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
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.
References (53)
- et al.
Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis
Pain
(1988) - et al.
Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways
Pain
(2000) - et al.
Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis
J Urol
(2000) - et al.
High affinity binding sites for [3H] substance P in urinary bladders of cats with interstitial cystitis
J Urol
(1998) - et al.
Interstitial cystitis: increased sympathetic innervation and related neuropeptide synthesis
J Urol
(1992) - et al.
Potentiation by bradykinin and substance P of purinergic neurotransmission in urinary bladder
J Urol
(1996) - et al.
Preliminary study on urinary cytokine levels in interstitial cystitis: does intravesical bacille Calmette-Guerin treat interstitial cystitis by altering the immune profile in the bladder?
Urology
(1999) - et al.
Release of substance P, calcitonin gene-related peptide and prostaglandin E2 from rat dura mater encephali following electrical and chemical stimulation in vitro
Neuroscience
(1999) - et al.
Possible role of inflammatory mediators in tactile hypersensitivity in rat models of mononeuropathy
Pain
(2000) - et al.
Increases in the concentration of brain derived neurotrophic factor in the lumbar spinal dorsal horn are associated with pain behavior following chronic constriction injury in rats
Neurosci Lett
(2002)