Changes in Anxiety and Depression Are Mediated by Changes in Pain Severity in Patients Undergoing Lower-Extremity Total Joint Arthroplasty.

BACKGROUND: Depression and anxiety are common comorbidities in chronic pain including osteoarthritis patients undergoing total joint arthroplasty (TJA). What is not clear is whether psychiatric comorbidity precedes the manifestation of painful states or represents a reaction to living with chronic pain and associated functional impairment. The objective of this research was to explore whether decreases in depressive and anxiety symptoms after lower-extremity TJA could be due to postsurgical reductions in pain. METHODS: We conducted a secondary analysis of data from 1448 TJA patients enrolled in the Analgesics Outcome Study. Patients completed measures of pain intensity, functional status, and depressive and anxiety symptoms preoperatively and at 3 and 6 months postoperatively. Data were analyzed using a structural equation modeling approach. RESULTS: We found that improvement in pain and physical function from baseline to 6 months postoperatively was associated with improvement in depression and anxiety symptoms. We also found that a change in overall body pain at 3 months after surgery significantly mediated changes in both the depression and anxiety scores at 6 months after surgery even when controlling for age, sex, baseline body pain, education, opioid use, and type of surgery. CONCLUSIONS: Presurgical affective symptoms not only have an effect on change in postsurgical pain, whereby lower preoperative scores on depression and anxiety were associated with lower postsurgical pain, but also postsurgical decreases in pain were associated with lower levels of depression and anxiety after surgery. Taking these points into consideration may prove useful in working toward better outcomes for TJA.

Alternative splicing as a mechanism for regulating 14-3-3 binding: interactions between hD53 (TPD52L1) and 14-3-3 proteins.

D52 (TPD52)-like proteins are coiled-coil motif-bearing proteins first identified through their expression in human breast carcinoma, which have been proposed to represent signalling intermediates and regulators of vesicle trafficking. D52-like gene transcripts are subject to alternative splicing, with sequences encoding a region termed insert 3 being affected in all three D52-like genes. We have now identified a 14-3-3 binding motif within one of two alternatively spliced exons encoding insert 3. As predicted from the distribution of 14-3-3 binding motifs in four hD52-like bait proteins tested, only a hD53 isoform encoding a 14-3-3 binding motif bound both 14-3-3beta and 14-3-3zeta preys in the yeast two-hybrid system. Since D53 proteins carrying 14-3-3 binding motifs are predicted to be widely expressed, polyclonal antisera were derived to specifically detect these isoforms. Using soluble protein extracts from breast carcinoma cell lines, pull-down assays replicated interactions between recombinant 14-3-3beta and 14-3-3zeta isoforms and exogenously expressed hD53, and co-immunoprecipitation analyses demonstrated interactions between endogenous 14-3-3 and both endogenously and exogenously-expressed hD53 protein. Co-expressed hD53 and 14-3-3 proteins were similarly demonstrated to co-localise within the cytoplasm of breast carcinoma cell lines. These results identify 14-3-3 proteins as partners for hD53, and alternative splicing as a mechanism for regulating 14-3-3 binding.