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CGRP and Painful Pathologies Other than Headache

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Calcitonin Gene-Related Peptide (CGRP) Mechanisms

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 255))

Abstract

CGRP has long been suspected as a mediator of arthritis pain, although evidence that CGRP directly mediates human musculoskeletal pain remains circumstantial. This chapter describes in depth the evidence surrounding CGRP’s association with pain in musculoskeletal disorders and also summarises evidence for CGRP being a direct cause of pain in other conditions. CGRP-immunoreactive nerves are present in musculoskeletal tissues, and CGRP expression is altered in musculoskeletal pain. CGRP modulates musculoskeletal pain through actions both in the periphery and central nervous system. Human observational studies, research on animal arthritis models and the few reported randomised controlled trials in humans of treatments that target CGRP provide the context of CGRP as a possible pain biomarker or mediator in conditions other than migraine.

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Abbreviations

ATF3:

Activating transcription factor-3

BDNF:

Brain-derived neurotrophic factor

CCL:

Chemokine ligand

CGRP:

Calcitonin gene-related polypeptide

CNS:

Central nervous system

COX2:

Cyclooxygenase-2

CRPS:

Complex regional pain syndrome

CSF:

Cerebrospinal fluid

DRG:

Dorsal root ganglion

GFAP:

Glial fibrillary acidic protein

GI:

Gastrointestinal

IKK-β:

Inhibitor of nuclear factor kappa-B kinase subunit beta

MIA:

Monoiodoacetate

NGF:

Nerve growth factor

NSAID:

Non-steroidal anti-inflammatory drug

OA:

Osteoarthritis

PGP9.5:

Protein gene product 9.5

PKA:

Protein kinase-A

RA:

Rheumatoid arthritis

RAMP:

Receptor activity-modifying protein

TNF:

Tumour necrosis factor-alpha

TrkA:

Receptor for nerve growth factor

TRPV:

Transient receptor potential cation channel subfamily V member

VAS:

Visual analogue scale

WOMAC:

Western Ontario and McMaster Universities Osteoarthritis Index

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Disclosures

DAW has undertaken paid consultancy to Pfizer Ltd., Eli Lilly and Company and GSK Consumer Healthcare. DMcW has been supported by Arthritis Research UK (grant number 20777) and the National Institute for Health Research (NIHR) UK via the NIHR Nottingham Biomedical Research Centre.

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Authors and Affiliations

  1. Pain Centre Versus Arthritis, NIHR Nottingham Biomedical Research Centre and Division of ROD, University of Nottingham, Nottingham, UK

    David A. Walsh & Daniel F. McWilliams

  2. Rheumatology, Sherwood Forest Hospitals NHS Foundation Trust, Nottinghamshire, UK

    David A. Walsh

Authors
  1. David A. Walsh
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  2. Daniel F. McWilliams
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Correspondence to David A. Walsh .

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Editors and Affiliations

  1. School of Cardiovascular Medicine & Sciences, King’s College London, London, UK

    Susan D. Brain

  2. Department of Health Sciences, University of Florence, Florence, Italy

    Pierangelo Geppetti

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Walsh, D.A., McWilliams, D.F. (2019). CGRP and Painful Pathologies Other than Headache. In: Brain, S., Geppetti, P. (eds) Calcitonin Gene-Related Peptide (CGRP) Mechanisms. Handbook of Experimental Pharmacology, vol 255. Springer, Cham. https://doi.org/10.1007/164_2019_242

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