Abstract
Human experimental pain models are important tools in pain research. The primary aims of pain research in normal man is 1) to provide insight in pain mechanisms, 2) to provide a rational basis for clinical trials of pain relieving interventions, and 3) to confirm the anti-nociceptive effects demonstrated in animal models. Most often clinical pain is due to tissue damage leading to acute inflammation and hyperalgesia, but only few human pain models have examined pain responses in injured tissues. Therefore, models with controlled and reversible tissue trauma are needed. The human burn model is an example of such a model, and several groups have performed studies of analgesics and pain mechanisms based on the model. The thesis aims to provide a critical review of the human burn model as a tool in pain research, and to give suggestions for development of the model and future research. The pain and inflammatory responses to superficial thermal burns in skin have been studied in healthy volunteers. Burns have the potential for releasing most of the inflammatory and chemical mediators that produce sensitisation and excitation of nociceptors, and the intense nociceptive input during injury produces sensitisation of central neurones in the nociceptive pathway. Pain and hyperalgesia have been evaluated in the model by thermal, various mechanical, and electrical stimuli. The different methods of pain assessments are discussed to clarify the underlying neural mechanisms, the questions that can be addressed by the measurements, and the discrepancies in results between studies. Inflammation has been evaluated in the model by skin erythema intensity, area of flare, and blister formation. The major determinant of skin erythema intensity is the amount of blood in the most superficial part of the dermis, and burn-induced erythema may be primarily due to congestion of capillary loops and postcapillary venules. The area of flare may be used to evaluate the efferent function of heat-sensitive A delta- and C-fibre nociceptors, whereas blisters may be used to assess edema formation and the degree of injury. Hyperalgesia is induced immediately by the burns and lasts about 24 h dependent on the intensity of the heat stimulus. The burns heal without sequela. A study of the reproducibility of pain assessments in the burn model has shown that measures based on repeated measurements were significantly more reproducible than measures based on single time points. Further, within-day reproducibility was better than between-day reproducibility. Within-day variations of heat pain responses to 45 degrees C and 47 degrees C were smaller than that of pain responses to 43 degrees C, suggesting that assessments using clearly painful stimuli may be more reproducible. A methodological study also demonstrated that habituation to experimental pain developed as the study proceeded. Habituation is common in experimental pain models, and dividing analgesics and placebo evenly between the study days is one way of eliminating the effects of habituation. The use of simultaneous right-left comparisons represents the ideal design when possible. The burn model has been a valuable tool in the study of pain mechanisms. Hyperalgesia to heat in the burned area (primary hyperalgesia) is mediated by sensitisation of C-fibre mechano-heat-sensitive (CMH) nociceptors and A delta-fibre mechano-heat-sensitive (AMH) nociceptors of type I in hairy skin. A contribution from sensitised CNS neurones is likely, and the sensitisation of nociceptors is confined to the injured area. The presence of hyperalgesia to heat in normal skin surrounding a burn (secondary hyperalgesia) has been demonstrated in several studies, but the pain threshold may be unaltered. The mechanisms for primary hyperalgesia to mechanical stimuli may be both peripheral and central, but the importance of peripheral mechanisms is unclear and central mechanisms may account for mechanical hyperalgesia in both the primary and th
Bidragets oversatte titel | Inflammatory pain in experimental burns in man. |
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Originalsprog | Engelsk |
Tidsskrift | Danish Medical Bulletin |
Vol/bind | 47 |
Udgave nummer | 3 |
Sider (fra-til) | 168-195 |
Antal sider | 28 |
ISSN | 0907-8916 |
Status | Udgivet - 2000 |