Myofascial Pain

Etiology

When considering the etiology of myofascial pain, one must remember that the myofascial compartment is also constituted by the soft tissue that transports fluids (blood and lymph) and action potentials (afferent and efferent nerves). Vascular and nerve pathways can be a source of pain because they are innervated. The liquid fascia (blood and lymph) can be a source of pain because changes in flow velocity, direction, and type of flow can affect surrounding tissues, leading to myofascial pain.

The cause of myofascial pain is not fully understood; this may be due to one or more of the hypothesized causes given below:

• Constant microtrauma to the muscle system can increase oxidative metabolism and quickly deplete cellular energy reserves (ATP). This altered mechano-metabolic environment increases nociceptive sensation, particularly if the musculature has a majority of red fibers (postural muscle).[6] Type III and IV afferents transmit nociceptive messages from muscles, which can be activated by various substances, including potassium, prostaglandins, histamine, and kinins, leading to increased stiffness. This constant peripheral stimulation could alter the response of medullary interneurons, generating peripheral sensitization to pain in the first phase and central sensitization in the second temporal phase.[6]
• The presence of trigger points (TPs) may result from altering the synaptic plate of muscle fibers. An increase in acetylcholine concentration with consequent uncontrolled release from the motor endplate causes continued contraction of the muscle fibers in the absence of central innervation. This constant contraction would deplete the tissue of ATP, causing the release of pro-inflammatory substances and the formation of TPs.[6]
• In the presence of a constantly changing mechano-metabolic environment, there is a shift in the connective tissue that comprises the myofascial system. The fibroblasts are transformed into myofibroblasts, contributing to the shortening of surrounding tissue and increasing tone. The receptors present within the fascia can be transformed into nociceptors and become sensitive to mechanical stimuli (allodynia or mechanical hyperalgesia). We know that the myofascial system can carry neural signals, and any alteration in the connective tissue structure can alter the polarization of muscle fibers, leading to spontaneous muscle contraction.[8][9]
• Hyaluronan (HA) is a component of glycosaminoglycan polymer found in the extracellular matrix. Any change in the mechano-metabolic environment causing HA to change its properties creates a more viscous extracellular matrix. This causes the fascia to have difficulty sliding between layers, making muscle contraction harder.[10] The nerve endings of the fascia in the most vulnerable area stretch, becoming constantly activated, creating a trigger point.[11]
• An alteration of blood flow (an increase in systolic wave velocity and decreased diastolic velocity due to increased outflow resistance) may cause myofascial pain. The change in flow velocity induces alterations in the morphology and function of the muscular capillaries, leading to ischemia during small, active movements. This activates type IV nerve endings, contributing to the development of myofascial pain.[12]
• Iron deficiency in pregnant women and vitamin D deficiency in the general population.[13]
• Altered emotional, psychological, and psychiatric states may contribute to this condition as well.[13]

Epidemiology

The prevalence of myofascial pain syndrome in the United States is about 9 million, with an estimation that the same percentage of patients is found in Canada. Myofascial pain syndrome affects men and women equally, but it is more prevalent in people older than 60. There is no convincing data to suggest a relationship between myofascial pain and ethnicity or geographical location.[14]

According to recent data, pain underlying myofascial tissue involves a population aged between 30 and 60 years, where women have a 65% incidence compared to men, who have a presence of pain of about 37%. In people 65 and older, the prevalence rates can reach up to 85%. The location will depend on lifestyle, work, and previous medical history. In some clinical conditions, such as nonspecific muscle pain, the percentage of myofascial pain as the primary cause can reach 100%.[13]

Pathophysiology

To understand and effectively treat myofascial pain, it is essential to comprehend the underlying pathological processes that contribute to this syndrome. The myofascial trigger point is a site of latent ischemia, which could explain the cause of pain. This ischemia lowers the pH, creating an acidic environment in the myofascial compartment. This decreases acetylcholinesterase (AChE) levels while increasing acetylcholine's (ACh) effectiveness, thereby causing prolonged muscle contraction.[12] In this altered environment, the release of nociceptive substances, such as calcitonin gene-related peptide, results in an increased number of ACh receptors and ACh release, while decreasing the effectiveness of AChE.[12]

The amount of ATP within a TP is decreased. Ischemia causes decreased ATP, leading to a lack of muscle relaxation (ATP depletion prevents the calcium pump–calcium ATPase) from withdrawing the calcium in the muscle fibers. This leads to the accumulation of calcium within the myocytes. Suppose calcium is not completely withdrawn from the cytoplasm. In that case, it becomes cytotoxic, stimulating the release of inflammatory mediators such as bradykinin, calcitonin gene-related peptide, tumor necrosis factor-alpha, substance P, inflammatory interleukins (IL-6, IL-8, IL-1β), norepinephrine, and serotonin. Such inflammatory substances cause increased nociceptive sensitization that results in severe pain.[12][15]

According to a recent theory, TPs may derive nociceptive afferents through the subcutaneous accessory pain system, an extra-innervation pathway to the spinal cord via the dorsal rami.[16] Another theory states that myofascial pain could be due to dysfunction of spinal and supraspinal pathways. The cutaneous silent period (CSP) is a brief interruption of voluntary action after intense sensory stimulation; this helps evaluate sensory nervous system features poorly assessed by other electrodiagnostic studies and the spinal and supraspinal pathways. Abnormal CSP parameters in patients with myofascial pain may suggest a problem with spinal or supraspinal pathways.[17] Results from a study revealed a reduction in gray matter volume in the limbic area (including the thalamus, cingulate gyrus, insula, and parahippocampal gyrus) in patients with myofascial pain syndrome.[18] 

Nociceptive afferent signals from the myofascial system could cause structural and functional changes of the central nervous system, starting from the spinal cord (due to an accumulation of inflammatory substances), causing changes in medullary neurons (increase in neuronal excitability) with centrifugal progression.[14] This mechanism would lead to central sensitization, characterized by a lack of inhibition of the descending pain inhibitory pathways, thereby perpetuating inflammation and the formation of TPs.[14] Another possible cause stems from the idea known as the Cinderella Hypothesis. This hypothesis posits that myofascial pain may arise from inadequate neuromuscular coordination, whereby the smallest fibers are consistently recruited for low- to medium-intensity motor efforts. This constant activation (inadequate activation for the required effort) would lead to local metabolic alterations, with the onset of inflammatory phenomena.[19]

Histopathology

Myocytes in TPs are nonuniformly distributed, rounded in the center, and thinner at the periphery, with reduced mitochondria and an accumulation of inflammatory cells.[20] The thickness of the Z line of sarcomeres is smaller, with a wider band A and the absence of band I. These muscle cells are less elastic due to damage to proteins such as desmin, titin, and nebulin, and a reduced volume of capillaries.[20] Erythrocytes in patients with myofascial pain exhibit a deficiency in antioxidants, including selenium and zinc. This causes greater oxidative stress, stimulating a systemic inflammatory response; however, further studies are necessary to draw definitive conclusions.[21]

History and Physical

Myofascial pain syndrome comprises both acute and chronic pain. The pain experienced in this syndrome is usually dull, aching, poorly localized, and indistinguishable from other causes of somatic and visceral pain. Sensory paresthesias or dysesthesias may occasionally accompany myofascial pain. Sometimes, the pain associated with this condition can be felt at a point distant from the actual disease process; the pain may persist for many months or years after the initial insult, even if the initiating event is resolved. Constricting myofascial taut bands may cause entrapment of the nervous component of the myofascial system, leading to further pain and disability. 

The presence of myofascial trigger points and associated pain diagnoses is myofascial pain syndrome. Myofascial trigger points are located by palpation of the tender or painful areas of the patient. A trigger point is defined by the presence of a tight band that is palpable within the muscle tissue, which, through practice and experience, can be easily palpated in all types of muscles, whether superficial or deep. Such muscles containing trigger points are nonuniform, with heterogeneous areas that consist of soft, firm, or hard consistency, rather than a uniform homogeneous consistency. During daily activity, the contraction of trigger points typically causes exquisite and localized pain in the patient.

Sometimes, taut bands are not painful to palpation but can alter the typical sequence of muscle activation. The correct method of palpating trigger points consists of palpating the muscle perpendicular to the direction of the muscle fibers.[22] A Delphi study conducted in 2017 proposed that at least 2 of the following criteria must be positive for trigger point diagnosis: a taut band, a hypersensitive spot, and referred pain. The pain referred from a myofascial trigger point causes different sensory sensations, including pain traveling to a distant area, deep pain, dull aching, tingling, or burning pain.[22]

Evaluation

Several diagnostic tools are available to assess the presence of trigger points, with individual advantages.[10]

• Ultrasound imaging: Ultrasound is often used to analyze the thickness and consistency of muscle nodules and the movement of various tissue layers. Some studies analyzed TPs using ultrasound elastography by Doppler variance imaging while inducing vibrations with a handheld vibrator. Myofascial trigger points appear as focal, hypoechoic nodules, characterized by decreased vibration amplitude. (indicates increased stiffness and modified blood supply compared to normal tissue)[23]
• Microdialysis: This method is used to measure inflammatory mediators in TPs, including bradykinin, substance P, tumor necrosis factor-alpha, calcitonin gene–related peptide, interleukin-1 beta, serotonin, interleukin-6 and -8, and norepinephrine.[23]
• Electromyography: This is used to evaluate the electrical activity of active and latent TPs (ie, the test is performed at rest and during active motion). Generally, the TPs exhibit increased electromyographic activity during synergistic muscle contraction compared to normal muscles.[23]
• Infrared thermography: This tool is used to assess skin temperature in the areas of TPs. This is currently used as an auxiliary test due to conflicting results.[23]
• Magnetic resonance elastography: There is no consensus on the validity of results obtained from magnetic resonance elastography due to its low sensitivity.[23]
• Vibration elastography: This method allows for the testing of the movement of myofascial tissue.[24]

Treatment / Management

Pharmacotherapy

Nonsteroidal anti-inflammatory drugs

• Clinicians often use nonsteroidal anti-inflammatory drugs to manage patients with myofascial pain symptomatically. These medications are available in both oral and topical formulations; however, there is no scientific evidence to support their use in this form.[25]

Muscle Relaxants

• Muscle relaxants act on the central nervous system to reduce central pain stimulation. However, no scientific evidence exists in the literature for their use as a treatment for TPs.[25]

Benzodiazepines

• Benzodiazepines such as clonazepam and diazepam have several adverse effects. (ataxia, cognitive decline, and depression) Although a study showed promising results of benzodiazepines in treating TPs, it was not feasible to follow such a long-term therapeutic trial because of the side effects of benzodiazepines.[25]

Antidepressants

• Antidepressant drugs (tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and selective serotonin reuptake inhibitors) are used for relieving myofascial pain in the presence of mood disorders. Several recent studies support the use of amitriptyline in the treatment of myofascial pain. Nortriptyline has also been successful in some studies.[25]

Lidocaine Patches

• A transdermal patch of lidocaine has fewer adverse effects than a needle infiltration. One study showed that transdermal patches decreased pain at TPs. Larger studies are lacking at present.[25]

Botox

• Botulinum toxin targets central and peripheral nerve endings; it blocks the release of ACh from the nerve endings and hence decreases muscle spasm at TPs. Studies on the efficacy of botulinum toxin in reducing myofascial pain have yielded mixed results.[25]

Nonpharmacological Modalities

Exercise/physical therapy/postural regimens

• Regular and consistent physical exercise is an effective strategy for treating myofascial pain. Exercise improves the range of motion, mood, and pain threshold. One of the exercises prescribed for myofascial pain is stretching exercises, which lengthens the myofascial compartments containing the TPs and may prevent the further appearance of other tender areas.[25]
• A repeated load in undesirable positions predisposes to muscle injury and may cause microtrauma, increasing the risk of developing myofascial pain. Hence, postural rehabilitation is another strategy that can be used for this syndrome. [25]
• All nonpharmacological measures that reduce stress (yoga, meditation, behavioral therapy, and acupuncture) help reduce muscle tone, increasing the pain threshold.

Ultrasound

• Ultrasound applies mechanical and thermal energy to the underlying connective tissue, improving circulation, elasticity, and metabolism. A few studies' results show the usefulness of ultrasound in decreasing the pain of active TPs, even though the benefits are temporary.[25]

Dry Needling

• Dry needling involves the insertion of a needle directly into the trigger points, which reduces myofascial pain; this is one of the quickest ways to inactivate TPs. The use of dry needling seems promising in some studies with patients diagnosed with myofascial pain. This technique is thought to act on the cutaneous type A-delta fibers.[25] 

Manipulative Therapy 

• The manipulation of joints in the treatment of TPs has been observed to be effective, but there are no randomized studies to prove its efficacy at present.[26][27]
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Differential Diagnosis

Fibromyalgia can be confused with the presence of myofascial pain; some studies' results highlight an alteration in the connective tissue, possibly involving stem cells that produce adipose tissue. The latter could cause an inflammatory environment and local pain.[28] Fibromyalgia is hardly localized; this is already a good indication of differential diagnosis. Another syndrome that can be poorly framed concerning myofascial syndrome is chronic pelvic pain. The latter is a condition that must be present from 6 months onwards and not necessarily influenced by movements or the presence of menstruation (in women). Understanding if there are organic dysfunctions or only the musculature is involved through ultrasound examinations (the easiest way to make a differential diagnosis) is necessary.[29]

The temporomandibular joint can be involved in myofascial pain, but it can also be a part of a referred pain pattern. If trigger points do not improve after a manual or pharmacological approach, it could be a symptom of cardiac ischemia.[30] Throat or neck pain, if unilateral, could be caused by Eagle syndrome. Pain should improve with tissue treatment; if this does not happen, the causes must be investigated.[31] Inflammations of tendons or inflammations of purely connective formations (fasciitis, tendinopathies, and more) have a particular anatomical area of interest that can be delimited with palpation and do not have more tense areas than other areas of the same tissue.[32] Different causes and pathologies can lead to myofascial pain, where, in some cases, perpetuating factors may exist that have a feed-forward effect on myofascial pain.

There are perpetuating mechanical factors such as:

• Scoliosis
• Limb dysmetria
• Joint hypermobility
• Muscle hypertrophy
• Repetitive microtraumas
• Spondylotic radiculopathy

There are systemic or metabolic perpetuating factors:

• Hypothyroidism
• Iron deficiency
• Vitamin D insufficiency
• Vitamin C deficiency
• Vitamin B12 insufficiency

Psychosocial perpetuating factors:

• Stress
• Anxiety

Other possible perpetuating factors:

• Infectious diseases
• Parasitic diseases (eg, Lyme disease)
• Rheumatic polymyalgia
• Use of drugs such as statins
• Hyperalgesia
• Allodynia

Pertinent Studies and Ongoing Trials

A recent randomized controlled trial evaluated 50 healthy subjects to assess the efficacy of dry needling on soleus myofascial trigger points, aiming to determine if improving the pain threshold could enhance ankle range of motion in individuals with medial tibial stress syndrome. After treatment, pain decreased, but the range of motion did not improve.[33] Another recent randomised, placebo-controlled clinical trial (45 patients) evaluated the effect of using a laser (with different modalities depending on the group) in reducing trigger point pain at the level of the masseter muscle. The study's results highlighted that applying the laser to the painful myofascial areas decreased the pain the participants perceived, and with greater oxygenation to the tissues.[34] A 2025 randomized trial (30 participants) demonstrated that a manual technique of osteopathic origin, strain-counterstrain therapy, on trigger points in the lumbar area causing chronic low back pain, improves pain threshold, functional disability, and lumbar spine mobility.[35]

Treatment Planning

There is currently no curative, pharmacological, instrumental, or manual procedure that is considered the gold standard.

Prognosis

Myofascial pain syndrome usually resolves with consistent treatment and regular follow-up. However, most patients with this condition have had this problem for decades. Long-term morbidity is lowest when an interprofessional team of well-trained clinicians, nurses, and physiotherapists treats such patients and constantly monitors the response to various therapies.

Complications

Myofascial pain syndrome can significantly reduce the quality of life. Long-term pain is usually associated with mood disorders (depression and anxiety). This can decrease the patient's mobility, reduce daily activity, and exacerbate the condition. Undesirable effects of drug therapies may occur if the patient does not follow the clinician's instructions carefully. Similarly, if the approach to physical activity does not follow specific rules set by competent personnel, muscle trauma may occur.