Pain
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Experiencing early life stress or injury increases a woman's likelihood of developing vulvodynia and concomitant dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. To investigate the outcome of neonatal vaginal irritation (NVI), female mouse pups were administered intravaginal zymosan on postnatal days 8 and 10 and were assessed as adults for vaginal hypersensitivity by measuring the visceromotor response to vaginal balloon distension (VBD). Western blotting and calcium imaging were performed to measure transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) in the vagina and innervating primary sensory neurons. ⋯ Serum CORT, vaginal mast cell degranulation, and CRF1 protein expression were all significantly increased in NVI mice, as were colorectal and hind paw mechanical and thermal sensitivity. Neonatal treatment with a CRF1 antagonist, NBI 35965, immediately before zymosan administration largely attenuated many of the effects of NVI. These results suggest that NVI produces chronic hypersensitivity of the vagina, as well as of adjacent visceral and distant somatic structures, driven in part by increased HPA axis activation.
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The aim of this case-crossover study was to investigate the extent to which patients can accurately nominate what triggered their new episode of sudden-onset acute low back pain (LBP). We interviewed 999 primary care patients to record exposure to 12 standard triggers and also asked the patients to nominate what they believed triggered their LBP. Exposure to the patient-nominated trigger during the case window was compared with exposure in the control window. ⋯ The odds ratios for exposure to patient-nominated triggers ranged from 8.60 to 30.00, suggesting that exposure increases the risk of LBP. Patients' understanding of triggers however seems incomplete, as we found evidence that while some of the standard triggers were well recognised (such as lifting heavy loads), others (such as being distracted during manual tasks) were under-recognised as possible triggers of an episode of LBP. This study provides some evidence that patients can accurately nominate the activity that triggered their new episode of sudden-onset acute LBP.
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Overactivity is a frequently used term in chronic pain literature. It refers to the phenomenon whereby individuals engage in activity in a way that significantly exacerbates pain, resulting in periods of incapacity. Overactivity, as a construct, has been derived solely from patients' self-reports, raising concerns about the legitimacy of the construct. ⋯ Over the 5-day period, participants wore an activity monitor and recorded their pain intensity 6 times a day using a handheld computer. Associations were found between (1) high levels of pain and both high overactivity and high avoidance, (2) high levels of overactivity and more variation in pain and objective activity across days, and (3) high levels of overactivity and the reoccurrence of prolonged activity engagement followed by significant pain increases observed in data sets. These results offer some preliminary support for the validity of overactivity as a legitimate construct in chronic pain.
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In this study, we investigated the role of the endocannabinoid system (ECS) in the emotional and cognitive alterations associated with osteoarthritis pain. The monosodium iodoacetate model was used to evaluate the affective and cognitive manifestations of osteoarthritis pain in type 1 (CB1R) and type 2 (CB2R) cannabinoid receptor knockout and wild-type mice and the ability of CB1R (ACEA) and CB2R (JWH133) selective agonists to improve these manifestations during a 3-week time period. The levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured in plasma and brain areas involved in the control of these manifestations. ⋯ In agreement, an increase of 2-AG plasmatic levels and an upregulation of CB1R and CB2R gene expression in peripheral blood lymphocytes were observed in patients with osteoarthritis compared with healthy subjects. Changes found in these biomarkers of the ECS correlated with pain, affective, and cognitive symptoms in these patients. The ECS plays a crucial role in osteoarthritis and represents an interesting pharmacological target and biomarker of this disease.
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Tibia fracture induces exaggerated substance P (SP) and calcitonin gene-related peptide (CGRP) signaling and neuropeptide-dependent nociceptive and inflammatory changes in the hind limbs of rats similar to those seen in complex regional pain syndrome. Inflammatory changes in the spinal cord contribute to nociceptive sensitization in a variety of animal pain models. This study tested the hypothesis that fracture-induced exaggerated neuropeptide signaling upregulates spinal inflammatory mediator expression, leading to postfracture hind limb nociceptive sensitization. ⋯ Fracture-induced increases in spinal inflammatory mediators were not observed in fracture mice lacking SP or the CGRP receptor, and these mice had attenuated postfracture nociceptive sensitization. Intrathecal injection of selective receptor antagonists for SP, CGRP, TNF, IL-1, IL-6, CCL2, or nerve growth factor each reduced pain behaviors in the fracture rats. Collectively, these data support the hypothesis that facilitated spinal neuropeptide signaling upregulates the expression of spinal inflammatory mediators contributing to nociceptive sensitization in a rodent fracture model of complex regional pain syndrome.