Periaqueductal Grey EP3 Receptors Facilitate Spinal Nociception in Arthritic Secondary Hypersensitivity.

UNLABELLED: Descending controls on spinal nociceptive processing play a pivotal role in shaping the pain experience after tissue injury. Secondary hypersensitivity develops within undamaged tissue adjacent and distant to damaged sites. Spinal neuronal pools innervating regions of secondary hypersensitivity are dominated by descending facilitation that amplifies spinal inputs from unsensitized peripheral nociceptors. Cyclooxygenase-prostaglandin (PG) E2 signaling within the ventrolateral periaqueductal gray (vlPAG) is pronociceptive in naive and acutely inflamed animals, but its contributions in more prolonged inflammation and, importantly, secondary hypersensitivity remain unknown. In naive rats, PG EP3 receptor (EP3R) antagonism in vlPAG modulated noxious withdrawal reflex (EMG) thresholds to preferential C-nociceptor, but not A-nociceptor, activation and raised thermal withdrawal thresholds in awake animals. In rats with inflammatory arthritis, secondary mechanical and thermal hypersensitivity of the hindpaw developed and was associated with spinal sensitization to A-nociceptor inputs alone. In arthritic rats, blockade of vlPAG EP3R raised EMG thresholds to C-nociceptor activation in the area of secondary hypersensitivity to a degree equivalent to that evoked by the same manipulation in naive rats. Importantly, vlPAG EP3R blockade also affected responses to A-nociceptor activation, but only in arthritic animals. We conclude that vlPAG EP3R activity exerts an equivalent facilitation on the spinal processing of C-nociceptor inputs in naive and arthritic animals, but gains in effects on spinal A-nociceptor processing from a region of secondary hypersensitivity. Therefore, the spinal sensitization to A-nociceptor inputs associated with secondary hypersensitivity is likely to be at least partly dependent on descending prostanergic facilitation from the vlPAG. SIGNIFICANCE STATEMENT: After tissue damage, sensitivity to painful stimulation develops in undamaged areas (secondary hypersensitivity). This is found in many painful conditions, particularly arthritis. The periaqueductal gray (PAG) is an important center that controls spinal nociceptive processing, on which secondary hypersensitivity depends. Prostaglandins (PGs) are mediators of inflammation with pronociceptive actions within the PAG under normal conditions. We find that secondary hindpaw hypersensitivity in arthritic rats results from spinal sensitization to peripheral A-nociceptor inputs. In the PAG of arthritic, but not naive, rats, there is enhanced control of spinal A-nociceptor processing through PG EP3 receptors. The descending facilitatory actions of intra-PAG PGs play a direct and central role in the maintenance of inflammatory secondary hypersensitivity, particularly relating to the processing of A-fiber nociceptive information.

No correlation exists between vitamin B12 and quality of life in healthy young adult population.

BACKGROUND AND OBJECTIVES: Vitamin B12 (B12) is essential for well-being and healthy life, since it plays a critical role in DNA synthesis, hematopoiesis and neurologic function. B12 deficiency remains one of the most common nutrition deficiencies in the world and is associated with increasing risk of cardiovascular disease, cancer, mental health problem, osteoporosis, and defect-birth outcomes. The main objective of this study is to determine the impact of B12 levels on quality of life (QOL) among healthy university students. MATERIALS AND METHODS: This cross-sectional study involved 359 healthy university students (age 18-30 years) of both genders. Their QOL was as vitamin B12 level was measured using the IMx system (Abbott laboratories IMX, USA). RESULTS: No correlation was detected between B12 levels and the two major QOL subscales: the Physical Component Summary (PCS) and Mental Component Summary (MCS). Additionally, none of the other eight subscale of the SF-36 was significantly correlated with b12 levels. CONCLUSION: We conclude that no correlation exists between B12 levels and QOL scores among young adult healthy populations. Further investigations are required to confirm the impact of B12 status on QOL among healthy populations.

Prophylactic use of aspirin does not induce anaemia among adults.

BACKGROUND: Aspirin is considered one of the most prescribed drugs worldwide, predominantly for its cardioprotective effects. However, its use may be precluded by gastrointestinal and haematological side-effects. OBJECTIVE: To investigate the association between the prophylactic use of aspirin and the prevalence of anaemia among adults. Other demographic factors and co-morbid conditions such as kidney or liver failure, diabetes mellitus, hypertension, hyperlipidemia, coronary artery disease, ulcer, ulcer medications, and the use of non-steroidal anti-inflammatory drugs, which might be associated with anaemia, were also investigated. RESULTS: No association between aspirin use and prevalence of anaemia was observed. Age and smoking were the only factors contributing significantly to the occurrence of anaemia. Moreover, gender, age and the use of peptic ulcer medication were associated with reduced haemoglobin levels. CONCLUSION: The results may help in minimizing concerns about the development of anaemia among patients on aspirin. They highlight the importance of age, gender, smoking and ulcer medication in determining the incidence of anaemia among those patients.