**2. Osteoarthritis**

Osteoarthritis (OA) is a complex musculoskeletal condition that effects people of all ages but particularly those over 55 years [167–171]. According to the Osteoarthritis Research Society International (OARSI) OA can be defined as;

*"…a disorder involving movable joints characterized by cell stress and extracellular matrix degradation initiated by micro- and macro-injury that activates maladaptive repair responses including pro-inflammatory pathways of innate immunity. The disease manifests first as a molecular derangement (abnormal joint tissue metabolism) followed by anatomic, and/or physiologic derangements (characterized by cartilage degradation, bone remodelling, osteophyte formation, joint inflammation and loss of normal joint function), that can culminate in illness" [172].*

OA is a pro-inflammatory branch of rheumatic disease that effects synovial joints progressively and is caused by the failure of joint tissues to repair following damage. This damage may have been caused by stresses due to an abnormality in the articular cartilage, subchondral bone, ligaments, menisci, periarticular muscles, peripheral nerves or synovium [173, 174]. While cartilage degradation is the traditionally structural trademark of OA, it is generally considered a whole joint disease with many other morphological features [175–178]. For example, an osteoarthritic joint may exhibit sclerosis in the subchondral bone, osteophytes [179], local inflammation such as synovitis [177, 178, 180, 181] and bone marrow lesions [182]. Failure of normal biological repair processes that leads to breakdown of cartilage and bone [183] is characterised by symptoms of pain, stiffness, functional disability [184] that can lead to negative impacts on fatigue, mood, sleep, overall quality of life [185, 186].

OA confers a number of modifiable and non-modifiable risk factors [174, 187]. Non-modifiable risk factors include previous joint injury [188, 189], malalignment and other mechanical factors [175, 176, 190–193], age [189], sex [194], ethnicity [195] and genetic predisposition [196–198]. Modifiable risk factors include obesity [181, 189, 199–202], metabolic syndrome [181, 203–206], in particular diabetes mellitus [207–209] and habitual diet [187, 210].

**169**

*Nutraceutical Alternatives to Pharmaceutical Analgesics in Osteoarthritis*

highest contributor to years lived with disability [159].

The condition is one of the most common causes of chronic pain and the most common cause of joint pain [211] with conservative estimates suggesting that there are approximately 500 million suffers worldwide [167, 212]. OA affects ~13% of all over 50's (~7% in all ages; [213]) and has no cure [214–218] while being the 11th

Chronic inflammatory-associated pain can have multiple mechanisms [219–223] and can stem from mechanical stress or central sensitization either concurrently and/or vary in their influences over time [224]. Pain derived from OA can generally be characterised into two common clinical forms of pain, intermittent but severe/ intense and persistent pain or aching [225]. These pain experiences can come from neuropathic and nociceptive process, as discussed above. The prevalence of neuropathic pain features at the knee in OA patients ranges from 19% to 29% [221, 226, 227]. However, recent studies of peripheral and central nerve sensitization [228], as well as nerve ending damage and regrowth [229, 230] have shown that neuropathic pain contributes substantially to the condition. This central sensitization is prominent in those that experience a high level of pain that is not proportional to radiographic evidence of structural damage [219] and contributes more to the pain experienced in women with symptomatic OA, compared to men [231]. Generally, a higher degree of central sensitization or neuropathic pain is associated with high pain intensity and a greater chance of developing chronic pain following joint replacement [232, 233]. The remaining 70-80% of knee OA pain appears to be nociceptive in nature, thus OA can be described as a chronic mild to moderate nociceptive dominant pain condition [24, 234] and should be considered as such

The diversity of pathophysiological maladaptation in OA effected joints and the low associations of these changes with pain, suggests doubt over the link between joint structural condition and the experience of pain. This is evident from the poor relationship between radiographic images and reported pain. A recent systematic review showed that the prevalence of knee pain in patients with radiographic knee OA ranged from 15% to 81% [235]. However, some studies reported associations between the structural damage of the joint (cartilage and bone) and pain [236] but at higher levels of X-ray derived pathology (Kellgren/Lawrence grade; [237]). Nonetheless, pain may still indicate a level of disease activity. In a number of studies looking more specifically at joint morphological characterises, OA pain has been associated with the rate of medial cartilage loss (also after adjustment for radiographic OA stage; [238]), osteophytes [239], more erosive OA compared to non-erosive OA [240] and changes of bone marrow lesions and synovitis [182]. These data show the complexity of the disease-pain nexus and suggests that the disease should, in the first instance (i.e. mild OA), be treated generally with lifestyle and nutritional intervention rather that pharmaceuticals that target specific pathological pathways (**Figure 1**) [241]. Regardless, pharmaceutical therapies remain the main treatment

OA is a progressive condition with no cure where opioids, acetaminophen and non-steroidal anti-inflammatory drugs (NSAID) are the traditional, nonlifestyle, approach for early management. However, as eluded to earlier, these pharmaceutical treatments are often accompanied with significant side effects. For example, NSAIDs are the traditional approach for early clinical management

*DOI: http://dx.doi.org/10.5772/intechopen.95919*

**2.1 Pain and osteoarthritis**

with regards to initial treatment [24].

for such conditions [242].

**2.2 Pharmaceutical analgesics in osteoarthritis**

The condition is one of the most common causes of chronic pain and the most common cause of joint pain [211] with conservative estimates suggesting that there are approximately 500 million suffers worldwide [167, 212]. OA affects ~13% of all over 50's (~7% in all ages; [213]) and has no cure [214–218] while being the 11th highest contributor to years lived with disability [159].
