On “Pain treatments for patients with osteoarthritis…” Lluch Girbés E, Nijs J, Torres-Cueco R, López Cubas C. Phys Ther. 2013;93:842–851.

Lluch Girbés et al¹ present an interesting proposition on symptom treatment while acknowledging that they have little idea of the etiology of osteoarthritis (OA) and its resultant pain. It is encouraging to note their brief reference to a “chronic inflammatory response,” citing 1997² and 2005³ articles. They contend that the pain might be related more to “neuroplastic changes in the nervous system than to an inflammatory condition of the joint” based on a rodent model study.¹ Their use of the term “might” implies use of a proposed model or paradigm to describe the observations. The danger of such use is the formation and entrenching of informational cascades,⁴ seen too often in history. When you add to this the acknowledgment of ignorance surrounding OA, we are at risk of simply describing a phenomenon frequently seen in pain conditions being applied to OA. At best, we find ourselves treating symptoms without an understanding of the current evidence-based pathophysiology behind or associated with the symptoms.

Lluch Girbés et al note the tissue modification and destruction as an historical agent of this pain. They make the surprising assertion that OA is “an incurable pathology.” They are not alone, as Kumar et al in Robbins Basic Pathology say much the same.^5(p818) There is mounting evidence that OA is not an inevitable consequence of aging.⁶ The relevant question is: At what point of tissue degradation does OA become “incurable”? Aside from the brief mention of “chronic inflammatory response,” there is no other mention of the nature and character of this chronic inflammation in the article by Lluch Girbés et al.

The literature is replete with current research on chronic systemic inflammation observed in many chronic disease processes, including OA. According to recent science, this type of chronic inflammation is different from what has traditionally been understood⁷; subsequently, attempts to name this unique chronic systemic inflammation are appearing in the literature. Until science agrees on the appropriate term, we will continue to see it variously termed “chronic inflammation,”⁸ “chronic systemic inflammation,”⁸ “metaflammation,”⁸ “para-inflammation,”⁹ “pseudo-inflammation,”¹⁰ “neuroinflammation,”¹⁰ and “inflammaging.”⁷

Lluch Girbés et al do not mention a cause for the chronic inflammatory response being related to advanced glycation end-products (AGEs) and their receptors (RAGEs)¹¹ that generate this destructive chronic inflammation in slow turnover tissue as is found in bone, tendons, and cartilage.^12–15 Oxidative stress also is noted in OA.¹⁶ The AGE-related biomarkers are associated with whole-body cartilage degradation.¹⁷ RAGEs stimulate chondrocyte and synoviocyte activity and are observed in cartilage degradation.¹¹ Lluch Girbés et al, along with others,¹⁸ note that cartilage attempts to regenerate, especially in initial stages of OA.

The statement that “chronic pain in people with OA is related more to neuroplastic changes in the nervous system than to an inflammatory condition of the joint” is troubling. This seeming statement of fact is based on a rodent study that induced “a histopathology with ‘similarities’ to osteoarthrtis.”¹⁹ Current evidence, linking OA with evidence that cytokines or prostaglandins increase the production of matrix metalloproteinases by chondrocytes, has stimulated the study engendered from this effect from metaflammation.⁷

It is noted that the article by Lluch Girbés and colleagues focuses primarily on OA and a central sensitization paradigm for the resultant pain. Getting to the latest science behind the process will have an impact on this analysis. Inflammatory markers have been noted in OA.²⁰ Euteneuer et al²¹ noted “for the first time” the presence of inflammatory markers (tumor necrosis factor alpha, [TNF-α], interleukin-1 receptor antagonist [IL-1ra], interleukin-6 [IL-6], and neopterin) accompanying inhabitation of tone in the dorsal horn that supports central sensitization. With a connection between chronic inflammation and central sensitization combined with the presence of the inflammation in the destruction of slow turn over tissue, a plausible paradigm for the associated pain could be that chronic inflammation causes or accompanies cartilage degradation²² and the resultant pain. At this point, we would be identifying the origin of the pathology and resultant pain and allowing the incorporation of novel evidence-based intervention strategies that could incorporate central sensitization into its model.

If we state the obvious (ie, the OA pain is from inflammation^7,23 and tissue destruction^23,24) and follow the current evidence from AGEs and RAGEs, we can propose a paradigm for prevention, treatment, and recovery (PTR) from osteoarthritis that is steeped in current science with evidence for yielding diminished pain.²⁵ There also is little to no recognition of the role of myokines²⁶ and adipokines^22,27,28 in the pain associated with exercise in chronic inflammatory conditions, including OA.²⁹ This is a fertile area of research now in its infancy and one of keen interest to physical therapists. Increased pain and stiffness are positively associated with elevated inflammatory markers.²⁰ Lifestyle behavior change that would include exercise and nutrition can be a “first-line” strategy for preventing, controlling, and potentially reversing the disease process.²⁵

The point is that with science answering or at least offering evidence-based information on origins of pathology such as OA, it will allow us to construct and test paradigms for PTR with more specificity. Science is busy identifying the causes of many chronic disease conditions such as OA. Although the evidence is still quite incomplete, there is a mountain of evidence to focus on as far as the pathophysiology of these chronic diseases. As the evidence continues to roll in monthly, we will refine and confirm our new evidence-based models to the point where we will be addressing these basic malfunctions of normal physiology with science as opposed to symptom-based models open to too much conjecture.

• © 2013 American Physical Therapy Association