Human Studies

The opioid crisis remains a major public health concern. In ambulatory surgery, persistent postoperative opioid use is poorly described and temporal trends are unknown. A population-based retrospective cohort study was undertaken in Ontario, Canada using routinely collected administrative data for adults undergoing ambulatory surgery between 1 January 2013 and 31 December 2017. The primary outcome was persistent postoperative opioid use, defined using best-practice methods. Multivariable generalised linear models were used to estimate the association of persistent postoperative opioid use with prognostic factors. Temporal trends in opioid use were examined using monthly time series, adjusting for patient-, surgical- and hospital-level variables. Of 340,013 patients, 44,224 (13.0%, 95%CI 12.9-13.1%) developed persistent postoperative opioid use after surgery. Following multivariable adjustment, the strongest predictors of persistent postoperative opioid use were pre-operative: utilisation of opioids (OR 9.51, 95%CI 8.69-10.39); opioid tolerance (OR 88.22, 95%CI 77.21-100.79); and utilisation of benzodiazepines (OR 13.75, 95%CI 12.89-14.86). The time series model demonstrated a small but significant trend towards decreasing persistent postoperative opioid use over time (adjusted percentage change per year -0.51%, 95%CI -0.83 to -0.19%, p = 0.003). More than 10% of patients who underwent ambulatory surgery experienced persistent postoperative opioid use; however, there was a temporal trend towards a reduction in persistent opioid use after surgery. Future studies are needed that focus on interventions which reduce persistent postoperative opioid use.

Human pain is a salient stimulus composed of two main components: a sensorysomatic component, carrying peripheral nociceptive sensation via the spino-thalamic tract and brainstem nuclei to the thalamus and then to sensory cortical regions, and an affective (suffering) component, where information from central thalamic nuclei is carried to the anterior insula, dorsal anterior cingulate cortex and other regions. While the sensory component processes information about stimulus location and intensity, the affective component processes information regarding pain-related expectations, motivation to reduce pain, and pain unpleasantness. Unlike investigations of acute pain that are based on the introduction of real-time stimulus during brain recordings, chronic pain investigations are usually based on longitudinal and case-control studies, which are limited in their ability to infer the functional network topology of chronic pain. In the current study, we utilized the unique opportunity to target the central nervous system's pain pathways in two different hierarchical locations to establish causality between pain relief and specific connectivity changes seen within the salience and sensorimotor networks. We examined how lesions to the affective and somatic pain pathways affect resting-state network topology in cancer patients suffering from severe intractable pain. Two procedures have been employed: percutaneous cervical cordotomy (n = 15), hypothesized to disrupt the transmission of the sensory component of pain along the spino-thalamic tract, or stereotactic cingulotomy (n = 7), which refers to bilateral intra-cranial ablation of an area in the dorsal anterior cingulate cortex and is known to ameliorate the affective component of pain. Both procedures led to immediate significant alleviation of experienced pain and decreased functional connectivity within the salience network. However, only the sensory procedure (cordotomy) led to decreased connectivity within the sensorimotor network. Thus, our results support the existence of two converging systems relaying experienced pain, showing that pain-related suffering can be either directly influenced by interfering with the affective pathway, or indirectly influenced by interfering with the ascending spino-thalamic tract.

Relying on anthropomorphism research, Illness Personification Theory (ILL-PERF) posits that individuals living with a chronic illness ascribe human-like characteristics to their illness. Herein we examine the personification of chronic pain using a new measure: the Ben-Gurion University Illness Personification Scale (BGU-IPS). Three samples of chronic pain patients (Sample 1 and 2 are distinct samples sharing similar characteristics, collected in the context of a cross-sectional design, Ns = 259, 263; Sample 3: a 2-waves longitudinal, N =163) completed the 12-item BGU-IPS, and measures of pain and related factors. An orthogonal, two-factor structure was revealed for the BGU-IPS pertaining to negative vs. positive personifications. Negative personification was associated with pain intensity and illness-related distress (e.g., depression and low adjustment to pain). Positive personification was correlated with hope, pain-related sense of control, and low depression. However, positive personification also augmented the associations between negative personification and several risk factors. : Pain personification, particularly as assessed via the BGU-IPS, plays a major role in (mal)adaptation to chronic pain.

Non-specific low back pain (LBP) is a major global disease burden and childhood adversity predisposes to its development. The mechanisms are largely unknown. Here, we investigated if adversity in young rats augments mechanical hyperalgesia and how spinal cord microglia contribute to this. Adolescent rats underwent restraint stress, control animals were handled. In adulthood, all rats received two intramuscular injections of NGF/saline or both into the lumbar multifidus muscle. Stress induced in rats at adolescence lowered low back pressure pain threshold (PPT; p = 0.0001) and paw withdrawal threshold (PWT; p = 0.0007). The lowered muscle PPT persisted throughout adulthood (p = 0.012). A subsequent NGF in adulthood lowered only PPT (d = 0.87). Immunohistochemistry revealed changes in microglia morphology: stress followed by NGF induced a significant increase in ameboid state (p < 0.05). Repeated NGF injections without stress showed significantly increased cell size in surveilling and bushy states (p < 0.05). Thus, stress in adolescence induced persistent muscle hyperalgesia that can be enhanced by a mild-nociceptive input. The accompanying morphological changes in microglia differ between priming by adolescent stress and by nociceptive inputs. This novel rodent model shows that adolescent stress is a risk factor for the development of LBP in adulthood and that morphological changes in microglia are signs of spinal mechanisms involved.

The use of off-label pharmacotherapies for neuropathic pain (NP) is growing relating to the many unmet needs of patients. However, clinical guidelines fail to address it, and the available evidence is sparse and fragmented. We arranged a formal expert consensus to address this controversial issue and provide some guidance on judicious use.

To evaluate the effect of statin use on osteoarthritis (OA) incidence/progression using magnetic resonance imaging (MRI) in a population-based cohort with predominantly pre-radiographic knee OA.

We sought to predict analgesic response to daily oral nonsteroidal anti-inflammatory drugs (NSAIDs) or subcutaneous tanezumab 2.5 mg (every 8 weeks) at week 16 in patients with moderate-to-severe osteoarthritis, based on initial treatment response over 8 weeks.

Manifestations of psoriasis in special areas are difficult to treat and are associated with a high disease burden and significant quality of life (QoL) impairment. Topical therapies may be inadequate for these patients, necessitating systemic treatment.

Long-term prescriptions of strong opioids for chronic noncancer pain-which are not supported by scientific evidence-suggest miscalibrated risk perceptions among those who prescribe, dispense, and take opioids. Because risk perceptions and behaviors can differ depending on whether people learn about risks through description or experience, we investigated the effects of descriptive versus simulated-experience educative formats on physicians' risk perceptions of strong opioids and their prescription behavior for managing chronic noncancer pain.