Changes to the activity and sensitivity of nerves innervating

Thank you to APS members Michael Morgan, Vida Nazemian, Jason Ivanusic and their colleagues Jenny Thai and Richard Song for sharing the following recent publication.

Article first published online: 3rd June 2021

Journal Reference: Pain. 2022 Feb 1;163(2):390-402.

DOI: 10.1097/j.pain.0000000000002355

Link: https://journals.lww.com/pain/ Fulltext/2022/02000/Changes_to_the_activity_ and_sensitivity_of_nerves.14.aspx

Abstract

Introduction

Whilst it is clear that osteoarthritis (OA) pain involves activation and/or sensitisation of nociceptors that innervate knee joint articular tissues, much less is known about the role of the innervation of surrounding bone. In this study, we used an animal model of mono-iodoacetate (MIA)-induced OA to test the idea that pain in OA is driven by differential contributions from nerves that innervate knee joint articular tissues vs the surrounding bone.

Methods

OA was induced by injection of MIA into the left hind knee joint of male rats. Control animals received injections of saline into the left hind knee joint. The time-course of pain behaviour (reduction in weight bearing) was assayed using the advanced dynamic weight bearing device. Histopathological changes in the knee joint and surrounding bones were assessed using Haematoxylin and Eosin at days 3 and 28 after injection of MIA or saline. In vivo, extracellular electrophysiological recordings were made for both knee joint and bone afferent neurons, at each of these timepoints, to determine if their function was altered in osteoarthritic (MIA-injected) relative to control (saline-injected) animals.

Results

There was a rapid decrease in weight bearing on the injected limb of MIA-injected animals, but not saline-injected animals, that was established by day 1, peaked at days 2 and 3 (early MIA-induced OA), and persisted to at least day 28 (late MIAinduced OA). We observed MIA-induced changes in the function of knee joint afferent neurons, but not bone afferent neurons, at day 3 when there was histological evidence of inflammation in the joint capsule, but no damage to the articular cartilage or subchondral bone. Changes in the function of bone afferent neurons were only observed at day 28, when there was additional histological evidence of damage to the articular cartilage and surrounding subchondral bone.

Conclusions

This study shows that pain early in MIA-induced OA involves altered function of nerves that innervate the joint capsule but not the underlying subchondral bone, and that pain in late MIAinduced OA involves an additional and altered function of nerves that innervate the subchondral bone. Our new finding that pain in late MIAinduced OA is associated with changes to the function of nerves that innervate subchondral bone suggests they are likely to be important targets for development of mechanism-based therapies to treat pain late in disease progression.

Implications/Discussion

Nerves that innervate bone should be considered important targets for development of mechanismbased therapies to treat pain in late OA.

Declaration

This work was supported by funding from the National Health and Medical Research Council (NHMRC; #1185981).