh release), however, is only one way to interpret the “endplate hypothesis.” We can expand the hypothesis to include presynaptic, intrasynaptic, and postsynaptic dysfunctions9. Intrasynaptic ACh must be deactivated; otherwise, it will continue to activate nAChRs in the muscle cell membrane. ACh is normally deactivated by the enzyme acetylcholinesterase (AChE), which is held in the synaptic cleft by a structural protein (collagen Q, ColQ) that anchors it to the plasma mem- brane (Figure 1). AChE deficiency permits excess ACh Fig. 1: The motor endplate – proposed site of trigger point dysfunction. Top illustration: The junction between the -motor neuron and the muscle fiber. Bottom il- lustration: Presynaptic boutons are separated from the postsynaptic muscle cell by the synaptic cleft. Within each bouton are many vesicles containing ACh, clus- tered around dense bars (Db). Also clustered around the Db are calcium channels. The Db is the site of ACh release into the synaptic cleft. Across the synaptic cleft from the Db, the postsynaptic muscle cell membrane forms junctional folds that are lined with nicotinic ACh receptors (nACh). ACh released into the synaptic cleft activates nACh receptors, then is inactivated by the acetylcholinesterase enzyme (AChE). Illustration courtesy of McpArtLand. 234 / The Journal of Manual & Manipulative Therapy, 2006 to accumulate in the synaptic cleft, tonically activating nAChRs. Several genetic mutations cause AChE defi- ciency, including mutations in ColQ. The gene for AChE expresses several splice variants10, which are alternative ways in which a gene’s protein-coding sections (exons) are joined together to create a messenger RNA molecule and its translated protein. AChE splice variants are less effective at deactivating ACh, and the expression of these splice variants can be induced by psychological and physi- cal stress10. Drugs and other chemicals may cause AChE deficiency. DFP, the drug used in the aforementioned experiment by Mense et al6, is an AChE antagonist. Organophosphate pesticides are AChE antagonists, and poisoning by these pesticides causes changes in motor endplates and MFTrP-like pathology11-13. Muscle damage caused by AChE antagonists has been reduced by pre- treatment with postsynaptic L-type VsCC blockers such as quinidine12 and diltiazem13. Postsynaptically, a “gain-of-function” defect of the nAChR may confer muscle hyperexcitability, a hallmark of MFTrPs. Gain of function refers to an increased response by the nAChR, via several possible mechanisms: nAChR overexpression, constitutively-active nAChRs14, nAChRs that gain responsiveness to choline (an ordinary serum metabolite)14, or nACHRs whose channels remain open longer than normal15. The nAChR is an assembly of five subunits; at least 16 genes encode these subunits, so that the nAChR is particularly susceptible to mutational defects. Motor endplate nAChRs express a unique subunit assembly, whereas nAChRs in the central nervous system and in autonomic nerves express a different subunit configuration16. The relative consequences of presynaptic, synaptic, and postsynaptic dysfunctions are under debate. Wang et al17 used a variety of pharmacological tools to con- clude that presynaptic mechanisms modulate the motor endplate rather than synaptic (AChE) or postsynaptic (nAChR density) mechanisms. Conversely, Nakanishi et al18 determined that postsynaptic manipulation (using alpha-bungarotoxin, an nAChR antagonist) modulated motor endplates to a greater degree than presynaptic manipulation (using botulinum toxin, an inhibitor of ACh release). Motor Component MFTrPs have a motor component, whereas tender points found in patients with fibromyalgia do not. MFTrPs have been biopsied and found to contain “…contraction knots…” described as “…large, rounded, darkly staining muscle fibers and a statistically significant increase in the average diameter of muscle fibers…” 19. Thus the structure of contraction knots differed from that of normal muscle fibers. Functionally, excessive motor activity initiates several perverse mechanisms that cause MFTrPs to persist. Muscle contraction compresses local sensory nerves, which reduces the axoplasmic transport of molecules that normally inhibit ACh release20,21. Muscle contraction also compresses local blood vessels, reducing the local supply of oxygen. Reduced oxygen, combined with the metabolic demands generated by contracted muscles, results in a rapid depletion of local adenosine triphosphate (ATP). The resultant “ATP energy crisis” 1 triggers a cascade of pre- and postsynaptic decompensations. Presynaptic ATP directly inhibits ACh release22, so depletion of ATP increases ACh release. Postsynaptic ATP powers the Ca2+ pump that returns Ca2+ to the sarcoplasmic reticulum. Hence, loss of ATP impairs the reuptake of Ca2+, which increases contractile activity, creating a vicious cycle19. Excess Ca2+ may snowball into “Ca2+-induced Ca2+ release,” where Ca2+ induces further Ca2+ release from intracel- lular stores via ryanodine receptors, triggering actin and myosin, leading to muscle spasm. Some controversy surrounds adenosine, a breakdown product of ATP. Adenosine normally decreases motor endplate activity by activating presynaptic adenosine A1 receptors, which reduce P/Q VsCC currents, thus reducing ACh release23. However, high levels of synaptic adenosine, from excess ATP breakdown (as is hypothesized to occur in the ATP energy crisis model), may activate postsynap- tic adenosine A2 receptors, which recruit L-type VsCCs currents, thus triggering muscle contraction24. MFTrPs exert profound yet unpredictable influences upon motor function. MFTrPs may excite or inhibit normal motor activity in their muscle of origin or in functionally related muscles. Latent MFTrPs can be equally influential upon motor function. Motor inhibi- tion is often identified clinically as muscle weakness, but treatment often focuses on strengthening exercises that only augment abnormal muscle substitution until the inhibiting MFTrPs are inactivated. This inhibition can also cause poor coordination and muscle imbalances. These MFTrP effects have gone largely unrecognized because of a lack of published research studies. Headly has explored these effects using surface electromyography, describing inhibition of the trapezius by MFTrPs in the same muscle25, inhibition of anterior deltoid by MFTrPs in the infraspinatus25, inhibition of gluteal muscles by MFTrPs in the quadratus lumborum25, and excitation (referred spasm) of the paraspinals by MFTrPs in the tensor fascia lata26,27. Sensory Component MFTrPs are painful. Pain begins in peripheral tissues as nociception, transmitted by A and C-fiber afferent sensory neurons (nociceptors). Mechanical pressure, thermal stimuli, and many chemicals activate nocicep- tors; potassium ions, protons, and free O 2 radicals are by-products of muscle metabolism and the hypothesized “ATP energy crisis.” Histamine is released from mast cells that migrate into injured tissues. Serotonin is released from platelets after they are exposed to platelet activat- Myofascial Trigger Points: Translating Molecular Theory into Manual Therapy / 235 ing factor (released from the mast cells). Bradykinin is cleaved from serum proteins. All of these chemical “activators” bind to receptors in the nociceptor and initi- ate an action potential. “Sensitizers” are also released from damaged tissue; examples include prostaglandins, leukotrienes, and substance P. Sensitizers decrease the activation threshold of a neuron, so that the nociceptor fires with less activation. This leads to peripheral sen- sitization and hyperalgesia. Sensitizing substances may also generate a focal demyelination of sensory nerves. Demyelination creates abnormal impulse-generating sites (AIGS), capable of generating ectopic nociceptive impulses28. Shah et al29 used a microdialysis needle to sample tissue fluids from the upper trapezius muscle in nine subjects; elevated concentrations of protons, bradykinin, serotonin, substance P, norepinephrine, calcitonin gene-related peptide, tumor necrosis factor- a, and interleukin-1b were detected in active MFTrPs, compared to latent MFTrPs and control subjects without MFTrPs. The difference was statistically significant (P<0.01) despite the small sample size. A persistent barrage of nociceptive signals from MFTrPs may eventually cause “central sensitization,” a form of neural plasticity involving functional and/or structural change within the dorsal horn of the spinal cord. The sensitized dorsal horn becomes a “neurologic lens,” consolidating other nociceptive signals that converge upon the same segment of the spinal cord, including other somatic dysfunctions and visceral dysfunctions1. As a result, post-synaptic spinal neurons exhibit decreased activation thresholds, increased response magnitudes, and increased recruitment of receptive field areas. They fire with increased frequency or fire spontaneously, trans- mitting nociceptive signals to supraspinal sites, such as the thalamus and cerebral cortex. Central sensitization may also modulate spinal interneurons and descending inhibitory pathways. Central sensitization is symptomati- cally expressed as allodynia (pain to normally non-painful stimuli) and hyperalgesia (abnormally increased sensa- tion of pain). Simons, Travell, and Simons1 described the central nervous system (CNS) as an “integrator” of MFTrPs, akin to Korr’s description30 of the CNS as an “organizer” of somatic dysfunction. Autonomic Component Autonomic phenomena associated with MFTrPs include localized sweating, vasoconstriction or vasodilation, and pilomotor activity (“goosebumps”)1. MFTrPs located in the head and neck may cause lacrimation, coryza (nasal discharge), and salivation1. The autonomic nervous system (ANS) is primarily involved in reflex arcs, exerting control of cardiac muscle and smooth muscle in blood vessels, glands, and visceral organs. Hubbard and Berkoff3 re- viewed the literature that demonstrated ANS involvement in skeletal muscles and MPTrP formation. Sympathetic neurons innervating vessels in skeletal muscles may exit the perivascular space and terminate among intrafusal fibers within muscle spindles. Sympathetic neurons release norepinephrine, a neurotransmitter involved in the “fight-or-flight” response. Norepinephrine activates 1 -adrenergic receptors in the intrafusal muscle cell membrane. Activation of 1 -adrenergic receptors depresses the feedback control of muscle length, detrimentally affecting motor performance and possibly contributing to the “ATP energy crisis” 31. Norepinephrine has been shown to augment the amplitude and duration of MEPPs in frog leg motor endplates32. Pentolamine, an antagonist of 1 -adrenergic receptors, decreases SEA in MFTrPs33. Similar effects have been seen with local intramuscular injections of phenoxybenzamine, another 1 -adrenergic antagonist34. The ANS may indirectly exacerbate MFTrP formation via viscerosomatic reflexes. Visceral autonomic afferents from disturbed viscera carry signals to the dorsal horn. Chronic input eventually facilitates neurotransmission at that spinal level35. This form of central sensitization accelerates in the presence of nociceptor AIGS and ep- haptic crosstalk with neighboring autonomic nerves9. Ephaptic crosstalk (cross-excitation) is the nonsynaptic interaction between two nerves that are parallel and relatively close together so that their action potentials influence each other. Translating Theory to Therapy The motor endplate and “ATP energy crisis” hypoth- eses have changed our approach to treating MFTrPs. For example, the 1999 edition of Myofascial Pain and Dysfunction: The Trigger Point Manual1, abandoned the application of heavy ischemic compression upon MFTrPs. Deep digital pressure that produces additional ischemia is not beneficial. Instead, Simons, Travell, and Simons1 recommended applying gentle digital pressure to MFTrPs to avoid exacerbating tissue hypoxia. They named their technique ‘”trigger point pressure release.” A single finger pad palpates the MFTrP while the affected muscle is pas- sively lengthened to a point of tissue resistance. Next, the MFTrP is pressed with slowly increasing pressure until the palpating finger encounters a barrier (local tissue resistance). The engaged barrier is held until a release of tension is palpated. The finger “follows” the released tissue by taking up tissue slack, engaging a new barrier, and repeating the sequence. This “press and stretch” is believed to restore abnormally contracted sarcomeres to their normal resting length. We hypothesize that “press and stretch” mechanically uncouples myosin from actin, a process that normally requires ATP, so that the technique reduces ATP demand and breaks the energy crisis cycle. Press and stretch may also help release the “stuck” spring function of the titin connection to the Z bands within sarcomeres. Simons, Travell, and Simons’ new Manual1 also em- phasized the relationship between MFTrPs and nearby 236 / The Journal of Manual & Manipulative Therapy, 2006 articular dysfunctions. They correlated suboccipital MFTrPs with occipito-atlantal dysfunction, semispinalis capitus MFTrPs with occipito-atlantal and atlanto-axial dysfunctions, and splenius MFTrPs with upper thoracic articular dysfunctions1. This close association between MFTrPs and articular dysfunctions is the result of a positive feedback loop. Lewit has emphasized this close association in several publications36,37. A MFTrP in a muscle that crosses an articulation reduces this articulation’s full range of motion, and the MFTrP taut band exerts continuous compression upon the articula- tion. Soft tissues surrounding the articulation cannot withstand chronic compression or tension, and they respond with increased sensitivity. When sufficiently sensitized, these structures send continuous nociceptive messages to the central nervous system, which responds by further activation of MFTrPs, which in turn increases the muscle tension. This positive feedback loop aggra- vates the articular distress. Articular dysfunctions can be treated directly by muscle energy technique (similar to contract-relax or post-isometric relaxation techniques), joint mobilization, and high-velocity, low-amplitude thrust techniques. Articular dysfunctions can be treated indirectly with techniques that address dysfunctional muscles or fascia that cross the articulations, such as strain-counterstrain and myofascial release. Indications and precautions for these techniques are the same as with any articular dysfunctions. Methods for treating MFTrPs and articular dysfunctions work best when combined with patient education. Patient Education Postural training is paramount. Postural disorders often contribute to the perpetuation of MFTrPs. For example, postural strain of the suboccipital muscles may cause MFTrPs in these muscles1, thus leading to further deterioration in muscle structure and function, including radiating somatic pain and atrophic changes, such as muscle atrophy, fibrosis, and decreased tensile strength38. Suboccipital muscles contain a high density of proprioceptors39, so muscle atrophy leads to a loss in proprioceptive balance and a loss of proprioceptive “gate control” at the dorsal horn. This gives rise to chronic pain syndromes including neck pain and headache38. In these patients, proprioceptive exercises can be very helpful, such as close-eyed balance training. Biomechanical factors that stress muscles, such as repetitive activities, must be avoided. Biomechanical stress of a cold muscle is a key factor in the formation of MFTrPs1. Cooling the muscle apparently upregulates nAChR activity at the motor endplate40. Patients with MFTrPs should avoid excess coffee41; caffeine up-regulates the motor endplate by acting as a ryanodine receptor agonist42. Tobacco should also be avoided, as nicotine upregulates L-type VsCCs and nAChR expression, which may lead to muscle hyperexcitability43. Nicotine activates nAChRs in the CNS and autonomic nerves. Although nAChRs in motor endplates are not normally activated by nicotine, mutational defects may sensitize motor endplate nAChRs. One study indicated that ethanol also facilitates motor-end plate activity, via a presynaptic mechanism44. Simons, Travell, and Simons1 recommended a diet adequate in vitamins and minerals for the prevention of MFTrPs. Amazingly, in the 20+ years since that recom- mendation, no well-designed study has been published concerning the effects of vitamin supplementation upon MFTrPs. However, a wealth of clinical experience suggests that low-normal and subnormal levels of vita- mins and minerals act as strong perpetuating factors of MFTrPs. Many case histories attest to patients who responded weakly to manual and/or injection treatment, but adequate supplementation (the return of blood vitamin levels to within mid-normal range) brought about an effective response to the same treatment and with continued supplementation, the patients had no relapse. Interestingly, in two cases, a VA hospital physi- cian advised discontinuation of “unnecessary” vitamin supplements, and within a few months the patients re- turned to the myofascial pain clinic with active MFTrPs as before. Reinstatement of their supplement regimen and a replication of previous treatment restored their health (Simons, unpublished data). Similarly, anemia is a perpetuating factor of MFTrPs that must be corrected to achieve lasting results from treatment45. Inadequate hemoglobin perpetuates the hypoxia present in MFTrPs46. The importance of calcium and magnesium for normal muscle function is well documented, and trace elements are well known to be essential for many body functions including muscle function. Supplementing the diet with phosphatidyl choline has been recommended for the treatment of fibromyalgia47, but this may actually provoke MFTrPs in some patients. Choline is a percur- sor to ACh, and a nAChR gain-of-function mutation may enable choline to directly activate the mutated recep- tors14. High doses of phosphatidyl choline are found in supplements containing lecithin, with lower amounts in raw egg yoke, organ meats, soybeans, peanuts, wheat germ, and brewer’s yeast. An estimated 50% of patients with chronic muscu- loskeletal pain take herbal remedies, so it behooves all health practitioners to understand the mechanisms of herbal medicines48. Clinical experience has shown that myofascial pain can be improved with many herbal rem- edies and essential oils47, including lavender (Lavandula angustifolia), lemon balm (Melissa officinalis), rosemary (Rosmarinus officinalis), kava kava (Piper methysticum), skullcap (Scutellaria lateriflora), passionflower (Passiflora incarnata), rose (Rosa species), and valerian (Valeriana officinalis). Nearly all these herbs contain linalool, a monoterpene that inhibits ACh release (a presynaptic mechanism) and nAChRs (a postsynaptic mechanism)49. Myofascial Trigger Points: Translating Molecular Theory into Manual Therapy / 237 Marijuana (Cannabis species) also produces linalool, although the herb’s efficacy may be due to tetrahydro- cannabinol (THC), which inhibits P/Q-, N-, and L-type VsCCs via cannabinoid receptors found in the motor endplate50. Sativex, a standardized extract dispensed as an oromucosal spray, has been approved for the treat- ment of muscle spasticity and pain in Canada51. THC works by mimicking an endogenous neurotransmitter named anandamide50. Anandamide and THC bind to the same neuroreceptor, known as the cannabinoid receptor. Enhanced release of “endocannabinoids” may be one of the mechanisms of osteopathic manipulative treatment52, parallel to the effects of manipulative treatment upon serum endorphin levels53. Getting to the Point Needling may be necessary to inactivate MFTrPs. The “motor endplate hypothesis” led to the injection of MFTrPs with botulinum toxin type A (BoToxA), which blocks ACh release54. A variety of VsCC blockers have also been injected. Recall that P/Q-type and L-type VsCCs are the primary pre- and post-synaptic Ca2+ chan- nels (respectively) in normal adult motor endplates. The P/Q-specific antagonist omega-agatoxin IVA (also known as omega-conotoxin GVIIC) has shown promise in rat studies55, while verapamil, a L-type VsCC blocker, reduced MFTrP excitability in rabbits56. The drug had no effect on MEPP (a presynaptic measure), but it decreased post-synaptic currents57. Thus, verapamil may function as a nAChR antagonist, rather than by way of its known VsCC antagonism. Similarly, quinidine, another L-type antagonist, also downregulates nAChRs and may restore AChE activity12. Diltiazem also merits investigation. This L-type Ca2+ channel blocker corrects myopathies caused by defects in AChE activity13. However, nifedipine, yet another L-type antagonist, unexpectedly increased ACh activity at motor endplates, due to a unique effect upon ryanodine-sensitive intracellular Ca2+ stores58. Hence, research with VsCC blockers has generated conflicting results, and recent clinical trials with BoToxA have produced mixed results59. Dry needling is usually as ef- fective as injecting anything; if the procedure elicits a local twitch response, dry needling should be as effective as BoTox and much less expensive. Some nAChR antagonists and channel blockers can directly penetrate skin, so they need not be injected. Lidocaine patches have recently been suggested60. As cited by Simons et al1, Simons, Travell, and Simons in 1983 recommended dimethisoquin ointment (Quotane ) for massaging MFTrPs in superficial muscles such as the orbicularis oculi, frontalis, and occipitalis. Dimethisoquin, a local anesthetic, inhibits voltage-gated Na+ channels (conferring its anaesthetic effect), but it also acts as an nAChR antagonist61. Its potency is much greater than lidocaine and procaine, and dimethisoquin is uniquely selective for the motor endplate nAChR subtype. Massage with capsaicin cream (available over the counter as a 0.075% cream) is useful for treating MFTrPs located in surgical scars62, which are particularly refractory to treatment1. This seems contra-intuitive: Capsaicin is the primary active ingredient in hot peppers, and it activates the vanilloid receptor (TRPV1) in nociceptors. However, with repeated exposure to capsaicin, TRPV1 receptors become desensitized, which explains the seemingly paradoxical use of capsaicin as an analgesic63. Another “massage” treatment of MFTrPs uses frequency specific micro-current (FSM), which delivers electromagnetic currents through graphite-conducting gloves. In relation to the MFTrP “energy crisis” model, studies have shown that FSM increases ATP production in muscle tissues as well as reducing cytokine levels64. To successfully treat MFTrPs with FSM, a clinician must be skillful at finding MFTrPs. Conclusion The MfTrP, according to our working hypothesis, centers upon dysregulated motor endplates, sustained by a neural loop of sensory afferents and autonomic effer- ents. The resulting “ATP energy crisis” links with a spinal reflex disorder known as central sensitization. Treatment must simultaneously address the symptomatic trigger points and their underlying causes. Appropriate treat- ment includes dry needling (also know as acupuncture), vapocoolant spray-and-stretch, and thermal treatment (including ultrasound and infrared laser), some of which are discussed in other articles presented in this JMMT series. 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Shah-archives2007.pdf Biochemicals Associated With Pain and Inflammation are Elevated in Sites Near to and Remote From Active Myofascial Trigger Points METHODS Participants Instrumentation Procedures Statistical Design and Analysis RESULTS DISCUSSION Study Limitations CONCLUSIONS APPENDIX 1: COLLECTION SCHEDULE FOR DIALYSATE SAMPLES References Suppliers katagiri sniff test 2003.pdf Neck and abdominal muscle activity during a sniff Introduction Methods Electrode insertion Measurement techniques EMG analysis Statistical analysis Results SNIP and raw EMG of scalene and sternocieldomastoid Relationship between increasing SNIP and neck muscle moving average EMG Impact of posture on SNIP and neck muscle EMG Relationship between SNIP and TA EMG activity Discussion Validity of SNIP values Sniff measurement of inspiratory muscle strength Activity of respiratory muscles during sniff Acknowledgements References Gerwin et al expansion simons 2004.pdf An Expansion of Simons’ Integrated Hypothesis of Trigger Point Formation An Expansion of Simons’ Integrated Hypothesis of Trigger Point Formation Robert Robert D. Gerwin, MD*, Jan Dommerholt, PT, MPS, and Jay P. Shah, MD Address Address *Johns Hopkins University, *Johns Hopkins University, Pain and Rehabilitation Medicine, 7830 Old Georgetown Road, Suite C-15, Bethesda, MD 20814-2432, USA. E-mail: gerwin@painpoints.com Current Pain and Headache Reports Current Pain and Headache Reports 2004, Current Science Inc. ISSN Copyright © 2004 by Current Science Inc.
Simons’ integrated hypothesis proposed a model of trigger point (TrP) activation to explain known... Introduction Introduction Myofascial pain syndrome (MPS) is a myalgic condition characterized by local and referred pain th... Local myofascial pain occurs because of the release of substances from damaged muscle, such as ad... This article presents known data about the TrP and discusses in detail salient features of muscle... Features of Myofascial Trigger Points and Muscle Nociceptors Features of Myofascial Trigger Points and Muscle Nociceptors Certain features of the myofascial TrP relevant to the problem of how the taut band develops and ... A taut muscle band may contain a latent TrP, without tenderness. However, in MPS, tenderness is a... A marked increase in the frequency of low-voltage (50– 100 microvolts) electrical activity is fou... Areas of intense focal sarcomere contraction have been described in the muscles of animals with n... There are a number of biochemical alterations identified by microdialysis sampling techniques at ... Exercise under ischemic conditions [ Tendon organs (sensory receptors located at the muscle -tendon junction in skeletal muscle) are r... Intramuscular hypoperfusion is likely to occur in myalgic syndromes such as myofascial pain [ Hypoxia (extremely low PO Individuals with work-related trapezius myalgia have a deficit of cytochrome C oxidase [ a a Muscle nociceptors are dynamic structures whose receptors can undergo conformational change depen... The nociceptor terminal contains stored substances, ( Implications Implications Taken together, these points suggest that a possible activating event in MPS is exercise under co... The increase in CGRP that occurs in ischemia-induced muscle injury could result in an apparent in... The work of Shah Muscle Injury Related to Eccentric Muscle Contraction and Maximal Concentric Muscle Contraction Muscle Injury Related to Eccentric Muscle Contraction and Maximal Concentric Muscle Contraction Unaccustomed or intense exercise-induced weakness and muscle damage is well documented, particula... Eccentric exercise is associated with muscle soreness and muscle damage. Immediate injurious effe... Muscle fiber injury occurs rapidly in eccentric muscle contraction. Desmin is a muscle cytoskelet... The regions of sarcomere disruption are thought to act as foci for further damage with repeated, ... One result of muscle damage is an immediate reduction of muscle force-generating capacity [ Calcitonin Gene-related Peptide, Acetylcholine Receptors, and Acetylcholinesterase Calcitonin Gene-related Peptide, Acetylcholine Receptors, and Acetylcholinesterase Calcitonin gene-related peptide Calcitonin gene-related peptide Calcitonin gene-related peptide coexists with ACh at the synaptic endings of the motor nerve and ... Calcitonin gene-related peptide receptors consist of protein complexes that span the membrane and... Calcitonin gene-related peptide increases the contractile force of nerve-induced muscle contracti... Calcitonin gene-related peptide increases or decreases ACh release from motor nerve terminals as ... Acetylcholine receptors Acetylcholine receptors The AChR is a transmembrane complex that has an outer ligand-binding configuration, an intramembr... When the AChR is activated, ionic channel currents are generated that result in miniature endplat... Acetylcholine release Acetylcholine release Acetylcholine release is quantal and nonquantal. Quantal release is calcium-dependent whereas non... Muscle contraction takes place through depolarization of the muscle fiber membrane at the motor e... Acetylcholine also acts through a feedback mechanism to regulate its own release at the neuromusc... Presynaptic sympathetic nerve modulation of acetylcholine release Presynaptic sympathetic nerve modulation of acetylcholine release The sympathetic nervous system modulated the observed endplate noise at the TrP, reducing it by a... Acetylcholinesterase Acetylcholinesterase Acetylcholinesterase is present in the synaptic cleft. It breaks down ACh and thereby can inhibit... Acidic pH and Muscle Pain Acidic pH and Muscle Pain The work of Sluka
Figure 1. A schematic outline of the expanded trigger point hypothesis. The activating event is ... Figure 1. A schematic outline of the expanded trigger point hypothesis. The activating event is ... Hypothesis Hypothesis It can be hypothesized that the activating event in the development of the TrP is the performance... Conclusions Conclusions There normally is an equilibrium between the release of ACh, the breakdown of ACh, and its remova... References and Recommended Reading References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1. •• Simons 1. •• Simons 1. •• Simons DG, Travell JG, Simons LS: Myofascial Pain and Dysfunction: The Trigger Point Manual, vol 1, edn 2. Baltimore: Williams and Wilkins; 1999. This is the authoritative work in the field. It contains the most comprehensive introduction to m... 2. 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E-mail: john.jarrell@calgaryhealthregion.ca Current Pain and Headache Reports Current Pain and Headache Reports 2004, Current Science Inc. ISSN Copyright © 2004 by Current Science Inc.
Chronic pelvic pain is a potentially devastating condition that affects many women with severe co... Introduction Introduction Chronic pelvic pain in women is defined as persistent pain in the pelvic region that has been pre... The causes of the condition are poorly understood for many reasons. Initial studies of the causes... The exact prevalence is unknown. Alberta Health and Wellness reported the presence of chronic pai... The spectrum of diseases that have been associated with chronic pelvic pain are manifold. They in... A further confounding problem in addition to depression and poor social interactions has been an ... Common Visceral Conditions Associated with Chronic Pelvic Pain Observed at Laparoscopy Common Visceral Conditions Associated with Chronic Pelvic Pain Observed at Laparoscopy Endometriosis is a degenerative condition that commonly acts like a benign tumor because of its l... Adhesions are areas of tissue growth that cause the union of tissues that usually are free of one... At laparoscopy, the presence of endometriosis and adhesions make up most of the diagnoses of cond... Myofascial Dysfunction: The Great Pretender Myofascial Dysfunction: The Great Pretender Myofascial dysfunction is an important consideration because it may represent a substantial porti... The clinical presentation of the syndrome is the presence of severe tenderness and a nodule or ba... The management of myofascial disorders is based on the principle that the vicious cycle can be br... Approach to the Intrapelvic Muscles Approach to the Intrapelvic Muscles There is a significant muscular composition to the pelvis. The major muscles include the levator ... Examination of patients with chronic pelvic pain should be modified to eliminate the possibility ...
Table 1. Clinical characteristics of subjects
Age Gravida Para Number Duration, y
Number 52 53 53 55 49
Mean 35 1 0.9 3.7 4.8
Minimum 19 0 0 1 0.2
Maximum 71 9 5 9 19
Standard deviation 11.6 1.9 1.2 2.4 4.5 The approach to the treatment of these bands is as presented by Gerwin [ As in abdominal wall problems, one must be cautious in the simple treatment of the trigger points... Cross-sectional Study of Patients with Pelvic Pain and Myofascial Dysfunction Cross-sectional Study of Patients with Pelvic Pain and Myofascial Dysfunction Just as it is important not to miss muscle pain in the clinical evaluation of the abdomen and pel...
Figure 1. The relationship of age and the number of myofascial trigger points identified. Figure 1. The relationship of age and the number of myofascial trigger points identified. In this analysis, the number of trigger points was found to range from one to nine. The duration ... In this limited study, the presence or absence of a trigger point in the abdominal wall was a ver...
Table 2. Presence of visceral disease among subjects with abdominal wall trigger points
Visceral disease Positive Negative
Tender point Positive Negative Total predictive value predictive value
Present 37 4 11
Absent 4 7 41 0.9
41 11 52 0.64
Sensitivity 0.9
Specificity 0.64
Prevalence 79.8 Furthermore, there was an interesting observation that the actual number of trigger points that c... Conclusions Conclusions This study was done to determine if the link between myofascial dysfunction and visceral disease ... The processes of myofascial dysfunction appear somewhat dynamic on the basis that there are age-r... The relationship of abdominal wall trigger points and visceral disease is of interest because it ... From a clinical perspective, this study is relevant to the management of myofascial dysfunction. ... References and Recommended Reading References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1. •• Steege 1. •• Steege 1. •• Steege JF, Metzger DA. Chronic Pelvic Pain, edn 1. Philadelphia: WB Saunders Company; 1998. The current standard for a comprehensive but readable text of a complex societal and medical prob... 2. Health Surveillance Alberta Health and Wellness EA: 2. Health Surveillance Alberta Health and Wellness EA: 2. Health Surveillance Alberta Health and Wellness EA: Chronic pain in Alberta: A Portrait from the 1996 National Population Health Survey and the 2001 ... http://www.health.gov.ab.ca/public/diseases/pdf/ChronicPainReport.pdf . Accessed May 1, 2004. 3. Mathias 3. Mathias 3. Mathias SD, Kupperman M, Lieberman RF, et al. 4. Olive 4. Olive 4. Olive DL, Pritts EA: The treatment of endometriosis: a review of the evidence. Ann N Y Acad Sci 2002, 955: 360– 372. 5. Schroeder 5. Schroeder 5. Schroeder AK, Diedrich K, Ludwig M: Medical management of endometriosis. Drugs 2004, 7: 451– 463. 6. Wenzyl 6. Wenzyl 6. Wenzyl R, Kiesel L, Huber JC, Wieser F: Endometriosis: a genetic disease. Drugs Today (Barc) 2003, 39: 961– 972. 7. Bischoff 7. Bischoff 7. Bischoff FZ, Simpson JL. Heritability and molecular genetic studies of endometriosis. Hum Reprod Update 2000, 6: 37– 44. 8. Barbieri 8. Barbieri 8. Barbieri RL: Etiology and epidemiology of endometriosis. Am J Obstet Gynecol 1990, 162: 565– 567. 9. Sampson 9. Sampson 9. Sampson JA: Perforating hemorrhagic (chocolate) cysts of the ovary. Arch Surg 1921, 3: 245– 250. 10. Sampson 10. Sampson 10. Sampson JA: Ovarian hematomas of endometrial type (perforating hemorrhagic cysts of the ovary) and implantati... Boston Med Surg J 1922, 186: 445. 11. Redwine 11. Redwine 11. Redwine DB: Was Sampson wrong? Fertil Steril 2002, 78: 686– 693. 12. Paul 12. Paul 12. Paul DW, Braun DP: Immunology of endometriosis. Best Pract Res Clin Obstet Gynaecol 2004, 18: 245– 263. 13. Rier 13. Rier 13. Rier SE: The potential role of exposure to environmental toxicants in the pathophysiology of endometriosis. Ann N Y Acad Sci 2002, 955: 201– 212. 14. Rier 14. Rier 14. Rier SE, Turner WE, Martin DC, et al. 15. De Felip 15. De Felip 15. De Felip E, Porpora MG, di Domenico A, et al. 16. Guo 16. Guo 16. Guo SW: The link between exposure to dioxin and endometriosis: a critical reappraisal of primate data. Gynecol Obstet Invest 2004, 57: 157– 173. 17. Simons 17. Simons 17. Simons DG: The nature of myofascial trigger points. Clin J Pain 1995, 11: 83– 84. 18. Gerwin 18. Gerwin 18. Gerwin RD: Neurobiology of the myofascial trigger point. Baillieres Clin Rheumatol 1994, 8: 747– 762. 19. • Gerwin 19. • Gerwin 19. • Gerwin RD: Classification, epidemiology, and natural history of myofascial pain syndrome. Curr Pain Headache Rep 2001, 5: 412– 420. Gerwin's description of myofascial disorders is a helpful reference when applied to the pelvic mu... 20. Travell 20. Travell 20. Travell JG, Simons DG: Myofascial Pain and Dysfunction: The Trigger Point Manual. Baltimore: Williams and Wilkins; 1983. 2007.CNP.itoh.pdf Randomised trial of trigger point acupuncture compared with other acupuncture for treatment of chronic neck pain Introduction Methods Patients Design Blinding Treatment Standard acupuncture (SA) group Trigger point acupuncture (TrP) or non-trigger point (non-TrP) group Sham acupuncture (SH) group Evaluation Assessment of blinding technique Statistical analysis Results Patient characteristics VAS score Functional impairment Assessment of the blinding technique Discussion Effectiveness of the trigger point as a treatment site of acupuncture Acknowledgments References chen-Elastography-MRI-2007.pdf Identification and Quantification of Myofascial Taut Bands With Magnetic Resonance Elastography METHODS Bovine Gel Phantom Finite Element Simulation Participants RESULTS Taut Band Phantom Finite Element Simulation Participants DISCUSSION Study Limitations CONCLUSIONS References chen et al elastography 2008.pdf Ability of magnetic resonance elastography to assess taut bands Introduction Methods Magnetic resonance elastography on bovine gel phantom Finite element modeling Magnetic resonance elastography on human subjects Results Magnetic resonance elastography on bovine gel phantom Finite element simulation Magnetic resonance elastography on human subjects Discussion Acknowledgments References shah et al review 2008 jbmt.pdf Uncovering the biochemical milieu of myofascial trigger points using in vivo microdialysis: An application of muscle pain concepts to myofascial pain syndrome Introduction Historical terminology Myofascial trigger point diagnostic criteria Motor abnormalities of the myofascial trigger point Electrophysiology The Integrated Trigger Point Hypothesis The Cinderella Hypothesis Sensory abnormalities of the myofascial trigger point Nociceptor properties Chemical activation of afferent nerves Peripheral and central sensitization Uncovering the biochemical milieu of myofascial trigger points Microdialysis sampling of the trapezius Microdialysis sampling of the trapezius and gastrocnemius Roles of biochemical substances associated with pain and inflammation pH Neuropeptides Catecholamines Cytokines Conclusion References chang chen chang neuroaxonal degeneration.pdf Evidence of neuroaxonal degeneration in myofascial pain syndrome: A study of neuromuscular jitter by axonal microstimulation Introduction Subjects and methods Patients profile Stimulated SFEMG study Statistical analysis Results Discussion Acknowledgements References ge et al topography TrP 208.pdf Topographical mapping and mechanical pain sensitivity of myofascial trigger points in the infraspinatus muscle Introduction Materials and methods Patients Experimental protocol Assessment of muscle mechanical pain sensitivity Topographical PPT mapping Dry needling procedure Statistical analysis Results The number of MTrPs bilaterally in the infraspinatus muscles PPT bilaterally in the infraspinatus Location of MTrPs bilaterally in the infraspinatus muscles Discussion Multiple active MTrPs are associated with unilateral shoulder pain Presence of latent MTrPs bilaterally in the infraspinatus Peripheral sensitization is crucial to the development of myofascial pain syndrome References Ge et al induction of muscle cramps and latent MTrP exp brain res.pdf Induction of muscle cramps by nociceptive stimulation of latent myofascial trigger points Abstract Introduction Materials and methods Subjects Experimental protocol EMG-guided intramuscular injection EMG-guided injection needle recordings Muscle cramp as deWned by EMG Assessment of local muscle pain intensity Statistical analysis Results Pain intensity EMG activity before and after glutamate and isotonic saline injections Occurrence of muscle cramps Discussion Association of muscle cramps with MTrPs Increased nociceptive sensitivity at MTrPs mediates the occurrence of muscle cramps References Ge sympathetic facilitation.pdf Sympathetic facilitation of hyperalgesia evoked from myofascial tender and trigger points in patients with unilateral shoulder pain Introduction Subjects and methods Subjects Experimental protocol Measurement of PPT and PTRP Statistical analysis Results Effect of increased sympathetic activity on PPT at the tender and trigger points Effect of increased sympathetic activity on PPT in the tibialis anterior muscle Effect of increased sympathetic activity on PPT, referred pain threshold (PTRP), and local and referred pain intensities at the trigger point Discussion Sympathetic hyperactivity at myofascial tender and trigger points Sympathetic hyperactivity and referred muscle pain Acknowledgements References Giamberardino TrP and Migraines.pdf Contribution of Myofascial Trigger Points to Migraine Symptoms Materials and Methods Phase 1: Main Experiment Patients and Subjects Experimental Procedures Palpation of Cervical Muscles for Trigger Point Assessment Pain Thresholds and TrP Treatment Migraine Parameters Technique of Pain Threshold Measurement to Electrical Stimulation Cutaneous Thresholds in Migraine Sites of Patients Without Active Cervical Trigger Points TrP Infiltration Technique Phase 2: Secondary Experiment Statistical Analysis Results Phase 1: Main Experiment Pain Thresholds Cutaneous Thresholds in Migraine Sites of Patients Without Active Cervical Trigger Points Migraine Parameters Pain Thresholds Versus Migraine Parameters in Treated Patients Phase 2: Secondary Experiment Pain Thresholds Migraine Parameters Discussion Acknowledgments References pathogenesis of muscle pain mense.pdf The Pathogenesis of Muscle Pain The Pathogenesis of Muscle Pain Siegfried Siegfried Mense, MD Address Address Institut für Anatomie und Zellbiologie III, Universität Heidelberg, Institut für Anatomie und Zellbiologie III, Universität Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany. E-mail: mense@urz.uni-heidelberg.de Current Pain and Headache Reports Current Pain and Headache Reports 2003, Current Science Inc. ISSN Copyright © 2003 by Current Science Inc.
Nociceptive nerve endings in muscles and other tissues are equipped with a multitude of receptor ... Introduction Introduction In recent years, it has become more obvious that muscle pain differs in several aspects from cuta... This article focuses on peripheral and central nervous mechanisms of muscle pain and discusses pa... Peripheral Mechanisms Peripheral Mechanisms Neurobiology of muscle nociceptors Neurobiology of muscle nociceptors The term neurobiology includes neurophysiologic and neuroanatomic aspects. Morphologically, a no... Recordings of the electrical activity of single muscle afferent fibers in cats and rats have show... Well-known stimulants for muscle nociceptors are endogenous pain-producing substances such as bra... This type of nociceptor would be well suited to mediate the pain of tonic muscle contractions, wh...
Figure 1. Schematic drawing of a nociceptive nerve ending showing membrane receptor molecules an... Figure 1. Schematic drawing of a nociceptive nerve ending showing membrane receptor molecules an... Data from nociceptors in joints and other tissues have shown that the previously mentioned endoge... Receptor molecules for clinical cases of muscle pain are the so-called purinergic receptors ( Another receptor molecule of particular clinical interest is VR-1. It responds to an increase in ...
Figure 2. Proportion of rat muscle nociceptors that responded to adenosine triphosphate (ATP), ... Figure 2. Proportion of rat muscle nociceptors that responded to adenosine triphosphate (ATP), ... In experiments by the author’s group, ATP and acidic solutions were effective stimulants for musc... Theoretically, the pain during tooth clenching, bruxism, and tension-type headache could be media... Neuropeptide content of muscle nociceptors Neuropeptide content of muscle nociceptors There is no neuropeptide that can be regarded as specific for sensory fibers from muscle or for m... Interactions between stimulants at the receptive nerve ending Interactions between stimulants at the receptive nerve ending Prostaglandin E The concentration of PG E Sensitization of nociceptors as the peripheral neurophysiologic basis of tenderness and hyperalgesia Sensitization of nociceptors as the peripheral neurophysiologic basis of tenderness and hyperalgesia Many substances released from pathologically altered tissue increase the mechanical sensitivity o...
Figure 3. Expansion of the spinal target area of the gastrocnemius-soleus (GS) muscle nerves aft... Figure 3. Expansion of the spinal target area of the gastrocnemius-soleus (GS) muscle nerves aft... Longer-lasting pathologic alterations of muscle tissue sensitize nociceptors and increase the inn... Mechanisms of Muscle Pain at the Spinal Level Mechanisms of Muscle Pain at the Spinal Level Myositis-induced neuroplastic changes in the spinal dorsal horn Myositis-induced neuroplastic changes in the spinal dorsal horn Input from peripheral nociceptors to the spinal cord or brain stem is known to lead to changes in... The cellular mechanism underlying the myositis- induced expansion of the responding neuron popula... Neurotransmitters involved in central sensitization Neurotransmitters involved in central sensitization Experiments with intrathecal administration of antagonists to SP and NMDA receptors showed that t... Patients with myositis complain of hyperalgesia, hyper aesthesia, spontaneous pain, and dysaesthe... Mechanism of referral of muscle pain Mechanism of referral of muscle pain The expansion of the input region of the inflamed GS muscle nerve likely underlies the spread an... The transition from acute to chronic muscle pain The transition from acute to chronic muscle pain The functional reorganization in the spinal dorsal horn is an expression of neuroplasticity becau... Tissue sections from animals with an acute myositis (10- hour duration) showed a significant incr... The last step in the transition from acute to chronic muscle pain is morphologic changes in the c... In patients, the development of lesion-induced structural changes in the dorsal horn and in highe... Conclusions Conclusions The data obtained in studies on nociceptive nerve endings in muscle and other tissues show that t... The transition from acute to chronic muscle pain is considered to be a series of processes that s... References and Recommended Reading References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1. • Mense 1. • Mense 1. • Mense S, Simons DG: Muscle Pain: Understanding Its Nature, Diagnosis, and Treatment, Baltimore and London: Lippincott Williams & Wilkins; 2001. This book addresses all of the known clinical conditions with muscle pain and attempts to give ex... 2. Keay 2. Keay 2. Keay KA, Bandler R: Deep and superficial noxious stimulation increases Fos-like immunoreactivity in different regions... Neurosci Lett 1993, 154: 23– 26. 3. Yu 3. Yu 3. Yu XM, Mense S: Response properties and descending control of rat dorsal horn neurons with deep receptive fields. 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J Physiol 1983, 342: 383– 397. 14. Kidd 14. Kidd 14. Kidd BL, Morris VH, Urban L: Pathophysiology of joint pain. Ann Rheum Dis 1996, 55: 276– 283. 15. Caterina 15. Caterina 15. Caterina MJ, David J: Sense and specificity: a molecular identity for nociceptors. Curr Opin Neurobiol 1999, 9: 525– 530. 16. • McCleskey 16. • McCleskey 16. • McCleskey EW, Gold MS: Ion channels of nociception. Ann Rev Physiol 1999, 61: 835– 856. Recommended reading for anyone who wants to understand the molecular receptors and ion channels t... 17. Perkins 17. Perkins 17. Perkins MN, Kelly D: Induction of bradykinin-B1 receptors in vivo in a model of ultraviolet irradiation-induced therma... Br J Pharmacol 1993, 110: 1441– 1444. 18. Burnstock 18. Burnstock 18. Burnstock G: P2X receptors in sensory neurones. Br J Anaesth 2000, 84: 476– 488. 19. Ding 19. Ding 19. Ding Y, Cesare P, Drew L, et al. 20. Hamilton 20. Hamilton 20. Hamilton SG, McMahon SB: ATP as a peripheral mediator of pain. J Auton Nerv Syst 2000, 81: 187– 194. 21. Cook 21. Cook 21. Cook SP, McCleskey EW: Cell damage excites nociceptors through release of cytosolic ATP. Pain 2002, 95: 41– 47. 22. Carlton 22. Carlton 22. Carlton SM, Coggesshall RE: Peripheral capsaicin receptors increase in the inflamed rat hindpaw: a possible mechanism for per... Neurosci Lett 2001, 310: 53– 56. 23. • Marchettini 23. • Marchettini 23. • Marchettini P, Simone DA, Caputi G, Ochoa JL: Pain from excitation of identified muscle nociceptors in humans. Brain Res 1996, 40: 109– 116. This is the only report available on microneurographic recordings from human muscle nociceptors. 24. • Sluka 24. • Sluka 24. • Sluka KA, Kalra A, Moore SA: Unilateral intramuscular injections of acidic saline produce a bilateral long-lasting hyperalgesia. Muscle Nerve 2001, 24: 37– 46. A highly important report on a rather simple hypothesis that may turn out to be the basis for the... 25. Molander 25. Molander 25. 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A classic paper emphasizing that input from muscle has a stronger effect on central nervous funct... 31. Hoheisel 31. Hoheisel 31. Hoheisel U, Koch K, Mense S: Functional reorganization in the rat dorsal horn during an experimental myositis. Pain 1994, 59: 111– 118. 32. • Woolf 32. • Woolf 32. • Woolf CJ, Salter MW: Neuronal plasticity: increasing the gain in pain. Science 2000, 288: 1765– 1768. A short, but important report by two of the most distinguished experts in the field. 33. Baranauskas 33. Baranauskas 33. Baranauskas G, Nistri A: Sensitization of pain pathways in the spinal cord: cellular mechanisms. Prog Neurobiol 1998, 54: 349– 365. 34. Hoheisel 34. Hoheisel 34. Hoheisel U, Sander B, Mense S: Myositis-induced functional reorganization of the rat dorsal horn: effects of spinal superfusion... Pain 1997, 69: 219– 230. 35. Hoheisel 35. Hoheisel 35. Hoheisel U, Sander B, Mense S: Blockade of nitric oxide synthase differentially influences background activity and electrical e... 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Arthritis Rheum 1997, 40: 446– 452. muscle pain graven nielsen.pdf Induction and Assessment of Muscle Pain, Referred Pain, and Muscular Hyperalgesia Induction and Assessment of Muscle Pain, Referred Pain, and Muscular Hyperalgesia Thomas Thomas Graven-Nielsen, PhD Address Address Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Fredrik Bajers Vej 7D-3, DK-9220 Aalborg E, Denmark. E-mail: tgn@smi.auc.dk Current Pain and Headache Reports Current Pain and Headache Reports 2003, Current Science Inc. ISSN Copyright © 2003 by Current Science Inc.
Muscle pain can be induced and assessed experimentally by a variety of methods. Ischemic and exer... Introduction Introduction The pain from deep somatic structures represents a major part of pain complaints in patients. Dee... The neurobiologic mechanisms involved in muscle pain often are difficult to resolve from clinical... Pain is a multidimensional perception and the reaction to a single standardized stimulus of a giv...
Table 1. Assessment methods and quantitative parameters of muscle pain
Methods Quantitative parameter
Response-dependent Intensity
Visual analogue scale
Verbal descriptor scale
Numerical scale
Cross-modality matching
Stimulus-response function
Quality
McGill Pain Questionnaire
Unpleasantness
Visual analogue scale
Distribution
Drawings (area, location)
Stimulus-dependent Detection threshold (methods of limits/constant stimuli)
Pain threshold (methods of limits/constant stimuli)
Pain tolerance threshold (methods of limits/constant stimuli) Most experimental pain research has been done on cutaneous pain, although cutaneous pain is far l... Quantitative Assessment of Experimental Muscle Pain Quantitative Assessment of Experimental Muscle Pain The assessment methods of muscle pain are based on psychophysical, electrophysiologic, and imagin... Psychophysical determinations can be divided into response-dependent and stimulus-dependent metho... The stimulus-dependent methods are based on the adjustment of the stimulus intensity until a pred... Stimulus-response functions are more informative than a threshold determination because suprathre...
Table 2. Stimulus modalities for induction of experimental muscle pain in humans
Type Modality Stimulus
Endogenous Ischemia Tourniquet plus contractions
Exercise Concentric contractions
Eccentric contractions
Exogenous Electrical Intramuscular
Intraneural
Mechanical Pressure
Tourniquet pressure
Focused ultrasound
Chemical Hypertonic saline, potassium, levoascorbic acid, capsaicin, bradykinin, serotonin, calcitonin gen...
Thermal Heated isotonic saline
(Focused ultrasound) Verbal assessments of the experienced muscle pain intensity and other subjective characteristics ... Experimental Muscle Pain Experimental Muscle Pain Various procedures can induce muscle pain and they can be divided into endogenous and exogenous t... Ischemia Ischemia Lewis [ Exercise Exercise Exercise-induced muscle pain by concentric muscle work normally is short lasting and results from... Electrical Electrical In human studies, intramuscular electrical stimulation can be used to assess the sensitivity of m... Mechanical Mechanical Mechanical, painful stimulation can be achieved with pressure algometers. The most widely used te... Tender points are anatomically determined soft-tissue body sites. Among other criteria, the patie... An alternative to pressure algometry, with the inherent variability-related manual application, i... Chemical Chemical Intramuscular injections of algogenic substances have been used to induce human muscle pain [ The sensitization of muscle nociceptors is the best established peripheral mechanism for the subj... Glutamate receptors (ionotropic and metabotropic) are other receptor types that potentially are i... Svensson Referral of pain represents a common clinical sign in many musculoskeletal pain disorders and in ... Experimentally induced referred pain is an important indicator of central sensitization in patien...
Figure 1. Assessment of the deep tissue sensitivity by automated pressure algometry. A, Pressur... Figure 1. Assessment of the deep tissue sensitivity by automated pressure algometry. The plasticity of the central nervous system also may alter the somatosensory sensitivity and acc... Other modalities Other modalities From animal studies, afferent recordings have shown that a subgroup of muscle nociceptors respond... Focused ultrasound has been used to induce muscle, joint, and skin pain [ Conclusions Conclusions Reliable methods for quantitative induction and assessment of muscle pain, referred pain, and sen... Acknowledgment Acknowledgment The Danish Technical Research Council supported the time spent writing this review. References and Recommended Reading References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1. 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