Abstract
Pain is one of the most disabling symptoms of several clinical conditions. Neurobiologically, it is classified as nociceptive, inflammatory, neuropathic and dysfunctional. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are conventionally prescribed for the treatment of pain. Long-term administration of opioids results in the loss of analgesic efficacy, leading to increased dosage, tolerance, and addiction as the main drawbacks of their use, while the adverse effects of NSAIDs include gastric ulcer formation, intestinal bleeding, acute kidney injury, and hepatotoxicity. Lactoferrin is an iron-binding, anti-inflammatory glycoprotein that displays analgesic activities associated, in part, by interacting with the low-density lipoprotein receptor-related protein (LRP), which may result in the regulation of the DAMP–TRAF6–NFκB, NO–cGMP–ATP K+-sensitive channel and opioid receptor signaling pathways. This review summarizes and discusses for the first time the analgesic effects of lactoferrin and its presumable mechanisms based on pre-clinical trials. Given its anti-nociceptive and anti-inflammatory properties, lactoferrin may be used as an adjunct to enhance the efficacy and to decrease the tolerogenic effects of canonical therapeutic drugs prescribed for pain treatment.
Highlights
Dominique Massotte and GaryPain is an unpleasant sensory and emotional experience with double-edged sword effects
Bovine lactoferrin is a multifunctional, iron-binding glycoprotein with anti-inflammatory effects produced by reducing the activation of neural inflammatory signaling pathways associated with pain [29]
Several studies have demonstrated that the activation of nuclear factor κB (NFκB) takes place in dorsal root ganglia and the spinal cord, both of which are involved in the transmission and processing of pain
Summary
Pain is an unpleasant sensory and emotional experience with double-edged sword effects. Several drugs have been proposed as adjuncts for traditional analgesic drugs in order to increase their efficacy and to reduce their noxious side effects [15] In this regard, milk is a source of natural components with anti-nociceptive and anti-inflammatory properties, including bovine lactoferrin (bLf) [16,17]. Bovine lactoferrin is a multifunctional, iron-binding glycoprotein with anti-inflammatory effects produced by reducing the activation of neural inflammatory signaling pathways associated with pain [29] Taking into account their effects against pain, potential therapeutic and prophylactic applications of bLf and bLf-peptide derivatives to several pathologic conditions—for example, osteoarthritis—have been proposed [30]. This contribution has been proposed in order to consider the application of bLf as an adjunct to opioids and other painkiller drugs to potentiate their efficacy and help reduce the risk of tolerance, dependence, addiction, and life-threatening drug abuse
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