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Pain Analgesic Developments in the Genomic Era

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Genomics of Pain and Co-Morbid Symptoms

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Abstract

Relief from chronic pain symptoms has been sought throughout history. Subdivided into nociceptive, inflammatory, nociplastic, and neuropathic conditions, pain requires diverse and targeted therapies for symptom management. Achieving precise and personalized targeting of pain is made possible with an understanding of the evolution and structure of pain pathways and the challenges with current therapies. Here, we present an objective discussion of various analgesic therapies over time, and note the issues and effectiveness of each approach. We begin by exploring analgesic foundations, including opioids, salicin, and cocaine. We then present chemically modified, safer alternatives such as aspirin, paracetamol, and capsaicin, among others. We follow by presenting more modern approaches, which include genetic-based therapies such as targeted inhibitors, repurposed antidepressants, and CRISPR/Cas9 genome editing. With this modern focus on pain genes such as certain voltage-gated ion channels and nerve growth factor, which selectively modulate sensory neurons, we can expect a new era of analgesia that will lead to more personalized medical care with limited side effects. In the following discussion of pain therapies, we highlight the evolution of analgesia from empirical foundations to more rational and effective pain therapies with an emphasis on the benefits of genomic targeting.

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Abbreviations

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

AP:

Action potentials

ASICs:

Acid-sensing ion channels

Aδ:

A-delta

BH4:

Tetrahydrobiopterin

CGRP:

Calcitonin gene-related peptide

CIP:

Congenital insensitivity to pain

CNS:

Central nervous system

COMT:

Catechol-O-methyltransferase

COX:

Cyclooxygenase

CRISPR:

Clustered regularly interspaced short palindromic repeats

DRG:

Dorsal root ganglion

FAAH:

Fatty acid amide hydrolase

GCH1:

GTP cyclohydrolase 1

GPCRs:

G-protein coupled receptors

GWAS:

Genome-wide association studies

MrgprX2:

Mas-related G-protein-coupled receptor

NGF:

Nerve growth factor

NK1R:

Neurokinin 1 receptor

NMDARs:

N-methyl-D-aspartate receptors

NSAIDs:

Non-steroidal anti-inflammatory drugs

NTRK1:

Tropomyosin receptor kinase A

PG:

Prostaglandin

SNRIs:

Serotonin–norepinephrine reuptake inhibitors

SP:

Substance P

STX:

Saxitoxin

TCAs:

Tricyclic antidepressants

TRPs:

Transient receptor potential channels

TTX:

Tetrodotoxin

VGCCs:

Voltage-gated calcium channels

VGKCs:

Voltage-gated potassium channels

VGSCs:

Voltage-gated sodium channels

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Acknowledgments

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Conflict of Interest

The authors declare that this study received funding from Amgen. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.

Funding

We thank Amgen for funding. RG-C was supported by the Alfonso Martín Escudero Fellowship.

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Author notes

  1. Aaron Jesuthasan and Daniel Bullock contributed equally.

Authors and Affiliations

  1. Anesthesia Department, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Aaron Jesuthasan, Daniel Bullock, Rafael González-Cano & Michael Costigan

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  1. Aaron Jesuthasan
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Correspondence to Michael Costigan .

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Editors and Affiliations

  1. Department of Pain and Translational Symptom Science, University of Maryland School of Nursing, Baltimore, MD, USA

    Susan G. Dorsey

  2. University of Connecticut School of Nursing, Storrs, CT, USA

    Angela R. Starkweather

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Jesuthasan, A., Bullock, D., González-Cano, R., Costigan, M. (2020). Pain Analgesic Developments in the Genomic Era. In: Dorsey, S., Starkweather, A. (eds) Genomics of Pain and Co-Morbid Symptoms. Springer, Cham. https://doi.org/10.1007/978-3-030-21657-3_16

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