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Review
. 2020 Jul;17(3):784-825.
doi: 10.1007/s13311-020-00937-z. Epub 2020 Oct 15.

Novel Analgesics with Peripheral Targets

Cosmin I Ciotu  1 , Michael J M Fischer  2
Affiliations
Review

Novel Analgesics with Peripheral Targets

Cosmin I Ciotu et al. Neurotherapeutics. 2020 Jul.

Abstract

A limited number of peripheral targets generate pain. Inflammatory mediators can sensitize these. The review addresses targets acting exclusively or predominantly on sensory neurons, mediators involved in inflammation targeting sensory neurons, and mediators involved in a more general inflammatory process, of which an analgesic effect secondary to an anti-inflammatory effect can be expected. Different approaches to address these systems are discussed, including scavenging proinflammatory mediators, applying anti-inflammatory mediators, and inhibiting proinflammatory or facilitating anti-inflammatory receptors. New approaches are contrasted to established ones; the current stage of progress is mentioned, in particular considering whether there is data from a molecular and cellular level, from animals, or from human trials, including an early stage after a market release. An overview of publication activity is presented, considering a IuPhar/BPS-curated list of targets with restriction to pain-related publications, which was also used to identify topics.

Keywords: Inflammation; cytokine; pain; receptor; sensory neuron..

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Pathophysiological concept, also serving as outline for the review. Neuronal and non-neuronal cells were separated to provide a schematic for therapeutic approaches. These are discussed in the review, first considering direct inhibition of the neurons and then antagonizing mediators acting on neurons. For modulation of the immune response, separated in local modulation and chemoattraction as well as addressing systemic inflammation, the reader is referred to the reviews of the respective topic. In the neuron, a receptor and an enzyme are visualized as targets
Fig. 2
Fig. 2
Pain targets identified by Pubmed scraping. The search was performed in April 2020. (a) “Large topics,” assessed by total publications without time restriction to indicate overall interest in this topic, sorted by the Total column. (b) “Rising topics,” sorted by the difference between the publications within the last 3 years minus the 3 years before. (c) “Novel topics,” considering targets exceeding 10 publications within the last 3 years but not in the 3 years earlier; the delta was used for sorting. The cumulative bar chart at the bottom shows the distribution by target type. VGIC = voltage-gated ion channel, GPCR = G protein-coupled receptor, T = transporter, C = catalytic receptor, L = ligand-gated ion channel, O = other
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