Human Studies

Chronic postsurgical pain (CPSP) is a debilitating chronic pain condition that has a substantial effect on quality of life. CPSP shows considerable clinical overlap with different chronic peripheral pain syndromes, suggesting a shared aetiology. This study aims to assess the genetic overlap between different chronic pain syndromes and CPSP, providing relevant biological context for potential chronic pain markers of CPSP. To analyse the genetic overlap between CPSP and chronic peripheral pain syndromes, recent GWAS studies were combined for polygenic risk scores (PRS) analysis, using a cohort of CPSP patients as starting point. Biological contextualisation of genetic marker, overlap between CPSP and chronic pain syndromes, was assessed through Gene Ontology (GO), using Pathway Scoring Algorithm (PASCAL) and REVIGO. PRS analyses suggest a significant genetic overlap between CPSP and 3 chronic pain disorders: chronic widespread pain (CWP, p value threshold = 0.003, R 0.06, p = 0.003), rheumatoid arthritis (RA, p value threshold = 0.0177, R = 0.04, p = 0.017) and possibly sciatica (p value threshold = 0.00025, R = 0.03, p = 0.045). Whereas no significant genetic overlap was found with cluster headache and migraine, the outcome for osteoarthritis (OA) was inconsistent between the cohorts. This is likely related to cohort composition, as repeated random reallocation of patients' nullified CPSP/OA outcome variation between the discovery and replication cohorts. GO analyses suggested an aetiological involvement of genetic markers that control neurological signalling (specifically sodium channels) and inflammatory response. The current study reaffirms the impact of sample size, cohort composition and open data accessibility on the unbiased identification of genetic overlap across disorders. In conclusion, this study is the first to report genetic overlap between regulatory processes implicated in CPSP and chronic peripheral pain syndromes. Interaction between neurological signalling and inflammatory response may explain the genetic overlap between CPSP, CWP and RA. Enhanced understanding of mechanisms underlying chronification of pain will aid the development of new therapeutic strategies for CPSP with sodium channel biochemistry as a potential candidate.

Neuroinflammation is implicated in the development and maintenance of persistent pain states, but there is limited data linking cerebrospinal fluid (CSF) inflammatory mediators with neurophysiological pain processes in humans.In a prospective observational study, CSF inflammatory mediators were compared between patients with osteoarthritis (OA) who were undergoing total hip arthroplasty due to disabling pain symptoms (n=52) and pain-free comparison controls (n=30). In OA patients only, detailed clinical examination and quantitative sensory testing were completed. CSF samples were analyzed for ten proinflammatory mediators using Meso Scale Discovery platform.Compared to controls, OA patients had higher CSF levels of interleukin 8 (IL-8) (P=0.002), intercellular adhesion molecule (ICAM) 1 (P=0.007) and vascular cell adhesion molecule (VCAM) 1 (P=0.006). OA patients with central sensitization possibly indicated by arm pressure pain detection threshold (PPDT) <250 kPa showed significantly higher CSF levels of Fms related tyrosine kinase 1 (Flt-1) (P=0.044) and interferon gamma-induced protein 10 (IP-10) (P=0.024), as compared to subjects with PPDT above that threshold. In patients reporting pain numerical rating scale score ≥3/10 during peripheral venous cannulation (PVC), Flt-1 was elevated (P=0.025), and in patients with punctate stimulus wind-up-ratio ≥2, CSF monocyte chemoattractant protein 1 (MCP-1) was higher (P=0.011). Multiple logistic regression models showed that increased Flt-1 was associated with central sensitization, assessed by remote site PPDT and PVC pain, and MCP-1 with temporal summation in the area of maximum pain.Multiple proinflammatory mediators measured in CSF are associated with persistent hip OA-related pain. Pain phenotype may be influenced by specific CSF neuroinflammatory profiles.

Targeted Drug Delivery (TDD) is commonly used for the management of patients with intractable pain. Past studies have proven efficacy in pain relief and reduction in opioid use and cost-effectiveness in long-term pain management. There are few studies investigating satisfaction among patients with implanted pain pumps that are managed with targeted intrathecal medications.

To estimate the effects of excess body mass and leisure time physical activity on the incidence and persistence of chronic pain.

: To examine rates and correlates of dual cannabis and prescription pain reliever (PPNR) use and misuse among U.S. individuals aged 50+ who reported past-year cannabis use.: Using the 2015-2018 National Survey of Drug Use and Health, we examined cannabis nonuse/use and PPNR nonuse/use/misuse among all 35,229 respondents, and then focused on 2,632 past-year cannabis users to examine the risk of PPNR use but no misuse and the risk of PPNR misuse, compared to PPNR nonuse.: More than one-half of older cannabis users used PPNR in the past year. Multinomial logistic regression results show that the risks of PPNR use/no misuse and PPNR misuse were higher among those who had more chronic medical conditions and a major depressive episode. The risk of PPNR use/no misuse was also associated with high frequency and medical cannabis use. The risk of PPNR misuse was also associated with younger cannabis initiation age and cannabis and other illicit drug use disorders.: Correlates of dual cannabis and PPNR use/misuse among older adults are poor physical and mental health problems and problematic cannabis use.: Older adults with cannabis and PPNR misuse need access to evidence-based treatment, including medication-assisted treatment when needed.