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Table 2 Strengths and limitations of SMD for the study of inflammation and allergy in the skin (see text for further information and references)

From: Skin microdialysis: methods, applications and future opportunities—an EAACI position paper

Strengths

Limitations

• Can be used with equal efficacy in both healthy and diseased skin

• Allows dynamic, real-time assessment of intercellular messengers

• Provides objective information on signaling pathways between resident inflammatory cells, sensory nerves and the vasculature

• Used to explore the temporal and spatial variations in mediator or metabolic profiles

• Probes with different MWCO allow the recovery of small molecules (e.g. histamine) away from metabolic enzymes and the recovery of larger molecules (e.g. cytokines and neuropeptides)

• Use of low perfusion rates and/or the addition of colloid or lipid emulsions to the probe perfusate enhances solute recovery and limit hydrostatic fluid loss

• Can be used in conjunction with other techniques, such as laser Doppler blood flux imaging and/or tissue histology in studies of dermal inflammatory and allergic reactions

• Probe insertion is easy for the physician and relatively pain free, particularly when inserted under local anesthetic

• Probes may be left in place for up to several days

• Probes leave no scarring

• Analysis platforms are continually improving e.g. development of microfluidic platforms for continuous on-line assay of dialysates

• Introduction of a microdialysis probe into the skin is a (minimally) invasive procedure necessitating appropriate controls in order to assess whether particular molecules are truly related to the disease state under investigation or have been generated as part of the tissue response to probe implantation

• Despite application of local anesthetic, the insertion of microdialysis probes may be associated with mild pain

• Diffusion of chemicals in the skin, particularly large molecules, is very limited. Consequently, maximum probe perfusion rates need to be low (0.1–5 µl/min)

• Small recovery volumes and low concentrations of recovered chemicals make the use of assays with an appropriate sensitivity an absolute necessity

• Microdialysis recovery of high-molecular-mass substances, such as cytokines and neuropeptides, has proved particularly problematic

• Reduced recovery due to reduced solute bioavailability within the tissue space or to the adherence of bioactive molecules onto the material of the implanted probe

• Long-term studies require the use of portable pumps, which may affect the ability of study participants to move freely depending on the duration and the anatomical site

• Experienced personnel are required for optimal results (e.g. to insert probes at a consistent depth)