Nature Neuroscience, Published online: 01 October 2019; doi:10.1038/s41593-019-0522-0
Publisher Correction: A neural circuit for comorbid depressive symptoms in chronic painChronic primary pain (CPP) is one of seven diagnostic groups within the proposed classification of chronic pain in ICD‐11. Our aims were to apply the proposed ICD‐11 criteria in a large cohort of chronic pain patients participating in the Chronic Pain Self‐Management Program (CPSMP) and further investigate whether participants with CPP differed from participants with chronic secondary pain (CSP) regarding health, health expenditure, and the effect of participating in the CPSMP.
A secondary analysis of a randomized, controlled trial on the effect of the CPSMP. Four examiners categorized participants’ pain according to ICD‐11 using register‐based medical diagnoses and patients’ self‐reported symptoms. Afterwards, differences between CPP and CSP were examined.
Out of 394 participants, 312 were successfully classified into CPP (n=164) or CSP (n=148) whereas 76 had a mixed pain condition. Participants with CPP were younger, more likely to be women, and had a longer pain duration compared to participants with CSP. Participants with CPP reported worse health‐related quality of life on the SF‐36 Mental Component Summary and subscales of vitality, social functioning, and bodily pain. Participants with CSP had more physical comorbidities and higher total health expenditure. None of the groups benefitted from the CPSMP.
We successfully applied the new classification of chronic pain in ICD‐11 on the basis of ICD‐10 medical diagnoses and symptom self‐report. Participants with CPP differed significantly from participants with CSP on baseline characteristics, self‐reported health measures, and total health expenditure. The CPSMP was not effective in any of the groups.
Tobacco smoking is associated with adverse health effects, and its relationship to pain is complex. The longitudinal effect of smoking on patients attending a tertiary pain management center is not well established. Using the Collaborative Health Outcomes Information Registry of patients attending the Stanford Pain Management Center from 2013 to 2017, we conducted a propensity-weighted analysis to determine independent effects of smoking on patients with chronic pain. We adjusted for covariates including age, sex, body mass index, depression and anxiety history, ethnicity, alcohol use, marital status, disability, and education. We compared smokers and nonsmokers on pain intensity, physical function, sleep, and psychological and mood variables using self-reported NIH PROMIS outcomes. We also conducted a linear mixed-model analysis to determine effect of smoking over time. A total of 12,368 patients completed the CHOIR questionnaire of which 8584 patients had complete data for propensity analysis. Smokers at time of pain consultation reported significantly worse pain intensities, pain interference, pain behaviors, physical functioning, fatigue, sleep-related impairment, sleep disturbance, anger, emotional support, depression, and anxiety symptoms than nonsmokers (all P < 0.001). In mixed-model analysis, smokers tended to have worse pain interference, fatigue, sleep-related impairment, anger, emotional support, and depression over time compared with nonsmokers. Patients with chronic pain who smoke have worse pain, functional, sleep, and psychological and mood outcomes compared with nonsmokers. Smoking also has prognostic importance for poor recovery and improvement over time. Further research is needed on tailored therapies to assist people with chronic pain who smoke and to determine an optimal strategy to facilitate smoking cessation.
Mounting evidence suggests that the spinal dorsal horn (SDH) contains multiple subpopulations of inhibitory interneurons that play distinct roles in somatosensory processing, as exemplified by the importance of spinal dynorphin-expressing neurons for the suppression of mechanical pain and chemical itch. Although it is clear that GABAergic transmission in the SDH undergoes significant alterations during early postnatal development, little is known about the maturation of discrete inhibitory “microcircuits” within the region. As a result, the goal of this study was to elucidate the gene expression profile of spinal dynorphin (pDyn)-lineage neurons throughout life. We isolated nuclear RNA specifically from pDyn-lineage SDH interneurons at postnatal days 7, 21, and 80 using the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) technique, followed by RNA-seq analysis. Over 650 genes were ≥2-fold enriched in adult pDyn nuclei compared with non-pDyn spinal cord nuclei, including targets with known relevance to pain such as galanin (Gal), prepronociceptin (Pnoc), and nitric oxide synthase 1 (Nos1). In addition, the gene encoding a membrane-bound guanylate cyclase, Gucy2d, was identified as a novel and highly selective marker of the pDyn population within the SDH. Differential gene expression analysis comparing pDyn nuclei across the 3 ages revealed sets of genes that were significantly upregulated (such as Cartpt, encoding cocaine- and amphetamine-regulated transcript peptide) or downregulated (including Npbwr1, encoding the receptor for neuropeptides B/W) during postnatal development. Collectively, these results provide new insight into the potential molecular mechanisms underlying the known age-dependent changes in spinal nociceptive processing and pain sensitivity.