Pain
-
To determine the impact of occupational psychological/social and mechanical factors on neck pain, a prospective cohort study with a follow-up period of 2 years was conducted with a sample of Norwegian employees. The following designs were tested: (i) cross-sectional analyses at baseline (n=4569) and follow-up (n=4122), (ii) prospective analyses with baseline predictors, (iii) prospective analyses with average exposure over time [(T1+T2)/2] as predictor, and (iv) prospective analyses with measures of change in exposure from T1 to T2 as predictors. A total of 2419 employees responded to both the baseline and follow-up questionnaire. ⋯ The most consistent protective factors were empowering leadership (lowest OR 0.53, 99% CI: 0.35-0.81) and decision control (lowest OR 0.60, 99% CI: 0.36-1.00). Hence, psychological and social factors are important precursors of neck pain, along with mechanical factors. Although traditional factors such as quantitative demands and decision control play a part in the etiology of neck pain at work, in this study several new factors emerged as more important.
-
We examined age, period, and cohort patterns in musculoskeletal pain prevalence between 1968 and 2002 in the Swedish population. A repeated nationally representative survey allowed cross-sectional comparisons of ages 18-75 (5 waves n≈5000), and ages 77+ at later waves (2 waves n≈500). Cross-sectional 10-year age group differences in 5 waves, time-lag differences between waves (shifts across time) for age groups, and within-cohort differences between waves for 10-year birth cohorts followed over time were analyzed using graphs and ordered logistic regressions. ⋯ The prevalence of pain in the adult population thus increased with the passage through age and time of the 1940s cohorts. While there were no pronounced cohort differences at baseline in 1968, results demonstrated strong age effects in pain. The results indicate that the prevalence of musculoskeletal pain among the oldest age groups may increase in the future, when more baby-boomers are entering their oldest ages.
-
Protein interacting with C kinase 1 (PICK1) is a PDZ-containing protein that binds to AMPA receptor (AMPAR) GluR2 subunit and protein kinase Cα (PKCα) in the central neurons. It functions as a targeting and transport protein, presents the activated form of PKCα to synaptic GluR2, and participates in synaptic AMPAR trafficking in the nervous system. Thus, PICK1 might be involved in many physiological and pathological processes triggered via the activation of AMPARs. ⋯ Injection of CFA into a hind paw, but not a hind paw incision, increased PKCα-mediated GluR2 phosphorylation at Ser880 and GluR2 internalization in dorsal horn. These increases were absent when spinal cord PICK1 was deficient. Given that dorsal horn PKCα-mediated GluR2 phosphorylation at Ser880 and GluR2 internalization contribute to the maintenance of CFA-induced inflammatory pain, our findings suggest that spinal PICK1 may participate in the maintenance of persistent inflammatory pain, but not in incision-induced post-operative pain, through promoting PKCα-mediated GluR2 phosphorylation and internalization in dorsal horn neurons.
-
Tolerance to morphine-induced analgesia is an intractable phenomenon, often hindering its prolonged applications in the clinics. The enhanced pronociceptive actions of spinal pain-related molecules such as calcitonin gene-related peptide (CGRP) may underlie this phenomenon and could be a promising target for intervention. We demonstrate here how CGRP regulates the development of morphine analgesic tolerance at the spinal level. ⋯ Chronic morphine-induced behavioural responses and biochemical events were all subjugated to modulation by disrupting CGRP receptor signaling. Together, these data suggest that CGRP contributes to the development of tolerance to morphine-induced analgesia by regulating the activation of the neuronal CaMKII-CREB, microglial p38-NFκB and astroglial ERK-Stat1/3 cascades. Targeting CGRP-associated signaling molecules may prolong or restore morphine's analgesic properties upon a chronic exposure.
-
NMDA receptors have an important role in pain facilitation in rostral ventromedial medulla (RVM) and the NR1 subunit is essential for its function. Studies suggest that the NMDA receptors in RVM are critical to modulate both cutaneous and muscle hypersensitivity induced by repeated intramuscular acid injections. We propose that increased expression of the NR1 subunit in the RVM is critical for the full development of hypersensitivity. ⋯ We also downregulated the expression of NR1 in the RVM and measured the hyperalgesia produced by repeated-acid injections. Increasing the expression of NR1 in the RVM reduces cutaneous and muscle withdrawal threshold, and decreasing the expression of NR1 in the RVM increases the muscle withdrawal threshold and prevents the development of hyperalgesia in an animal model of muscle pain. These results suggest that the NR1 subunits in the RVM are critical for modulating NMDA receptor function, which in turn sets the 'tone' of the nervous system's response to noxious stimuli and tissue injury.