Arthritic pain
Arthritic pain is prevalent and is linked with poorer functional outcomes and lower quality of life compared with a variety of other chronic diseases. A confusing multitude of guidelines and other evidence-based materials are at hand, but the heterogeneity of therapeutic responses can cause frustration and disappointment for patients and health professionals alike.
This review classifies various pain states of arthritis and addresses the degree to which knowledge of underlying mechanisms can be applied to guide the selection of analgesic therapy. While a comprehensive and systematic analysis of individual interventions is not within the scope of the review, evidence for the effectiveness of general strategies is provided. The limitations of existing methods for assessment and management are addressed along with the need for use of integrated care in patients with chronic pain.
Joint pain causes
Inflammation in the joint causes peripheral sensitization increase of sensitivity of nociceptive primary afferent neurons and central sensitization hyperexcitability of nociceptive neurons in the nervous system. The processes of sensitization are thought to be the basis of arthritic pain that appears as spontaneous pain joints at rest and hyperalgesia augmented pain response on noxious stimulation and pain on normally nonpainful stimulation. Sensitization also facilitates efferent neuronal processes through which the nervous system influences the inflammatory process. Peripheral sensitization is generated by the activity of inflammatory mediators like bradykinin, prostaglandins, neuropeptides, and cytokines that activate respective receptors in ratios of nerve fibers.
Further, the induction of receptors such as bradykinin and neurokinin 1 receptors is increased during inflammation. The formation of hyperexcitability of spinal cord neurons is generated by different transmitter receptor systems that make up and modulate synaptic activation of the neurons. Blockade of these receptors prevents and reduces central sensitization. Excitatory neuropeptide substance P and calcitonin gene-related peptide further central sensitization. Central sensitization also is facilitated by mediators that have complex actions with prostaglandin E2. Spinal PGE2 binds to receptors at presynaptic endings of primary afferent neurons thus influencing synaptic release and to receptors on postsynaptic spinal cord neurons.
Classification of pain
Historically, pain has been seen as either nociceptive occurring as a reaction to tissue damage, or neuropathic occurring as a reaction to nerve damage. While this dichotomy has been of some therapeutic benefit, it has helped preserve the Cartesian notion of an immutable fixed pain system accurately conveying information from an area of damage to pain centers in the brain. While this is generally the case following acute injury, it is evident from epidemiological research that in the context of chronic disease a variety of other factors, frequently not related to the musculoskeletal system, act to modulate activity within pain pathways.
Implicit in new classification systems is the concept that acute and chronic pain states are different entities and that functional alterations within the nociceptive system are pertinent in determining the signs and symptoms the somatic disease patient endures. Four discrete pain states are now identified. The first is nociceptive pain, i.e., those reversible signs and symptoms that arise secondary to acute injury and are the stimulation of special pain receptors and associated activity in more central channels. In these cases, symptoms usually follow the inciting stimulus or injury; treatment at the level of a peripheral agent will be effective.
This can be compared with neuroplastic pain that occurs as a result of more chronic tissue damage and is the most common musculoskeletal pain state to link with disease. It occurs as a result of mediators from damaged tissue that act to increase the excitability of the nociceptive pathway and has the effect of causing pain into such normal functions as walking or standing. Treatment is successful if both the initiating injury and those other factors influencing nociceptive activity are attended to.
Third, neuropathic pain tracks nerve injury, as can occur in association with carpal tunnel syndrome or after lumbar disc prolapse. Ectopic expression of ion channels, receptors, and associated phenomena in injured and nearby non-injured neurons are succeeded by regional pain hypersensitivity and sensory disturbance.
There is controversy at present about the etiology of a fourth pain category, idiopathic pain, which includes such medically unexplained diseases as fibromyalgia syndrome, irritable bowel syndrome, and tension headache. In all of these diseases, peripheral pathology is minimal and evidence for and symptoms are believed to reflect disordered pain processing at more central levels.
Arthritic pain
Locally, mediators released from bone or other tissues, or synovium will sensitize articular pain receptors. The clinical counterpart to this peripheral sensitization is that musculoskeletal symptoms will be localized and with relatively close correspondence to mechanical stimuli such as standing or walking. Systemic or local treatment with treatments that aim to reduce inflammatory mediators would be predicted to yield a beneficial effect that is consistent with clinical practice.
In osteoarthritis or rheumatoid arthritis disease, sensitization of the neurons will not only be confined to the periphery. The finding of increased areas of punctate hyperalgesia in RA patients after local injection of capsaicin is by increased excitability of spinal neurons in the disease. Clinically, this translates into exaggerated pain perception at the point of injury and, as a consequence, the onset of pain and tenderness in uninjured tissues surrounding as well as remote from the point of injury.
Descending inhibitory controls and inputs from other somatic structures regulate spinal nociceptive processing in arthritic patients. Both genetics and previous pain incidents are also suspected to modulate activity. It is reasonable to assume, though not yet proven, that external inputs modulate supraspinal or cortical processing of the nociception. In all, the effect is to sensitize pain and increase reporting and behavioral change, including disability.
Hindrance of dependency on peripherally or spinally acting agents alone will be unlikely to achieve success in these patients with more diffuse symptoms resulting from central sensitization. The prostanoid and opioid receptors are constitutively located on cortical tissues, and the drug of choice of appropriate therapeutic drugs is most surely exerting a response at this level. Even so, much more is most often required, often utilizing methods non-pharmacologic in nature, including cognitive behavioral therapy as well as education.
Despite progress in recent decades toward the characterization of key pain processes, more is required to translate this information into better assessment methods and more efficient treatment of pain. Attempts at creating mechanism-based treatments have been equivocal, in part owing to a lack of adequate clinical methods for characterizing some nociceptive processes. Quantitative sensory tests and cortical imaging can be used to quantify central changes associated with articular disease but not for broader clinical use. Practically speaking, the duration of symptoms is relevant: the longer, the more probable a significant central component. Referral pain and pain tenderness off the site of joint disease signal a neuroplastic pain state, and radicular pain is inexorably associated with neuropathic syndromes.