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Background: Chronic pain involves communication between neural and immune systems. Recent data suggest localization of glial (brain immune cells) activation to the sensorimotor regions of the brain cortex (S1/M1) in chronic low back pain (LBP). As glia perform diverse functions that impact neural function, activation might contribute to sensorimotor changes, particularly in LBP maintained by increased nervous system sensitivity (i.e., nociplastic pain). This preliminary proof‐of‐concept study aimed to: (i) compare evidence of neuroinflammatory activation in S1/M1 between individuals with and without LBP (and between nociceptive and nociplastic LBP phenotypes), and (ii) evaluate relationships between neuroinflammatory activation and sensorimotor function. Methods: Simultaneous PET‐fMRI measured neuroinflammatory activation in functionally defined S1/M1 in pain‐free individuals (n = 8) and individuals with chronic LBP (n = 9; nociceptive: n = 4, nociplastic: n = 5). Regions of S1/M1 related to the back were identified using fMRI during motor tasks and thermal stimuli. Sensorimotor measures included single and paired‐pulse transcranial magnetic stimulation (TMS) and quantitative sensory testing (QST). Sleep, depression, disability and pain questionnaires were administered. Results: Neuroinflammatory activation was greater in the lower back cortical representation of S1/M1 of the nociplastic LBP group than both nociceptive LBP and pain‐free groups. Neuroinflammatory activation in S1/M1 was positively correlated with sensitivity to hot (r = 0.52) and cold (r = 0.55) pain stimuli, poor sleep, depression, disability and BMI, and negatively correlated with intracortical facilitation (r = −0.41). Conclusion: This preliminary proof‐of‐concept study suggests that neuroinflammation in back regions of S1/M1 in individuals with nociplastic LBP could plausibly explain some characteristic features of this LBP phenotype. Significance Statement: Neuroinflammatory activation localized to sensorimotor areas of the brain in individuals with nociplastic pain might contribute to changes in sensory and motor function and aspects of central sensitization. If cause–effect relationships are established in longitudinal studies, this may direct development of therapies that target neuroinflammatory activation. [ABSTRACT FROM AUTHOR]

Background. Aging is associated with greater risk for many illnesses and the prospect of multiple, concurrent disease states. Chronic pain is also very common in advanced age, and there is likely to be a relationship with comorbid burden, but few studies have examined this issue. This study tests the hypothesis that comorbid burden is associated with greater levels of self-reported pain and associated disturbance in mood and function. Methods. Psychometric and medical data were collected from 562 patients (mean age = 76.3 years) attending a geriatric pain clinic. The number of categories endorsed on the Cumulative Illness Rating Scale (CIRS) score was used to measure accumulated comorbid burden. These groups were tested for differences in the severity of self-reported pain. The predictive capacity of comorbid burden for explaining variance in mood disturbance and functional disability was assessed after controlling for any differences in age and severity of pain. Results. Over 50% of the sample had three or more comorbid problems. Groups with greater levels of comorbidity scored higher on the Present Pain Intensity Index, the sensory and affective subscales of the McGill Pain Questionnaire. Multiple regression analysis showed that the CIRS score explained a significant proportion of the variance in scores on the Geriatric Depression Scale (4.1%), Human Activities Profile (4.8%), and the physical domain of the Sickness Impact Profile (5.9%). Conclusion. Greater levels of comorbidity are associated with reports of more severe pain, more depressive symptoms, reduced activity levels, and higher physical impact from pain.

Zebrafish is a simple vertebrate that has many attributes that make it ideal for the study of developmental genetics. One feature that has been lacking in this model system is the ability to disable specifically targeted genes. Recently, double-stranded RNA has been used to silence gene expression in the nematode Caenorhabditis elegans. We have found that expression of the green fluorescent protein (GFP) from a microinjected plasmid vector can be suppressed in zebrafish embryos by the coinjection of a double-stranded RNA that is specifically targeted to GFP. To determine that double-stranded RNA can attenuate endogenous gene expression, single-cell zebrafish embryos were injected with double-stranded RNA specifically targeted to Zf-T and Pax6.1. We found that microinjection of double-stranded Zf-T RNA resulted in a high incidence of a phenotype similar to that of ntl. Furthermore, Zf-T gene expression could not be detected by in situ hybridization and the message was decreased by 75% by semiquantitative RT-PCR in 12-h embryos that had been injected with the double-stranded RNA. Expression of the zebrafish genes sonic hedgehog and floating head was altered in the embryos microinjected with the Zf-T double-stranded RNA in a manner that is remarkably similar to the zebrafish no-tail mutant. Microinjection of double-stranded RNA targeted to Pax6.1 was associated with depressed expression of Pax6.1 and resulted in absent or greatly reduced eye and forebrain development, similar to the phenotype seen in mouse mutants. Simultaneous injection of Pax6.1 and Zf-T resulted in embryos lacking notochords, eyes, and brain structures.