Pain
-
This study explored diverse care trajectories (CTs) for low back pain (LBP) and other musculoskeletal disorders (MSDs), over a 5-year period following a first episode of LBP. Based on Quebec's administrative health data from 2007 to 2011, this longitudinal cohort study involved 12,608 adults seeking health care for LBP. Using a new multidimensional state sequence analysis, we identified 6 distinct types of CTs. ⋯ Patients in types 4 and 6 (mainly older age groups and women) sought care for other MSDs from general practitioners or specialists, while middle-aged patients in type 5 experienced persistent nonspecific LBP with frequent general practitioner consultations over 5 years. The CTs typology revealed several key areas for improvement in nonpharmacological interventions, including the need to address possible inappropriate medical imaging and invasive interventions for older women with MSDs and the lack of ambulatory care access for younger patients with trauma-related LBP. Finally, results clearly highlighted poor access to rehabilitation physicians and rehabilitation services for all patients suffering from LBP and MSDs.
-
Early life stress (ELS) is associated with an increased risk of experiencing chronic pain during adulthood, but surprisingly little is known about the short-term influence of ELS on nociceptive processing in the immature nervous system and the concomitant effects on somatosensation in the neonate. Here, we investigate how ELS modulates pain in neonatal mice and the transcriptional and electrophysiological signatures of immature dorsal root ganglia (DRG). Shortly after the administration of a neonatal limiting bedding (NLB) paradigm from postnatal days (P)2 to P9, both male and female pups exhibited robust hypersensitivity in response to tactile, pressure, and noxious cold stimuli compared with a control group housed under standard conditions, with no change in their sensitivity to noxious heat. ⋯ Nonetheless, ex vivo whole-cell patch-clamp recordings from putative A- and C-fiber sensory neurons in the neonatal DRG found no significant changes in their intrinsic membrane excitability following NLB. Overall, these findings suggest that ELS triggers hyperalgesia in neonates across multiple pain modalities that is accompanied by transcriptional plasticity within developing sensory neurons. A better understanding of the mechanisms governing the interactions between chronic stress and pain during the neonatal period could inform the future development of novel interventional strategies to relieve pain in infants and children who have experienced trauma.
-
Traumatic brain injury (TBI) annually impacts 69 million individuals worldwide. Mild TBI constitutes approximately 90% of all TBIs. Chronic pain post-mTBI occurs in 29% to 58% of patients. ⋯ The optimized predictive model demonstrated high efficacy, with an accuracy of 83%, a sensitivity of 92%, and an area under the receiver operating characteristic curve of 0.8. Our findings indicate feasibility in predicting chronic post-MVA pain within the critical 72-hour window postinjury using simple bedside metrics. This approach offers a promising avenue for the early detection of individuals at increased risk for chronic pain, enabling the implementation of targeted early interventions.
-
Decoding pain: uncovering the factors that affect the performance of neuroimaging-based pain models.
Neuroimaging-based pain biomarkers, when combined with machine learning techniques, have demonstrated potential in decoding pain intensity and diagnosing clinical pain conditions. However, a systematic evaluation of how different modeling options affect model performance remains unexplored. This study presents the results from a comprehensive literature survey and benchmark analysis. ⋯ Specifically, incorporating more pain-related brain regions, increasing sample sizes, and averaging less data during training and more data during testing improved performance. These findings offer useful guidance for developing neuroimaging-based biomarkers, underscoring the importance of strategic selection of modeling approaches to build better-performing neuroimaging pain biomarkers. However, the generalizability of these findings to clinical pain requires further investigation.
-
Persistent or chronic pain is the primary reason people seek medical care, yet current therapies are either limited in efficacy or cause intolerable side effects. Diverse mechanisms contribute to the basic phenomena of nociceptor hyperexcitability that initiates and maintains pain. Two prominent players in the modulation of nociceptor hyperexcitability are the transient receptor potential vanilloid type 1 (TRPV1) ligand-gated ion channel and the voltage-gated potassium channel, Kv7.2/3, that reciprocally regulate neuronal excitability. ⋯ Importantly, this specific MOA is not associated with any previously described Kv7.2/3 or TRPV1 class-specific side effects. We suggest that the therapeutic potential of this MOA is derived from the selective and specific targeting of a subpopulation of nociceptors found in rodents and humans. This efficacy and safety profile supports the advancement of dual TRPV1-Kv7.2/3 modulating compounds into preclinical and clinical development for the treatment of chronic pain.