RESUMEN

BACKGROUND AND OBJECTIVE: Temporal summation of pain (TSP) and conditioned pain modulation (CPM) are the two most commonly used clinical measures of central sensitization (CS). However, the effectiveness of exercise on TSP and CPM has yet to be evaluated. This review aims to investigate the effect of exercise alone on CS outcomes in individuals with chronic musculoskeletal pain. DATABASES AND DATA TREATMENT: This is a systematic review and meta-analysis. MEDLINE, EMBASE, CINAHL, PEDro and Cochrane databases were searched. Data were extracted based on the exercise modality and grouped into aerobic, resistance, isometric, or motor control modalities. Risk of bias was assessed using RoB2, RoB2 for crossover trials and ROBINS-I tools. Quality of evidence was assessed using GRADE. Random-effects meta-analyses were conducted, with subgroup analysis conducted for each exercise modality. RESULTS: The meta-analyses included thirteen studies, consisting of eight non-randomized studies, three randomized controlled trials and three randomized crossover trials. Data were categorized into four subgroups for analyses based on exercise modality. No statistically significant effect existed for both TSP and conditioned pain modulation. However, motor control exercise was found to have a significant enhancing effect on conditioned pain modulation. No significant differences were found between the exercise subgroup for both TSP and conditioned pain modulation. CONCLUSIONS: We did not find an overall effect of physical exercise on TSP and CPM. However, subgroup analysis shows favourable effects of motor control exercise in individuals with chronic neck pain. Future research should focus on exercise modality and dosage and their role in the mechanism involved in TSP and CPM in predefined populations. SIGNIFICANCE STATEMENT: Results from this study found that motor control exercise has a significant enhancing effect on conditioned pain modulation, with subgroup analysis showing favourable effects of motor control exercise in individuals with chronic neck pain. This indicates that physical exercise may have a positive effect on central sensitisation in individual with chronic neck pain. However, differential effects may exist between different types of exercise. These findings will inform understanding of neurobiological effects underlying chronic neck pain and may guide the development of more effective, personalised treatments.

RESUMEN

Exercise-induced hypoalgesia (EIH) has been found to vary widely within individuals with chronic neck pain (NP). Research has suggested that the presence of central sensitization within a subgroup of individuals with chronic NP might be a mediating factor to explain the relationship between exercise and improvements in patient-reported outcomes. Furthermore, recent work has found that lactate might play a role in the development and maintenance of chronic pain. The immediate effect of a single bout of physical exercise on central sensitization in individuals with chronic NP and the relationship between lactate concentration, central sensitization and pain sensitivity are to be investigated. Eighty adult participants with chronic NP will be recruited for this randomized crossover trial. Outcome measures, including temporal summation, conditioned pain modulation, EIH and lactate concentration, will be assessed before and after low- and high-intensity bicycling exercise. The outcomes of this study will provide new insights into the mechanistic effect of exercise on central sensitization in individuals with chronic NP and have the potential to add important information to the current exercise prescription guidelines for individuals with chronic NP. This study has been approved by the Human Research Ethics Committee, The University of Adelaide (H-2022-082) and registered in the Australian New Zealand Clinical Trials Registry (ACTRN12622000642785p).

Asunto(s)

RESUMEN

Cancer patients may experience symptom clusters, including chemotherapy-induced (CI) gut toxicity (CIGT) and cognitive impairment. Analgesic selection for pain associated with CIGT is difficult as opioids induce glial reactivity and unwanted side effects. This study quantified central glial reactivity and proinflammatory effects in rats with CIGT using three mechanistically different analgesics. Regional adaptations were indicative of immune-to-brain signaling routes. Utilizing a 5-fluorouracil-induced GT (5IGT) rat model and analgesic intervention (carprofen (CAR), buprenorphine (BUP), and tramadol (TRAM)), spinal and brain neuroimmune modulation was examined via microglial, astrocyte, and proinflammatory (cluster of differentiation molecule 11b; CD11b, glial fibrillary associated protein; GFAP, and interleukin-1 beta; IL1ß) reactivity marker expression changes by western blot analysis. 5IGT significantly increased thoracic GFAP (p < 0.05) and IL-1ß (p < 0.0001) expression, CAR and BUP ameliorated these effects. BUP and TRAM with 5-FU synergistically increased hippocampal GFAP expression. CAR administered with 5IGT significantly elevated hippocampal and thoracic CD11b expression levels (p < 0.05). The neuroimmune responses observed in this study suggest activation of peripheral-to-central immune signaling pathways. We speculate that the opioid-induced hippocampal changes inferred a humorally mediated mechanism, whereas thoracic neuroimmune modifications indicated activation of an indirect neural route. Although TRAM ameliorated 5IGT-intestinal inflammation, this opioid presents complications relating to bodyweight and regional glial dysregulation (neuroinflammation) and may not be optimal in the management of pain associated with 5IGT. The chemotherapy-induced gut-derived neuroimmune consequences observed suggest a potential mechanistic contribution to central components of the cancer symptom cluster experience, while the opioid-related glial changes have implications for optimal pain management in this setting warranting further investigation.

Asunto(s)

RESUMEN

Corticosterone (CORT), a critical mediator of the hypothalamus pituitary adrenal axis in rodents, is a stress hormone that is classically viewed as possessing immune-suppressive properties. CORT is now appreciated to also mediate the neuroimmune-priming effect of stress to innate-immune stimulation, and hence serves as a mechanistic link to the neuroimmune involvement in stress-related disorders. However, these dichotomous actions of CORT remain poorly defined. This study investigated the conditions and concentration dependency of CORT's actions required to prime the innate-immune system. Here, we measured the effect of CORT pretreatment on the downstream pro-inflammatory responses of BV2 mouse microglia-like cells stimulated by lipopolysaccharide (LPS). We quantified the concentration-dependent CORT-mediated attenuation and enhancement of LPS-stimulated inflammatory response. A high physiological concentration (500 nM) of CORT attenuated LPS-induced inflammatory IL-1ß cytokine production in a glucocorticoid receptor-dependent manner. However, a low concentration (50 nM) of CORT increased expression and release of IL-1ß in a mineralocorticoid receptor-dependent manner, with accompanied increases in NF-κB translocation and changes to related gene transcription. These results suggest that a mild elevation in CORT may cause selective adaptations in microglia-like cells to overrespond to a second immune challenge in a non-classical manner, thus partially explaining both pro- and anti-inflammatory effects of CORT reported in the literature.

Asunto(s)

RESUMEN

The electroencephalogram (EEG) records the electrical activity of the brain and enables effects of anaesthetic drugs on brain functioning to be monitored. Identification of genes contributing to EEG variability during anaesthesia is important to the clinical application of anaesthesia monitoring and may provide an avenue to identify molecular mechanisms underlying the generation and regulation of brain oscillations. Central immune signalling can impact neuronal activity in the brain and accumulating evidence suggests an important role for cytokines as neuronal modulators. We tested 21 single-nucleotide polymorphisms (SNPs) in immune-related genes for associations with three anaesthesia-induced EEG patterns; spindle amplitude, delta power and alpha power, during general anaesthesia with desflurane in 111 patients undergoing general, gynaecological or orthopaedic surgery. Wide inter-patient variability was observed for all EEG variables. MYD88 rs6853 (p = 6.7 × 10(-4)) and IL-1ß rs1143627 in conjunction with rs6853 (p = 1.5 × 10(-3)) were associated with spindle amplitude, and IL-10 rs1800896 was associated with delta power (p = 1.3 × 10(-2)) suggesting involvement of cytokine signalling in modulation of EEG patterns during desflurane anaesthesia. BDNF rs6265 was associated with alpha power (p = 3.9 × 10(-3)), suggesting differences in neuronal plasticity might also influence EEG patterns during desflurane anaesthesia. This is the first study we are aware of that has investigated genetic polymorphisms that may influence the EEG during general anaesthesia.

Asunto(s)