The biochemical origin of pain: The origin of all pain is inflammation and the inflammatory response. Part 2 of 3 – Inflammatory profile of pain syndromes

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Summary

Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby briefly describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome/reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and serve as a foundation to be built upon by other researchers and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: the origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing a re-classification and treatment of pain syndromes based upon their inflammatory profile.

Section snippets

Prior theories

The prior theories do not contain any unifying Law of Pain. Each disease entity e.g., fibromyalgia, complex regional pain syndrome/reflex sympathetic dystrophy (RSD/CRPS), carpal tunnel syndrome, rheumatoid arthritis and ankylosing spondylitis is considered distinct from the other entities and is classified in terms of symptomatology, structural pathology, genetic markers, presence of autoantibodies etc. The prior theories assign a different mechanism to nociceptive and neuropathic pain, a

Arthritis

Arthritis means inflammation of the joints. People of all ages including children and young adults can develop arthritis. The symptoms are intermittent pain, swelling, redness and stiffness in the joints. There are many different types of arthritis, some of which are rheumatoid arthritis, osteoarthritis, infectious arthritis and spondylitis. In rheumatoid arthritis, and other autoimmune diseases like systemic lupus erythematosus (SLE), the joints are destroyed by the immune system.

Back and neck pain

Back and neck pain most commonly result from injury to the muscle, disk, nerve, ligament or facet joints with subsequent inflammation and spasm. Degeneration of the disks or joints produces the same symptoms and occurs subsequent to aging, previous injury or excessive mechanical stresses that this region is subjected to because of its proximity to the sacrum in the lower back.

Herniation of disk tissue (nucleus pulposus) produces a profound inflammatory reaction with release of inflammatory

Fibromyalgia

Fibromyalgia is a chronic, painful musculoskeletal disorder characterized by widespread pain, pressure hyperalgesia, morning stiffness, sleep disturbances including restless leg syndrome, mood disturbances, and fatigue. Other syndromes commonly associated with fibromyalgia include irritable bowel syndrome, interstitial cystitis, migraine headaches, temporomandibular joint dysfunction, dysequilibrium including nerve mediated hypotension, sicca syndrome, and growth hormone deficiency.

Interstitial cystitis

Interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency. This sterile painful bladder disorder is associated with a defective glycosaminoglycan bladder mucosal layer and an increased number of activated mast cells. Mast cells are ubiquitous cells derived from the bone marrow and are responsible for allergic reactions as they release numerous vasodilatory, nociceptive and pro-inflammatory mediators in response to

Migraine

Migraine headache is caused by activation of trigeminal sensory fibers by known and unknown migraine triggers. There is subsequent release of inflammatory mediators from the trigeminal nerve. This leads to distention of the large meningeal blood vessels in the skull and brain and the development of a central sensitization within the trigeminal nucleus caudalis (TNC). Genetic abnormalities may be responsible for altering the response threshold to migraine specific trigger factors in the brain of

Nerve (neuropathic) pain syndromes

Nociceptive pain is mediated by receptors on A-delta and C nerve fibers, which are located in skin, bone, connective tissue, muscle and viscera. These receptors serve a biologically useful role at localizing noxious chemical, thermal and mechanical stimuli. Nociceptive pain can be somatic or visceral in nature. Somatic pain tends to be well-localized, constant pain that is described as sharp, aching, throbbing, or gnawing. Visceral pain, on the other hand, tends to be vague in distribution,

Reflex sympathetic dystrophy/complex regional pain syndrome (RSD/CRPS)

Reflex Sympathetic Dystrophy (RSD) syndrome also called Complex Regional Pain Syndrome (CRPS) has been recognized clinically for many years. It is most often initiated by trauma to a nerve, neural plexus, or soft tissue. Diagnostic criteria are the presence of regional pain and other sensory changes following a painful injury. The pain is associated with changes in skin color, skin temperature, abnormal sweating, tissue swelling. With time, tissue atrophy may occur as well as involuntary

Sports injuries/bursitis/tendonitis/rotator cuff tears

Inflammation of the bursa is known as bursitis. A bursa is a small sac containing fluid that lies between bone and other moving structures such as muscles, skin or tendons. The bursa allows smooth gliding between these structures. A bursa allows a tendon or muscle to move smoothly over a bone by acting as an anti-friction device and shielding the structures from rubbing against bones. Bursae are found in the knee, elbow, shoulder and wrist. If the tendons become thickened and bumpy from

Stress

During times of stress or inflammation Substance P, IL-1 and IL-6 levels are increased. IL-6, in turn, can induce release of corticotrophin-releasing factor [50], [51], which results in elevated systemic levels of corticosteroids.

Vulvar vestibulitis syndrome (VVS)/vulvodynia

Vulvar vestibulitis syndrome is a major subtype of vulvodynia. It is a constellation of symptoms and findings involving and limited to the vulvar vestibule that consists of (1) severe pain on vestibular touch to attempted vaginal entry, (2) tenderness to pressure localized within the vulvar vestibule, and (3) physical findings confined to vulvar erythema of various degrees. The syndrome has been seen in association with subclinical human papillomavirus, chronic recurrent candidiasis, chronic

Conclusion

In accordance with our Law of Pain, the origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals,

Conflicts of interest

There is no conflict of interest.

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