Pain
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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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Microelectrode recordings of impulse activity in nociceptive C fibres were performed in cutaneous fascicles of the peroneal nerve at the knee level in healthy human subjects. Mechano-heat responsive C units (CMH), mechano-insensitive but heat-responsive (CH) as well as mechano-insensitive and heat-insensitive C units (CM(i)H(i)) were identified. A subgroup of the mechano-insensitive units was readily activated by histamine. ⋯ In conclusion, we have shown that ATP injections at high concentrations activate C-nociceptors in healthy human skin, without preference for mechano-responsive or mechano-insensitive units. ATP did not sensitise human C fibres for mechanical or heat stimuli. We discuss how various mechanisms might contribute to the observed responses to ATP.
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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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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.
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Cutaneous laser stimulation activates predominantly the A-delta and C mechano-heat nociceptors. Applied to the perioral region, low intensity CO(2)-laser pulses evoke reproducible trigeminal cortical evoked potentials (LEPs). High intensity CO(2)-laser stimuli induce a reflex response in the contracted jaw-closing muscle, the so-called laser silent period (LSP). ⋯ In all experiments experimental tonic pain decreased the subjective ratings of the perioral laser stimulation (P< 0.001). Experimental tonic pain, either from muscle or from skin, induced bilateral inhibitory effects on the trigeminal laser evoked potentials and brainstem reflex responses and on the subjective ratings of the laser pulses. These effects could be mediated through the activation of segmental and suprasegmental inhibitory systems that may function interdependently.