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Analgesic and anti-inflammatory agents used in compounded topical creams can be selected based on having a multitude of effects at different targets in the skin, thus influencing various biological functions related to nociception and immunity [6]. Keratinocytes for instance are in close functional contact with sensory afferent nerves. In response to noxious stimuli, keratinocytes release various growth factors and pro-inflammatory cytokines [7-9]. These molecules trigger the expression of nociceptive relevant receptors, such as the adrenoceptor, on nerve fibers and other cells in the injured tissue [10,11]. Autonomic nerve endings in the skin release norepinephrine, whereas sensory nerve fibers release neuropeptides [12]. This again leads to a further production of pro-inflammatory cytokines, such as interleukin-6, creating a pain-inflammation sensitization cascade [13]. The cross-talk between nerve endings, keratinocytes and other cells of the skin make the skin a valuable target for compounded multi-target analgesic creams.

Topical analgesic creams and nociception in diabetic neuropathy: towards a rationale fundament