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Global Regenerative Trade

BPB MEDICA®

PAIN MANAGEMENT

WHAT IS REGENERATIVE MEDICINE?

Regenerative Medicine encompasses many medical fields – Orthopedics and Spine Surgery, Sports Medicine, Gynecology, Urology, Oncology, Dermatology, Plastic surgery, Vascular Surgery, Cardiac surgery, etc.

Regenerative Medicine is the branch of medicine that develops methods to regrow, repair or replace damaged or diseased cells, organs or tissues. Regenerative medicine includes the generation and use of therapeutic stem cells, tissue engineering and the production of artificial organs. It uses autologous blood, bone marrow or adipose components to stimulate the body’s own repair processes. A common source for regenerative cells and growth factors are bone marrow aspirate concentrate (BMAC), platelet rich plasma (obtained from one’s own blood) and adipose derived stem cells.

PATHOLOGY

Chronic Pain

Chronic pain is pain that persists or recurs for > 3 months, persists > 1 month after resolution of an acutetissue injury, or accompanies a nonhealing lesion. Causes include chronic disorders (eg, cancer, arthritis,diabetes), injuries (eg, herniated disk, torn ligament), and many primary pain disorders (eg, neuropathicpain, fibromyalgia, chronic headache). Various drugs and psychologic treatments are used.

Unresolved, long-lasting disorders (eg, cancer, rheumatoid arthritis, herniated disk) that produce ongoing nociceptivestimuli may account completely for chronic pain. Alternatively, injury, even mild injury, may lead to long-lasting changes(sensitization) in the nervous system—from peripheral receptors to the cerebral cortex—that may produce persistent painin the absence of ongoing nociceptive stimuli. With sensitization, discomfort that is due to a nearly resolved disorder and might otherwise be perceived as mild or trivial is instead perceived as significant pain.
Psychologic factors may also amplify persistent pain. Thus, chronic pain commonly appears out of proportion toidentifiable physical processes. In some cases (eg, chronic back pain after injury), the original precipitant of pain is obvious; in others (eg, chronicheadache, atypical facial pain, chronic abdominal pain ), the precipitant is remote or occult.
In most patients, physical processes are undeniably involved in sustaining chronic pain and are sometimes the main factor(eg, in cancer pain ). However, even in these patients, psychologic factors usually also play a role. Patients who have to continually prove that they are sick to obtain medical care, insurance coverage, or work relief may unconsciously reinforce their pain perceptions, particularly when litigation is involved. This response differs from malingering, which is conscious exaggeration of symptoms for secondary gain (eg, time off, disability payments).
Various factors in the patient’s environment (eg, family members, friends) may reinforce behaviors that perpetuate chronic pain.
Chronic pain can lead to or exacerbate psychologic problems (eg, depression, anxiety). Distinguishing psychologic causefrom effect is often difficult.

 

Symptoms and Signs

Chronic pain often leads to vegetative signs (eg, lassitude, sleep disturbance, decreased appetite, loss of taste for food,weight loss, diminished libido, constipation), which develop gradually. Constant, unremitting pain may lead to depressionand anxiety and interfere with almost all activities. Patients may become inactive, withdraw socially, and becomepreoccupied with physical health. Psychologic and social impairment may be severe, causing virtual lack of function.
Some patients, particularly those without a clear-cut ongoing cause, have a history of failed medical and surgicaltreatments, multiple (and duplicative) diagnostic tests, use of many drugs (sometimes involving abuse or addiction), andinappropriate use of health care.

Diagnosis

Evaluation for physical cause initially and if symptoms change a physical cause of chronic pain should always be sought—even if a prominent psychologic contribution to the pain is likely. Physical processes associated with the pain should be evaluated appropriately and characterized. However, once a full evaluation is done, repeating tests in the absence of new findings is not useful. The best approach is often to stop testing and focus on relieving pain and restoring function.
The effect of pain on the patient’s life should be evaluated; evaluation by an occupational therapist may be necessary. Formal psychiatric evaluation should be considered if a coexisting psychiatric disorder (eg, major depression , an anxiety disorder) is suspected as cause or effect. Pain relief and functional improvement are unlikely if concomitant psychiatric disorders are not managed.

Key Points

  • Nociceptive stimuli, sensitization of the nervous system, and psychologic factors can contribute to chronic pain.
  • Distinguishing between the psychologic causes and effects of chronic pain may be difficult.
  • Seek a physical cause even if psychologic factors are prominent, and always evaluate the effect of pain on the patient’s life.
  • Treat poorly controlled pain with multimodal therapy (eg, appropriate physical, psychologic, behavioral, and interventional treatments; drugs).

Muscle injuries

Muscle injuries can occur through direct causes (e.g., lacerations, contusions, and strains) or indirect causes (e.g., ischemia, neurological dysfunction and hereditary myopathies). They are the most frequent cause of physical incapacity in sports practice. Currently, the management of muscle injury is rest, ice, compression and elevation. Anti-inflammatory medications, rehabilitation exercise programs, electrotherapeutic modalities, and hyperbaric oxygen therapy are used as well.

Muscle strain, muscle pull, or even a muscle tear refers to damage to a muscle or its attaching tendons. You can put undue pressure on muscles during the course of normal daily activities, with sudden heavy lifting, during sports, or while performing work tasks. Muscle damage can be in the form of tearing (part or all) of the muscle fibers and the tendons attached to the muscle. The tearing of the muscle can also damage small blood vessels, causing local bleeding, or bruising, and pain caused by irritation of the nerve endings in the area.

Symptoms of muscle strain include:

  • Swelling, bruising, or redness due to the injury
  • Pain at rest
  • Pain when the specific muscle or the joint in relation to that muscle is used
  • Weakness of the muscle or tendons
  • Inability to use the muscle at all

When to Seek Medical Care
If you have a significant muscle injury (or if home remedies bring no relief in 24 hours), call your doctor. If you hear a “popping” sound with the injury, cannot walk, or there is significant swelling, pain, fever, or open cuts, you should be examined in a hospital’s emergency department.

 

 

Bone injuries

Bone injuries represent a challenging problem in traumatology. They entail a sustained increase in hospitalization, increased risk of complication, and associated increase in expense. The gold standard treatment for bone defect is the use of autologous bone graft. However, it is associated with significant donor site morbidity and limited by the amount available for grafting, which has resulted in efforts to obtain biocompatible bone substitutes.

Osteochondral lesions

Osteochondral lesions represent an important type of bone injury as they result in significant health problems and are a leading cause of disability worldwide. Specifically, osteochondral lesions are defects on cartilage surfaces and are often related to traumatic origin (joint dislocation, ligament tear, meniscus tear, and fall/impact). The biomechanical properties of hyaline cartilage are easily compromised by traumatic injuries and cartilage has poor healing ability. Thereby, the lesion may be irreparable and lead to chronic symptoms and early osteoarthritis (OA). Currently, treatments involve surgical procedures (chondroplasty, microfracture and spongialisation) or transplantation with an autograft or allograft. When the cartilage is severely damaged, a surgical procedure is necessary to replace the damaged tissue with a prosthetic device. Despite all these advances in orthopedic field, the treatment for cartilage injuries remains challenging.

Joint pain (called arthralgia) may or may not be related to joint inflammation (called arthritis). Arthritis may cause swelling as well as pain. A wide variety of disorders can cause arthritis, including inflammatory arthritis (such as rheumatoid arthritis), osteoarthritis, infectious arthritis, gout and related disorders, autoimmune disorders (such as systemic lupus erythematosus) and vasculitic disorders (such as immunoglobulin A–associated vasculitis), osteonecrosis, and injuries affecting the part of a bone inside a joint. Arthritic pain can be new (acute, for example, when caused by infections, injuries, or gout), or longstanding (chronic, for example, when caused by rheumatoid arthritis or osteoarthritis). Pain resulting from arthritis is typically worse when the joint is moved but usually is present even when the joint is not being moved. Sometimes pain originating in structures near the joint, such as ligaments, tendons, and bursae, seems to be coming from the joint.

Tendon and ligament pain

Tendon and ligament pain is often less intense than bone pain. It is often described as “sharp” and is worse when the affected tendon or ligament is stretched or moved and is usually relieved by rest. Common causes of tendon pain include tendinitis, tenosynovitis, lateral epicondylitis or medial epicondylitis, and tendon injuries. The most common cause of ligament pain is injury (sprains).

Bursae pain

can be caused by trauma, overuse, gout, or infection. Bursae are small fluid-filled sacs that provide a protective cushion around joints. Usually, pain is worse with movement involving the bursa and is relieved by rest. The affected bursa may swell.

Some musculoskeletal disorders cause pain by compressing nerves. These conditions include the tunnel syndromes (for example, carpal tunnel syndrome, cubital tunnel syndrome, and tarsal tunnel syndrome). The pain tends to radiate along the path supplied by the nerve and may be burning. It is usually accompanied by tingling, numbness, or both.

Tendinitis

is inflammation of a tendon. Tenosynovitis is tendinitis accompanied by inflammation of the protective covering around the tendon (tendon sheath).

  • The cause is not always known.
  • Tendons are painful, particularly when moved, and sometimes swollen.
  • The diagnosis is usually based on symptoms and results of a physical examination.
  • Using a splint, applying heat or cold, and taking nonsteroidal anti-inflammatory drugs can help.
  • Tendons are fibrous cords of tough tissue that connect muscles to bones. Some tendons are surrounded by tendon sheaths. (See also Introduction to Muscle, Bursa, and Tendon Disorders.)

The cause of tendinitis is often unknown. Tendinitis usually occurs during middle or older age, as the tendons weaken and become more susceptible to injury and inflammation. (Weakening of the tendon, called tendinopathy, usually results from many small tears that occur over time. Affected tendons may gradually or suddenly tear completely.) Tendinitis also occurs in younger people who exercise vigorously (who may develop rotator cuff tendinitis—see also Rotator Cuff Injury/Subacromial Bursitis) and in people who do repetitive tasks.

Certain tendons are particularly susceptible to inflammation:

  • Tendons of the shoulder (rotator cuff): Inflammation of these tendons is the most common cause of shoulder pain (see Rotator Cuff Injury/Subacromial Bursitis).
  • The two tendons that extend the thumb away from the hand:
  • Inflammation of these tendons is called De Quervain syndrome.
  • The flexor tendons that clench the fingers: Inflammation causes these tendons to get caught in their sheaths, resulting in a popping feeling (trigger finger).
  • The tendon above the biceps muscle in the upper arm (bicipital tendon): Pain can occur when the elbow is bent or the arm is elevated or rotated.
  • Achilles tendon in the heel: Pain occurs at the back of the heel (Achilles tendinitis).
  • A tendon that runs over the side of the knee (popliteus tendon):
  • Pain occurs on the outer part of the knee.
  •  Tendons near the hip bone (trochanter): Because bursae may also be affected, the term trochanteric bursitis is often used to include inflammation of these tendons.

Some antibiotics, such as fluoroquinolones, may increase the risk of tendinopathy (weakening of the tendon) and rupture of the tendon.

Certain joint diseases, such as rheumatoid arthritis, systemic sclerosis, gout, diabetes, and reactive arthritis (previously called Reiter syndrome), can increase the risk of tenosynovitis. In people with gonorrhea, especially women, gonococcal bacteria can cause tenosynovitis, usually affecting the tissues of the shoulders, wrists, fingers, hips, ankles, or feet.

Rotator Cuff Tendinitis


Tendinitis may develop in the tendons of the muscles that help move, rotate, and hold the shoulder in place (rotator cuff).
Rotator cuff tendinitis (see Rotator Cuff Injury/Subacromial Bursitis) is the most common cause of shoulder pain. It causes pain when the arm is raised (particularly between 40° and 120°) or when people dress. People often have pain during the night, especially when they lie on the affected arm.

Symptoms of rotator cuff tendinitis may occur suddenly and be severe, especially after physical activity, or they may develop more slowly and be milder.

Fibromyalgia

Fibromyalgia may cause pain in the muscles, tendons, or ligaments. The pain is usually felt or causes tenderness in multiple locations and may be difficult to describe precisely but is usually not coming from the joints. Affected people usually have other symptoms, such as fatigue and poor sleep.

  • Fibromyalgia is characterized by poor sleep, fatigue, mental cloudiness, and widespread aching and stiffness in soft tissues, including muscles, tendons, and ligaments.
  • Poor sleep, stress, strains, injury, and possibly certain personality characteristics may increase the risk of fibromyalgia.
  • Pain is widespread, and certain parts of the body are tender to touch.

The diagnosis of fibromyalgia is based on established criteria and symptoms such as widespread pain and fatigue.
Improving sleep, taking pain relievers, exercising, applying heat, and getting massages may help.
Fibromyalgia used to be called fibrositis or fibromyositis syndrome. But because inflammation (indicated by the “itis” suffix) is not present, the suffix was dropped, and the name became fibromyalgia.

Fibromyalgia is common. It is about 7 times more common among women. It usually occurs in young or middle-aged women but can also occur in men, children, and adolescents.

Fibromyalgia is not dangerous or life threatening. Nonetheless, persistent symptoms can be very disruptive.

Causes
People with fibromyalgia seem to have a heightened sensitivity to pain. That is, areas in their brain that process pain interpret painful sensations as being more intense than seems to occur in people who do not have fibromyalgia. Usually, the cause of fibromyalgia is unknown. However, certain conditions may contribute to developing the disorder. They include poor sleep, repetitive strains, or an injury. Mental stress may also contribute. However, stress per se may not be the problem. Rather it may be how people react to the stress.

Some affected people may also have a connective tissue disorder, such as rheumatoid arthritis or systemic lupus erythematosus (lupus). Sometimes a viral or other infection (such as Lyme disease) or traumatic event can trigger fibromyalgia.

Symptoms
Most people feel a general achiness, stiffness, and pain. Symptoms can occur throughout the body. Any soft tissue (muscles, tendons, and ligaments) may be affected. But soft tissue of the neck, upper shoulders, chest, rib cage, lower back, thighs, arms, and areas around certain joints are especially likely to be painful. Less often, the lower legs, hands, and feet are painful and stiff. Symptoms may occur periodically (in flare-ups) or most of the time (chronically).

Pain may be intense. It usually worsens with fatigue, straining, or overuse. Specific areas of muscle are often tender when firm fingertip pressure is applied. These areas are called tender points. During flare-ups, muscles become tight, or spasms may occur.

Many affected people do not sleep well and feel anxious, and sometimes depressed or tense. Fatigue is common, as are mental problems such as difficulty concentrating and a general feeling of mental cloudiness. Many affected people are perfectionists, or have a type A personality. They may also have migraines or tension headaches, interstitial cystitis (a type of bladder inflammation that causes pain when urinating), and irritable bowel syndrome (with some combination of constipation, diarrhea, abdominal discomfort, and bloating). People may have pins-and-needles sensations, typically affecting both sides of the body.

The same conditions that may contribute to the development of fibromyalgia can make symptoms worse. They include emotional stress, poor sleep, injury, and fatigue. Fearing that symptoms represent a serious illness can also make symptoms worse. Having a doctor, family member, or friend imply that the disorder is “all in the head” can worsen symptoms as well. People may also feel frustrated because they are often told that they “look good” even though they are feeling unwell.

Diagnosis
Established criteria
A doctor’s examination and testing to rule out other disorders
Doctors suspect fibromyalgia in people who have the following:

  • Generalized pain and tenderness
  • Negative laboratory test results despite widespread symptoms
  • Fatigue as a main symptom

Doctors consider the diagnosis of fibromyalgia in people who have had widespread pain for at least 3 months, particularly when it is accompanied by various other physical symptoms such as fatigue. Pain is considered widespread when people have pain in the left and right side of the body, above and below the waist, and in the top of the spine, wall of the chest or middle of the spine, or low back.

In the past, doctors based the diagnosis in part on the presence of tenderness at some of 18 designated tender points. Now, however, the number of tender points is not considered as important as the presence of typical symptoms, especially widespread pain.

Doctors want to be sure that another disorder (such as hypothyroidism, polymyalgia rheumatica, or another muscle disorder) is not causing the symptoms, often by doing blood tests. But no test can confirm the diagnosis of fibromyalgia.

Fibromyalgia may not be easily recognized in people who also have rheumatoid arthritis or lupus because these disorders cause some similar symptoms, such as fatigue and pain in the muscles, joints, or both.

SUPPORTING EVIDENCE

PAIN MANAGEMENT

PUBLICATIONS

Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study.
Kumar H, Ha DH, Lee EJ, Park JH, Shim JH, Ahn TK, Kim KT, Ropper AE, Sohn S, Kim CH, Thakor DK, Lee SH, Han IB.
Stem Cell Res Ther. 2017 Nov 15;8(1):262. doi: 10.1186/s13287-017-0710-3.
 
Low back pain treated with disc decompression and autologous micro-fragmented adipose tissue: a case report
P. Grossi, S. Giarratana, S. Cernei, S. Grossi, F.M. Doniselli
CellR4 2016; 4 (1): e1772
 
Intervertebral Disc Repair Using Adipose Tissue-Derived Stem and Regenerative Cells: Experiments in a Canine Model
Ganey, Timothy, PhD; Hutton, William C., DSc; Moseley, Timothy, PhD; Hedrick, Mark, MD; Meisel, Hans-Joerg, MD, PhD
Spine: October 1, 2009 – Volume 34 – Issue 21 – p 2297-2304
doi: 10.1097/BRS.0b013e3181a54157
 
Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration
Giovanni Marfia, Rolando Campanella, Stefania Elena Navone, Ileana Zucca, Alessandro Scotti, Matteo Figini, Clara Di Vito, Giulio Alessandri, Laura Riboni and Eugenio Parati
Marfia et al. Arthritis Research & Therapy 2014, 16:457
http://arthritis-research.com/content/16/6/457
 
PRP and BMAC for Musculoskeletal Conditions via Biomaterial Carriers

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862231/ 

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THE VIVOSTAT® SYSTEM

The uniqueness of the Vivostat® system is a novel patented biotechnological process that enables reliable and reproducible preparation of autologous Fibrin Sealant or Platelet Rich Fibrin (PRF®) without using cryoprecipitation and without the need for a separate thrombin component.

THE FULLY AUTOMATED VIVOSTAT® SYSTEM CONSISTS OF THREE COMPONENTS: