Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus ( TP53 ) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.
Catastrophizing has been discussed as a cognitive precursor to the emergence of posttraumatic stress disorder (PTSD) symptoms following the experience of stressful events. Implicit in cognitive models of PTSD is that treatment-related reductions in catastrophizing should yield reductions in PTSD symptoms. The tenability of this prediction has yet to be tested. The present study investigated the sequential relation between changes in a specific form of catastrophizing-symptom catastrophizing-and changes in PTSD symptom severity in a sample of 73 work-disabled individuals enrolled in a 10-week behavioral activation intervention. Measures of symptom catastrophizing and PTSD symptom severity were completed at pre-, mid-, and posttreatment assessment points. Cross-sectional analyses of pretreatment data revealed that symptom catastrophizing accounted for significant variance in PTSD symptom severity, β = .40, p < .001, sr = .28 (medium effect size), even when controlling for known correlates of symptom catastrophizing, such as pain and depression. Significant reductions in symptom catastrophizing and PTSD symptoms were observed during treatment, with large effect sizes, ds = 1.42 and 0.94, respectively, ps < .001. Cross-lagged analyses revealed that early change in symptom catastrophizing predicted later change in PTSD symptoms; early changes in PTSD symptom severity did not predict later change in symptom catastrophizing. These findings are consistent with the conceptual models that posit a causal relation between catastrophizing and PTSD symptom severity. The clinical implications of the findings are discussed. Posttraumatic stress disorder (PTSD) is a debilitating mental health condition that can emerge after exposure to traumatic events; it is characterized by symptom clusters that include reexperiencing symptoms, negative cognitions, distressing emotions, avoidance, and hyperarousal (American Psychiatric Association [APA], 2013).
Objectives: Pain catastrophizing has been shown to be correlated with measures of mental health problems such as depression and post-traumatic stress disorder (PTSD). However, the clinical implications of findings reported to date remain unclear. To date, no study has been conducted to determine meaningful cut-scores on measures of catastrophizing indicative of the heightened risk of mental health comorbidity. One objective of the present study was to identify the cut-score on the Pain Catastrophizing Scale (PCS) indicative of the heightened risk of the comorbidity of depression and PTSD. A second objective was to determine whether mental health comorbidity mediated the relationship between catastrophizing and occupational disability. Materials and Methods: The sample consisted of 143 individuals with whiplash injuries. Pain severity, pain catastrophizing, depression, and post-traumatic stress symptoms were assessed after admission to a rehabilitation program. Mental health comorbidity was operationally defined as obtaining a score above the clinical threshold on measures of depressive and/or post-traumatic stress symptom severity. Results: A receiver operating characteristic curve analysis revealed that a PCS score of 22 best distinguished between participants with and without mental health comorbidity. Results also revealed that mental health comorbidity mediated the relationship between catastrophizing and occupational disability. Discussion: The findings suggest that a score of ≥22 on the PCS should alert clinicians to the possibility that patients might also be experiencing clinically significant symptoms of depression or PTSD. Greater attention to the detection and treatment of mental health conditions associated with whiplash injury might contribute to more positive recovery outcomes.
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