Monoclonal Antibodies For Chronic Pain: A Practical Review Of Mechanisms And Clinical Applications

Context Monoclonal antibodies are being investigated for chronic pain to overcome the shortcomings of current treatment options. Objective To provide a practical overview of monoclonal antibodies in clinical development for use in chronic pain conditions, with a focus on mechanisms of action and relevance to specific classes. Methods Qualitative review using a systematic strategy to search for randomized controlled trials, systematic and nonsystematic (narrative) reviews, observational studies, nonclinical studies, and case reports for inclusion. Studies were identified via relevant search terms using an electronic search of MEDLINE via PubMed (1990 to June 2017) in addition to hand-searching reference lists of retrieved systematic and nonsystematic reviews. Results Monoclonal antibodies targeting nerve growth factor, calcitonin gene-related peptide pathways, various ion channels, tumor necrosis factor-α, and epidermal growth factor receptor are in different stages of development. Mechanisms of action are dependent on specific signaling pathways, which commonly involve those related to peripheral neurogenic inflammation. In clinical studies, there has been a mixed response to different monoclonal antibodies in several chronic pain conditions, including migraine, neuropathic pain conditions (e.g., diabetic peripheral neuropathy), osteoarthritis, chronic back pain, ankylosing spondylitis, and cancer. Adverse events observed to date have generally been mild, although further studies are needed to ensure safety of monoclonal antibodies in early stages of development, especially where there is an overlap with non-pain-related pathways. High acquisition cost remains another treatment limitation. Conclusion Monoclonal antibodies for chronic pain have the potential to overcome the limitations of current treatment options, but strategies to ensure their appropriate use need to be determined

Critical values of facet joint angulation and tropism in the development of lumbar degenerative spondylolisthesis: an international, large-scale multicenter study by the AOSpine Asia Pacific Research Collaboration Consortium

Study Design An international, multicenter cross-sectional image-based study performed in 33 institutions in the Asia Pacific region. Objective The study addressed the role of facet joint angulation and tropism in relation to L4-L5 degenerative spondylolisthesis (DS). Methods The study included 349 patients (63% females; mean age: 61.8 years) with single-level DS; 82 had no L4-L5 DS (group A) and 267 had L4-L5 DS (group B). Axial computed tomography and magnetic resonance imaging were utilized to assess facet joint angulations and tropism (i.e., asymmetry between facet joint angulations) between groups. Results There was a statistically significant difference between group A (left mean: 46.1 degrees; right mean: 48.2 degrees) and group B (left mean: 55.4 degrees; right mean: 57.5 degrees) in relation to bilateral L4-L5 facet joint angulations (p < 0.001). The mean bilateral angulation difference was 7.4 and 9.6 degrees in groups A and B, respectively (p = 0.025). A critical value of 58 degrees or greater significantly increased the likelihood of DS if unilateral (adjusted OR: 2.5; 95% CI: 1.2 to 5.5; p = 0.021) or bilateral facets (adjusted OR: 5.9; 95% CI: 2.7 to 13.2; p < 0.001) were involved. Facet joint tropism was found to be relevant between 16 and 24 degrees angulation difference (adjusted OR: 5.6; 95% CI: 1.2 to 26.1; p = 0.027). Conclusions In one of the largest studies assessing facet joint orientation in patients with DS, greater sagittal facet joint angulation was associated with L4-L5 DS, with a critical value of 58 degrees or greater increasing the likelihood of the condition for unilateral and bilateral facet joint involvement. Specific facet joint tropism categories were noted to be associated with DS

Is lumbar facet joint tropism developmental or secondary to degeneration? An international, large-scale multicenter study by the AOSpine Asia Pacific Research Collaboration Consortium

Background: Facet joint tropism is asymmetry in orientation of the bilateral facets. Some studies have shown that tropism may increase the risk of disc degeneration and herniations, as well as degenerative spondylolisthesis (DS). It remains controversial whether tropism is a pre-existing developmental phenomena or secondary to progressive remodeling of the joint structure due to degenerative changes. As such, the following study addressed the occurrence of tropism of the lower lumbar spine (i.e. L3-S1) in a degenerative spondylolisthesis patient model. Methods: An international, multi-center cross-sectional study that consisted of 349 patients with single level DS recruited from 33 spine institutes in the Asia Pacific region was performed. Axial MRI/CT from L3-S1 were utilized to assess left and right facet joint sagittal angulation in relation to the coronal plane. The angulation difference between the bilateral facets was obtained. Tropism was noted if there was 8° or greater angulation difference between the facet joints. Tropism was noted at levels of DS and compared to immediate adjacent and distal non-DS levels, if applicable, to the index level. Age, sex-type and body mass index (BMI) were also noted and assessed in relation to tropism. Results: Of the 349 subjects, there were 63.0 % females, the mean age was 61.8 years and the mean BMI was 25.6 kg/m. Overall, 9.7, 76.5 and 13.8 % had L3-L4, L4-L5 and L5-S1 DS, respectively. Tropism was present in 47.1, 50.6 and 31.3 % of L3-L4, L4-L5 and L5-S1 of levels with DS, respectively. Tropism involved 33.3 to 50.0 % and 33.3 to 58.8 % of the immediate adjacent and most distal non-DS levels from the DS level, respectively. Patient demographics were not found to be significantly related to tropism at any level (p > 0.05). Conclusions: To the authors' knowledge, this is one of the largest studies conducted, in particular in an Asian population, addressing facet joint tropism. Although levels with DS were noted to have tropism, immediate adjacent and distal levels with no DS also exhibited tropism, and were not related to age and other patient demographics. This study suggests that facet joint tropism or perhaps subsets of facet joint orientation may have a pre-disposed orientation that may be developmental in origin or a combination with secondary changes due to degenerative/slip effects. The presence of tropism should be noted in all imaging assessments, which may have implications in treatment decision-making, prognostication of disease progression, and predictive modeling. Having a deeper understanding of such concepts may further elaborate on the precision phenotyping of the facets and their role in more personalized spine care. Additional prospective and controlled studies are needed to further validate the findings