Osteoarthritis is a chronic, degenerative disease associated with joint pain and loss of joint function. Evaluate the evidence to discuss in physiological terms why osteoarthritis results in chronic pain.

Osteoarthritis is a chronic, degenerative disease associated with joint pain and loss of joint function. Evaluate the evidence to discuss in physiological terms why osteoarthritis results in chronic pain.

 

Introduction

            The most common form of arthritis is osteoarthritis (2004), also called degenerative joint disease. The latter name is especially appropriate because this form of arthritis which appears with advancing years, is not primarily an inflammatory process as are most of the others but is due to degenerative changes in the cartilaginous portions of joints and in bones.

It is characterized by degenerative loss of articular cartilage that lines and lubricates the joints, subchondral bony sclerosis, and cartilage and bone proliferation at the joint margins with subsequent osteophyte formation. The ends of the bones within the joint are thus left unprotected, leading to pain and stiffness.

It is also called “wear-and-tear” arthritis. Over the years, there is a softening, fraying, and eventual breakdown of the cartilage. As the disease progresses, the exposed bone thickens and extra bone tissue, called bone spurs, grows around the margins of the eroded cartilage. The bone spurs protrude into the joint cavity. Patients complain of stiffness on arising that lessens with activity, and the affected joints may make a crunching noise (crepitus) when moved. The joints most commonly affected are those of the fingers, the cervical and lumbar joints of the spine, and the large, weight-bearing joints of the lower limbs (2004). Clearly, an important factor is wear and tear. Hence it is more apt to appear in weight-bearing joints of persons who are overweight, or in joints which have been damaged by some other form of arthritis, injuries or congenital defects.

            The course of osteoarthritis is usually slow, but it is rarely crippling. In most cases, its symptoms are controllable with a mild analgesic such as aspirin, moderate activity to maintain joint mobility, and rest when the joint becomes very painful ( 2004). The pattern of spread is additive; however, only one joint may be involved. It is slowly progressive, with temporary exacerbations after periods of overuse ( 2003).

Few data are available on the incidence of osteoarthritis because of the problems of defining it and how to determine its onset. It afflicts millions around the world. However, only a small fraction of this number is significantly incapacitated. The prevalence of osteoarthritis increases indefinitely with age, because the condition is not reversible. Men are affected more often than women among those 45 years and below, whereas women are affected more frequently among those 55 years and above (2003).

 

Etiology and Incidence

            The cause is unknown, but genetic, metabolic, endocrine, biochemical, and hydrolytic enzyme factors have been suggested. Abnormal biochemical stresses may lead to chondrocyte damage and proteolytic enzyme release resulting in articular cartilage degeneration. Osteoarthritis may also be secondary to chronic trauma or underlying joint disease.

            Aging is the single most important factor in the development of osteoarthritis. Virtually all persons over the age of 50 have at least traces of this condition. However, it should be pointed out that some aged individuals have little evidence of it, whereas other, relatively young, persons may develop widely disseminated incapacitating arthritis (1998).

            Osteoarthritis is an insidious disease that is usually first noticed as a slight stiffness or decreased mobility in the affected joints. It is generally believed that faulty posture, obesity and occupational stress all predispose to the development of the condition. As the patient ages, the pain, stiffness and limited motion become more marked. There are no constitutional signs of an inflammatory disease, and the joints rarely have local evidence of inflammation. Usually, the disorder is slowly progressive over the remaining years of life ( 1998).

A small number of the cases of osteoarthritis are due to mutations in the COL1A genes. In various types of arthritis, proteoglycans may act as autoantigens, thus contributing to the pathologic features of these conditions. The amount of chondroitin sulfate in cartilage diminishes with age, whereas the amounts of keratin sulfate and hyaluronic acid increase. These changes may contribute to the development of osteoarthritis (2000).

 

Pathology

            Osteoarthritis is a non-inflammatory disease of joints characterized by deterioration and erosion of articular cartilage and by the formation of new bone at the articular margins sometimes producing so-called spurs (1998).  Osteoarthritis may occur as a monoarticular or polyarticular involvement. The large joints of the body and the spine are principally affected. The principal anatomic alterations are degeneration of the cartilage rather than inflammation of the synovia.

            With the destruction of the articular cartilage, the underlying bone is exposed. The subarticular bone becomes thickened because of either compression or new bone formation. The marrow spaces in this region are often filled with fibrous tissue and small islands of cartilage that are either driven in by traumatic injury or are formed from the endosteum or connective tissue in the marrow spaces. At the same time, small islands of cartilage, which later become ossified, project above the surface of the articular cartilage, usually about its margins, to produce the characteristic bony spurs of osteoarthritis. When large spurs project from opposing bones, they may come into contact with each other to cause pain and limitation of motion (1998).

Grossly, the cartilage becomes yellow-white and soft. Fibrillation, pitting, and ulcers are found in superficial cartilage layers. Marginal osteophytes form. Histologically, fissuring and fibrillation are prominent. Degenerating chondrocytes and reactive clonal chondrocyte proliferation are present. Subchondral bone is thickened; cyst formation occurs. Synovitis is mild to moderate.

 

Symptoms and Signs

            Onset is usually gradual and localized to one or a few joints. The main symptoms are pain aggravated by motion or the pressure of weight, stiffness after inactivity, and limitation of motion (1998). Pain is greatest after exercise. Stiffness or fibrosis commonly follows inactivity but is usually of short duration. Joint motion is limited in severe cases. Tenderness and crepitus or grating are present. Joint enlargement is present due to proliferative chondrocyte reactions in cartilage and bone. Synovial effusion may occur. Deformity and subluxation are late findings. Constitutional symptoms and extra-articular manifestations are absent.

            The specific clinical picture varies with the joints involved. Enlargement of the terminal interphalangeal joints, called Heberden’s nodes (Koestler & Myers, 2002), is common; painful gelatinous cysts may also be present. Women are affected by this form of disease ten times as often as men. Similar deformities may develop at the proximal interphalangeal joints (Bouchard’s nodes). Disease of the first carpometacarpal joint causes pain and limitation of use of the thumb. Knee involvement produces pain, swelling and instability. Osteoarthritis of the hip causes local pain and a limp (Snell, 2000. Spinal osteoarthritis is common; severe degenerative changes may occur without symptoms. Osteoarthritic changes are most common in the midcervical and lower lumbar areas of maximal spinal motion. Compression of contiguous neurologic structures by large osteophytes or a degenerated disc may cause severe radicular pain. Vascular insufficiency syndromes may follow compromise of cervical vascular structures.

 

Physiology of Pain

            Many, if not most, ailments of the body cause pain. The sense organs for pain are the naked nerve endings found in almost every tissue of the body. Pain has been classified into two major types: fast pain and slow pain. Fast pain is felt within about 0.1 second after a pain stimulus is applied, whereas slow pain begins only after 1 second or more and then increases slowly over many seconds and sometimes even minutes (2000).

Fast pain is also described in many alternative names, such as sharp pain, pricking pain, electric pain and acute pain. Acute pain is generally the result of a specific injury and can be clearly explained in terms of where we feel it in the body. This type of pain is felt when a needle is stuck into the skin, when the skin is cut with a knife, or when the skin is acutely burned. It is also felt when the pain is subjected to electric shock. Fast, sharp pain is not felt in most deeper tissues of the body.

            Slow pain also goes by multiple additional names, such as slow burning pain, aching pain, throbbing pain, nauseous pain, and chronic pain. This type of pain is usually associated with tissue destruction. It can lead to prolonged, unbearable suffering. It can occur both in skin and in almost any deep tissue or organ. Chronic pain is the other type of pain which is so called because it can continue for months or years and even trigger additional health problems such as depression and lead to lifestyle changes in attempts to remedy the situation. It is pain that has not responded to traditional medical interventions, or one for which a medical “cure” is not available (2002).

            Osteoarthritis or joint inflammation is a type of slow or chronic pain. Pain of musculoskeletal origin – as the case of osteoarthritis – largely results from overstimulation of nerve endings. The nerve endings may be stimulated by inflammatory substances that are produced by damaged cells and released from the surrounding capillary network. The resulting sensitization results to a lower pain threshold so that even a mild stimulus like pressure and joint motion are interpreted as pain.

The pain receptors, also called nociceptors, in the skin and other tissues are all free nerve endings. They are widespread in the superficial layers of the skin as well as in certain internal tissues, such as the joint surfaces. Most other deep tissues are not extensively supplied with pain endings but are sparsely supplied; nevertheless, any widespread tissue damage can still summate to cause the slow-chronic-aching type of pain in most of these areas (2000).

            Pain can be elicited by multiple types of stimuli. They are classified as mechanical, thermal, and chemical pain stimuli. Slow pain can be elicited by all three types. Some chemicals that excite the chemical type of pain are bradykinin, serotonin, histamine, potassium ions, acids, acetylcholine, and proteolytic enzymes. In addition, prostaglandins and substance P enhance the sensitivity of pain endings but do not directly excite them. The chemical substances are especially important in stimulating the slow, chronic type of pain that occurs after tissue injury.

            In contrast to most other sensory receptors of the body, the pain receptors adapt very little and sometimes not at all. In fact, under some conditions, the excitation of the pain fibers becomes progressively greater, especially so for slow-aching-nauseous pain, as the pain stimulus continues. This increase in sensitivity of pain receptors is called hyperalgesia (2000).

            One can readily understand the importance of this failure of pain receptors to adapt, because it allows the pain to keep the person apprised of a tissue-damaging stimulus as long as it persists (2000).

            The average person first begins to perceive pain when the skin is heated above 45°C. This is also the temperature at which the tissues begin to be damaged by heat; indeed, the tissues are eventually destroyed if the temperature remains above this level indefinitely. The intensity of pain is also closely correlated with the rate of tissue damage from other causes as well as from heat – bacterial infection, tissue ischemia, tissue contusion, and so forth.

            Even though all pain receptors are free nerve endings, these endings use two separate pathways for transmitting pain signals into the central nervous system. The two pathways mainly correspond to the two types of pain, a fast-sharp pain pathway and a slow-chronic pain pathway (2000).

            The slow-chronic type of pain is mostly elicited by chemical types of pain stimuli but also at times by persisting mechanical or thermal stimuli (2000). Pain impulses are transmitted to the central nervous system by two fiber systems. The nociceptor system responsible for the pain felt in osteoarthritis consists of unmyelinated (2001) C fibers 0.4-1.2 µm in diameter. This slow-chronic pain is transmitted in the peripheral nerves to the spinal cord by the type C fibers at velocities between 0.5 and 2 m/sec. These roots are found in the lateral division of the dorsal roots and are often called dorsal root C fibers (2001). A separate peripheral pain type A delta fiber also carries the fast-sharp pain stimuli.

            Because of this dual system of pain innervation, a sudden painful stimulus often gives a double pain sensation: a fast-sharp pain that is transmitted to the brain by the A fiber pathway followed a second or so later by a slow pain that is transmitted by the C fiber pathway.

            The sharp pain apprises the person rapidly of a damaging influence and, therefore, plays an important role in making the person react immediately to remove himself or herself from the stimulus. The slow pain tends to become greater over time. This sensation eventually gives one the intolerable suffering of long-continued pain and makes the person continue to try to relieve the cause of pain.

            On entering the spinal cord from the dorsal spinal roots, the pain fibers terminate on neurons in the dorsal horns. Here again, there are two systems for processing the pain signals on their way to the brain (2001).

            On entering the spinal cord, the pain signals take two pathways to the brain, through (1) the neospinothalamic tract and (2) the paleospinothalamic tract. The neospinothalamic tract is the pain pathway for fast or acute pain (2000).

            The paleospinothalamic pathway is an older system and transmits pain mainly from the peripheral slow-chronic type C pain fibers, although it does transmit some signals from type A fibers as well. In this pathway, the peripheral fibers terminate almost entirely in laminae II and III of the dorsal horns, which together are called substantia gelatinosa (2000).  The synaptic junctions between the peripheral nociceptor fibers and the dorsal horn cells in the spinal cord are the sites of considerable plasticity. For this reason, the dorsal horn has been called a gate, where pain impulses can be “gated” or modified ( 2001).

            Most of the signals then pass through one or more additional short fiber neurons within the dorsal horns themselves before entering mainly lamina V, also in the dorsal horn. Here the last neuron in the series gives rise to long axons that mostly join the fibers from the fast pain pathway, passing first through the anterior commissure to the opposite side of the cord, then upward to the brain in the anterolateral pathway.

            Research experiments suggest that the type C pain fiber terminals entering the spinal cord secrete both glutamate transmitter and substance P transmitter. The glutamate transmitter acts instantaneously and lasts for only a few milliseconds. Conversely, substance P is released much more slowly, building up in concentration over a period of seconds or even minutes (2000).

            The slow-chronic paleospinothalamic pathway terminates widely in the brain stem. Only one tenth to one fourth of the fibers pass all the way to the thalamus. Instead, they terminate principally in one of the three areas: (1) the reticular nuclei of the medulla, pons, and mesencephalon; (2) the tectal area of the mesencephalon deep to the superior and inferior colliculi; or (3) the periaqueductal gray region surrounding the aqueduct of Sylvius (2000).

            These lower regions of the brain appear to be important in the appreciation of the suffering types of pain because animals with their brains sectioned above the mesencephalon to block any pain signals reaching the cerebrum still evince undeniable evidence of suffering when any part of the body is traumatized.

            From the brain stem pain areas, multiple short-fiber neurons relay pain signals upward into the intralaminar and ventrolateral nuclei of the thalamus and into certain portions of the hypothalamus and other adjacent regions of the basal brain (2000).

            Localization of pain transmitted in the paleospinothalamic pathway is poor. For instance, the slow-chronic type of pain can usually be localized only to a major part of the body, such as to one arm or leg but not to a specific point on the arm or leg. This is in keeping with the multisynaptic, diffuse connectivity of this pathway. It explains why patients often have serious difficulty in localizing the source of some chronic types of pain.

A simplified diagram of the pain pathway in osteoarthritis is provided below:

 

 

Complete removal of the somatic sensory areas of the cerebral cortex does not destroy an animal’s ability to perceive pain. Therefore, it is likely that pain impulses entering the brain stem reticular formation, the thalamus, and other lower centers can cause conscious perception of pain. This does not mean that the cerebral cortex has nothing to do with normal pain appreciation; indeed, electrical stimulation of the cortical somatosensory areas causes a human being to perceive mild pain in about 3 per cant of the pints stimulated. It is believed that the cortex plays an important role in interpreting the quality of pain, even though pain perception might be principally a function of lower centers (2000).

            It has been suggested that pain is chemically mediated and that stimuli which provoke it have in common the ability to liberate a chemical agent that stimulates the nerve endings. The chemical agent might be Adenosine Triphosphate (ATP). ATP opens ligand-gated channels on sensory neurons via P2X receptors (2001).

 

Analysis and discussion

            Volumes of printed articles and books already stress the pain that is felt in osteoarthritis. However, there is only limited information regarding the physiologic pathway of the pain in osteoarthritis. Literature regarding the specific events that occur inside the body in the transmission of pain in osteoarthritis is very limited. Most articles or journals offer only a brief overview on the pain felt but do not dig deeper into the pain pathway itself. Most information regarding the pathway of pain is found in physiology books. Many websites offer information on pain. But it deals mostly with the cause of pain, its description and its management. There are though a small number of websites that provide sufficient understanding on the pathway of pain.

 provided a very detailed pathway of pain which results from tissue destruction – which is the case for osteoarthritis. Although the discussion in their book is not specific to the pain in osteoarthritis alone, it generally applies to pain that is felt from tissue destruction or that which is felt from any deep tissue or organ.  also provided that specific chemical agents can trigger the pain in osteoarthritis that will set off the pain transmission through the pathway.

Although the literature regarding the pain pathway of osteoarthritis is very limited, the books and other sources used for this research offered relevant and useful information in understanding the pain pathway. The information offered in the books is already accepted and held true in the entire medical field.

           

Summarization and Conclusion

The chronic (persistent) pain experienced by individuals with osteoarthritis may be caused by the ongoing tissue damage. Osteoarthritis dries out the protective and lubricating properties of the cartilage which in turn starts to soften and crack.  As a result, abnormal bone hardening can occur in the body’s effort to repair itself, fluid can build up in pockets around the affected bone, and as the cartilage wears away, the bony spurs rub together causing pain. Repetitive activation of nociceptors can sensitize the paleospinothalamic neural pathway and produce the pain felt in osteoarthritis.

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