Pain
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Analgesics currently available for the treatment of pain following ophthalmic surgery or injury are limited by transient effectiveness and undesirable or adverse side effects. The cornea is primarily innervated by small-diameter C-fiber sensory neurons expressing TRPV1 (transient receptor potential channel, subfamily V, member 1), a sodium/calcium cation channel expressed abundantly by nociceptive neurons and consequently a target for pain control. Resiniferatoxin (RTX), a potent TRPV1 agonist, produces transient analgesia when injected peripherally by inactivating TRPV1-expressing nerve terminals through excessive calcium influx. ⋯ Importantly, RTX analgesia (a) did not impair epithelial wound healing, (b) left the blink reflex intact and (c) occurred without detectable histological damage to the cornea. Immunohistochemistry showed that loss of CGRP immunoreactivity, a surrogate marker for TRPV1-expressing fibers, extended at least to the corneal-scleral boundary and displayed a progressive return, coincident with the return of capsaicin sensitivity. These data suggest that RTX may be a safe and effective treatment for post-operative or post-injury ophthalmic pain.
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In the past two decades, functional brain imaging has considerably advanced our knowledge of cerebral pain processing. However, many important links are still missing in our understanding of brain activity in relation to the regulation of pain-related physiological responses. This fMRI study investigates the cerebral correlates of pain (rating), motor responses (RIII-reflex) and autonomic activity (skin conductance response; SCR) evoked by noxious electrical stimulation. ⋯ Additionally, trial-to-trial fluctuations of RIII-reflex and SCR (within-subjects) were proportional to shock-evoked responses in subgenual cingulate cortex (RIII), anterior insula (SCR) and midcingulate cortex (SCR and RIII). Together, these results confirm that individual differences in perceptual, motor, and autonomic components of pain reflect robust individual differences in brain activity. Furthermore, the brain correlates of trial-to-trial fluctuations in pain responses provide additional evidence for a partial segregation of sub-systems involved more specifically in the ongoing monitoring, and possibly the regulation, of pain-related motor and autonomic responses.
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Pain is the dominant symptom in osteoarthritis (OA) and sensitization may contribute to the pain severity. This study investigated the role of sensitization in patients with painful knee OA by measuring (1) pressure pain thresholds (PPTs); (2) spreading sensitization; (3) temporal summation to repeated pressure pain stimulation; (4) pain responses after intramuscular hypertonic saline; and (5) pressure pain modulation by heterotopic descending noxious inhibitory control (DNIC). Forty-eight patients with different degrees of knee OA and twenty-four age- and sex-matched control subjects participated. ⋯ No correlations were found between standard radiological findings and clinical/experimental pain parameters. However, patients with lesions in the lateral tibiofemoral knee compartment had higher pain ratings compared with those with intercondylar and medial lesions. This study highlights the importance of central sensitization as an important manifestation in knee OA.
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Temporal variations in cancer pain intensity are highly prevalent, and are often difficult to manage. However, the phenomenon is not well understood: several definitions and approaches to classification and bedside assessment of cancer breakthrough pain (BTP) have been described. The present study is a systematic review of published literature on cancer BTP to answer the following questions: which terms and definitions have been used; are there validated assessment tools; which domains of BTP do the tools delineate, and which items do they contain; how have assessment tools been applied within clinical studies; and are there validated classification systems for BTP. ⋯ Analysis of these publications indicates a range of overlapping but distinct definitions have been used to characterize BTP; 42 of the included papers presented one or more ways of classifying BTP; and while 10 tools to assess patients' experience of BTP were identified, only 2 have been partially validated. We conclude that there is no widely accepted definition, classification system or well-validated assessment tool for cancer-related breakthrough pain, but there is strong concurrence on most of its key attributes. With further work in this area, an internationally agreed upon definition and classification system for cancer-related breakthrough pain, and a standard approach on how to measure it, hold the promise to improve patient care and support research in this poor-prognosis cancer pain syndrome.