Human Studies

Pain often occurs in parallel with neuropsychiatric disorders. However, the underlying mechanisms and potential causality have not been well studied. We collected the genome-wide association study (GWAS) summary statistics of 26 common pain and neuropsychiatric disorders with sample size ranging from 17,310 to 482,730 in European population. The genetic correlation between pair of pain and neuropsychiatric disorders, as well as the relevant cell types were investigated by linkage disequilibrium (LD) score regression analyses. Then, transcriptome-wide association study (TWAS) was applied to identify the potential shared genes by integrating the gene expression information and GWAS. In addition, Mendelian randomization (MR) analyses were conducted to infer the potential causality between pain and neuropsychiatric disorders. Among the 169 pairwise pain and neuropsychiatric disorders, 55 pairs showed positive correlations (median r = 0.43) and 9 pairs showed negative correlations (median r =  -0.31). Using MR analyses, 26 likely causal associations were identified, including that neuroticism and insomnia were risk factors for most of short-term pain, and multisite chronic pain was risk factor for neuroticism, insomnia, major depressive disorder and attention deficit/hyperactivity disorder, and vice versa. The signals of pain and neuropsychiatric disorders tended to be enriched in the functional regions of cell types from central nervous system (CNS). A total of 19 genes shared in at least one pain and neuropsychiatric disorder pair were identified by TWAS, including AMT, NCOA6, and UNC45A, which involved in glycine degradation, insulin secretion, and cell proliferation, respectively. Our findings provided the evidence of shared genetic structure, causality and potential shared pathogenic mechanisms between pain and neuropsychiatric disorders, and enhanced our understanding of the comorbidities of pain and neuropsychiatric disorders.

Pain and spasms of urinary and biliary tracts are conditions causing poor quality of life. Treatment with analgesic drugs such as non-steroidal anti-inflammatory drugs and modulators of the parasympathetic system are not always tolerated, and often additional therapeutic options are necessary. The present analysis aimed to evaluate the pharmacokinetics and effectiveness of oral and parenteral preparations based on phloroglucinol in reducing pain and spasms associated with renal or biliary colic in phase 3, multicentre, open-label, randomized, comparative studies on clinical effectiveness and safety.

Complex regional pain syndrome (CRPS) is marked by disproportionate pain after trauma. While long-term outcome is crucial to patients, predictors or biomarkers of the course of pain or CRPS symptoms are still lacking. In particular, microRNAs, such as miR-223, decreased in CRPS, have been described only in cross-sectional studies.

Acute anterior disc displacement without reduction (ADDWoR) is characterized by permanent TMJ disc displacement, pain and functional limitations. Occlusal appliances (OA) are among the therapies of choice.

The aim of this study was to investigate the feasibility and effect of a multimodal program for the management of chronic nonspecific neck pain CNSNP with the addition of a 3D adjustable posture corrective orthotic (PCO), with a focus on patient recruitment and retention. This report describes a prospective, randomized controlled pilot study with twenty-four participants with CNSNP and definite 3D postural deviations who were randomly assigned to control and study groups. Both groups received the same multimodal program; additionally, the study group received a 3D PCO to perform mirror image therapy for 20-30 min while the patient was walking on a treadmill 2-3 times per week for 10 weeks. Primary outcomes included feasibility, recruitment, adherence, safety, and sample size calculation. Secondary outcomes included neck pain intensity by numeric pain rating scale (NPRS), neck disability index (NDI), active cervical ROM, and 3D posture parameters of the head in relation to the thoracic region. Measures were assessed at baseline and after 10 weeks of intervention. Overall, 54 participants were screened for eligibility, and 24 (100%) were enrolled for study participation. Three participants (12.5%) were lost to reassessment before finishing 10 weeks of treatment. The between-group mean differences in change scores indicated greater improvements in the study group receiving the new PCO intervention. Using an effect size of 0.797, α > 0.05, β = 80% between-group improvements for NDI identified that 42 participants were required for a full-scale RCT. This pilot study demonstrated the feasibility of recruitment, compliance, and safety for the treatment of CNSNP using a 3D PCO to a multimodal program to positively affect CNSNP management.

In humans, persistent pain often leads to decreased appetite. However, the neural circuits underlying this behaviour remain unclear. Here, we show that a circuit arising from glutamatergic neurons in the anterior cingulate cortex (Glu) projects to glutamatergic neurons in the lateral hypothalamic area (Glu) to blunt food intake in a mouse model of persistent pain. In turn, these Glu neurons project to pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus (POMC), a well-known neuronal population involved in decreasing food intake. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that the Glu → Glu → Arc circuit is activated in mouse models of persistent pain and is accompanied by decreased feeding behaviour in both males and females. Inhibition of this circuit using chemogenetics can alleviate the feeding suppression symptoms. Our study indicates that the Glu → Glu → Arc circuit is involved in driving the suppression of feeding under persistent pain through POMC neuronal activity. This previously unrecognized pathway could be explored as a potential target for pain-associated diseases.

Ehlers-Danlos syndromes are hereditary disorders of connective tissue that are characterized by joint hypermobility, skin hyperextensibility and tissue fragility. The most common subtype is the hypermobile type. In addition to symptoms of small fibre neuropathy (SFN) due to damage to the small peripheral nerve fibres with degeneration of the distal nerve endings, autonomic disorders such as postural tachycardia syndrome are frequently reported features in patients with hypermobile Ehlers-Danlos syndromes (hEDS). To date, the underlying pathophysiological mechanisms are still not completely understood.