Accepted

Melatonin (MLT) has been implicated in several pathophysiological states, including pain. MLT mostly activates two G protein-coupled receptors, MT and MT. MLT displays analgesic properties in several animal paradigms of acute, inflammatory, and neuropathic pain. Although the analgesic mechanism of action of MLT is not yet completely elucidated, there is strong preclinical evidence suggesting the pharmacological potential of melatonergic compounds for treating pain. Importantly, MLT and melatonergic compounds seem to have a favorable toxicological profile than currently approved analgesic drugs. These compounds may thus deserve to be further developed as novel analgesic drugs, but this process relies on the use of appropriate and standardized experimental procedures. Therefore, in this chapter, we present the methodology to study the analgesic properties of MLT and melatonergic drugs in a preclinical model of chronic and acute pain. In addition to technical details of the surgical technique, details of anesthesia and perioperative care are also included.

Public health issues related to chronic pain management and the risks of opioid misuse and abuse remain a challenge for practitioners. Data on the prevalence of disorders related to the use of prescribed opioids in patients suffering from chronic pain remains rather patchy, in particular because of the absence of a gold standard for their clinical assessment. We estimated the prevalence of prescription opioid misuse (POM), using a specific and validated opioid misuse scale (POMI-5F scale), in adults with chronic non-cancer pain. Nine-hundred-fifty-one (951) patients with opioids prescription and followed-up in pain clinics and addictology centers for chronic non-cancer pain (CNCP) completed the survey interview. The results suggest that 44.4% of participants have POM, accompanied by overuse (42.5%), use of opioids for effects other than analgesia (30.9%), withdrawal syndrome (65.7%), and craving (6.9%). The motivations cited for POM, apart from pain relief, were to calm down, relax and improve mood. POM was shown to be related to male sex (OR 1.52), young age (OR 2.21) and the presence of nociplastic pain (OR 1.62) of severe intensity (OR 2.31), codeine use (OR 1.72) and co-prescription of benzodiazepines (OR 1.59). Finally, despite the presence of three subgroups of misusers, no factor was associated with the intensity of misuse, reinforcing the view that distinguishing between strong and weak opioids is not appropriate in the context of use disorder. Almost half of patients with CNCP misuse their prescribed opioid. Practitioners should be attentive of profiles of patients at risk of POM, such as young, male patients suffering from severe nociplastic pain, receiving prescription for codeine and a co-prescription for benzodiazepine. We encourage French-speaking practitioners to use the POMI-5F scale to assess the presence of POM in their patients receiving opioid-based therapy. clinicaltrials.gov, identifier NCT03195374.

This systematic review aimed to investigate immune-inflammatory and hypothalamic-pituitary-adrenal (HPA) axis biomarkers in individuals with non-specific low back pain (NSLBP) compared to healthy control. The search was performed in five databases until 4 November 2021. Two reviewers independently conducted screenings, data extraction, risk of bias, and methodological quality assessment of 14 unique studies. All studies reported the source of the fluid analyzed: nine studies used serum, two used plasma, one used serum and plasma, and two studies used salivary cortisol. We found preliminary and limited evidence (only one study for each biomarker) of increased levels in growth differentiation factor 15 (GDF-15), interleukin-23 (IL-23), transforming growth factor-beta (TGF-β), and soluble tumor necrosis factor receptor 1 (sTNF-R1) in NSLBP. Inconsistent and limited evidence was identified for interleukin-10 (IL-10). Although C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels appear to increase in NSLBP, only one study per each biomarker reported statistically significant differences. Interleukin-1 beta (IL-1β), interleukin-17 (IL-17), interferon gamma (IFN-γ), and high-sensitivity CRP (hsCRP) showed no significant differences. Regarding cortisol, one study showed a significant increase and another a significant decrease. More robust evidence between GDF-15, IL-23, TGF-β, and sTNF-R1 with NSLBP is needed. Moreover, contrary to the findings reported in previous studies, when comparing results exclusively with healthy control, insufficient robust evidence for IL-6, TNF-α, and CRP was found in NSLBP. In addition, cortisol response (HPA-related biomarker) showed a dysregulated functioning in NSLBP, with incongruent evidence regarding its directionality. Therefore, our effort is to find adjusted evidence to conclude which immune-inflammatory and HPA axis biomarkers are altered in NSLBP and how much their levels are affected.

Although most cases of pain-related temporomandibular disorders (TMD) are mild and self-limiting, about 10% of TMD patients develop severe disorders associated with chronic pain and disability. It has been suggested that pain intensity contributes to the transition from acute to chronic pain-related TMD. Therefore, the aims of this current prospective cohort study were to assess if pain intensity, pain always being present, pain or stiffness on awakening, jaw activities, and interference, were associated with the transition from acute to chronic pain-related TMD at 3 months of follow-up. One hundred and nine participants, recruited from four clinics in Montreal and Ottawa, received examinations and completed the required instruments at baseline and at the 3rd month of follow-up. In a multivariable analysis including sex, age, characteristic pain index (CPI) (OR = 1.03, 95%CI = 1.01-1.06, = 0.005), moderate to severe average pain intensity (OR = 3.51, 95%CI = 1.24-9.93, = 0.02), disability points score (OR = 1.29, 95%CI = 1.06-1.57, = 0.01), interferences (ORs = 1.30-1.32, = 0.003-0.005), screening score (OR = 1.37, 95%CI = 1.08-1.76, = 0.01), and pain always present (OR = 2.55, 95%CI = 1.08-6.00, = 0.03) assessed at first-visit were related to the transition outcome at the 3rd month of follow-up. Further, we found that if 4 patients with acute pain-related TMD on average were exposed to these risk factors at baseline, 1 would have the transition from acute to chronic pain at 3 months of follow-up. Results indicate that these factors are associated with the transition from acute to chronic pain-related TMD, and therefore should be considered as important factors when evaluating and developing treatment plans for patients with pain-related TMD.

The association between obesity and musculoskeletal chronic pain has attracted much attention these days; however, the causal relationship between them is uncertain. Hence, this study performed a Mendelian randomization (MR) analysis to investigate the causal effects of body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) on knee pain, hip pain, and back pain.

There is considerable diversity of outcome selections and methodologies for handling the multiple outcomes across all systematic reviews (SRs) of Interdisciplinary Pain Treatment (IPT) due to the complexity. This diversity presents difficulties for healthcare decision makers. Better recommendations about how to select outcomes in SRs (with or without meta-analysis) are needed to explicitly demonstrate the effectiveness of IPT.

Exercise is advocated in the treatment of rheumatoid arthritis (RA). However, uncertainty around the acute effects of exercise on pain and inflammation may be stopping people with RA from exercising more regularly.