Pain
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Randomized Controlled Trial Clinical Trial
Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy.
Tricyclic antidepressants have been reported to relieve the paresthesiae associated with peripheral neuropathies of many etiologies. We designed a randomized, double-blind, placebo-controlled, crossover trial to establish the efficacy of nortriptyline in the treatment of cis-diamminedichloroplatinum (CDDP)-induced paresthesiae. The study included 51 evaluable patients with CDDP-induced peripheral neuropathy and painful paresthesiae. ⋯ In summary, nortriptyline failed to demonstrate strong evidence of any effect on paresthesia or pain. The presence of a potential effect which appeared in the second period of the crossover design is questionable due to the observed carryover effect. Cross-validation sensitivity analysis of results support the conclusion that nortriptyline provides modest improvement at best over placebo in terms of chemotherapy-related neuropathy.
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Although activation of alpha(2)-adrenoceptors is known to play an important role in mediating antinociception, the contribution of various alpha(2)-adrenoceptor subtypes in modulating trigeminal nociception remains unknown since subtype specific agonists and antagonists are not available. The present study investigated the functional role of alpha(2)-adrenoceptor subtypes in modulating the N-methyl-D-aspartate-induced nociceptive behavior in the medullary dorsal horn by using antisense oligodeoxynucleotides to selectively knock-down the receptor subtypes. Microinjection of N-methyl-D-aspartate (2 nmol in 10 microl) through a cannula implanted dorsal to the medullary dorsal horn produced a total of 164.9+/-8.8 scratches in the facial region (n=14), and the scratching behavior lasted for 77.8+/-5.2s (n=14). ⋯ Antisense treatment reduced alpha(2A) and alpha(2C) receptor immunoreactivity in the medullary dorsal horn compared to the sense and the vehicle-treated animals. Quantitative image analysis revealed a significant decrease in pixel intensity following the antisense treatment. These results indicate that activation of alpha(2A) adrenoceptor plays an important role in mediating the antinociceptive effect of clonidine in the medullary dorsal horn in the rat.
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This study examined the degree of correspondence between lung cancer patients and their family caregivers in their perceptions of the patients' self-efficacy for managing pain and other symptoms of lung cancer, and the association of this correspondence to demographic, disease, and psychosocial variables. Thirty patients who were newly diagnosed with lung cancer and their primary family caregivers completed telephone interviews assessing the patient's symptoms, the patient's self-efficacy for managing symptoms, the quality of the relationship between the patient and caregiver, patient and caregiver psychological distress, and caregiver strain. ⋯ Caregivers were about evenly split in their tendency to overestimate versus underestimate the patient's self-efficacy. A poorer quality of relationship between the caregiver and the patient (as rated by the patient), high levels of patient-rated symptoms, and high levels of caregiver strain were associated with caregivers overestimating patient self-efficacy.
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Randomized Controlled Trial Clinical Trial
Interaction of a combination of morphine and ketamine on the nociceptive flexion reflex in human volunteers.
Experimental studies in animals have suggested that a combination of morphine and N-methyl-D-aspartate (NMDA) receptor antagonists may have additive or synergistic analgesic effects. To further study the nature of the interaction between these two classes of analgesic agents, we analyzed the effects of morphine, ketamine and their combination on electrophysiological recordings of the nociceptive flexion RIII reflex in 12 healthy volunteers. Morphine (0.1 mg/kg), ketamine (0.1 mg/kg followed by 4 microg/kg/min) or their combination were administered intravenously according to a double-blind, placebo controlled and cross-over design. ⋯ The wind-up of the RIII reflex and painful sensation was not significantly altered after the injection of placebo, ketamine, morphine or their combination. In conclusion, the present electrophysiological results in humans demonstrate a synergistic interaction between morphine and ketamine, which tends to confirm the interest of using this type of combination in the clinical context. The differential effects observed on the recruitment curve and wind-up indicate, however, that the mechanisms of the interaction between opiates and NMDA receptor antagonists are not univocal but depend on the modality of activation of the nociceptive afferents.
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The reproducibility of both the conscious experience of pain and the reproducibility of psychophysical assessments of pain remain critical, yet poorly characterized factors in pain research and treatment. To assess the reproducibility of both the pain experience and two methods of pain assessment, 15 subjects evaluated experimental heat pain during four weekly sessions. In each session, both brief (5s) and prolonged (90s) heat stimuli were utilized to determine effects of stimulus duration on reproducibility. ⋯ However, the VAS was significantly more sensitive to small differences in perceived pain intensity and pain unpleasantness, and did not exhibit some of the order effects present with the VDS. Taken together, these results indicate that the reproducibility of psychophysical ratings of pain can be maximized: (1) by averaging responses to multiple, brief stimuli; (2) by providing subjects with a training period distinct from the study period; and (3) by ensuring that interpretation of scale parameters remains constant over time. Thus, although the experiences of both experimental and clinical pain are highly variable, pain assessment procedures can be structured to minimize session-to-session variability.