The journal of pain : official journal of the American Pain Society
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Comparative Study
Do pain qualities and spatial characteristics make independent contributions to interference with physical and emotional functioning?
Although pain is acknowledged to be a multidimensional experience that can vary in intensity, quality (eg, burning, sensitive), and spatial characteristics (eg, location on body, perceived depth), its qualitative and spatial domains continue to be rarely assessed in pain clinical trials. One factor that may be contributing to the relatively rare assessment of pain quality and spatial characteristics is the lack of research addressing whether knowledge about these aspects of pain contributes important information beyond that provided by pain intensity alone. For example, there is no research that has examined whether measures of pain quality and perceived depth add anything to the understanding of the impact of pain on function. In the current study, secondary analyses of pretreatment data from clinical trials of patients from 3 diagnostic groups (osteoarthritis, low back pain, and peripheral neuropathy) indicated that measures of pain quality and perceived depth were significantly associated with pain interference with functioning, independent of global pain intensity and unpleasantness. No single pain descriptor emerged as universally important, however, although the findings suggest that: 1) sharp, deep, and perhaps especially sensitive pain may be important in patients with painful peripheral neuropathy; 2) sharp, sensitive, itchy, deep, and surface pain may be key pain descriptors important to persons with low back pain; and 3) perhaps deep pain may be the sole key pain descriptor important among persons with osteoarthritis. The findings support the potential utility of including measures of specific pain qualities and perceived depth in pain clinical trials and provide an initial empirical basis for determining which pain descriptors may be most closely linked to patient functioning. ⋯ Specific pain qualities, such as sharp, sensitive, and itchy pain, and perceived depth of pain appear to play a significant and unique role in the prediction of pain interference in addition to global pain intensity and unpleasantness. These findings suggest that measures of these specific pain domains could play an important role in understanding the impact of pain on patient functioning.
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Patients presenting to an emergency department (ED) with painful conditions continue to experience significant delay to analgesia. It remains unclear whether demographic and clinical factors are associated with this outcome. The objectives of this study were to determine 1) the proportion of patients that require parenteral opiate analgesia for pain in an ED and who receive the opiate in less than 60 minutes; and 2) whether any factors are predictive for the first dose of analgesia being delayed beyond 60 minutes. A retrospective cohort study with descriptive and comparative data analysis was conducted. Over a 3-month period, the medical record of every patient receiving parenteral opiates in a tertiary emergency department was reviewed and analyzed. Of 857 patients, 451 (52.6%) received analgesia in less then 60 minutes. Multiple demographic and clinical factors are associated with statistically significant delay to analgesia, including age, triage code, seniority of treating doctor, diagnosis, and disposition from the ED. ⋯ A considerable proportion of patients suffer delay to analgesia. Identifiable factors associated with a delay to analgesia exist. There is potential for clinicians to develop strategies to address the population in emergency departments at risk for delay to analgesia.
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We developed a rat model of oral cancer pain by inoculating cancer cells into the lower gingiva. A squamous cell carcinoma (SCC) derived from Fisher rats, SCC-158, was inoculated into the subperiosteal tissue on the lateral side of the lower gingiva in male Fisher rats. Inoculation of cancer cells induced marked mechanical allodynia and thermal hyperalgesia in the ipsilateral maxillary and mandibular nerve area. Infiltration of the tumor cells into the mandible and the completely encompassed inferior alveolar nerve was observed. Calcitonin gene-related peptide (CGRP)-, substance P (SP)-, ATP receptor (P2X(3))-, and capsaicin receptor (TRPV1)-immunoreactive cells strikingly increased in the small-cell group of trigeminal ganglia (TGs) after tumor cell inoculation. The TRPV1-immunoreactive cells also increased in the medium- and large-cell groups. Retrograde tracing combined with immunofluorescence techniques revealed the increased expression of peptides and the receptors in maxillary nerve afferent neurons. These results suggest that inoculation of SCC cells into the lower gingiva produces mechanical allodynia and thermal hyperalgesia, indicating the establishment of a novel rat model of oral cancer pain. Increased expression of CGRP, SP, P2X(3), and TRPV1 in the TG may be involved in the behavioral changes in this model. ⋯ To clarify the mechanisms of oral cancer pain, we examined the expression of calcitonin gene-related peptide, substance P, ATP receptor P2X(3), and capsaicin receptor TRPV1 in trigeminal ganglia. Characterizations of these molecular systems which mediate pain perception are important to develop novel clinical tools for promoting relief of oral cancer pain.
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Irritable bowel syndrome (IBS) is a common gastrointestinal disorder seen by gastroenterologists. We discuss some recent evidence for potential neural mechanisms that could contribute to somatic and visceral hyperalgesia in IBS patients. The combination of research studies of human IBS patients and studies of rats with delayed rectal hypersensitivity after recovery from experimentally induced neonatal colitis strongly suggests a mechanism wherein both primary visceral hyperalgesia and secondary widespread cutaneous hyperalgesia are dynamically maintained by tonic impulse input from the noninflamed colon and/or rectum. The secondary hyperalgesia is likely to be at least partly related to sensitization of spinal cord dorsal horn neurons and in this respect might be similar to other persistent pain conditions such as fibromyalgia and complex regional pain syndrome. ⋯ Pain in irritable bowel syndrome is likely to be at least partly maintained by peripheral impulse input from the colon/rectum and central sensitization, yet it is also highly modifiable by psychological factors such as nocebo and placebo effects. A synergistic interaction might occur between psychological factors and abnormal afferent processing.
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Randomized Controlled Trial
CHF3381, a N-methyl-D-aspartate receptor antagonist and monoamine oxidase-A inhibitor, attenuates secondary hyperalgesia in a human pain model.
CHF3381 is a new low-affinity, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and reversible monoamine oxidase-A (MAO-A) inhibitor. The analgesic activity of CHF3381 was investigated in the heat-capsaicin human pain model and compared with those of gabapentin. Twenty-seven young, healthy male volunteers received a single oral dose of CHF3381 (500 mg), gabapentin (1,200 mg), or placebo in a randomized, double-blind, crossover study design. Measurements were done before and 135 to 145 minutes after treatment administration and included area of secondary hyperalgesia around the sensitized skin of the forearm (45 degrees C for 5 minutes followed by topical capsaicin for 30 minutes), area of secondary hyperalgesia after thermal sensitization of the thigh (45 degrees C for 3 minutes), heat pain detection thresholds (degrees C), and pain on a visual analogue scale after long thermal stimulation (45 degrees C for 1 minute). Compared with placebo, both gabapentin and CHF3381 significantly reduced the area of secondary hyperalgesia on the dominant forearm. Median (and interquartile range) percent values over baseline were 86% after placebo (69% to 100%), 56% (41% to 76%) after gabapentin (P < .001), and 67% (49% to 88%) after CHF3381 (P < .009). Both drugs also significantly decreased the area of secondary hyperalgesia on the dominant thigh. The other pain variables were not significantly affected. Adverse events, mainly fatigue and dizziness, were mild to moderate. ⋯ This article presents the antihyperalgesic effect of CHF3381, a new NMDA receptor antagonist and reversible MAO-A inhibitor, in a human pain model and might guide the proper selection of CHF3381 doses to be used in Phase 2 studies in patients with neuropathic pain.