AUTHOR=Meregalli Cristina , Monza Laura , Jongen Joost L. M. 

TITLE=A mechanistic understanding of the relationship between skin innervation and chemotherapy-induced neuropathic pain

JOURNAL=Frontiers in Pain Research

VOLUME=Volume 3 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2022.1066069

DOI=10.3389/fpain.2022.1066069

ISSN=2673-561X

ABSTRACT=Neuropathic pain is a frequent complication of chemotherapy-induced peripheral neuropathy (CIPN). Chemotherapy-induced peripheral neuropathies may serve as a model to study mechanisms of neuropathic pain, since several common causes of peripheral neuropathy like painful diabetic neuropathy may be due to both neuropathic and non-neuropathic pain mechanisms like ischemia and inflammation. Experimental studies are ideally suited to study changes in morphology, phenotype and electrophysiologic characteristics of primary afferent neurons that are affected by chemotherapy and to correlate these changes to behaviors reflective of provoked pains, mainly hyperalgesia and allodynia. However, hyperalgesia and allodynia may only represent one aspect of human pain, i.e. the sensory-discriminative component, while patients with CIPN often describe their pain using words like annoying, tiring and dreadful, which are affective-emotional descriptors that cannot be tested in experimental animals. To understand why some patients with CIPN develop neuropathic pain and others not, and which are the components of neuropathic pain that they are experiencing, experimental and clinical pain research should be combined. Emerging evidence suggests that changes in subsets of primary afferent nerve fibers may contribute to specific aspects of neuropathic pain in both preclinical models and in patients with CIPN, as well as the role of cutaneous neuroimmune interactions is considered. Since obtaining nerve tissue in patients is problematic, analyses performed on skin biopsies from preclinical models as well as patients provide an opportunity to study changes in primary afferent nerve fibers and to correlate these changes to human pain.