18 increased range of axial rotation [58–61]. It has been postulated that the increase in axial rotation and subsequent instability place additional stressors upon the facet joint capsules leading to a molecular response, which results in ﬁbrocartilaginous metaplasia in the capsules of facet joints. Boszczyk et al. [62] reported hypertrophic and ﬁbrocarti- laginous changes in the facet joint capsules of patients who had undergone lumbar fusion for degenerative instability. Chemical model Changes in load distributions can lead to osteoarthrosis, osteophyte formation, and inﬂammation [43]. The cartilage and synovium of facet joints are sources of inﬂammatory cytokines [63]. It has been proposed that painful symptoms may arise not only from mechanical stress discussed pre- viously, but also from the associated inﬂammatory response involving cytokines such as tumor necrosis factor alpha, interleukin-6, interleukin 1 beta [63, 64], oxygen- free radicals such as nitric oxide [65, 66], and inﬂammatory mediators such as prostaglandins [63, 64, 66]. Interestingly, some have suggested that inﬂammatory cytokines origi- nating from inﬂamed synovium may spread to adjacent nerve roots and produce radicular lower extremity symp- toms [63, 67–70]. As with other diarthrodial joints, the cartilage of facet joints may also be sex-hormone sensitive [71]. Estrogen has been associated with chondrodestruction [72], although controversy exists as to its actual role in the development of osteoarthritis [73–76]. However, Ha et al. [77] have found a statistically signiﬁcant association between the increased expression of estrogen receptors on the articular cartilage of facet joints and the severity of facet arthritis. Diagnosis When evaluating a patient with low back pain, the initial differential diagnosis can be broad. While certain symp- toms in a patient’s history may suggest systemic disease, neoplasm, or acute nerve compression, the history cannot always differentiate the speciﬁc etiology of low back pain. Up to 85% of patients with low back pain do not obtain a speciﬁc diagnosis even after work up [78–80]. The diag- nosis of facet joint-mediated pain is no exception. The history, physical examination and imaging studies cannot consistently identify facet joint pain [14, 81–86]. A prospective statistical study by Jackson et al. [85], which included 390 patients and examined 127 variables, was not able to identify clinical facet joint syndromes or ﬁnd predictors of who may respond better to facet joint injections. Furthermore, although pain referral patterns Curr Rev Musculoskelet Med (2009) 2:15–24 have been identiﬁed, investigators have been unable to correlate speciﬁc patterns with individual levels [87, 88]. Mooney and Robertson [39] injected hypertonic saline into the facet joints of both symptomatic and asymptomatic patients and noted pain referral patterns that were indis- tinguishable from pain patterns associated with other etiologies (Fig. 3). While changes in facet joint architecture can be detected with imaging studies, correlation between radiologic ﬁnd- ings and symptoms has also proven unreliable [82]. Although Laslett and colleagues reported clinical guide- lines that may be helpful in predicting patient response to facet joint blocks, the study results have not been replicated thus far. At this time, accurately diagnosing facet joint- mediated pain by noninvasive techniques remains a chal- lenge [89]. Currently, the principal method of diagnosing facet joint-mediated pain as the cause of low back pain is through the use of controlled local anesthetic blocks of either the medial branches or the facet joint itself. Both of these techniques have been shown to be equally efﬁcacious [10, 82, 88, 90–92]. These procedures employ the use of local anesthetics with varying durations of action. For example, a short acting local anesthetic such as lidocaine is injected in either the intra-articular facet joint or upon the medial branches. The patient is observed for pain relief that is consistent with the duration of action of the local anes- thetic. Days to weeks after the initial diagnostic block, a second block is then employed with a local anesthetic that has a different duration of action such as bupivacaine. Fig. 3 Pain referral patterns for asymptomatic (normal) and symp- tomatic (abnormal) patients. From Mooney V. Robertson J. The facet syndrome. Clinical Orthopaedics & Related Research. (115):149–56, 1976 Mar–Apr. Reprinted with permission